Selection of a Clostridium perfringens type D epsilon toxin producer via dot-blot test.

PubMed

Gonçalves, Luciana A; Lobato, Zélia I P; Silva, Rodrigo O S; Salvarani, Felipe M; Pires, Prhiscylla S; Assis, Ronnie A; Lobato, Francisco C F

2009-11-01

Clostridium perfringens type D produces enterotoxemia, an enteric disease in ruminants, also known as pulpy kidney disease. Caused by epsilon toxin, enterotoxemia is a major exotoxin produced by this microorganism. Epsilon toxin is also the main component of vaccines against this enteric disorder. In this study, a standardized dot-blot was used to choose strains of C. perfringens type D that are producers of epsilon toxin. Clones producing epsilon toxin were chosen by limiting dilution; after three passages, lethal minimum dose titers were determined by soroneutralization test in mice. These clones produced epsilon toxin 240 times more concentrated than the original strain. The presence of the epsilon toxin gene (etx) was verified by polymerase chain reaction. All clones were positive, including those determined to be negative by dot-blot tests, suggesting that mechanisms in addition to the presence of the etx gene can influence toxin production. The dot-blot test was efficient for the selection of toxigenic colonies of C. perfringens type D and demonstrated that homogeneous populations selected from toxigenic cultures produce higher titers of epsilon toxin.

In silico Analysis of Toxins of Staphylococcus aureus for Validating Putative Drug Targets.

PubMed

Mohana, Ramadevi; Venugopal, Subhashree

2017-01-01

Toxins are one among the numerous virulence factors produced by the bacteria. These are powerful poisonous substances enabling the bacteria to encounter the defense mechanism of human body. The pathogenic system of Staphylococcus aureus is evolved with various exotoxins that cause detrimental effects on human immune system. Four toxins namely enterotoxin A, exfoliative toxin A, TSST-1 and γ-hemolysin were downloaded from Uniprot database and were analyzed to understand the nature of the toxins and for drug target validation. The results inferred that the toxins were found to interact with many protein partners and no homologous sequences for human proteome were found, and based on similarity search in Drugbank, the targets were identified as novel drug targets. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Both epsilon-toxin and beta-toxin are important for the lethal properties of Clostridium perfringens type B isolates in the mouse intravenous injection model.

PubMed

Fernandez-Miyakawa, Mariano E; Fisher, Derek J; Poon, Rachael; Sayeed, Sameera; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Uzal, Francisco A

2007-03-01

Clostridium perfringens is capable of producing up to 15 toxins, including alpha-toxin (CPA), beta-toxin (CPB), epsilon-toxin (ETX), enterotoxin, beta2-toxin (CPB2), and perfringolysin O. Type B isolates, which must produce CPA, CPB, and ETX, are associated with animal illnesses characterized by sudden death or acute neurological signs, with or without intestinal damage. Type B pathogenesis in ruminants is poorly understood, with some animals showing lesions and clinical signs similar to those caused by either type C or type D infections. It is unknown whether host or environmental conditions are dominant for determining the outcome of type B disease or if disease outcomes are determined by variable characteristics of type B isolates. To help clarify this issue, 19 type B isolates were evaluated for toxin production during late-log-phase growth via quantitative Western blotting and by biological activity assays. Most type B isolates produced CPB levels similar to those produced by type C isolates in vitro and have the potential to produce genotype C-like disease. The lethality of type B isolate supernatants administered intravenously to mice was evaluated with or without prior trypsin treatment, and monoclonal antibody neutralization studies also were performed. Correlation analyses comparing toxin levels in type B supernatants versus lethality and neutralization studies both found that the main contributor to lethality without pretreatment with trypsin was CPB, whereas neutralization studies indicated that CPB and ETX were both important after trypsin pretreatment. At least part of the CPB produced by type B isolates remained active after trypsin treatment. However, the overall lethalities of most supernatants were lower after trypsin pretreatment. Also, there was a significant association between ETX, CPB2, and CPA production in vitro among type B isolates. However, our results suggest that both CPB and ETX are likely the most important contributors to the

Boron Nitride Nanoribbons from Exfoliation of Boron Nitride Nanotubes

NASA Technical Reports Server (NTRS)

Hung, Ching-Cheh; Hurst, Janet; Santiago, Diana

2017-01-01

Two types of boron nitride nanotubes (BNNTs) were exfoliated into boron nitride nanoribbons (BNNR), which were identified using transmission electron microscopy: (1) commercial BNNTs with thin tube walls and small diameters. Tube unzipping was indicated by a large decrease of the sample's surface area and volume for pores less than 2 nm in diameter. (2) BNNTs with large diameters and thick walls synthesized at NASA Glenn Research Center. Here, tube unraveling was indicated by a large increase in external surface area and pore volume. For both, the exfoliation process was similar to the previous reported method to exfoliate commercial hexagonal boron nitride (hBN): Mixtures of BNNT, FeCl3, and NaF (or KF) were sequentially treated in 250 to 350 C nitrogen for intercalation, 500 to 750 C air for exfoliation, and finally HCl for purification. Property changes of the nanosized boron nitride throughout this process were also similar to the previously observed changes of commercial hBN during the exfoliation process: Both crystal structure (x-ray diffraction data) and chemical properties (Fourier-transform infrared spectroscopy data) of the original reactant changed after intercalation and exfoliation, but most (not all) of these changes revert back to those of the reactant once the final, purified products are obtained.

Design and synthesis of type-III mimetics of ShK toxin

NASA Astrophysics Data System (ADS)

Baell, Jonathan B.; Harvey, Andrew J.; Norton, Raymond S.

2002-04-01

ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.

Management of exfoliative glaucoma: challenges and solutions.

PubMed

Holló, Gábor; Katsanos, Andreas; Konstas, Anastasios Gp

2015-01-01

Exfoliative glaucoma is the most common type of secondary open-angle glaucoma worldwide. It is characterized by high intraocular pressure (IOP) and worse 24-hour IOP characteristics. In order to minimize progression, treatment of exfoliative glaucoma has to provide a low long-term mean IOP and good 24-hour IOP control. To achieve these goals, fixed-dose combination eye drops, argon and selective laser trabeculoplasty, and various forms of surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, ab interno trabeculotomy, trabecular aspiration, and cataract surgery) all need to be considered during the long-term management of the disease. Since exfoliative glaucoma is a disease of the elderly, and is frequently associated with systemic vascular disease, interdisciplinary consultations are of great clinical importance. These management aspects and the current medical, laser, and surgical results are covered in this review, with a special focus on the needs of the general ophthalmologist.

Management of exfoliative glaucoma: challenges and solutions

PubMed Central

Holló, Gábor; Katsanos, Andreas; Konstas, Anastasios GP

2015-01-01

Exfoliative glaucoma is the most common type of secondary open-angle glaucoma worldwide. It is characterized by high intraocular pressure (IOP) and worse 24-hour IOP characteristics. In order to minimize progression, treatment of exfoliative glaucoma has to provide a low long-term mean IOP and good 24-hour IOP control. To achieve these goals, fixed-dose combination eye drops, argon and selective laser trabeculoplasty, and various forms of surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, ab interno trabeculotomy, trabecular aspiration, and cataract surgery) all need to be considered during the long-term management of the disease. Since exfoliative glaucoma is a disease of the elderly, and is frequently associated with systemic vascular disease, interdisciplinary consultations are of great clinical importance. These management aspects and the current medical, laser, and surgical results are covered in this review, with a special focus on the needs of the general ophthalmologist. PMID:26045655

Clinical recovery and circulating botulinum toxin type F in adult patient.

PubMed

Sobel, Jeremy; Dill, Tracy; Kirkpatrick, Christina L; Riek, Laurel; Luedtke, Patrick; Damrow, Todd A

2009-06-01

A 56-year-old woman in Helena, Montana, USA, who showed clinical signs of paralysis, received antitoxins to botulinum toxins A, B, and E within 24 hours; nevertheless, symptoms progressed to complete quadriplegia. On day 8, she began moving spontaneously, even though blood tests later showed botulinum toxin type F remained.

Clostridium perfringens type A–E toxin plasmids

PubMed Central

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

2014-01-01

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

Clinical Recovery and Circulating Botulinum Toxin Type F in Adult Patient

PubMed Central

Dill, Tracy; Kirkpatrick, Christina L.; Riek, Laurel; Luedtke, Patrick; Damrow, Todd A.

2009-01-01

A 56-year-old woman in Helena, Montana, USA, who showed clinical signs of paralysis, received antitoxins to botulinum toxins A, B, and E within 24 hours; nevertheless, symptoms progressed to complete quadriplegia. On day 8, she began moving spontaneously, even though blood tests later showed botulinum toxin type F remained. PMID:19523306

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems.

PubMed

Chan, Wai Ting; Espinosa, Manuel; Yeo, Chew Chieng

2016-01-01

In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I-VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

PubMed Central

Chan, Wai Ting; Espinosa, Manuel; Yeo, Chew Chieng

2016-01-01

In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I–VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall

Serological Studies of Types A, B, and E Botulinal Toxins by Passive Hemagglutination and Bentonite Flocculation

PubMed Central

Johnson, H. M.; Brenner, K.; Angelotti, R.; Hall, H. E.

1966-01-01

Johnson, H. M. (Robert A. Taft Sanitary Engineering Center, Cincinnati, Ohio), K. Brenner, R. Angelotti, and H. E. Hall. Serological studies of types A, B, and E botulinal toxins by passive hemagglutination and bentonite flocculation. J. Bacteriol. 91:967–974. 1966.—Formalinized sheep red blood cells (SRBC), sensitized with types A, B, and E botulinal toxoids and toxins by bis-diazotized benzidine (BDB), were tested against A, B, and E antitoxins prepared in horses and rabbits. Type B antitoxin cross-reacted with A toxoid SRBC, but the reciprocal cross-reaction was not observed. E toxin SRBC were specifically agglutinated by E antitoxin. Flocculation of antigen-sensitized bentonite particles was less sensitive in titration of antitoxin than hemagglutination. Also, reciprocal cross-reactions were observed between types A and B antitoxins. Cross-reactions in both serological tests were eliminated by titration of antitoxins in the presence of the heterologous antigens, with no inhibitory effect on the homologous antitoxins. Generally, equine antitoxins were less suitable for agglutinations, especially of antigen-sensitized bentonite particles. Types A, B, and E antitoxins were specifically inhibited by 43, 39, and 245 mouse ld50 of their respective homologous toxins in the hemagglutination-inhibition test. A, B, and E antitoxins were specifically inhibited by 500, 950, and 1,500 mouse ld50 of their respective homologous toxins in bentonite flocculation inhibitions. Formalinized SRBC sensitized with rabbit types A and B antitoxins by BDB were respectively clumped by as little as 0.75 to 1.3 mouse ld50 of A toxin and 2.3 ld50 of B toxin, whereas bentonite particles sensitized by the same antitoxins were specifically clumped by 150 ld50 of A toxin and 630 ld50 of B toxin. E antitoxin sensitization of SRBC or bentonite particles was not successful. Evidence is presented that indicates that the serological procedures are applicable to the detection of botulinal toxins

Toward Single Atom Chains with Exfoliated Tellurium.

PubMed

Churchill, Hugh O H; Salamo, Gregory J; Yu, Shui-Qing; Hironaka, Takayuki; Hu, Xian; Stacy, Jeb; Shih, Ishiang

2017-08-10

We demonstrate that the atom chain structure of Te allows it to be exfoliated as ultra-thin flakes and nanowires. Atomic force microscopy of exfoliated Te shows that thicknesses of 1-2 nm and widths below 100 nm can be exfoliated with this method. The Raman modes of exfoliated Te match those of bulk Te, with a slight shift (4 cm -1 ) due to a hardening of the A 1 and E modes. Polarized Raman spectroscopy is used to determine the crystal orientation of exfoliated Te flakes. These experiments establish exfoliation as a route to achieve nanoscale trigonal Te while also demonstrating the potential for fabrication of single atom chains of Te.

Determination of staphylococcal exotoxins, SCCmec types, and genetic relatedness of Staphylococcus intermedius group isolates from veterinary staff, companion animals, and hospital environments in Korea

PubMed Central

Youn, Jung-Ho; Ahn, Kuk Ju; Lim, Suk-Kyung

2011-01-01

The Staphylococcus (S.) intermedius group (SIG) has been a main research subject in recent years. S. pseudintermedius causes pyoderma and otitis in companion animals as well as foodborne diseases. To prevent SIG-associated infection and disease outbreaks, identification of both staphylococcal exotoxins and staphylococcal cassette chromosome mec (SCCmec) types among SIG isolates may be helpful. In this study, it was found that a single isolate (one out of 178 SIG isolates examined) harbored the canine enterotoxin SEC gene. However, the S. intermedius exfoliative toxin gene was found in 166 SIG isolates although the S. aureus-derived exfoliative toxin genes, such as eta, etb and etd, were not detected. SCCmec typing resulted in classifying one isolate as SCCmec type IV, 41 isolates as type V (including three S. intermedius isolates), and 10 isolates as non-classifiable. Genetic relatedness of all S. pseudintermedius isolates recovered from veterinary staff, companion animals, and hospital environments was determined by pulsed-field gel electrophoresis. Strains having the same band patterns were detected in S. pseudintermedius isolates collected at 13 and 18 months, suggesting possible colonization and/or expansion of a specific S. pseudintermedius strain in a veterinary hospital. PMID:21897094

Determination of staphylococcal exotoxins, SCCmec types, and genetic relatedness of Staphylococcus intermedius group isolates from veterinary staff, companion animals, and hospital environments in Korea.

PubMed

Youn, Jung-Ho; Koo, Hye Cheong; Ahn, Kuk Ju; Lim, Suk-Kyung; Park, Yong Ho

2011-09-01

The Staphylococcus (S.) intermedius group (SIG) has been a main research subject in recent years. S. pseudintermedius causes pyoderma and otitis in companion animals as well as foodborne diseases. To prevent SIG-associated infection and disease outbreaks, identification of both staphylococcal exotoxins and staphylococcal cassette chromosome mec (SCCmec) types among SIG isolates may be helpful. In this study, it was found that a single isolate (one out of 178 SIG isolates examined) harbored the canine enterotoxin SEC gene. However, the S. intermedius exfoliative toxin gene was found in 166 SIG isolates although the S. aureus-derived exfoliative toxin genes, such as eta, etb and etd, were not detected. SCCmec typing resulted in classifying one isolate as SCCmec type IV, 41 isolates as type V (including three S. intermedius isolates), and 10 isolates as non-classifiable. Genetic relatedness of all S. pseudintermedius isolates recovered from veterinary staff, companion animals, and hospital environments was determined by pulsed-field gel electrophoresis. Strains having the same band patterns were detected in S. pseudintermedius isolates collected at 13 and 18 months, suggesting possible colonization and/or expansion of a specific S. pseudintermedius strain in a veterinary hospital.

Thermal influences on spontaneous rock dome exfoliation

USGS Publications Warehouse

Collins, Brian D.; Stock, Greg M.; Eppes, Martha C.; Lewis, Scott W.; Corbett, Skye C.; Smith, Joel B.

2018-01-01

Rock domes, with their onion-skin layers of exfoliation sheets, are among the most captivating landforms on Earth. Long recognized as integral in shaping domes, the exact mechanism(s) by which exfoliation occurs remains enigmatic, mainly due to the lack of direct observations of natural events. In August 2014, during the hottest days of summer, a granitic dome in California, USA, spontaneously exfoliated; witnesses observed extensive cracking, including a ~8000 kg sheet popping into the air. Subsequent exfoliation episodes during the following two summers were recorded by instrumentation that captured—for the first time—exfoliation deformation and stress conditions. Here we show that thermal cycling and cumulative dome surface heating can induce subcritical cracking that culminates in seemingly spontaneous exfoliation. Our results indicate that thermal stresses—largely discounted in dome formation literature—can play a key role in triggering exfoliation and therefore may be an important control for shaping domes worldwide.

Thermally exfoliated graphite oxide

NASA Technical Reports Server (NTRS)

Prud'Homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor); Abdala, Ahmed (Inventor)

2011-01-01

A modified graphite oxide material contains a thermally exfoliated graphite oxide with a surface area of from about 300 sq m/g to 2600 sq m/g, wherein the thermally exfoliated graphite oxide displays no signature of the original graphite and/or graphite oxide, as determined by X-ray diffraction.

Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

PubMed

Kim, Sena; Ahn, Moonsang; Piao, Yibo; Ha, Yooseok; Choi, Dae-Kyoung; Yi, Min-Hee; Shin, Nara; Kim, Dong Woon; Oh, Sang-Ha

2016-11-01

One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts. In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway. Therapeutic, V.

Endoribonuclease type II toxin-antitoxin systems: functional or selfish?

PubMed

Ramisetty, Bhaskar Chandra Mohan; Santhosh, Ramachandran Sarojini

2017-07-01

Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids. However, the programmed cell death and persistence hypotheses have been challenged because of conceptual, methodological and/or strain issues. In an alternative view, chromosomal TAs seem to be retained by virtue of addiction at two levels: via a poison-antidote combination (TA proteins) and via transcriptional reprogramming of the downstream core gene (due to integration). Any perturbation in the chromosomal TA operons could cause fitness loss due to polar effects on the downstream genes and hence be detrimental under natural conditions. The endoribonucleases encoding chromosomal TAs are most likely selfish DNA as they are retained by bacterial genomes, even though TAs do not confer a direct advantage via the TA proteins. TAs are likely used by various replicons as 'genetic arms' that allow the maintenance of themselves and associated genetic elements. TAs seem to be the 'selfish arms' that make the best use of the 'arms race' between bacterial genomes and plasmids.

[Morphologic changes in cultures of different tissues exposed to the toxins of C1. perfringens types B, C, E and F].

PubMed

Ermakova, M P; Zemlianitskaia, E P

1975-11-01

There were revealed morphological peculiarities of the action of C1. perfringens toxins, types B, C, D, E and F on the cultures of fibroblasts of chick embryo, amniotic cells and intestinal tissue. The toxin type B was characterized by a marked vocuolization of the cell cytoplasm; the action of the toxin of type C was expressed in the swelling of the nuclei and the lysis of the chromatine substance, the toxin of type E casued kariorhexis, and the toxin of type F--hyperchromatosis of the nuclei. All the cultures proved to be insensitive to the toxin of type D. Peculiarity of the morphological affection of the cells permitted to differentiate toxin of type B in the cultures of the fibroblasts of chick embryo, whereas the toxins of types C, E and F--in the cultures of the amniotic cells under control of the reaction of neutralization with the homologous antitoxic sera.

Covalent functionalization and passivation of exfoliated black phosphorus via aryl diazonium chemistry.

PubMed

Ryder, Christopher R; Wood, Joshua D; Wells, Spencer A; Yang, Yang; Jariwala, Deep; Marks, Tobin J; Schatz, George C; Hersam, Mark C

2016-06-01

Functionalization of atomically thin nanomaterials enables the tailoring of their chemical, optical and electronic properties. Exfoliated black phosphorus (BP)-a layered two-dimensional semiconductor-exhibits favourable charge-carrier mobility, tunable bandgap and highly anisotropic properties, but it is chemically reactive and degrades rapidly in ambient conditions. Here we show that covalent aryl diazonium functionalization suppresses the chemical degradation of exfoliated BP even after three weeks of ambient exposure. This chemical modification scheme spontaneously forms phosphorus-carbon bonds, has a reaction rate sensitive to the aryl diazonium substituent and alters the electronic properties of exfoliated BP, ultimately yielding a strong, tunable p-type doping that simultaneously improves the field-effect transistor mobility and on/off current ratio. This chemical functionalization pathway controllably modifies the properties of exfoliated BP, and thus improves its prospects for nanoelectronic applications.

Identification of four type II toxin-antitoxin systems in Actinobacillus pleuropneumoniae.

PubMed

Zheng, Chengkun; Zhao, Xigong; Zeng, Ting; Cao, Manman; Xu, Jiali; Shi, Guolin; Li, Jinquan; Chen, Huanchun; Bei, Weicheng

2017-07-03

Toxin-antitoxin (TA) systems are small genetic elements that are widely prevalent in the genomes of bacteria and archaea. These modules have been identified in various bacteria and proposed to play an important role in bacterial physiology and virulence. However, their presence in the genomes of Actinobacillus species has received no attention. In this study, we describe the identification of four type II TA systems in Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia. Reverse transcription PCR analysis revealed that the genes encoding the toxin and antitoxin are co-transcribed. Overexpression of each toxin inhibited the growth of Escherichia coli, and the toxic effect could be counteracted by its cognate antitoxin. The pull-down experiments demonstrated that each toxin interacts with its cognate antitoxin in vivo. The promoter activity assays showed that each antitoxin could autoregulate either positively or negatively the TA operon transcription. In addition, the APJL_0660/0659 TA system is present in half of the detected serovars of A. pleuropneumoniae, while the others are present in all. Collectively, we identified four type II TA systems in A. pleuropneumoniae, and this study has laid the foundation for further functional study of these TA systems. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Botulinum toxin type A as treatment of partially accommodative esotropia.

PubMed

Flores-Reyes, E M; Castillo-López, M G; Toledo-Silva, R; Vargas-Ortega, J; Murillo-Correa, C E; Aguilar-Ruiz, A

2016-03-01

To determine the effectiveness of a botulinum toxin type A injection in both medial rectus muscles in patients with partially accommodative esotropia. Residual deviation and stability of strabismus were evaluated at 18 months follow up. A prospective, analytical, quasi-experimental study was conducted on a cohort of 21 patients who underwent total cycloplegic refraction and with a residual deviation of at least 14 DP. A botulinum toxin type A dose of 5 IU was injected into each medial rectus muscle for a residual deviation greater than 18 DP, with a dose of 2.5 IU being used for a deviation between 14 and 18 DP. Multivariate logistic regression analyses were performed to relate residual deviation to variables recorded as potential predictors. A total of 21 patients were included, 33.3% (n=7) males and 66.6% (n=14) females. Mean visual acuity was -.28±.25 logMAR for right eye (range 0 to -1) and -.42±.31 logMAR for left eye (range 0 to -1.3). Mean angle of residual deviation before application of botulinum toxin was 40.95±8.6DP without spectacles correction, and 22.3±7.99 DP with full cycloplegic refraction. Adverse effects were ptosis in 14.2% (n=3), diplopia 23.8% (n=5), and vertical deviation in 33% (n=7). One patient had a poor outcome, therefore required surgical treatment. At one year follow up, 85.71% of patients showed good results with esotropia of 12 DP or less, dropping to 71.43% at 18 months of follow up. Botulinum toxin type A is an effective long-term treatment with a good response in 71.43% of patients. No predictors of good response were demonstrated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Sequential structural and optical evolution of MoS2 by chemical synthesis and exfoliation

NASA Astrophysics Data System (ADS)

Kim, Ju Hwan; Kim, Jungkil; Oh, Si Duck; Kim, Sung; Choi, Suk-Ho

2015-06-01

Various types of MoS2 structures are successfully obtained by using economical and facile sequential synthesis and exfoliation methods. Spherically-shaped lumps of multilayer (ML) MoS2 are prepared by using a conventional hydrothermal method and were subsequently 1st-exfoliated in hydrazine while being kept in autoclave to be unrolled and separated into five-to-six-layer MoS2 pieces of several-hundred nm in size. The MoS2 MLs are 2nd-exfoliated in sodium naphthalenide under an Ar ambient to finally produce bilayer MoS2 crystals of ~100 nm. The sequential exfoliation processes downsize MoS2 laterally and reduce its number of layers. The three types of MoS2 allotropes exhibit particular optical properties corresponding to their structural differences. These results suggest that two-dimensional MoS2 crystals can be prepared by employing only chemical techniques without starting from high-pressure-synthesized bulk MoS2 crystals.

Covalent functionalization and passivation of exfoliated black phosphorus via aryl diazonium chemistry

NASA Astrophysics Data System (ADS)

Ryder, Christopher R.; Wood, Joshua D.; Wells, Spencer A.; Yang, Yang; Jariwala, Deep; Marks, Tobin J.; Schatz, George C.; Hersam, Mark C.

2016-06-01

Functionalization of atomically thin nanomaterials enables the tailoring of their chemical, optical and electronic properties. Exfoliated black phosphorus (BP)—a layered two-dimensional semiconductor—exhibits favourable charge-carrier mobility, tunable bandgap and highly anisotropic properties, but it is chemically reactive and degrades rapidly in ambient conditions. Here we show that covalent aryl diazonium functionalization suppresses the chemical degradation of exfoliated BP even after three weeks of ambient exposure. This chemical modification scheme spontaneously forms phosphorus-carbon bonds, has a reaction rate sensitive to the aryl diazonium substituent and alters the electronic properties of exfoliated BP, ultimately yielding a strong, tunable p-type doping that simultaneously improves the field-effect transistor mobility and on/off current ratio. This chemical functionalization pathway controllably modifies the properties of exfoliated BP, and thus improves its prospects for nanoelectronic applications.

Identification of RNA species in the RNA-toxin complex and structure of the complex in Clostridium botulinum type E.

PubMed

Kitamura, Masaru

2002-02-15

Clostridium botulinum type E toxin was isolated in the form of a complex with RNA(s) from bacterial cells. Characterization of the complexed RNA remains to be elucidated. The RNA is identified here as ribosomal RNA (rRNA) having 23S and 16S components. The RNA-toxin complexes were found to be made up of three types with different molecular sizes. The three types of RNA-toxin complex are toxin bound to both the 23S and 16S rRNA, toxin bound to the 16S rRNA and a small amount of 23S rRNA, and toxin bound only to the 16S rRNA. ©2002 Elsevier Science (USA).

Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

PubMed Central

Sager, Cristian; Burek, Carol; Durán, Victor; Corbetta, Juan Pablo; Weller, Santiago; Juan, Bortagaray; López, Juan Carlos

2012-01-01

When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative. The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory with a low incidence of adverse effects. Due to its transitory effect, it is necessary to repeat the injections in order to sustain its therapeutic effect. In these review article we talk about Mechanism of Action, Indications, effects, administration and presentations of the Botulinum Neurotoxin Type A in pediatric patients. Also, we make references to controversial issues surrounding its use. A bibliographic search was done selecting articles and revisions from Pubmed. The key words used were botulinum toxin A, neurogenic bladder, and children. The search was limited to patients younger than 18 years of age and reports written in English in the past ten years. PMID:22720170

Delayed Antitoxin Treatment of Two Adult Patients with Botulism after Cosmetic Injection of Botulinum Type A Toxin.

PubMed

Fan, Kit-Ling; Wang, Yan-Li; Chu, Gary; Leung, Ling-Pong

2016-12-01

Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. Two female adult patients with clinical botulism after botulinum toxin type A injection are described. Both patients had received intramuscular injection of botulinum toxin type A in their calves at beauty shops for cosmetic reasons. They developed clinical botulism about 3 days postinjection. They presented late to the emergency department. Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom onset, respectively. Both patients showed clinical improvement after the antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may present to the emergency department with systemic effects of botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum antitoxin treatment was observed in two patients who were given the drug 7 and 9 days after the occurrence of symptoms of botulism after cosmetic injection of botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even if patients present late. Copyright © 2016 Elsevier Inc. All rights reserved.

Epsilon toxin: a fascinating pore-forming toxin.

PubMed

Popoff, Michel R

2011-12-01

Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β-pore-forming toxins including aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β-barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons. © 2011 The Author Journal compilation © 2011 FEBS.

Longitudinal Phonatory Characteristics after Botulinum Toxin Type A Injection.

ERIC Educational Resources Information Center

Fisher, Kimberly V.; And Others

1996-01-01

A study investigated the long-term effects of a Botulinum Toxin Type A injection on the glottal competency of a man with adductor spasmodic dysphonia. Results suggest that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. (CR)

Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes.

PubMed

Steele, Margaret I; Kwong, Waldan K; Whiteley, Marvin; Moran, Nancy A

2017-12-12

Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi , a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola , a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections.

PubMed

Sina, Haziz; Ahoyo, Théodora A; Moussaoui, Wardi; Keller, Daniel; Bankolé, Honoré S; Barogui, Yves; Stienstra, Ymkje; Kotchoni, Simeon O; Prévost, Gilles; Baba-Moussa, Lamine

2013-08-08

Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin.

Inhibition of cholera toxin and other AB toxins by polyphenolic compounds

USDA-ARS?s Scientific Manuscript database

All AB-type protein toxins have intracellular targets despite an initial extracellular location. These toxins use different methods to reach the cytosol and have different effects on the target cell. Broad-spectrum inhibitors against AB toxins are therefore hard to develop because the toxins use dif...

Edge orientations of mechanically exfoliated anisotropic two-dimensional materials

NASA Astrophysics Data System (ADS)

Yang, Juntan; Wang, Yi; Li, Yinfeng; Gao, Huajian; Chai, Yang; Yao, Haimin

2018-03-01

Mechanical exfoliation is an approach widely applied to prepare high-quality two-dimensional (2D) materials for investigating their intrinsic physical properties. During mechanical exfoliation, in-plane cleavage results in new edges whose orientations play an important role in determining the properties of the as-exfoliated 2D materials especially those with high anisotropy. Here, we systematically investigate the factors affecting the edge orientation of 2D materials obtained by mechanical exfoliation. Our theoretical study manifests that the fractured direction during mechanical exfoliation is determined synergistically by the tearing direction and material anisotropy of fracture energy. For a specific 2D material, our theory enables us to predict the possible edge orientations of the exfoliated flakes as well as their occurring probabilities. The theoretical prediction is experimentally verified by examining the inter-edge angles of the exfoliated flakes of four typical 2D materials including graphene, MoS2, PtS2, and black phosphorus. This work not only sheds light on the mechanics of exfoliation of the 2D materials but also provides a new approach to deriving information of edge orientations of mechanically exfoliated 2D materials by data mining of their macroscopic geometric features.

A Micro-Raman Study of Exfoliated Few-Layered n-Type Bi2Te2.7Se0.3 (Postprint)

DTIC Science & Technology

2017-11-28

filtering process. 15. SUBJECT TERMS thermoelectric (TE); bulk n-type Bi2Te2.7Se0.3; chemical or mechanical exfoliation; densification; restacking...enhanced TE properties via the energy filtering process. Bulk pristine (undoped) and doped Bi2Te3 are some of the most efficient room temperature...and charged defect scattering dominates. Puneet et al. attributed the increase in n to selective filtering of charge carriers by positively charged

Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes

PubMed Central

Whiteley, Marvin

2017-01-01

ABSTRACT Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola, a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli. Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo. Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. PMID:29233893

Graphene via Molecule-Assisted Ultrasound-Induced Liquid-Phase Exfoliation: A Supramolecular Approach

NASA Astrophysics Data System (ADS)

Eredia, Matilde; Ciesielski, Artur; Samorì, Paolo

2016-12-01

Graphene is a two-dimensional (2D) material holding unique optical, mechanical, thermal and electrical properties. The combination of these exceptional characteristics makes graphene an ideal model system for fundamental physical and chemical studies as well as technologically ground breaking material for a large range of applications. Graphene can be produced either following a bottom-up or top-down method. The former is based on the formation of covalent networks suitably engineered molecular building blocks undergoing chemical reaction. The latter takes place through the exfoliation of bulk graphite into individual graphene sheets. Among them, ultrasound-induced liquid-phase exfoliation (UILPE) is an appealing method, being very versatile and applicable to different environments and on various substrate types. In this chapter, we describe the recently reported methods to produce graphene via molecule-assisted UILPE of graphite, aiming at the generation of high-quality graphene. In particular, we will focus on the supramolecular approach, which consists in the use of suitably designed organic molecules during the UILPE of graphite. These molecules act as graphene dispersion-stabilizing agents during the exfoliation. This method relying on the joint effect of a solvent and ad hoc molecules to foster the exfoliation of graphite into graphene in liquid environment represents a promising and modular method toward the improvement of the process of UILPE in terms of the concentration and quality of the exfoliated material. Furthermore, exfoliations in aqueous and organic solutions are presented and discussed separately.

Cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia.

PubMed

Kazerooni, Rashid; Broadhead, Christine

2015-02-15

A cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia (CD) was conducted. A cost-utility analysis of botulinum toxin type A products was conducted from the U.S. government perspective using a decision-analysis model with a one-year time horizon. Probabilities of the model were taken from several studies using the three botulinum type A products approved by the Food and Drug Administration for the treatment of CD: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). The main outcome measurement was successful treatment response with botulinum toxin type A, measured in quality-adjusted life years (QALYs). Response was defined as a patient who experienced improvement of CD symptoms without a severe adverse event. Probabilistic sensitivity analysis was conducted to test robustness of the base-case results. All three botulinum toxin type A agents were cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Xeomin was the most cost-effective with a cost-effectiveness ratio of $27,548 per QALY. Xeomin was dominant over the alternative agents with equivalent efficacy outcomes and lower costs. Dysport had the second lowest cost-effectiveness ratio ($36,678), followed by Botox ($49,337). The probabilistic sensitivity analysis supported the results of the base-case analysis. Dysport was associated with the lowest wastage (2.2%), followed by Xeomin (10%) and Botox (22.9%). A cost-utility analysis found that Xeomin was the more cost-effective botulinum toxin type A product compared with Botox and Dysport for the treatment of CD. Wastage associated with the respective products may have a large effect on the cost-effectiveness of the agents. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Granite Exfoliation, Cosumnes River Watershed, Somerset, California

NASA Astrophysics Data System (ADS)

Crockett, I. Q.; Neiss-Cortez, M.

2015-12-01

In the Sierra Nevada foothills of California there are many exposed granite plutons within the greater Sierra Nevada batholith. As with most exposed parts of the batholith, these granite slabs exfoliate. It is important to understand exfoliation for issues of public safety as it can cause rock slides near homes, roads, and recreation areas. Through observation, measuring, and mapping we characterize exfoliation in our Cosumnes River watershed community.

Botulinum toxin type a for chronic migraine.

PubMed

Ashkenazi, Avi

2010-03-01

Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.

The Mechanism of the Beneficial Effect of Botulinum Toxin Type a Used in the Treatment of Temporomandibular Joints Dysfunction.

PubMed

Malgorzata, Pihut; Piotr, Ceranowicz; Edward, Kijak

2017-01-01

In the course of temporomandibular joint, dysfunctions very often occur to the excessive increase in tension of masticatory muscles, so the main aim of the treatment is reduction of this hypertension of muscles. For this reason, we use botulinum toxin type A, which is produced by Grampositive Clostridium bacteria. There are six serotypes of the toxin: A, B, C, D, E, F, and G. The botulinum toxin type A was first isolated in 1920s. Today, botulinum toxin type A is used increasingly more often as an efficient and patient-friendly therapy in neurology, ophthalmology, neurology, urology and laryngology. The aim of the article was to review the literature and description of the current knowledge concerned with mechanism of action of botulinum toxin type A, clinical applications and metabolic determinants of muscle contraction and the beneficial effect of this drug on the state of muscle tension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

PubMed

Dai, Alper I; Demiryürek, Abdullah T

2017-06-01

The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P < .001). The modified Ashworth scale improved significantly following botulinum toxin type A in the serial casting group ( P < .05), but not in botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

Dual Toxin-Producing Strain of Clostridium botulinum Type Bf Isolated from a California Patient with Infant Botulism

PubMed Central

Barash, Jason R.; Arnon, Stephen S.

2004-01-01

A retrospective study of Clostridium botulinum strains isolated from patients from California with infant botulism identified the fourth known C. botulinum strain that produces both type B and type F botulinum toxins. This unique strain represented 0.12% of the California infant botulism case isolates from 1976 to 2003. The relative concentrations of type B and F toxins produced were temperature dependent. PMID:15071029

Exfoliated cells of the oral mucosa for HPV typing by SPF10 in head and neck cancer.

PubMed

Morbini, Patrizia; Dal Bello, Barbara; Alberizzi, Paola; Mannarini, Laura; Mevio, Niccolò; Bertino, Giulia; Benazzo, Marco

2012-12-01

HPV infection in the superficial cells of the oral mucosa could reflect the presence of HPV in head and neck cancer cells. Due mostly to the use of heterogeneous analytical methods, discordant data exist in the literature regarding the agreement between the presence of HPV in non-neoplastic oral mucosa and in tumour tissue from the same patient. The presence of HPV DNA and viral types were compared in paired cytological and biopsy samples from 56 patients with head and neck neoplastic and preneoplastic lesions using the highly sensitive SPF10 LiPA Extra assay, which has been validated recently for formalin-fixed paraffin-embedded tissue using paired cervical cytology and biopsy samples. Kappa statistics were used to measure the inter-rater agreement. The overall agreement with respect to HPV infection was 96.43% (kappa=0.8367). For 76.79% of subjects (kappa=0.6937), the same number of HPV types was detected in cytological and biopsy specimens. The overall positive typing agreement was 90.90%, comprising 130 out of 143 individual HPV type analyses. The agreement shown was good for HPV 18, 44, 45, 54 and 66 (kappa=0.6585-0. 7321), excellent for HPV 6, 16, 40, and 54 (kappa=0.8108-0.8679), and absolute for HPV 11, 31, 33, 35, 39, 51, 52, 53, 59, 74, and 69-71 (kappa=1.0000). The high sensitivity of the SPF10 LiPA and its excellent performance both for recognising HPV infection and for identifying the viral types present in tumour tissue and in oral exfoliated cells make it a useful method for the assessment of HPV infection in patients with head and neck cancer. The excellent agreement for HPV infection and genotyping in paired samples suggests that oral exfoliated cells can be used for HPV detection in the head and neck region. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of different fluids for detection of Clostridium perfringens type D epsilon toxin in sheep with experimental enterotoxemia.

PubMed

Layana, Jorge E; Fernandez Miyakawa, Mariano E; Uzal, Francisco A

2006-08-01

Enterotoxemia caused by Clostridium perfringens type D is a highly lethal disease of sheep, goats and other ruminants. The diagnosis of this condition is usually confirmed by detection of epsilon toxin, a major exotoxin produced by C. perfringens types B and D, in the intestinal content of affected animals. It has been suggested that other body fluids can also be used for detection of epsilon toxin. This study was performed to evaluate the usefulness of intestinal content versus other body fluids in detecting epsilon toxin in cases of sheep enterotoxemia. Samples of duodenal, ileal and colon contents, pericardial and abdominal fluids, aqueous humor and urine from 15 sheep with experimentally induced enterotoxemia, were analysed for epsilon toxin using a capture ELISA. Epsilon toxin was detected in 92% of the samples of ileal content, 64% of the samples of duodenal content, 57% of the samples of colon content and in 7% of the samples of pericardial fluid and aqueous humor. No epsilon toxin was found in samples of abdominal fluid or urine from the animals with enterotoxemia or in any samples from six clinically healthy sheep used as negative controls. The results of this study indicate that with the diagnostic capture ELISA used, intestinal content (preferably ileum) should be used for C. perfringens type D epsilon toxin detection in suspected cases of sheep enterotoxemia.

Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

PubMed Central

2013-01-01

Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

Molecular cloning and expression of epsilon toxin from Clostridium perfringens type D and tests of animal immunization.

PubMed

Souza, A M; Reis, J K P; Assis, R A; Horta, C C; Siqueira, F F; Facchin, S; Alvarenga, E R; Castro, C S; Salvarani, F M; Silva, R O S; Pires, P S; Contigli, C; Lobato, F C F; Kalapothakis, E

2010-02-18

Epsilon toxin produced by Clostridium perfringens types B and D causes enterotoxemia in sheep, goats and calves. Enterotoxemia can cause acute or superacute disease, with sudden death of the affected animal. It provokes huge economic losses when large numbers of livestock are affected. Therapeutic intervention is challenging, because the disease progresses very rapidly. However, it can be prevented by immunization with specific immunogenic vaccines. We cloned the etx gene, encoding epsilon toxin, into vector pET-11a; recombinant epsilon toxin (rec-epsilon) was expressed in inclusion bodies and was used for animal immunization. Serum protection was evaluated and cross-serum neutralization tests were used to characterize the recombinant toxin. To analyze the potency of the toxin (as an antigen), rabbits were immunized with 50, 100 or 200 microg recombinant toxin, using aluminum hydroxide gel as an adjuvant. Titers of 10, 30 and 40 IU/mL were obtained, respectively. These titers were higher than the minimum level required by the European Pharmacopoeia (5 IU/mL) and by the USA Code of Federal Regulation (2 IU/mL). This rec-epsilon is a good candidate for vaccine production against enterotoxemia caused by epsilon toxin of C. perfringens type D.

Aqueous Dispersions of Graphene from Electrochemically Exfoliated Graphite.

PubMed

Sevilla, Marta; Ferrero, Guillermo A; Fuertes, Antonio B

2016-11-21

A facile and environmentally friendly synthetic strategy for the production of stable and easily processable dispersions of graphene in water is presented. This strategy represents an alternative to classical chemical exfoliation methods (for example the Hummers method) that are more complex, harmful, and dangerous. The process is based on the electrochemical exfoliation of graphite and includes three simple steps: 1) the anodic exfoliation of graphite in (NH 4 ) 2 SO 4 , 2) sonication to separate the oxidized graphene sheets, and 3) reduction of oxidized graphene to graphene. The procedure makes it possible to convert around 30 wt % of the initial graphite into graphene with short processing times and high yields. The graphene sheets are well dispersed in water, have a carbon/oxygen atomic ratio of 11.7, a lateral size of about 0.5-1 μm, and contain only a few graphene layers, most of which are bilayer sheets. The processability of this type of aqueous dispersion has been demonstrated in the fabrication of macroscopic graphene structures, such as graphene aerogels and graphene films, which have been successfully employed as absorbents or as electrodes in supercapacitors, respectively. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-Year Relapse of Mandibular Distraction for Hemifacial Microsomia Using Masseteric Botulinum Toxin Type A Injections.

PubMed

Yin, Hong-Yu; Wang, Chuan; Zhang, Zhi-Yong; Shi, Lei; Yin, Lin; Liu, Wei; Feng, Shi; Cao, Yi-Lin; Tang, Xiao-Jun

2018-06-11

The relapse of hemifacial microsomia was thought to be highly related to the soft tissue envelope around the mandible angle mainly composed by masseter and medial pterygoid. According to the reason, we tried to apply masseter injection of type A botulinum toxin to weaken the soft envelope tension on the early stage post mandible distraction in adult HFM patients. Eight patients diagnosed with HFM were studied and randomly assigned to an experimental or control group. Patients in the experimental group were treated with DO, orthognathic surgeries, autologous fat grafting, and bilateral masseter muscle injection with type A botulinum toxin. The patients in control group were treated with the same procedures as the patients in experimental group except for masseter muscle injection with type A botulinum toxin. The recurrence rates of both groups were evaluated and analyzed after nearly 1 year of follow-up. The mean recurrence rate was 26.30% ± 11.84% (range 7.62%-37.27%) in the 8 patients after 1-year follow-up. The relapse rate was 16.32% ± 7.78% (7.62%-26.22%) in the experimental group and 36.28% ± 1.03% (34.84%-37.27%) in the control group. There was a significant difference (P = 0.002) between the experimental group and the control group. The combination of DO, orthognathic surgeries, autologous fat particle transplantation, and masseter muscle type A botulinum toxin injection technique could be a comprehensive treatment plan for adult patients of HFM. Furthermore, masseter injection of type A botulinum toxin might be an alternative method to reduce the early recurrence rate of postoperative adult patients of HFM.

Thirty-five units of botulinum toxin type A for treatment of axillary hyperhidrosis in female patients.

PubMed

Marcella, Stefanie; Goodman, Greg; Cumming, Simon; Foley, Peter; Morgan, Vanessa

2011-05-01

We present a retrospective audit on efficacy and impact of 35 units of botulinum toxin type A per axilla on quality of life in female patients with axillary hyperhidrosis. This audit shows that 35 units of botulinum toxin type A is a reasonable starting dose and could significantly improve patients' quality of life and reduce the cost of treatment. © 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

PubMed Central

Naumann, M; Lowe, N J

2001-01-01

Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type

Immunogold localisation of laminin in normal and exfoliative iris.

PubMed Central

Konstas, A. G.; Marshall, G. E.; Lee, W. R.

1990-01-01

Immunoelectron microscopic studies of exfoliative iris tissue (seven specimens) revealed the presence of laminin in the fibrillar component of exfoliation material. The immunogold label was uniformly distributed on the exfoliation fibres. Deposition of laminin labelled exfoliation material in the dilator muscle was a noteworthy feature, as was an apparent depletion of laminin in the basement membranes of ostensibly unaffected vessels. In control iris tissue (five enucleated eyes) laminin was identified in the basement membrane round vascular contractile cells, but not beneath the endothelium. Images PMID:2390517

Ultrasound exfoliation of inorganic analogues of graphene

PubMed Central

2014-01-01

High-intensity ultrasound exfoliation of a bulk-layered material is an attractive route for large-scale preparation of monolayers. The monolayer slices could potentially be prepared with a high yield (up to 100%) in a few minutes. Exfoliation of natural minerals (such as tungstenite and molybdenite) or bulk synthetic materials (including hexagonal boron nitride (h-BN), hexagonal boron carbon nitride (h-BCN), and graphitic carbon nitride (g-C3N4)) in liquids leads to the breakdown of the 3D graphitic structure into a 2D structure; the efficiency of this process is highly dependent upon the physical effects of the ultrasound. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) were employed to verify the quality of the exfoliation. Herein, this new method of exfoliation with ultrasound assistance for application to mono- and bilayered materials in hydrophobic and hydrophilic environments is presented. PMID:24708572

Ultrasound exfoliation of inorganic analogues of graphene.

PubMed

Stengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

2014-04-05

High-intensity ultrasound exfoliation of a bulk-layered material is an attractive route for large-scale preparation of monolayers. The monolayer slices could potentially be prepared with a high yield (up to 100%) in a few minutes. Exfoliation of natural minerals (such as tungstenite and molybdenite) or bulk synthetic materials (including hexagonal boron nitride (h-BN), hexagonal boron carbon nitride (h-BCN), and graphitic carbon nitride (g-C3N4)) in liquids leads to the breakdown of the 3D graphitic structure into a 2D structure; the efficiency of this process is highly dependent upon the physical effects of the ultrasound. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) were employed to verify the quality of the exfoliation. Herein, this new method of exfoliation with ultrasound assistance for application to mono- and bilayered materials in hydrophobic and hydrophilic environments is presented.

Staphylococci isolated from ready-to-eat meat - Identification, antibiotic resistance and toxin gene profile.

PubMed

Fijałkowski, Karol; Peitler, Dorota; Karakulska, Jolanta

2016-12-05

The aim of this study was to analyse the staphylococci isolated from ready-to-eat meat products, including pork ham, chicken cold cuts, pork sausage, salami and pork luncheon meat, sliced in the store to the consumer's specifications, along with species identification and determination of antibiotic resistance. Genes encoding staphylococcal enterotoxins, staphylococcal enterotoxin-like proteins, exfoliative toxins, and toxic shock syndrome toxin 1 were also investigated. From the 41 samples, 75 different staphylococcal isolates were obtained. Based on PCR-RFLP analysis of the gap gene using AluI and HpyCH4V restriction enzymes, the isolates were identified as Staphylococcus equorum (28%), S. vitulinus (16%), S. carnosus (14%), S. succinus (11%), S. xylosus (11%), S. saprophyticus (9%), S. warneri (9%), S. haemolyticus (1%) and S. pasteuri (1%). The incidence and number of resistances to antimicrobials was found to be species but not source of isolation dependent. All S. xylosus, S. saprophyticus, S. haemolyticus and S. pasteuri isolates showed antibiotic resistance. A lower percentage of resistance was recorded for S. warneri (71%) and S. vitulinus (58%), followed by S. equorum (57%), S. carnosus (50%) and S. succinus (50%). The most frequent resistance was observed to fusidic acid (43%). The mecA gene was amplified in 4% of the staphylococci. However, phenotypic resistance to methicillin was not confirmed in any of these isolates. On the other hand, the mecA gene was not detected in any of 9% of the isolates resistant to cefoxitin. It was also found that among 75 isolates, 60 (80%) harbored from 1 to 10 out of 21 analyzed superantigenic toxin genes. The most prevalent genes were: sei (36% isolates) among enterotoxins, seln (32% isolates) among enterotoxin-like proteins and eta encoding exfoliative toxin A (37% isolates). The findings of this study further extend previous observations that, when present in food, not only S. aureus but also other species of

Horizontal gene transfer of chromosomal Type II toxin-antitoxin systems of Escherichia coli.

PubMed

Ramisetty, Bhaskar Chandra Mohan; Santhosh, Ramachandran Sarojini

2016-02-01

Type II toxin-antitoxin systems (TAs) are small autoregulated bicistronic operons that encode a toxin protein with the potential to inhibit metabolic processes and an antitoxin protein to neutralize the toxin. Most of the bacterial genomes encode multiple TAs. However, the diversity and accumulation of TAs on bacterial genomes and its physiological implications are highly debated. Here we provide evidence that Escherichia coli chromosomal TAs (encoding RNase toxins) are 'acquired' DNA likely originated from heterologous DNA and are the smallest known autoregulated operons with the potential for horizontal propagation. Sequence analyses revealed that integration of TAs into the bacterial genome is unique and contributes to variations in the coding and/or regulatory regions of flanking host genome sequences. Plasmids and genomes encoding identical TAs of natural isolates are mutually exclusive. Chromosomal TAs might play significant roles in the evolution and ecology of bacteria by contributing to host genome variation and by moderation of plasmid maintenance. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs.

PubMed

Sawa, Teiji; Hamaoka, Saeko; Kinoshita, Mao; Kainuma, Atsushi; Naito, Yoshifumi; Akiyama, Koichi; Kato, Hideya

2016-10-26

Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species ( Ps. fluorescens , Ps. lundensis , Ps. weihenstephanensis , Ps. marginalis, Ps. rhodesiae, Ps. synxantha , Ps. libanensis , Ps. extremaustralis , Ps. veronii , Ps. simiae , Ps. trivialis , Ps. tolaasii , Ps. orientalis , Ps. taetrolens , Ps. syringae , Ps. viridiflava , and Ps. cannabina ) and 8 Gram-negative bacteria from three other genera ( Photorhabdus , Aeromonas , and Paludibacterium ). In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

Botulinum toxin in parkinsonism: The when, how, and which for botulinum toxin injections.

PubMed

Cardoso, Francisco

2018-06-01

The aim of this article is to provide a review of the use of injections of botulinum toxin in the management of selected symptoms and signs of Parkinson's disease and other forms of parkinsonism. Sialorrhea is defined as inability to control oral secretions, resulting in excessive saliva in the oropharynx. There is a high level of evidence for the treatment of sialorrhea in parkinsonism with injections of different forms of botulinum toxin type A as well as botulinum toxin type B. Tremor can be improved by the use of botulinum toxin injections but improved tremor control often leads to concomitant motor weakness, limiting its use. Levodopa induced dyskinesias are difficult to treat with botulinum toxin injections because of their variable frequency and direction. Apraxia of eyelid opening, a sign more commonly seen in progressive supranuclear palsy and other tauopathies, often improves after botulinum toxin injections. Recent data suggest that regardless of the underlying mechanism, pain in parkinsonism can be alleviated by botulinum toxin injections. Finally, freezing of gait, camptocormia and Pisa syndrome in parkinsonism almost invariably fail to respond to botulinum toxin injections. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-yield exfoliation of tungsten disulphide nanosheets by rational mixing of low-boiling-point solvents

NASA Astrophysics Data System (ADS)

Sajedi-Moghaddam, Ali; Saievar-Iranizad, Esmaiel

2018-01-01

Developing high-throughput, reliable, and facile approaches for producing atomically thin sheets of transition metal dichalcogenides is of great importance to pave the way for their use in real applications. Here, we report a highly promising route for exfoliating two-dimensional tungsten disulphide sheets by using binary combination of low-boiling-point solvents. Experimental results show significant dependence of exfoliation yield on the type of solvents as well as relative volume fraction of each solvent. The highest yield was found for appropriate combination of isopropanol/water (20 vol% isopropanol and 80 vol% water) which is approximately 7 times higher than that in pure isopropanol and 4 times higher than that in pure water. The dramatic increase in exfoliation yield can be attributed to perfect match between the surface tension of tungsten disulphide and binary solvent system. Furthermore, solvent molecular size also has a profound impact on the exfoliation efficiency, due to the steric repulsion.

Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas

PubMed Central

Diao, Jian-Bo; Jiang, Li-Ping; Tang, Xing; Liang, Song-Ping

2008-01-01

Background Kuntiz-type toxins (KTTs) have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking) were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. Principal Findings Here we report the presence of a new superfamily of KTTs in spiders (Tarantulas: Ornithoctonus huwena and Ornithoctonus hainana), which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI) as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (ω) for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins) derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications. Conclusions

Evaluation of the protective effect of Botulinum toxin type A injection on otitis media with effusion.

PubMed

Çalım, Ömer Faruk; Yıldırım, Yavuz Selim; Doğan, Remzi; Tuğrul, Selhattin; Gedik, Özge; Özturan, Orhan

2017-09-01

This study makes an analysis of the effect of Botulinum toxin type A on otitis media with effusion in rats. As part of the study, 24 male Wistar Albino rats were divided into three groups: Group 1: Botulinum toxin Type A and Histamıne (intratympanic 0.2 ml = 20 unit BTA); Group 2: Saline and Histamine (intratympanic 0.2 ml 0.9%); Group 3: Histamine (intratympanic 0.2 ml). Histamine (intratympanic 0.2 ml) was administered into the right ear for all groups. DPOAE and ABR tests were carried out on days 5, 10, 15 and 20 from the beginning of the study. There was no significant difference between DPOAE and ABR scores of the groups. In each group, the DPOAE scores for the right ear significantly decreased on day 5 when compared to the basal scores. In each group, there was no significant difference between days 5, 10 and 15 for the right ear. Botulinum toxin type A blocked the secretion of glands in the middle ear and showed no effect to prevent the formation of serous otitis. In addition, it was found out that Botulinum toxin did not lead to any morphological change in the cochlea.

Exfoliated YBCO filaments for second-generation superconducting cable

NASA Astrophysics Data System (ADS)

Solovyov, Vyacheslav; Farrell, Paul

2017-01-01

The second-generation high temperature superconductor (2G HTS) wire is the most promising conductor for high-field magnets such as accelerator dipoles and compact fusion devices. The key element of the wire is a thin Y1Ba2Cu3O7 (YBCO) layer deposited on a flexible metal substrate. The substrate, which becomes incorporated in the 2G conductor, reduces the electrical and mechanical performance of the wire. This is a process that exfoliates the YBCO layer from the substrate while retaining the critical current density of the superconductor. Ten-centimeter long coupons of exfoliated YBCO layers were manufactured, and detailed structural, electrical, and mechanical characterization were reported. After exfoliation, the YBCO layer was supported by a 75 μm thick stainless steel foil, which makes for a compact, mechanically stronger, and inexpensive conductor. The critical current density of the filaments was measured at both 77 K and 4.2 K. The exfoliated YBCO retained 90% of the original critical current. Similarly, tests in an external magnetic field at 4.2 K confirmed that the pinning strength of the YBCO layer was also retained following exfoliation.

New approach to elaborate exfoliated starch-based nanobiocomposites.

PubMed

Chivrac, Frédéric; Pollet, Eric; Schmutz, Marc; Avérous, Luc

2008-03-01

The present paper reports the successful elaboration of exfoliated plasticized starch-based nanobiocomposites. This was made possible by using cationic starch as a new clay organomodifier to better match the polarity of the matrix and thus to facilitate the clay exfoliation process. To demonstrate the efficiency of this new approach, either natural (MMT-Na) or organomodified (OMMT-CS) montmorillonite were incorporated into the starch nanobiocomposites by a melt blending process. The morphological analyses (SAXD and TEM) showed that MMT-Na leads to the formation of intercalated nanobiocomposites. On the contrary, OMMT-CS allowed the elaboration of well-exfoliated nanobiocomposites. Tensile tests performed on the obtained nanobiocomposites showed that exfoliated nanobiocomposites display enhanced mechanical properties compared to those of the intercalated nanobiocomposites and neat matrix. These results clearly highlight the great interest in using OMMT-CS to obtain starch-based nanobiocomposites with improved properties.

Separation medium containing thermally exfoliated graphite oxide

NASA Technical Reports Server (NTRS)

Prud'homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor); Herrera-Alonso, Margarita (Inventor)

2012-01-01

A separation medium, such as a chromatography filling or packing, containing a modified graphite oxide material, which is a thermally exfoliated graphite oxide with a surface area of from about 300 m.sup.2/g to 2600 m.sup.2/g, wherein the thermally exfoliated graphite oxide has a surface that has been at least partially functionalized.

Effect of water activity and pH on growth and toxin production by Clostridium botulinum type G.

PubMed Central

Briozzo, J; de Lagarde, E A; Chirife, J; Parada, J L

1986-01-01

The combined effect of water activity (aw) and pH on growth and toxin production by Clostridium botulinum type G strain 89 was investigated. The minimum aw at which growth and toxin formation occurred was 0.965, for media in which the pH was adjusted with either sodium chloride or sucrose. The minimum pH (at the optimum aw) for growth and toxin production of C. botulinum type G was found to be 5.6. Optimum conditions for toxin activation were a trypsin concentration of 0.1%, a pH of the medium of 6.5, and an incubation for 45 min at 37 degrees C. These data did not show evidence of heat-labile spores, since a heat shock of 75 degrees C for 10 min did not significantly decrease the spore count of strain 89G in media at pH 7.0 or 5.6. It was frequently observed that cells grown at reduced aw or pH experienced severe morphological changes. PMID:3518631

Triangular Black Phosphorus Atomic Layers by Liquid Exfoliation.

PubMed

Seo, Soonjoo; Lee, Hyun Uk; Lee, Soon Chang; Kim, Yooseok; Kim, Hyeran; Bang, Junhyeok; Won, Jonghan; Kim, Youngjun; Park, Byoungnam; Lee, Jouhahn

2016-03-30

Few-layer black phosphorus (BP) is the most promising material among the two-dimensional materials due to its layered structure and the excellent semiconductor properties. Currently, thin BP atomic layers are obtained mostly by mechanical exfoliation of bulk BP, which limits applications in thin-film based electronics due to a scaling process. Here we report highly crystalline few-layer black phosphorus thin films produced by liquid exfoliation. We demonstrate that the liquid-exfoliated BP forms a triangular crystalline structure on SiO2/Si (001) and amorphous carbon. The highly crystalline BP layers are faceted with a preferred orientation of the (010) plane on the sharp edge, which is an energetically most favorable facet according to the density functional theory calculations. Our results can be useful in understanding the triangular BP structure for large-area applications in electronic devices using two-dimensional materials. The sensitivity and selectivity of liquid-exfoliated BP to gas vapor demonstrate great potential for practical applications as sensors.

Triangular Black Phosphorus Atomic Layers by Liquid Exfoliation

PubMed Central

Seo, Soonjoo; Lee, Hyun Uk; Lee, Soon Chang; Kim, Yooseok; Kim, Hyeran; Bang, Junhyeok; Won, Jonghan; Kim, Youngjun; Park, Byoungnam; Lee, Jouhahn

2016-01-01

Few-layer black phosphorus (BP) is the most promising material among the two-dimensional materials due to its layered structure and the excellent semiconductor properties. Currently, thin BP atomic layers are obtained mostly by mechanical exfoliation of bulk BP, which limits applications in thin-film based electronics due to a scaling process. Here we report highly crystalline few-layer black phosphorus thin films produced by liquid exfoliation. We demonstrate that the liquid-exfoliated BP forms a triangular crystalline structure on SiO2/Si (001) and amorphous carbon. The highly crystalline BP layers are faceted with a preferred orientation of the (010) plane on the sharp edge, which is an energetically most favorable facet according to the density functional theory calculations. Our results can be useful in understanding the triangular BP structure for large-area applications in electronic devices using two-dimensional materials. The sensitivity and selectivity of liquid-exfoliated BP to gas vapor demonstrate great potential for practical applications as sensors. PMID:27026070

Solar Exposure and Residential Geographic History in Relation to Exfoliation Syndrome in the United States and Israel

PubMed Central

Pasquale, Louis R.; Jiwani, Aliya Z.; Zehavi-Dorin, Tzukit; Majd, Arow; Rhee, Douglas J.; Chen, Teresa; Turalba, Angela; Shen, Lucy; Brauner, Stacey; Grosskreutz, Cynthia; Gardiner, Matthew; Chen, Sherleen; Borboli-Gerogiannis, Sheila; Greenstein, Scott H.; Chang, Kenneth; Ritch, Robert; Loomis, Stephanie; Kang, Jae H.; Wiggs, Janey L.; Levkovitch-Verbin, Hani

2014-01-01

contribute to exfoliation syndrome. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in exfoliation syndrome etiology. PMID:25188364

Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and mice.

PubMed

Garcia, J P; Adams, V; Beingesser, J; Hughes, M L; Poon, R; Lyras, D; Hill, A; McClane, B A; Rood, J I; Uzal, F A

2013-07-01

Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.

Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

2014-11-01

The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

What are the necessary practice competencies for two providers: dermal fillers and botulinum toxin type A injections?

PubMed

Spear, Marcia

2010-01-01

There has been a steady increase in the number of individuals who undergo dermal fillers and botulinum toxin Type A injections. The majority of these procedures are performed by nurse providers. The purpose of this study was to collect national data on the current practice among nursing providers within the American Society of Plastic Surgical Nurses (ASPSN). The goal was to utilize the national data and develop a document of the necessary competencies to guide the practice of providers of dermal fillers and botulinum toxin Type A injections. A survey tool was developed and validated for content by expert nursing providers among the membership of the ASPSN and disseminated via e-mail to the membership of the ASPSN. In addition, data from investigator training, mentoring, and evidence from a review of the literature were also incorporated into the competency document utilizing the Competency Outcomes and Performance Assessment (COPA) model. Common core issues became apparent that included contraindications for the use of botulinum toxin Type A and dermal fillers, postprocedure complications as well as strategies in terms of managing complications. The data also revealed that there is no common method providers are taught to assess the aesthetic patient and a lack of a collaborative relationship in current practice. Overwhelmingly, the respondents supported the need for defined practice competencies. A competency document to guide the practice of providers of dermal fillers and botulinum toxin Type A has been developed for completion of this DNP project.

Identification and functional characterization of type II toxin/antitoxin systems in Aggregatibacter actinomycetemcomitans.

PubMed

Schneider, B; Weigel, W; Sztukowska, M; Demuth, D R

2018-06-01

Type II toxin/antitoxin (TA) systems contribute to the formation of persister cells and biofilm formation for many organisms. Aggregatibacter actinomycetemcomitans thrives in the complex oral microbial community subjected to continual environmental flux. Little is known regarding the presence and function of type II TA systems in this organism or their contribution to adaptation and persistence in the biofilm. We identified 11 TA systems that are conserved across all seven serotypes of A. actinomycetemcomitans and represent the RelBE, MazEF and HipAB families of type II TA systems. The systems selectively responded to various environmental conditions that exist in the oral cavity. Two putative RelBE-like TA systems, D11S_1194-1195 and D11S_1718-1719 were induced in response to low pH and deletion of D11S_1718-1719 significantly reduced metabolic activity of stationary phase A. actinomycetemcomitans cells upon prolonged exposure to acidic conditions. The deletion mutant also exhibited reduced biofilm biomass when cultured under acidic conditions. The D11S_1194 and D11S_1718 toxin proteins inhibited in vitro translation of dihydrofolate reductase (DHFR) and degraded ribosome-associated, but not free, MS2 virus RNA. In contrast, the corresponding antitoxins (D11S_1195 and D11S_1719), or equimolar mixtures of toxin and antitoxin, had no effect on DHFR production or RNA degradation. Together, these results suggest that D11S_1194-1195 and D11S_1718-1719 are RelBE-like type II TA systems that are activated under acidic conditions and may function to cleave ribosome-associated mRNA to inhibit translation in A. actinomycetemcomitans. In vivo, these systems may facilitate A. actinomycetemcomitans adaptation and persistence in acidic local environments in the dental biofilm. © 2018 The Authors. Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

USGS Publications Warehouse

Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.

1999-01-01

A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

Elevation of the Corner of the Mouth Using Botulinum Toxin Type A

PubMed Central

Goldman, Alberto; Wollina, Uwe

2010-01-01

Indications for botulinum toxin type A have been constantly evolving, and it can currently be used in virtually any area of the face and neck. The authors present their experience with this neurotoxin in treating the platysmal bands and depressor anguli oris muscle with the purpose of cosmetically improving the anterior neck and lifting the oral commissure. PMID:21430826

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

PubMed

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

2014-12-01

Epsilon toxin (ETX) is produced by Clostridium perfringens type B and D strains and causes enterotoxemia, a highly lethal disease with major impacts on the farming of domestic ruminants, particularly sheep. ETX belongs to the aerolysin-like pore-forming toxin family. Although ETX has striking similarities to other toxins in this family, ETX is often more potent, with an LD50 of 100 ng/kg in mice. Due to this high potency, ETX is considered as a potential bioterrorism agent and has been classified as a category B biological agent by the Centers for Disease Control and Prevention (CDC) of the United States. The protoxin is converted to an active toxin through proteolytic cleavage performed by specific proteases. ETX is absorbed and acts locally in the intestines then subsequently binds to and causes lesions in other organs, including the kidneys, lungs and brain. The importance of this toxin for veterinary medicine and its possible use as a biological weapon have drawn the attention of researchers and have led to a large number of studies investigating ETX. The aim of the present work is to review the existing knowledge on ETX from C. perfringens type B and D. Copyright © 2014 Elsevier Ltd. All rights reserved.

Phenotypic H-Antigen Typing by Mass Spectrometry Combined with Genetic Typing of H Antigens, O Antigens, and Toxins by Whole-Genome Sequencing Enhances Identification of Escherichia coli Isolates.

PubMed

Cheng, Keding; Chui, Huixia; Domish, Larissa; Sloan, Angela; Hernandez, Drexler; McCorrister, Stuart; Robinson, Alyssia; Walker, Matthew; Peterson, Lorea A M; Majcher, Miles; Ratnam, Sam; Haldane, David J M; Bekal, Sadjia; Wylie, John; Chui, Linda; Tyler, Shaun; Xu, Bianli; Reimer, Aleisha; Nadon, Celine; Knox, J David; Wang, Gehua

2016-08-01

Mass spectrometry-based phenotypic H-antigen typing (MS-H) combined with whole-genome-sequencing-based genetic identification of H antigens, O antigens, and toxins (WGS-HOT) was used to type 60 clinical Escherichia coli isolates, 43 of which were previously identified as nonmotile, H type undetermined, or O rough by serotyping or having shown discordant MS-H and serotyping results. Whole-genome sequencing confirmed that MS-H was able to provide more accurate data regarding H antigen expression than serotyping. Further, enhanced and more confident O antigen identification resulted from gene cluster based typing in combination with conventional typing based on the gene pair comprising wzx and wzy and that comprising wzm and wzt The O antigen was identified in 94.6% of the isolates when the two genetic O typing approaches (gene pair and gene cluster) were used in conjunction, in comparison to 78.6% when the gene pair database was used alone. In addition, 98.2% of the isolates showed the existence of genes for various toxins and/or virulence factors, among which verotoxins (Shiga toxin 1 and/or Shiga toxin 2) were 100% concordant with conventional PCR based testing results. With more applications of mass spectrometry and whole-genome sequencing in clinical microbiology laboratories, this combined phenotypic and genetic typing platform (MS-H plus WGS-HOT) should be ideal for pathogenic E. coli typing. Copyright © 2016 Cheng et al.

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

PubMed

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

2015-12-01

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

Magnesium and zinc borate enhance osteoblastic differentiation of stem cells from human exfoliated deciduous teeth in vitro.

PubMed

Liu, Yao-Jen; Su, Wen-Ta; Chen, Po-Hung

2018-01-01

Various biocompatible and biodegradable scaffolds blended with biochemical signal molecules with adequate osteoinductive and osteoconductive properties have attracted significant interest in hard tissue engineering regeneration. We evaluated the distinct effects of magnesium borate, zinc borate, and boric acid blended into chitosan scaffold for osteogenic differentiation of stem cells from exfoliated deciduous teeth. Stem cells from exfoliated deciduous teeth cells are a potential source of functional osteoblasts for applications in bone tissue engineering, but the efficiency of osteoblastic differentiation is low, thereby significantly limiting their clinical applications. Divalent metal borates have potential function in bone remodeling because they can simulate bone formation and decrease bone resorption. These magnesium, zinc, and B ions can gradually be released into the culture medium from the scaffold and induce advanced osteoblastic differentiation from stem cells from exfoliated deciduous teeth. Stem cells from exfoliated deciduous teeth with magnesium borate or zinc borate as inducer demonstrated more osteoblastic differentiation after 21 days of culture. Differentiated cells exhibited activity of alkaline phosphatase, bone-related gene expression of collagen type I, runt-related transcription factor 2, osteopontin, osteocalcin, vascular endothelial growth factor, and angiopoietin-1, as noted via real-time polymerase chain reaction analysis, as well as significant deposits of calcium minerals. Divalent mental magnesium and zinc and nonmetal boron can be an effective inducer of osteogenesis for stem cells from exfoliated deciduous teeth. This experiment might provide useful inducers for osteoblastic differentiation of stem cells from exfoliated deciduous teeth for tissue engineering and bone repair.

Comparative study of biological activity of four botulinum toxin type A preparations in mice.

PubMed

Chung, Myung Eun; Song, Dae Heon; Park, Joo Hyun

2013-01-01

Units of available botulinum toxin preparations are not interchangeable, and the dose-conversion ratios between such preparations remain controversial. To compare the efficacy and safety of four botulinum toxin type A preparations. Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high-dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. The dose-conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose-conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose-conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose-conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Chemically exfoliating large sheets of phosphorene via choline chloride urea viscosity-tuning

NASA Astrophysics Data System (ADS)

Ng, A.; Sutto, T. E.; Matis, B. R.; Deng, Y.; Ye, P. D.; Stroud, R. M.; Brintlinger, T. H.; Bassim, N. D.

2017-04-01

Exfoliation of two-dimensional phosphorene from bulk black phosphorous through chemical means is demonstrated where the solvent system of choice (choline chloride urea diluted with ethanol) has the ability to successfully exfoliate large-area multi-layer phosphorene sheets and further protect the flakes from ambient degradation. The intercalant solvent molecules, aided by low-powered sonication, diffuse between the layers of the bulk black phosphorus, allowing for the exfoliation of the multi-layer phosphorene through breaking of the interlayer van der Waals bonds. Through viscosity tuning, the optimal parameters (1:1 ratio between the intercalant and the diluting solvent) at which the exfoliation takes place is determined. Our exfoliation technique is shown to produce multi-layer phosphorene flakes with surface areas greater than 3 μm2 (a factor of three larger than what has previously been reported for a similar exfoliation method) while limiting exposure to the ambient environment, thereby protecting the flakes from degradation. Characterization techniques such as optical microscopy, Raman spectroscopy, ultraviolet-visible spectroscopy, and (scanning) transmission electron microscopy are used to investigate the quality, quantity, and thickness of the exfoliated flakes.

The efficiency of botulinum toxin type A for the treatment of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

PubMed

Pihut, Malgorzata; Ferendiuk, Ewa; Szewczyk, Michal; Kasprzyk, Katarzyna; Wieckiewicz, Mieszko

2016-01-01

Temporomandibular joint dysfunction are often accompanied by symptoms of headache such as tension-type headache which is the most frequent spontaneous primary headache. Masseter muscle pain is commonly reported in this group. The purpose of the study was to assess the efficiency of intramuscular botulinum toxin type A injections for treating masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. This prospective outcome study consisted of 42 subjects of both genders aged 19-48 years diagnosed with masseter muscle pain related to temporomandibular joint dysfunction and tension-type headache. The subjects were treated by the intramuscular injection of 21 U (mice units) of botulinum toxin type A (Botox, Allergan) in the area of the greatest cross-section surface of both masseter bellies. Pain intensity was evaluated using visual analogue scale (VAS) and verbal numerical rating scale (VNRS) 1 week before the treatment and 24 weeks after the treatment. The obtained data were analyzed using the Wilcoxon matched pairs test (p ≤ 0,005). The results of this study showed a decrease in the number of referred pain episodes including a decrease in pain in the temporal region bilaterally, a reduction of analgesic drugs intake as well as a decrease in reported values of VAS and VNRS after injections (p = 0,000). The intramuscular botulinum toxin type A injections have been an efficient method of treatment for masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

Simultaneous Graphite Exfoliation and N Doping in Supercritical Ammonia.

PubMed

Sasikala, Suchithra Padmajan; Huang, Kai; Giroire, Baptiste; Prabhakaran, Prem; Henry, Lucile; Penicaud, Alain; Poulin, Philippe; Aymonier, Cyril

2016-11-16

We report the exfoliation of graphite and simultaneous N doping of graphene by two methods: supercritical ammonia treatment and liquid-phase exfoliation with NH 4 OH. While the supercritical ammonia allowed N doping at a level of 6.4 atom % in 2 h, the liquid-phase exfoliation with NH 4 OH allowed N doping at a level of 2.7 atom % in 6 h. The N doped graphene obtained via the supercritical ammonia route had few layers (<5) and showed large lateral flake size (∼8 μm) and low defect density (I D /I G < 0.6) in spite of their high level of N doping. This work is the first demonstration of supercritical ammonia as an exfoliation agent and N doping precursor for graphene. Notably, the N doped graphene showed electrocatalytic activity toward oxygen reduction reaction with high durability and good methanol tolerance compared to those of commercial Pt/C catalyst.

Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

PubMed

Park, Amy J; Paraiso, Marie Fidela R

2009-08-01

Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

Toxin-Antitoxin Systems as Multilevel Interaction Systems

PubMed Central

Goeders, Nathalie; Van Melderen, Laurence

2014-01-01

Toxin-antitoxin (TA) systems are small genetic modules usually composed of a toxin and an antitoxin counteracting the activity of the toxic protein. These systems are widely spread in bacterial and archaeal genomes. TA systems have been assigned many functions, ranging from persistence to DNA stabilization or protection against mobile genetic elements. They are classified in five types, depending on the nature and mode of action of the antitoxin. In type I and III, antitoxins are RNAs that either inhibit the synthesis of the toxin or sequester it. In type II, IV and V, antitoxins are proteins that either sequester, counterbalance toxin activity or inhibit toxin synthesis. In addition to these interactions between the antitoxin and toxin components (RNA-RNA, protein-protein, RNA-protein), TA systems interact with a variety of cellular factors, e.g., toxins target essential cellular components, antitoxins are degraded by RNAses or ATP-dependent proteases. Hence, TA systems have the capacity to interact with each other at different levels. In this review, we will discuss the different interactions in which TA systems are involved and their implications in TA system functions and evolution. PMID:24434905

Evidence to Use Botulinum Toxin Injections in Tension-Type Headache Management: A Systematic Review.

PubMed

Wieckiewicz, Mieszko; Grychowska, Natalia; Zietek, Marek; Wieckiewicz, Gniewko; Smardz, Joanna

2017-11-15

Tension-type headache (TTH) is the most common type of chronic recurring head pain. It can occur twice as often in women as in men. It is the most common type of headache. Its lifetime prevalence is 30% to 78% in the general population. TTH treatment should be multilevel. It often consists of taking pain medication, muscle relaxants, antidepressants, using biofeedback therapy, acupuncture, and attending behavioral therapy. Several clinical trials also suggest that botulinum toxin (BTX) may be an effective treatment option for such patients. The aim of this study was to evaluate if BTX can be used as a treatment method in TTH in the light of current medical literature. The authors searched the PubMed, EBSCOhost, OVID, Web of Knowledge, Cochrane Library and CINAHL databases to identify relevant publications. The authors finally included 11 papers-prospective and retrospective cohort studies. Among most of the selected studies, there was a significant correlation between using BTX and reduction of TTH pain intensity and severity. By analyzing qualified studies, it can be concluded that botulinum toxin seems to be effective in TTH management.

BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.

PubMed

Huys, Isabelle; Xu, Chen-Qi; Wang, Cheng-Zhong; Vacher, Hélène; Martin-Eauclaire, Marie-France; Chi, Cheng-Wu; Tytgat, Jan

2004-03-15

A novel HERG channel blocker was isolated from the venom of the scorpion Buthus martensi Karsch, sequenced and characterized at the pharmacological level after chemical synthesis. According to the determined amino acid sequence, the cDNA and genomic genes were then cloned. The genomic gene consists of two exons interrupted by an intron of 65 bp at position -6 upstream from the mature toxin. The protein sequence of this toxin was completely identical with that of a known A-type K+ current blocker BmTx3, belonging to scorpion alpha-KTx subfamily 15. Thus BmTx3 is the first reported alpha-KTx peptide also showing HERG-blocking activity, like gamma-KTx peptides. Moreover, different from classical alpha-KTx peptides, such as charybdotoxin, BmTx3 cannot block Shaker -type K+ channels. Phylogenetic tree analysis reveals that this toxin takes an intermediate position between classical alpha-KTx and gamma-KTx toxins. From a structural point of view, we propose that two separate functional faces might exist on the BmTx3 molecule, responsible for the two different K+-current-blocking functions. Face A, composed of Arg18 and Lys19 in the alpha-helix side, might correspond to HERG blocking activity, whereas Face B, containing a putative functional dyad (Lys27 and Tyr36) in the beta-sheet side, might correspond to A-type blocking activity. A specific deletion mutant with the disrupted Face B, BmTx3-Y36P37del, loses the A-type current-blocking activity, but keeps a similar HERG-blocking activity, as seen with the wild-type toxin.

Apparently spontaneous fracture of a granitic exfoliation dome: observations and monitoring

NASA Astrophysics Data System (ADS)

Collins, B. D.; Stock, G. M.; Eppes, M. C.; Lewis, S. W.; Corbett, S.; Smith, J. B.

2016-12-01

Exfoliation sheet formation has attracted scientific attention for more than two centuries. Although a number of theories have been proposed, firm understanding of the cause of exfoliation has proved elusive, partly because observations of their formation are scarce. The 2014-2016 spontaneous exfoliation of Twain Harte Dome, located in the western foothills of California's Sierra Nevada Mesozoic granitic batholith, provides an unprecedented opportunity to study this phenomenon. Understanding such events can offer direct insight into similar exfoliating environments where spontaneous rock fracturing generates related geohazards such as rock falls. Twain Harte Dome fractured energetically on at least 5 occasions in August and September 2014, with slabs of rock thrust into the air 40 cm in a few seconds time and surficial fracture of rock occurring over a total area of 2,800 m2. Several of these events were witnessed first-hand and recorded by video. Additional (but non-energetic) cracking occurred during August 2015, followed by another energetic fracturing event in June 2016 over a much smaller (16 m2) area that again sent granite slabs airborne. No previous spontaneous exfoliation had been recorded here over the past 90 years and no obvious trigger (e.g., earthquake) occurred prior to the recent events. Using high-resolution topographic and fracture mapping, acoustic emission monitoring, and environmental monitoring, we show that these fracture events are correlated with hot summer periods - an indication that thermal stresses likely have an important role in causing exfoliation. Surface crackmeter, and subsurface borehole extensometer and rock bolt force measurements strengthen this relationship, with stresses and deformations spiking during hot summer afternoons. Our instrumentation data captured one of the exfoliation events and show that cumulative stress and deformation increases may have acted as precursor signals to the apparently spontaneous rock

A Conserved Structural Motif Mediates Retrograde Trafficking of Shiga Toxin Types 1 and 2.

PubMed

Selyunin, Andrey S; Mukhopadhyay, Somshuvra

2015-12-01

Shiga toxin-producing Escherichia coli (STEC) produce two types of Shiga toxin (STx): STx1 and STx2. The toxin A-subunits block protein synthesis, while the B-subunits mediate retrograde trafficking. STEC infections do not have definitive treatments, and there is growing interest in generating toxin transport inhibitors for therapy. However, a comprehensive understanding of the mechanisms of toxin trafficking is essential for drug development. While STx2 is more toxic in vivo, prior studies focused on STx1 B-subunit (STx1B) trafficking. Here, we show that, compared with STx1B, trafficking of the B-subunit of STx2 (STx2B) to the Golgi occurs with slower kinetics. Despite this difference, similar to STx1B, endosome-to-Golgi transport of STx2B does not involve transit through degradative late endosomes and is dependent on dynamin II, epsinR, retromer and syntaxin5. Importantly, additional experiments show that a surface-exposed loop in STx2B (β4-β5 loop) is required for its endosome-to-Golgi trafficking. We previously demonstrated that residues in the corresponding β4-β5 loop of STx1B are required for interaction with GPP130, the STx1B-specific endosomal receptor, and for endosome-to-Golgi transport. Overall, STx1B and STx2B share a common pathway and use a similar structural motif to traffic to the Golgi, suggesting that the underlying mechanisms of endosomal sorting may be evolutionarily conserved. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detecting and distinguishing among type 1 and type 2 Shiga toxins in human serum

USDA-ARS?s Scientific Manuscript database

Shiga toxins, also known as verotoxins, are a major virulence factor associated with Shiga toxin producing Escherichia coli (STEC). STEC are the E. coli responsible for many of the serious foodborne outbreaks of disease. We have developed a sensitive and specific mass spectrometry-based method of de...

Raman spectroscopy and oral exfoliative cytology

NASA Astrophysics Data System (ADS)

Sahu, Aditi; Shah, Nupur; Mahimkar, Manoj; Garud, Mandavi; Pagare, Sandeep; Nair, Sudhir; Krishna, C. Murali

2014-03-01

Early detection of oral cancers can substantially improve disease-free survival rates. Ex vivo and in vivo Raman spectroscopic (RS) studies on oral cancer have demonstrated the applicability of RS in identifying not only malignant and premalignant conditions but also cancer-field-effects: the earliest events in oral carcinogenesis. RS has also been explored for cervical exfoliated cells analysis. Exfoliated cells are associated with several advantages like non-invasive sampling, higher patient compliance, transportation and analysis at a central facility: obviating need for on-site instrumentation. Thus, oral exfoliative cytology coupled with RS may serve as a useful adjunct for oral cancer screening. In this study, exfoliated cells from healthy controls with and without tobacco habits, premalignant lesions (leukoplakia and tobacco-pouch-keratosis) and their contralateral mucosa were collected using a Cytobrush. Cells were harvested by vortexing and centrifugation at 6000 rpm. The cellular yield was ascertained using Neubauer's chamber. Cell pellets were placed on a CaF2 window and Raman spectra were acquired using a Raman microprobe (40X objective) coupled HE-785 Raman spectrometer. Approximately 7 spectra were recorded from each pellet, following which pellet was smeared onto a glass slide, fixed in 95% ethanol and subjected to Pap staining for cytological diagnosis (gold standard). Preliminary PC-LDA followed by leave-one-out cross validation indicate delineation of cells from healthy and all pathological conditions. A tendency of classification was also seen between cells from contralateral, healthy tobacco and site of premalignant lesions. These results will be validated by cytological findings, which will serve as the basis for building standard models of each condition.

Mechanical exfoliation of two-dimensional materials

NASA Astrophysics Data System (ADS)

Gao, Enlai; Lin, Shao-Zhen; Qin, Zhao; Buehler, Markus J.; Feng, Xi-Qiao; Xu, Zhiping

2018-06-01

Two-dimensional materials such as graphene and transition metal dichalcogenides have been identified and drawn much attention over the last few years for their unique structural and electronic properties. However, their rise begins only after these materials are successfully isolated from their layered assemblies or adhesive substrates into individual monolayers. Mechanical exfoliation and transfer are the most successful techniques to obtain high-quality single- or few-layer nanocrystals from their native multi-layer structures or their substrate for growth, which involves interfacial peeling and intralayer tearing processes that are controlled by material properties, geometry and the kinetics of exfoliation. This procedure is rationalized in this work through theoretical analysis and atomistic simulations. We propose a criterion to assess the feasibility for the exfoliation of two-dimensional sheets from an adhesive substrate without fracturing itself, and explore the effects of material and interface properties, as well as the geometrical, kinetic factors on the peeling behaviors and the torn morphology. This multi-scale approach elucidates the microscopic mechanism of the mechanical processes, offering predictive models and tools for the design of experimental procedures to obtain single- or few-layer two-dimensional materials and structures.

Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters

DOE PAGES

Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...

2014-05-22

Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ 70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less

Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes.

PubMed

Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

2009-06-03

The prokaryotic toxin-antitoxin systems (TAS, also referred to as TA loci) are widespread, mobile two-gene modules that can be viewed as selfish genetic elements because they evolved mechanisms to become addictive for replicons and cells in which they reside, but also possess "normal" cellular functions in various forms of stress response and management of prokaryotic population. Several distinct TAS of type 1, where the toxin is a protein and the antitoxin is an antisense RNA, and numerous, unrelated TAS of type 2, in which both the toxin and the antitoxin are proteins, have been experimentally characterized, and it is suspected that many more remain to be identified. We report a comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems in prokaryotes. Using sensitive methods for distant sequence similarity search, genome context analysis and a new approach for the identification of mobile two-component systems, we identified numerous, previously unnoticed protein families that are homologous to toxins and antitoxins of known type 2 TAS. In addition, we predict 12 new families of toxins and 13 families of antitoxins, and also, predict a TAS or TAS-like activity for several gene modules that were not previously suspected to function in that capacity. In particular, we present indications that the two-gene module that encodes a minimal nucleotidyl transferase and the accompanying HEPN protein, and is extremely abundant in many archaea and bacteria, especially, thermophiles might comprise a novel TAS. We present a survey of previously known and newly predicted TAS in 750 complete genomes of archaea and bacteria, quantitatively demonstrate the exceptional mobility of the TAS, and explore the network of toxin-antitoxin pairings that combines plasticity with selectivity. The defining properties of the TAS, namely, the typically small size of the toxin and antitoxin genes, fast evolution, and extensive horizontal mobility, make the task of

Comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes

PubMed Central

Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

2009-01-01

Background The prokaryotic toxin-antitoxin systems (TAS, also referred to as TA loci) are widespread, mobile two-gene modules that can be viewed as selfish genetic elements because they evolved mechanisms to become addictive for replicons and cells in which they reside, but also possess "normal" cellular functions in various forms of stress response and management of prokaryotic population. Several distinct TAS of type 1, where the toxin is a protein and the antitoxin is an antisense RNA, and numerous, unrelated TAS of type 2, in which both the toxin and the antitoxin are proteins, have been experimentally characterized, and it is suspected that many more remain to be identified. Results We report a comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems in prokaryotes. Using sensitive methods for distant sequence similarity search, genome context analysis and a new approach for the identification of mobile two-component systems, we identified numerous, previously unnoticed protein families that are homologous to toxins and antitoxins of known type 2 TAS. In addition, we predict 12 new families of toxins and 13 families of antitoxins, and also, predict a TAS or TAS-like activity for several gene modules that were not previously suspected to function in that capacity. In particular, we present indications that the two-gene module that encodes a minimal nucleotidyl transferase and the accompanying HEPN protein, and is extremely abundant in many archaea and bacteria, especially, thermophiles might comprise a novel TAS. We present a survey of previously known and newly predicted TAS in 750 complete genomes of archaea and bacteria, quantitatively demonstrate the exceptional mobility of the TAS, and explore the network of toxin-antitoxin pairings that combines plasticity with selectivity. Conclusion The defining properties of the TAS, namely, the typically small size of the toxin and antitoxin genes, fast evolution, and extensive horizontal mobility

Evaluation of Nanoclay Exfoliation Strategies for Thermoset Polyimide Nanocomposite Systems

NASA Technical Reports Server (NTRS)

Ginter, Michael J.; Jana, Sadhan C.; Miller, Sandi G.

2007-01-01

Prior works show exfoliated layered silicate reinforcement improves polymer composite properties. However, achieving full clay exfoliation in high performance thermoset polyimides remains a challenge. This study explores a new method of clay exfoliation, which includes clay intercalation by lower molecular weight PMR monomer under conditions of low and high shear and sonication, clay treatments by aliphatic and aromatic surfactants, and clay dispersion in primary, higher molecular weight PMR resin. Clay spacing, thermal, and mechanical properties were evaluated and compared with the best results available in literature for PMR polyimide systems.

Method for exfoliation of hexagonal boron nitride

NASA Technical Reports Server (NTRS)

Lin, Yi (Inventor); Connell, John W. (Inventor)

2012-01-01

A new method is disclosed for the exfoliation of hexagonal boron nitride into mono- and few-layered nanosheets (or nanoplatelets, nanomesh, nanoribbons). The method does not necessarily require high temperature or vacuum, but uses commercially available h-BN powders (or those derived from these materials, bulk crystals) and only requires wet chemical processing. The method is facile, cost efficient, and scalable. The resultant exfoliated h-BN is dispersible in an organic solvent or water thus amenable for solution processing for unique microelectronic or composite applications.

Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review.

PubMed

Mathevon, L; Michel, F; Decavel, P; Fernandez, B; Parratte, B; Calmels, P

2015-12-01

Botulinum toxin type A manages spasticity disorders in neurological central diseases. Some studies have reported that it might induce muscle changes. We present a literature review abiding by the PRISMA statement guidelines. The purpose was to explore the structural and passive biomechanical muscle properties after botulinum toxin type A injections in healthy and spastic limb muscles, on animals and humans, as well as methods for evaluating these properties. We searched the PubMed and Cochrane Library databases using the following keywords: "Botulinum toxin" AND ("muscle structure" OR "muscle atrophy") and, "Botulinum toxin" AND "muscle elasticity". From the 228 initially identified articles, 21 articles were included. Histological analyses were performed, especially on animals. A neurogenic atrophy systematically occurred. In humans, one year after a single injection, the histological recovery remained incomplete. Furthermore, 2D ultrasound analyses showed a reduction of the gastrocnemius thickness and pennation angle. MRI volumetric analysis evidenced muscular atrophy six months or one year after a single injection. Passive muscle stiffness depends on these structural changes. On the short term, the biomechanical analysis showed an elastic modulus increase in animals whereas no change was recorded in humans. On the short term, ultrasound elastography imaging showed a decreased elastic modulus. To date, few data are available, but all show a structural and mechanical muscle impact post injections, specifically muscle atrophy which can linger over time. Further studies are necessary to validate this element, and the possibility of change must be taken into account particularly with repeated injections. Thus, in clinical practice, 2D ultrasound and ultrasound elastography are two non-invasive techniques that will help physicians to develop an efficient long term monitoring. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Advances in the research of mechanism in prevention and treatment of scar with botulinum toxin type A and its clinical application].

PubMed

Li, Y H; Liu, J Q; Xiao, D; Zhang, W; Hu, D H

2017-04-20

Scar is a common complication in wound healing process, and how to effectively prevent and treat it is a hot and difficult problem in burns and plastic surgery field. Botulinum toxin type A is a neurotoxin that has been widely and effectively used in the cosmetic surgery field such as anti-wrinkle and thin face. In recent years, botulinum toxin type A has been applied in prevention and treatment of scar, which causes a great concern. Nowadays, the relevant reports have gradually increased, and the mechanisms have been explored more deeply. This article aims to summarize the possible mechanisms and clinical reports on the prevention and treatment of scar by botulinum toxin type A to provide a new way for the prevention and treatment of scar after surgery.

Botulinum Toxin Therapy: Is Syringe Type Related to Cost-Effectiveness?

PubMed

Foglietti, Mark Anthony; Wright, Lauren; Foglietti-Fostyk, Alanna

2018-03-01

Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference. Which syringe type is most efficient in minimizing product waste and most cost-effective for the patient and provider? We performed a single-center, open-label, analytical study using BT therapy and 2 types of syringes for analytics of cost-effectiveness. OnabotulinumtoxinA was the neuromodulator used in this report. Vials (100 U) of BT A were each reconstituted with 2.5 mL of 0.9% sodium chloride, for a final concentration of 4 U/0.1 mL. High-dead-space syringes are compared with low-dead-space syringes: 1-mL tuberculin (TB) luer slip syringe with detachable 25-gauge needle and 1-mL ultrafine insulin syringe with an attached 31-gauge needle, respectively. After each syringe was evacuated, the TB syringe was noted to contain 0.05 mL of the remaining product in the hub. Providers are discarding approximately 2 U of BT per TB syringe product injection. If the physician uses 30 syringes per day, 3 days a week, for 1 year, it equals to a lost revenue of approximately $155,500 per year. To individualize the cost-effective analysis, average quantity of syringes used per patient and overall patient volume must be considered, with corresponding adjustment of cost and units discarded. The American Society of Plastic Surgeons reported that the use of neuromodulators has increased by approximately 797% from 2000 to 2016. During that period, the price of neuromodulators has also increased by approximately 85%. Considering these statistics, the type of syringe used for BT neuromodular injection is a

Lignin-assisted exfoliation of molybdenum disulfide in aqueous media and its application in lithium ion batteries

NASA Astrophysics Data System (ADS)

Liu, Wanshuang; Zhao, Chenyang; Zhou, Rui; Zhou, Dan; Liu, Zhaolin; Lu, Xuehong

2015-05-01

In this article, alkali lignin (AL)-assisted direct exfoliation of MoS2 mineral into single-layer and few-layer nanosheets in water is reported for the first time. Under optimized conditions, the concentration of MoS2 nanosheets in the obtained dispersion can be as high as 1.75 +/- 0.08 mg mL-1, which is much higher than the typical reported concentrations (<1.0 mg mL-1) using synthetic polymers or compounds as surfactants. The stabilizing mechanism primarily lies in the electrostatic repulsion between negative charged AL, as suggested by zeta-potential measurements. When the exfoliated MoS2 nanosheets are applied as electrode materials for lithium ion batteries, they show much improved electrochemical performance compared with the pristine MoS2 mineral because of the enhanced ion and electron transfer kinetics. This facile, scalable and eco-friendly aqueous-based process in combination with renewable and ultra-low-cost lignin opens up possibilities for large-scale fabrication of MoS2-based nanocomposites and devices. Moreover, herein we demonstrate that AL is also an excellent surfactant for exfoliation of many other types of layered materials, including graphene, tungsten disulfide and boron nitride, in water, providing rich opportunities for a wider range of applications.In this article, alkali lignin (AL)-assisted direct exfoliation of MoS2 mineral into single-layer and few-layer nanosheets in water is reported for the first time. Under optimized conditions, the concentration of MoS2 nanosheets in the obtained dispersion can be as high as 1.75 +/- 0.08 mg mL-1, which is much higher than the typical reported concentrations (<1.0 mg mL-1) using synthetic polymers or compounds as surfactants. The stabilizing mechanism primarily lies in the electrostatic repulsion between negative charged AL, as suggested by zeta-potential measurements. When the exfoliated MoS2 nanosheets are applied as electrode materials for lithium ion batteries, they show much improved

Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases

PubMed Central

Uzal, F. A.; Vidal, J. E.; McClane, B. A.; Gurjar, A. A.

2013-01-01

Clostridium perfringens is a gram-positive anaerobic rod that is classified into 5 toxinotypes (A, B, C, D, and E) according to the production of 4 major toxins, namely alpha (CPA), beta (CPB), epsilon (ETX) and iota (ITX). However, this microorganism can produce up to 16 toxins in various combinations, including lethal toxins such as perfringolysin O (PFO), enterotoxin (CPE), and beta2 toxin (CPB2). Most diseases caused by this microorganism are mediated by one or more of these toxins. The role of CPA in intestinal disease of mammals is controversial and poorly documented, but there is no doubt that this toxin is essential in the production of gas gangrene of humans and several animal species. CPB produced by C. perfringens types B and C is responsible for necrotizing enteritis and enterotoxemia mainly in neonatal individuals of several animal species. ETX produced by C. perfringens type D is responsible for clinical signs and lesions of enterotoxemia, a predominantly neurological disease of sheep and goats. The role of ITX in disease of animals is poorly understood, although it is usually assumed that the pathogenesis of intestinal diseases produced by C. perfringens type E is mediated by this toxin. CPB2, a necrotizing and lethal toxin that can be produced by all types of C. perfringens, has been blamed for disease in many animal species, but little information is currently available to sustain or rule out this claim. CPE is an important virulence factor for C. perfringens type A gastrointestinal disease in humans and dogs; however, the data implicating CPE in other animal diseases remains ambiguous. PFO does not seem to play a direct role as the main virulence factor for animal diseases, but it may have a synergistic role with CPA-mediated gangrene and ETX-mediated enterotoxemia. The recent improvement of animal models for C. perfringens infection and the use of toxin gene knock-out mutants have demonstrated the specific pathogenic role of several toxins of C

Persistence of Clostridium botulinum type C toxin in blow fly (Calliphoridae) larvae as a possible cause of avian botulism in spring.

PubMed

Hubálek, Z; Halouzka, J

1991-01-01

Diverse samples were examined at a site of water-bird mortality, caused by Clostridium botulinum type C toxin in southern Moravia (Czechoslovakia). The toxin was detected in high concentrations in mute swan (Cygnus olor) carcasses (less than or equal to 1 x 10(6) LD50/g) as well as in necrophagous larvae and pupae of the blow flies Lucilia sericata and Calliphora vomitoria (less than or equal to 1 x 10(5) LD50/g) collected from them. It was detected in lower concentrations (less than or equal to 1 x 10(3) LD50/g) in other invertebrates (ptychopterid fly larvae, leeches, sow-bugs) associated with these carcasses, and occasionally in water samples (8 LD50/ml) close to the carrion. The toxin was not detected in the samples of water, mud or invertebrates collected at a distance greater than or equal to 5 m from the carcasses. The toxin-bearing larvae of L. sericata and C. vomitoria, containing 80,000 LD50/g of type C toxin, were exposed in the mud at the study site for 131 days from November to March. Although the toxin activity decreased 25-fold and 40-fold in the two samples of maggots exposed during this period, it remained very high (less than or equal to 3,200 LD50/g). Birds ingesting a relatively low number of these toxic larvae (or pupae) in the spring could receive a lethal dose of the toxin.

Clostridium perfringens iota toxin: synergism between two proteins.

PubMed

Stiles, B G; Wilkins, T D

1986-01-01

The iota toxin of Clostridium perfringens type E is a guinea pig dermonecrotic, mouse lethal toxin which cross-reacts with the iota-like toxin of Clostridium spiroforme. Antiserum raised against C. spiroforme or C. perfringens type E neutralizes the toxin from both species. By using C. spiroforme antiserum and crossed immunoelectrophoresis, we have found that there are two cross-reacting proteins, designated iota a (ia) and iota b (ib) in the culture filtrate of C. perfringens type E. Both proteins of C. perfringens were separated by preparative isoelectric focusing and had very little toxic activity when tested alone. However, when they were recombined there were 8- and 25-fold increases in bioactivity as determined by mouse lethal and guinea pig dermonecrotic assays, respectively. These results demonstrate that the iota toxin of C. perfringens requires two immunologically and biochemically different proteins for maximum activity.

Cloning and expression of Clostridium perfringens type D vaccine strain epsilon toxin gene in E. coli as a recombinant vaccine candidate.

PubMed

Aziminia, Parastoo; Pilehchian-Langroudi, Reza; Esmaeilnia, Kasra

2016-08-01

Clostridium perfringens, a Gram-positive obligate anaerobic bacterium, is able to form resistant spores which are widely distributed in the environment. C. perfringens is subdivided into five types A to E based on its four major alpha, beta, epsilon and iota toxins. The aim of the present study was cloning and expression of C. perfringens type D vaccine strain epsilon toxin gene. Genomic DNA was extracted and the epsilon toxin gene was amplified using Pfu DNA polymerase. The PCR product was cloned into pJET1.2/blunt cloning vector. The recombinant vector (pJETε) was sequenced using universal primers. At the next step epsilon toxin gene was subcloned into pET22b(+) expression vector and transformed into E. coli Rosetta (DE3) host strain. The recombinant protein has been expressed in E. coli Rosetta (DE3) cells after subcloning of C. perfringens etx gene (1008 bp) into the expression vector. We concluded that E. coli Rosetta strain was suitable for the expression of recombinant C. perfringens epsilon toxin protein from pET22ε expression vector. This recombinant cell can be used for further research on recombinant vaccine development.

Recompressed exfoliated graphite articles

DOEpatents

Zhamu, Aruna; Shi, Jinjun; Guo, Jiusheng; Jang, Bor Z

2013-08-06

This invention provides an electrically conductive, less anisotropic, recompressed exfoliated graphite article comprising a mixture of (a) expanded or exfoliated graphite flakes; and (b) particles of non-expandable graphite or carbon, wherein the non-expandable graphite or carbon particles are in the amount of between about 3% and about 70% by weight based on the total weight of the particles and the expanded graphite flakes combined; wherein the mixture is compressed to form the article having an apparent bulk density of from about 0.1 g/cm.sup.3 to about 2.0 g/cm.sup.3. The article exhibits a thickness-direction conductivity typically greater than 50 S/cm, more typically greater than 100 S/cm, and most typically greater than 200 S/cm. The article, when used in a thin foil or sheet form, can be a useful component in a sheet molding compound plate used as a fuel cell separator or flow field plate. The article may also be used as a current collector for a battery, supercapacitor, or any other electrochemical cell.

Intercalation Pseudocapacitance of Exfoliated Molybdenum Disulfide for Ultrafast Energy Storage

DOE PAGES

Yoo, Hyun Deog; Li, Yifei; Liang, Yanliang; ...

2016-05-23

In this study, we report intercalation pseudocapacitance of 250 F g -1 for exfoliated molybdenum disulfide (MoS 2) in non-aqueous electrolytes that contain lithium ions. The exfoliated MoS 2 shows surface-limited reaction kinetics with high rate capability up to 3 min of charge or discharge. The intercalation pseudocapacitance originates from the extremely fast kinetics due to the enhanced ionic and electronic transport enabled by the slightly expanded layer structure as well as the metallic 1T-phase. The exfoliated MoS 2 could be also used in a Li-Mg-ion hybrid capacitor, which shows full cell specific capacitance of 240 F g -1.

Clostridial toxins active locally in the gastrointestinal tract.

PubMed

Wilkins, T; Krivan, H; Stiles, B; Carman, R; Lyerly, D

1985-01-01

Clostridium difficile and Clostridium spiroforme have only in recent years been recognized as intestinal pathogens. They both produce toxins that are also produced by other clostridia. C. difficile toxins A and B are produced by C. sordellii and a few strains of C. perfringens whereas C. spiroforme produces the same toxins as C. perfringens Type E (iota toxin). Iota toxin activity may be the product of two proteins. Toxigenic strains of C. spiroforme and Type E produce two antigens which possess much more biological activity when administered together than when given alone. C. difficile was thought for some time to produce only a single toxin, but then the enterotoxic activity was shown to be due to a separate toxin (toxin A). This toxin increases the oral toxicity of toxin B (the main cytotoxin) and may increase the permeability of the colon. Toxin A binds to a specific receptor in hamster brush border membranes and in the membranes of rabbit erythrocytes. This receptor appears to be a glycoprotein. The receptor can be extracted from the membrane with Triton and binds to immobilized toxin A. The receptor can be extracted and used to coat plastic plates as a first phase in an ELISA assay. Another assay has been developed in which the toxin A binds to the red cells and then the erythrocytes are agglutinated with antitoxin. An even more sensitive assay consists of using rabbit erythrocyte ghosts to bind the toxin and then precipitating the ghosts with antibody to toxin A attached to latex beads. Monoclonal antibodies to toxin A also have been developed and are used in these and other assays.

Pore-forming toxins in Cnidaria.

PubMed

Podobnik, Marjetka; Anderluh, Gregor

2017-12-01

The ancient phylum of Cnidaria contains many aquatic species with peculiar lifestyle. In order to survive, these organisms have evolved attack and defense mechanisms that are enabled by specialized cells and highly developed venoms. Pore-forming toxins are an important part of their venomous arsenal. Along some other types, the most representative are examples of four protein families that are commonly found in other kingdoms of life: actinoporins, Cry-like proteins, aerolysin-like toxins and MACPF/CDC toxins. Some of the homologues of pore-forming toxins may serve other functions, such as in food digestion, development and response against pathogenic organisms. Due to their interesting physico-chemical properties, the cnidarian pore-forming toxins may also serve as tools in medical research and nanobiotechnological applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training.

PubMed

Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

2014-09-21

To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus.

Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins

PubMed Central

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

2014-01-01

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

Raman spectral signatures of cervical exfoliated cells from liquid-based cytology samples

NASA Astrophysics Data System (ADS)

Kearney, Padraig; Traynor, Damien; Bonnier, Franck; Lyng, Fiona M.; O'Leary, John J.; Martin, Cara M.

2017-10-01

It is widely accepted that cervical screening has significantly reduced the incidence of cervical cancer worldwide. The primary screening test for cervical cancer is the Papanicolaou (Pap) test, which has extremely variable specificity and sensitivity. There is an unmet clinical need for methods to aid clinicians in the early detection of cervical precancer. Raman spectroscopy is a label-free objective method that can provide a biochemical fingerprint of a given sample. Compared with studies on infrared spectroscopy, relatively few Raman spectroscopy studies have been carried out to date on cervical cytology. The aim of this study was to define the Raman spectral signatures of cervical exfoliated cells present in liquid-based cytology Pap test specimens and to compare the signature of high-grade dysplastic cells to each of the normal cell types. Raman spectra were recorded from single exfoliated cells and subjected to multivariate statistical analysis. The study demonstrated that Raman spectroscopy can identify biochemical signatures associated with the most common cell types seen in liquid-based cytology samples; superficial, intermediate, and parabasal cells. In addition, biochemical changes associated with high-grade dysplasia could be identified suggesting that Raman spectroscopy could be used to aid current cervical screening tests.

Detection of botulinum toxin types A, B, E, and F activity using the quail embryo

USDA-ARS?s Scientific Manuscript database

We recently demonstrated an effective new model for the detection of botulinum toxin type A using quail embryos in place of the mouse model. These experiments demonstrated that the Japanese quail embryo at 15 days of incubation was an effective vertebrate animal model to detect the activity of botu...

Involvement of substance P in the antinociceptive effect of botulinum toxin type A: Evidence from knockout mice.

PubMed

Matak, Ivica; Tékus, Valéria; Bölcskei, Kata; Lacković, Zdravko; Helyes, Zsuzsanna

2017-09-01

The antinociceptive action of botulinum toxin type A (BoNT/A) has been demonstrated in behavioral animal studies and clinical settings. It was shown that this effect is associated with toxin activity in CNS, however, the mechanism is not fully understood. Substance P (SP) is one of the dominant neurotransmitters in primary afferent neurons transmitting pain and itch. Thus, here we examined association of SP-mediated transmission and BoNT/A antinociceptive action by employing gene knockouts. Antinociceptive activity of intraplantarly (i.pl.) injected BoNT/A was examined in mice lacking the gene encoding for SP/neurokinin A (tac1 -/- ) or SP-preferred receptor neurokinin 1 (tac1r -/- ), compared to control C57Bl/6J wild type animals. BoNT/A action was assessed in inflammatory pain induced by formalin and CFA, and neuropathic pain induced by partial sciatic nerve ligation. BoNT/A activity in CNS was examined by c-Fos and BoNT/A-cleaved SNAP-25 immunohistochemistry. In wild type mice, acute (formalin-evoked) and chronic pain (neuropathic and inflammatory) was reduced by peripherally injected BoNT/A. In tac1 -/- and tac1r -/- knockout mice, BoNT/A exerted no analgesic effect. In control animals BoNT/A reduced the formalin-evoked c-Fos expression in lumbar dorsal horn, while in knockout mice the c-Fos expression was not reduced. After peripheral toxin injection, cleaved SNAP-25 occurred in lumbar dorsal horn in all animal genotypes. BoNT/A antinociceptive activity is absent in animals lacking the SP and neurokinin 1 receptor encoding genes, in spite of presence of toxin's enzymatic activity in central sensory regions. Thus, we conclude that the integrity of SP-ergic system is necessary for the antinociceptive activity of BoNT/A. Copyright © 2017. Published by Elsevier Ltd.

Ultrahigh-throughput exfoliation of graphite into pristine 'single-layer' graphene using microwaves and molecularly engineered ionic liquids.

PubMed

Matsumoto, Michio; Saito, Yusuke; Park, Chiyoung; Fukushima, Takanori; Aida, Takuzo

2015-09-01

Graphene has shown much promise as an organic electronic material but, despite recent achievements in the production of few-layer graphene, the quantitative exfoliation of graphite into pristine single-layer graphene has remained one of the main challenges in developing practical devices. Recently, reduced graphene oxide has been recognized as a non-feasible alternative to graphene owing to variable defect types and levels, and attention is turning towards reliable methods for the high-throughput exfoliation of graphite. Here we report that microwave irradiation of graphite suspended in molecularly engineered oligomeric ionic liquids allows for ultrahigh-efficiency exfoliation (93% yield) with a high selectivity (95%) towards 'single-layer' graphene (that is, with thicknesses <1 nm) in a short processing time (30 minutes). The isolated graphene sheets show negligible structural deterioration. They are also readily redispersible in oligomeric ionic liquids up to ~100 mg ml(-1), and form physical gels in which an anisotropic orientation of graphene sheets, once induced by a magnetic field, is maintained.

Continuous evolution of B. thuringiensis toxins overcomes insect resistance

PubMed Central

Badran, Ahmed H.; Guzov, Victor M.; Huai, Qing; Kemp, Melissa M.; Vishwanath, Prashanth; Kain, Wendy; Nance, Autumn M.; Evdokimov, Artem; Moshiri, Farhad; Turner, Keith H.; Wang, Ping; Malvar, Thomas; Liu, David R.

2016-01-01

The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. We developed a phage-assisted continuous evolution (PACE) selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively targeted by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (Kd = 11–41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome Bt toxin resistance in insects and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects. PMID:27120167

Further enhancement of facial appearance with a hydroquinone skin care system plus tretinoin in patients previously treated with botulinum toxin Type A.

PubMed

Schlessinger, Joel; Kenkel, Jeffrey; Werschler, Philip

2011-07-01

A hydroquinone (HQ) skin care system has been designed for use in conjunction with nonsurgical procedures. The authors evaluate the efficacy of this system plus tretinoin for improving facial appearance in comparison to a standard skin care regimen in users of botulinum toxin Type A (BoNT-A). In this multicenter, randomized, investigator-masked, parallel-group study, 61 patients who received upper facial treatment with BoNT-A at a plastic surgery or dermatology clinic were randomly assigned to apply either the HQ system (cleanser, toner, proprietary 4% hydroquinone, exfoliant, and sunscreen) plus 0.05% tretinoin cream or a standard skin care regimen (cleanser, moisturizer, and sunscreen) for 120 days. Outcomes were assessed by the investigators and through a patient questionnaire. Compared with standard skin care, the HQ system plus tretinoin resulted in significantly milder fine lines/wrinkles and hyperpigmentation at Days 30, 90, and 120 (p ≤ .05) and significantly superior overall ratings for each of nine patient assessments at Days 90 and 120 (p ≤ .05). A relatively greater proportion of patients using the HQ system plus tretinoin believed that their study treatment had further enhanced the improvements attained with BoNT-A (86% vs 8%). Both regimens were generally well tolerated. Adjunctive use of the HQ system plus tretinoin can further enhance the improvements in facial appearance attained with BoNT-A. Applying the HQ system plus tretinoin offers multiple clinical benefits over standard skin care, including significantly greater improvements in fine lines/wrinkles and hyperpigmentation.

Thermal Exfoliation of Natural Cellulosic Material for Graphene Synthesis

NASA Astrophysics Data System (ADS)

Ray, Ajoy Kumar; Chatterjee, Somenath; Singh, Jitendra Kumar; Bapari, Himangshu

2015-01-01

Hibiscus flower petals have been used as a cheap natural resource precursor for cost-effective synthesis of high quality graphene by thermal exfoliation process. In order to compare the quality of graphene obtained from the flower petals directly with the flower petals pretreated with nickel(II) chloride, Raman spectroscopic technique has been used as the structural probe. The role of temperature and the effect of nickel on thermal exfoliation process have been examined. It has been observed that graphene obtained via nickel incorporation is of better quality because NI2+ ions that get dispersed in the layered-structured cellulose at elevated temperatures get reduced to the metallic state, which in turn push the graphitic layers during thermal exfoliation to produce good quality graphene. In contrast, no such driving force is present in cellulose and hemi-cellulose of flower petals that contain lignin.

Use of enzyme-linked immunoassays for antibody to types C and D botulinum toxins for investigations of botulism in cattle.

PubMed

Gregory, A R; Ellis, T M; Jubb, T F; Nickels, R J; Cousins, D V

1996-02-01

The development of specific enzyme-linked immunosorbent assays (ELISA) for antibody to types C and D Clostridium botulinum toxins for investigation of botulism in cattle is described. Partially purified type C and D toxins were used as antigens to develop these ELISAs. Specificity of the ELISAs was evaluated on sera from 333 adult beef and dairy cattle from areas with no history or evidence of botulism in animals or water birds. The test was also evaluated on sera from 41 herds that included herds vaccinated against botulism, confirmed botulism cases and herds from areas where the disease is considered endemic. The ELISAs detected the presence of antibody to botulinum toxins in samples from vaccinated cattle and both convalescent and clinically normal animals from unvaccinated herds with outbreaks of botulism. Antibody was also found in unvaccinated animals from herds in which there had been no diagnosed botulism cases in areas where botulism was considered endemic. Sera from some unvaccinated cattle with high ELISA reactivity was shown to be protective for mice in botulinum toxin neutralisation tests. The use of these tests in investigations of botulism in cattle is discussed.

Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

PubMed

Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

2017-07-24

Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.

PubMed

Tenenholz, T C; Rogowski, R S; Collins, J H; Blaustein, M P; Weber, D J

1997-03-11

PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type

Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training

PubMed Central

Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

2014-01-01

AIM: To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. METHODS: This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. RESULTS: BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. CONCLUSION: BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus. PMID:25253964

Efficient fluorescence quenching in electrochemically exfoliated graphene decorated with gold nanoparticles

NASA Astrophysics Data System (ADS)

Hurtado-Morales, M.; Ortiz, M.; Acuña, C.; Nerl, H. C.; Nicolosi, V.; Hernández, Y.

2016-07-01

High surface area graphene sheets were obtained by electrochemical exfoliation of graphite in an acid medium under constant potential conditions. Filtration and centrifugation processes played an important role in order to obtain stable dispersions in water. Scanning electron microscopy and transmission electron microscopy imaging revealed highly exfoliated crystalline samples of ∼5 μm. Raman, Fourier transform infrared and x-ray photoelectron spectroscopy further confirmed the high quality of the exfoliated material. The electrochemically exfoliated graphene (EEG) was decorated with gold nanoparticles (AuNPs) using sodium cholate as a buffer layer. This approach allowed for a non-covalent functionalization without altering the desirable electronic properties of the EEG. The AuNP-EEG samples were characterized with various techniques including absorbance and fluorescence spectroscopy. These samples displayed a fluorescence signal using an excitation wavelength of 290 nm. The calculated quantum yield (Φ) for these samples was 40.04%, a high efficiency compared to previous studies using solution processable graphene.

First insights into a type II toxin-antitoxin system from the clinical isolate Mycobacterium sp. MHSD3, similar to epsilon/zeta systems.

PubMed

Jaén-Luchoro, Daniel; Aliaga-Lozano, Francisco; Gomila, Rosa Maria; Gomila, Margarita; Salvà-Serra, Francisco; Lalucat, Jorge; Bennasar-Figueras, Antoni

2017-01-01

A putative type II toxin-antitoxin (TA) system was found in the clinical isolate Mycobacterium sp. MHSD3, a strain closely related to Mycobacterium chelonae. Further analyses of the protein sequences of the two genes revealed the presence of domains related to a TA system. BLAST analyses indicated the presence of closely related proteins in the genomes of other recently published M. chelonae strains. The functionality of both elements of the TA system was demonstrated when expressed in Escherichia coli cells, and the predicted structure of the toxin is very similar to those of well-known zeta-toxins, leading to the definition of a type II TA system similar to epsilon/zeta TA systems in strains that are closely related to M. chelonae.

Note: Mechanical in situ exfoliation of van der Waals materials

NASA Astrophysics Data System (ADS)

Pásztor, Á.; Scarfato, A.; Renner, Ch.

2017-07-01

Exfoliation, namely, the peeling of layered materials down to a single unit-cell thin foil, opens promising avenues to fabricate novel electronic materials. New properties and original functionalities emerge in the single and few layer configurations of a number of layered compounds, in particular in transition metal dichalcogenides. However, many of these thin exfoliated materials are very sensitive to ambient conditions impeding the exploration of this new and fascinating parameter space. Here we describe a method of mechanical exfoliation in ultra-high vacuum (UHV). This technique is easily adaptable to any UHV system and allows preparing and studying air sensitive nanoflakes in situ. We present the basic design and proof-of-concept scanning tunneling microscopy imaging of VSe2 nanoflakes.

Fate of Fusarium Toxins during Brewing.

PubMed

Habler, Katharina; Geissinger, Cajetan; Hofer, Katharina; Schüler, Jan; Moghari, Sarah; Hess, Michael; Gastl, Martina; Rychlik, Michael

2017-01-11

Some information is available about the fate of Fusarium toxins during the brewing process, but only little is known about the single processing steps in detail. In our study we produced beer from two different barley cultivars inoculated with three different Fusarium species, namely, Fusarium culmorum, Fusarium sporotrichioides, and Fusarium avenaceum, producing a wide range of mycotoxins such as type B trichothecenes, type A trichothecenes, and enniatins. By the use of multi-mycotoxin LC-MS/MS stable isotope dilution methods we were able to follow the fate of Fusarium toxins during the entire brewing process. In particular, the type B trichothecenes deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol showed similar behaviors. Between 35 and 52% of those toxins remained in the beer after filtration. The contents of the potentially hazardous deoxynivalenol-3-glucoside and the type A trichothecenes increased during mashing, but a rapid decrease of deoxynivalenol-3-glucoside content was found during the following steps of lautering and wort boiling. The concentration of enniatins greatly decreased with the discarding of spent grains or finally with the hot break. The results of our study show the retention of diverse Fusarium toxins during the brewing process and allow for assessing the food safety of beer regarding the monitored Fusarium mycotoxins.

Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells.

PubMed

Goormaghtigh, Frédéric; Fraikin, Nathan; Putrinš, Marta; Hallaert, Thibaut; Hauryliuk, Vasili; Garcia-Pino, Abel; Sjödin, Andreas; Kasvandik, Sergo; Udekwu, Klas; Tenson, Tanel; Kaldalu, Niilo; Van Melderen, Laurence

2018-06-12

Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems. Cells in which TA systems are activated are thought to enter a dormancy state and therefore survive the antibiotic treatment. Using independently constructed strains and newly designed fluorescent reporters, we reassessed the roles of TA modules in persistence both at the population and single-cell levels. Our data confirm that the deletion of 10 TA systems does not affect persistence to ofloxacin or ampicillin. Moreover, microfluidic experiments performed with a strain reporting the induction of the yefM-yoeB TA system allowed the observation of a small number of type II persister cells that resume growth after removal of ampicillin. However, we were unable to establish a correlation between high fluorescence and persistence, since the fluorescence of persister cells was comparable to that of the bulk of the population and none of the cells showing high fluorescence were able to resume growth upon removal of the antibiotic. Altogether, these data show that there is no direct link between induction of TA systems and persistence to antibiotics. IMPORTANCE Within a growing bacterial population, a small subpopulation of cells is able to survive antibiotic treatment by entering a transient state of dormancy referred to as persistence. Persistence is thought to be the cause of relapsing bacterial infections and is a major public health concern. Type II toxin-antitoxin systems are

Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice.

PubMed

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

2010-12-01

Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

sRNA antitoxins: more than one way to repress a toxin.

PubMed

Wen, Jia; Fozo, Elizabeth M

2014-08-04

Bacterial toxin-antitoxin loci consist of two genes: one encodes a potentially toxic protein, and the second, an antitoxin to repress its function or expression. The antitoxin can either be an RNA or a protein. For type I and type III loci, the antitoxins are RNAs; however, they have very different modes of action. Type I antitoxins repress toxin protein expression through interacting with the toxin mRNA, thereby targeting the mRNA for degradation or preventing its translation or both; type III antitoxins directly bind to the toxin protein, sequestering it. Along with these two very different modes of action for the antitoxin, there are differences in the functions of the toxin proteins and the mobility of these loci between species. Within this review, we discuss the major differences as to how the RNAs repress toxin activity, the potential consequences for utilizing different regulatory strategies, as well as the confirmed and potential biological roles for these loci across bacterial species.

Liquid-phase exfoliated graphene self-assembled films: Low-frequency noise and thermal-electric characterization

NASA Astrophysics Data System (ADS)

Tubon Usca, G.; Hernandez-Ambato, J.; Pace, C.; Caputi, L. S.; Tavolaro, A.

2016-09-01

In few years, graphene has become a revolutionary material, leading not only to applications in various fields such as electronics, medicine and environment, but also to the production of new types of 2D materials. In this work, Liquid Phase Exfoliation (LPE) was applied to natural graphite by brief sonication or mixer treatment in suitable solvents, in order to produce Few Layers Graphene (FLG) suspensions. Additionally, zeolite 4A (Z4A) was added during the production of FLG flakes-based inks, with the aim of aiding the exfoliation process. Conductive films were obtained by drop casting three types of suspensions over Al2O3 substrates with interdigitated electrodes, with total channel surface of 1.39 mm2. The morphology characterization resulted in the verification of the presence of thin self-assembled flakes. Raman studies gave evidence of 4 to 10 layers graphene flakes. Electrical measurements were performed to state the Low-Frequency Noise and Thermal-Electric characteristics of the samples. We observe interesting relations between sample preparation procedures and electrical properties.

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

PubMed

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

2016-04-01

While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Controlled Gas Exfoliation of Boron Nitride into Few-Layered Nanosheets

DOE PAGES

Zhu, Wenshuai; Gao, Xiang; Li, Qian; ...

2016-07-22

The controlled exfoliation of hexagonal boron nitride (h-BN) into single- or few-layered nanosheets remains a grand challenge and becomes the bottleneck to essential studies and applications of h-BN. Here, we present an efficient strategy for the scalable synthesis of few-layered h-BN nanosheets (BNNS) via a novel gas exfoliation of bulk h-BN in liquid N 2 (L-N 2). The essence of this strategy lies in the combination of a high temperature triggered expansion of bulk h-BN and the cryogenic L-N 2 gasification to exfoliate the h-BN. The produced BNNS after ten cycles (BNNS-10) consisted primarily of fewer than five atomic layersmore » with high a mass yield of 16~20%. N 2 sorption and desorption isotherms show that the BNNS-10 exhibited a much higher specific surface area of 278 m 2/g –1 than that of bulk BN (10 m 2/g –1). Through the investigation of the exfoliated intermediates combined with a theoretical calculation, we found that the huge temperature variation initiates the expansion and curling of the bulk h-BN. Subseqently, the L-N 2 penetrates into the interlayers of h-BN along the curling edge, followed by an immediate drastic gasification of L-N 2, further peeling off h-BN. In conclusion, this novel gas exfoliation of high surface area BNNS not only opens up potential opportunities for wide applications, but also can be extended to produce other layered materials with high yeilds.« less

Ultrahigh-throughput exfoliation of graphite into pristine ‘single-layer’ graphene using microwaves and molecularly engineered ionic liquids

NASA Astrophysics Data System (ADS)

Matsumoto, Michio; Saito, Yusuke; Park, Chiyoung; Fukushima, Takanori; Aida, Takuzo

2015-09-01

Graphene has shown much promise as an organic electronic material but, despite recent achievements in the production of few-layer graphene, the quantitative exfoliation of graphite into pristine single-layer graphene has remained one of the main challenges in developing practical devices. Recently, reduced graphene oxide has been recognized as a non-feasible alternative to graphene owing to variable defect types and levels, and attention is turning towards reliable methods for the high-throughput exfoliation of graphite. Here we report that microwave irradiation of graphite suspended in molecularly engineered oligomeric ionic liquids allows for ultrahigh-efficiency exfoliation (93% yield) with a high selectivity (95%) towards ‘single-layer’ graphene (that is, with thicknesses <1 nm) in a short processing time (30 minutes). The isolated graphene sheets show negligible structural deterioration. They are also readily redispersible in oligomeric ionic liquids up to ~100 mg ml-1, and form physical gels in which an anisotropic orientation of graphene sheets, once induced by a magnetic field, is maintained.

Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

2010-01-01

The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction.

PubMed

De Boulle, Koenraad; Fagien, Steven; Sommer, Boris; Glogau, Richard

2010-04-26

Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names) mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA) are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.

Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

PubMed

Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

2008-07-01

A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

Immunological and functional comparison between Clostridium perfringens iota toxin, C. spiroforme toxin, and anthrax toxins.

PubMed

Perelle, S; Scalzo, S; Kochi, S; Mock, M; Popoff, M R

1997-01-01

Clostridium perfringens iota and C. spiroforme toxins consist of two separate proteins. One is the binding component and the other the enzymatic component. The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen, lethal factor, and edema factor. As shown by Western blotting and ELISA, the binding component of anthrax toxin shares common epitopes with that of iota toxin and C. spiroforme toxin which are closely related immunologically. However, no functional complementation was observed between iota toxin and anthrax toxin components. The binding components can form toxins active on macrophages only in combination with their respective enzymatic components. Agents which prevent acidification of endosomes do not have the same effects on anthrax toxin activity as they do on iota and C. spiroforme toxins. Therefore, the mechanisms of entry into the cells are presumably different. Since the binding components of anthrax toxins and iota toxin share a conserved putative translocation domain, these binding components could have a common mode of insertion into the cell membranes.

Botulinum Toxin

DTIC Science & Technology

2009-01-01

neuroblastomas and rat gliomas, but not to human neuroblastoma cell lines ( Yokosawa et ai., 1989). Yokosawa et ai. (1989) suggested that reduced...12764-72. Yndestad, M., Loftsgard, G. (1970). Susceptibility of mink to Clostridium botulinum type C toxin. Acta Vet. Scand. 11: 594-9. Yokosawa , N

Acetone improves the topographical homogeneity of liquid phase exfoliated few-layer black phosphorus flakes.

PubMed

Gomez Perez, Juan; Konya, Zoltan; Kukovecz, Akos

2018-06-12

Liquid phase exfoliation of 2D materials has issues related to the sorption of the solvent, the oxidation of the sample during storage, and the topographical inhomogeneity of the exfoliated material. N-methyl-2-pyrrolidone (NMP), a common solvent for black phosphorus (BP) exfoliation, has additional drawbacks like the formation of by-products during sonication and poor solvent volatility. Here we demonstrate an improvement in the topographical homogeneity (i.e. thickness and lateral dimensions) of NMP-exfoliated BP flakes after resuspension in acetone. The typical size of monolayers and bilayers stabilised in acetone was 99.8±27.4 nm and 159.1±57 nm, respectively. These standard deviations represent a threefold improvement over those of the NMP-exfoliated originals. Phosphorene can also be exfoliated directly in acetone by very long ultrasonication. The product suspension enjoys the same dimensional homogeneity benefits, which confirms that this effect is an intrinsic property of the acetone-BP system. The quality and stability of the exfoliated flakes was checked by XRD, TEM, electron diffraction and Raman spectroscopy. Thermal expansion coefficients of the A1g, B2g and A2g Raman modes were calculated for drop-casted samples as -0.01828 cm-1/K, -0.03056 cm-1/K and -0.03219 cm-1/K, respectively. The flakes withstand 20 minutes in O2 flow at 373 K without lattice distortion. . © 2018 IOP Publishing Ltd.

Comparison of Anorectic Potencies of the Trichothecenes T-2 Toxin, HT-2 Toxin and Satratoxin G to the Ipecac Alkaloid Emetine.

PubMed

Wu, Wenda; Zhou, Hui-Ren; Pan, Xiao; Pestka, James J

Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON) and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin), airborne Type D trichothecenes (e.g. satratoxin G [SG]) or functionally analogous metabolites that impair protein synthesis. Here, we utilized a well-described mouse model of food intake to compare the anorectic potencies of T-2 toxin, HT-2 toxin, and SG to that of emetine, a medicinal alkaloid derived from ipecac that inhibits translation. Intraperitoneal (IP) administration with T-2 toxin, HT-2 toxin, emetine and SG evoked anorectic responses that occurred within 0.5 h that lasted up to 96, 96, 3 and 96 h, respectively, with lowest observed adverse effect levels (LOAELs) being 0.1, 0.1, 2.5 and 0.25 mg/kg BW, respectively. When delivered via natural routes of exposure, T-2 toxin, HT-2 toxin, emetine (oral) and SG (intranasal) induced anorectic responses that lasted up to 48, 48, 3 and 6 h, respectively with LOAELs being 0.1, 0.1, 0.25, and 0.5 mg/kg BW, respectively. All four compounds were generally much more potent than DON which was previously observed to have LOAELs of 1 and 2.5 mg/kg BW after IP and oral dosing, respectively. Taken together, these anorectic potency data will be valuable in discerning the relative risks from trichothecenes and other translational inhibitors of natural origin.

Exfoliation syndrome: assembling the puzzle pieces.

PubMed

Pasquale, Louis R; Borrás, Terete; Fingert, John H; Wiggs, Janey L; Ritch, Robert

2016-09-01

To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. The highlights of three categories of talks on cutting edge research in the field were summarized. Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Reliable Exfoliation of Large-Area High-Quality Flakes of Graphene and Other Two-Dimensional Materials.

PubMed

Huang, Yuan; Sutter, Eli; Shi, Norman N; Zheng, Jiabao; Yang, Tianzhong; Englund, Dirk; Gao, Hong-Jun; Sutter, Peter

2015-11-24

Mechanical exfoliation has been a key enabler of the exploration of the properties of two-dimensional materials, such as graphene, by providing routine access to high-quality material. The original exfoliation method, which remained largely unchanged during the past decade, provides relatively small flakes with moderate yield. Here, we report a modified approach for exfoliating thin monolayer and few-layer flakes from layered crystals. Our method introduces two process steps that enhance and homogenize the adhesion force between the outermost sheet in contact with a substrate: Prior to exfoliation, ambient adsorbates are effectively removed from the substrate by oxygen plasma cleaning, and an additional heat treatment maximizes the uniform contact area at the interface between the source crystal and the substrate. For graphene exfoliation, these simple process steps increased the yield and the area of the transferred flakes by more than 50 times compared to the established exfoliation methods. Raman and AFM characterization shows that the graphene flakes are of similar high quality as those obtained in previous reports. Graphene field-effect devices were fabricated and measured with back-gating and solution top-gating, yielding mobilities of ∼4000 and 12,000 cm(2)/(V s), respectively, and thus demonstrating excellent electrical properties. Experiments with other layered crystals, e.g., a bismuth strontium calcium copper oxide (BSCCO) superconductor, show enhancements in exfoliation yield and flake area similar to those for graphene, suggesting that our modified exfoliation method provides an effective way for producing large area, high-quality flakes of a wide range of 2D materials.

Characterization of Alpha-Toxin hla Gene Variants, Alpha-Toxin Expression Levels, and Levels of Antibody to Alpha-Toxin in Hemodialysis and Postsurgical Patients with Staphylococcus aureus Bacteremia

PubMed Central

Wu, Yuling; Tabor, David E.; Mok, Hoyin; Sellman, Bret R.; Jenkins, Amy; Yu, Li; Jafri, Hasan S.; Rude, Thomas H.; Ruffin, Felicia; Schell, Wiley A.; Park, Lawrence P.; Yan, Qin; Thaden, Joshua T.; Messina, Julia A.; Esser, Mark T.

2014-01-01

Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study. PMID:25392350

Surface Characterization of Mechanochemically Modified Exfoliated Halloysite Nanoscrolls.

PubMed

Zsirka, Balázs; Táborosi, Attila; Szabó, Péter; Szilágyi, Róbert K; Horváth, Erzsébet; Juzsakova, Tatjána; Fertig, Dávid; Kristóf, János

2017-04-11

Surface modifications fundamentally influence the morphology of kaolinite nanostructures as a function of crystallinity and the presence of contaminants. Besides morphology, the catalytic properties of 1:1-type exfoliated aluminosilicates are also influenced by the presence of defect sites that can be generated in a controlled manner by mechanochemical activation. In this work, we investigated exfoliated halloysite nanoparticles with a quasi-homogeneous, scroll-type secondary structure toward developing structural/functional relationships for composition, atomic structure, and morphology. The surface properties of thin-walled nanoscrolls were studied as a function of mechanochemical activation expressed by the duration of dry-grinding. The surface characterizations were carried out using N 2 , NH 3 , and CO 2 adsorption measurements. The effects of grinding on the nanohalloysite structure were followed using thermoanalytical thermogravimetric/derivative thermogravimetric (TG/DTG) and infrared spectroscopic [Fourier transform infrared/attenuated total reflection (FTIR/ATR)] techniques. Grinding results in partial dehydroxylation with similar changes as those observed for heat treatment above 300 °C. Mechanochemical activation shows a decrease in the dehydroxylation mass loss and the DTG peak temperature, a decrease in the specific surface area and the number of mesopores, an increase in the surface acidity, blue shift of surface hydroxide bands, and a decrease in the intensity of FTIR/ATR bands as a function of the grinding time. The experimental observations were used to guide atomic-scale structural and energetic simulations using realistic molecular cluster models for a nanohalloysite particle. A full potential energy surface description was developed for the mechanochemical activation and/or heating toward nanometahalloysite formation that aids the interpretation of experimental results. The calculated differences upon dehydroxylation show a remarkable

An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production.

PubMed

Ihekwaba, Adaoha E C; Mura, Ivan; Walshaw, John; Peck, Michael W; Barker, Gary C

2016-11-01

Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics.

An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

PubMed Central

Walshaw, John; Peck, Michael W.; Barker, Gary C.

2016-01-01

Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161

Biomolecule-assisted exfoliation and dispersion of graphene and other two-dimensional materials: a review of recent progress and applications.

PubMed

Paredes, J I; Villar-Rodil, S

2016-08-25

Direct liquid-phase exfoliation of layered materials by means of ultrasound, shear forces or electrochemical intercalation holds enormous promise as a convenient, cost-effective approach to the mass production of two-dimensional (2D) materials, particularly in the form of colloidal suspensions of high quality and micrometer- and submicrometer-sized flakes. Of special relevance due to environmental and practical reasons is the production of 2D materials in aqueous medium, which generally requires the use of certain additives (surfactants and other types of dispersants) to assist in the exfoliation and colloidal stabilization processes. In this context, biomolecules have received, in recent years, increasing attention as dispersants for 2D materials, as they provide a number of advantages over more conventional, synthetic surfactants. Here, we review research progress in the use of biomolecules as exfoliating and dispersing agents for the production of 2D materials. Although most efforts in this area have focused on graphene, significant advances have also been reported with transition metal dichalcogenides (MoS2, WS2, etc.) or hexagonal boron nitride. Particular emphasis is placed on the specific merits of different types of biomolecules, including proteins and peptides, nucleotides and nucleic acids (RNA, DNA), polysaccharides, plant extracts and bile salts, on their role as efficient colloidal dispersants of 2D materials, as well as on the potential applications that have been explored for such biomolecule-exfoliated materials. These applications are wide-ranging and encompass the fields of biomedicine (photothermal and photodynamic therapy, bioimaging, biosensing, etc.), energy storage (Li- and Na-ion batteries), catalysis (e.g., catalyst supports for the oxygen reduction reaction or electrocatalysts for the hydrogen evolution reaction), or composite materials. As an incipient area of research, a number of knowledge gaps, unresolved issues and novel future

Botulinum toxin in pain treatment.

PubMed

Colhado, Orlando Carlos Gomes; Boeing, Marcelo; Ortega, Luciano Bornia

2009-01-01

Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the treatment of pain of different origins. Botulinum toxin is produced by fermentation of Clostridium botulinum, a Gram-positive, anaerobic bacterium. Commercially, BTX comes in two presentations, types A and B. Botulinum toxin, a neurotoxin with high affinity for cholinergic synapses, blocks the release of acetylcholine by nerve endings without interfering with neuronal conduction of electrical signals or synthesis and storage of acetylcholine. It has been proven that BTX can selectively weaken painful muscles, interrupting the spasm-pain cycle. Several studies have demonstrated the efficacy and safety of BTX-A in the treatment of tension headaches, migraines, chronic lumbar pain, and myofascial pain. Botulinum toxin type A is well tolerated in the treatment of chronic pain disorders in which pharmacotherapy regimens can cause side effects. The reduction in the consumption of analgesics and length of action of 3 to 4 months per dose represent other advantages of its use. However, further studies are necessary to establish the efficacy of BTX-A in chronic pain disorders and its exact mechanism of action, as well as its potential in multifactorial treatments.

High-efficiency exfoliation of large-area mono-layer graphene oxide with controlled dimension.

PubMed

Park, Won Kyu; Yoon, Yeojoon; Song, Young Hyun; Choi, Su Yeon; Kim, Seungdu; Do, Youngjin; Lee, Junghyun; Park, Hyesung; Yoon, Dae Ho; Yang, Woo Seok

2017-11-27

In this work, we introduce a novel and facile method of exfoliating large-area, single-layer graphene oxide using a shearing stress. The shearing stress reactor consists of two concentric cylinders, where the inner cylinder rotates at controlled speed while the outer cylinder is kept stationary. We found that the formation of Taylor vortex flow with shearing stress can effectively exfoliate the graphite oxide, resulting in large-area single- or few-layer graphene oxide (GO) platelets with high yields (>90%) within 60 min of reaction time. Moreover, the lateral size of exfoliated GO sheets was readily tunable by simply controlling the rotational speed of the reactor and reaction time. Our approach for high-efficiency exfoliation of GO with controlled dimension may find its utility in numerous industrial applications including energy storage, conducting composite, electronic device, and supporting frameworks of catalyst.

Evaluating the functional outcomes of ultrasound-guided botulinum toxin type A injections using the Euro-musculus approach for upper limb spasticity treatment in post-stroke patients; an observational study.

PubMed

Buyukavci, Raikan; Akturk, Semra; Ersoy, Yüksel

2018-02-07

Ultrasound-guided botulinum toxin type A injection is an effective treatment for spasticity. Euro-musculus spasticity approach is a new method for administering injections to the correct point of the correct muscle. The clinical outcomes of this practical approach is not yet available in the literature. The purpose of this study was to evaluate the effects on spasticity and the functional outcomes of ultrasound guided botulinum toxin type A injections via the Euro-musculus spasticity approach to treat upper limb spasticity in post-stroke patients. An observational study. Inpatient post-stroke patients. Twenty five post-stroke patients with post-stroke upper limb spasticity were recruited. The ultrasound-guided botulinum toxin type A injections were administered into the spastic target muscles using the Euro-musculus spasticity approach, and all of the patients were enrolled in rehabilitation programmes after the injections. This research included the innervation zone and injection site figures and ultrasound images of each muscle in the upper limb. The degree of spasticity was assessed via the Modified Ashworth Scale and the upper limb motor function via the Fugl Meyer Upper Extremity Scale at the baseline and 4 and 12 weeks after the botulinum toxin type A injection. Significant decreases in the Modified Ashworth Scale scores of the upper limb flexor muscle tone measured 4 and 12 weeks after the botulinum toxin type A injection were found when compared to the baseline scores (p<0.025). When compared with the baseline Fugl Meyer Upper Extremity subgroup scores, the sitting position, wrist and total scores at 4 and 12 weeks were significantly improved (p<0.025). However, only the Fugl Meyer Upper Extremity hand scores were significantly improved 12 weeks after the injection (p<0.025). Ultrasound-guided botulinum toxin type A injection via the Euro- musculus spasticity approach is a practical and effective method for administering injections to the correct point of

Multiplex PCR Targeting tpi (Triose Phosphate Isomerase), tcdA (Toxin A), and tcdB (Toxin B) Genes for Toxigenic Culture of Clostridium difficile

PubMed Central

Lemee, Ludovic; Dhalluin, Anne; Testelin, Sabrina; Mattrat, Marie-Andre; Maillard, Karine; Lemeland, Jean-François; Pons, Jean-Louis

2004-01-01

A multiplex PCR toxigenic culture approach was designed for simultaneous identification and toxigenic type characterization of Clostridium difficile isolates. Three pairs of primers were designed for the amplification of (i) a species-specific internal fragment of the tpi (triose phosphate isomerase) gene, (ii) an internal fragment of the tcdB (toxin B) gene, and (iii) an internal fragment of the tcdA (toxin A) gene allowing distinction between toxin A-positive, toxin B-positive (A+B+) strains and toxin A-negative, toxin B-positive (A−B+) variant strains. The reliability of the multiplex PCR was established by using a panel of 72 C. difficile strains including A+B+, A−B−, and A−B+ toxigenic types and 11 other Clostridium species type strains. The multiplex PCR assay was then included in a toxigenic culture approach for the detection, identification, and toxigenic type characterization of C. difficile in 1,343 consecutive human and animal stool samples. Overall, 111 (15.4%) of 721 human samples were positive for C. difficile; 67 (60.4%) of these samples contained A+B+ toxigenic isolates, and none of them contained A−B+ variant strains. Fifty (8%) of 622 animal samples contained C. difficile strains, which were toxigenic in 27 (54%) cases, including 1 A−B+ variant isolate. Eighty of the 721 human stool samples (37 positive and 43 negative for C. difficile culture) were comparatively tested by Premier Toxins A&B (Meridian Bioscience) and Triage C. difficile Panel (Biosite) immunoassays, the results of which were found concordant with toxigenic culture for 82.5 and 92.5% of the samples, respectively. The multiplex PCR toxigenic culture scheme described here allows combined diagnosis and toxigenic type characterization for human and animal C. difficile intestinal infections. PMID:15583303

Botulinum toxin type-A in therapy of patients with anismus.

PubMed

Ron, Y; Avni, Y; Lukovetski, A; Wardi, J; Geva, D; Birkenfeld, S; Halpern, Z

2001-12-01

Anismus is a common cause of constipation and outlet obstruction. Standard therapy with laxatives or biofeedback has conflicting results. Surgical treatment gives poor results and has practically been abandoned. This study was designed to evaluate the efficacy of botulinum toxin type-A (Botox) injection to the puborectalis muscle in patients with anismus. Twenty-five patients (15 females; mean age, 23.2) with history of constipation and symptoms of outlet obstruction underwent anorectal perfusion manometry and video-proctography. All patients were found to have a nonrelaxing puborectalis muscle on both modalities. All have been unable to expel a rectal balloon. Each patient who participated in the study was randomly assigned to undergo local injection of Botox--10 units to each side of the puborectalis or 20 units to the posterior aspect of this muscle. Eight patients underwent further injections1-5 every 3 months in accordance with previous results. Follow-up was conducted 1, 4, 12, and 24 weeks after injection. Straining, anorectal pain, and overall satisfaction were assessed on a visual analog scale. Weekly evacuation, fecal incontinence, and complications were recorded. At the weekly meeting, each patient underwent anorectal manometry with a balloon expulsion test. Manometric relaxation was achieved after the first injection in 18 patients (75 percent). Once relaxation was achieved, it lasted throughout the follow-up. Nine patients (37.5 percent) expelled the rectal balloon after the first injection. Seven of 16 patients who failed the first injection had an additional one. In 2 patients it was successful (28.6 percent). Symptom improvement of 29.2 percent in straining index was recorded during follow-up. In 3 patients (12.5 percent) pain developed after injection. No other complications were observed. Overall satisfaction with Botox injection results was observed in 58.3 percent. Botox injection to the puborectalis muscle has been found to have a limited

Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen.

PubMed

Ohki, Atsuko; Abe, Nobutsugu; Yoshimoto, Eri; Hashimoto, Yoshikazu; Takeuchi, Hirohisa; Nagao, Gen; Masaki, Tadahiko; Mori, Toshiyuki; Ohkura, Yasuo; Sugiyama, Masanori

2018-04-25

Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.

Sulfur-doped graphene via thermal exfoliation of graphite oxide in H2S, SO2, or CS2 gas.

PubMed

Poh, Hwee Ling; Šimek, Petr; Sofer, Zdeněk; Pumera, Martin

2013-06-25

Doping of graphene with heteroatoms is an effective way to tailor its properties. Here we describe a simple and scalable method of doping graphene lattice with sulfur atoms during the thermal exfoliation process of graphite oxides. The graphite oxides were first prepared by Staudenmaier, Hofmann, and Hummers methods followed by treatments in hydrogen sulfide, sulfur dioxide, or carbon disulfide. The doped materials were characterized by scanning electron microscopy, high-resolution X-ray photoelectron spectroscopy, combustible elemental analysis, and Raman spectroscopy. The ζ-potential and conductivity of sulfur-doped graphenes were also investigated in this paper. It was found that the level of doping is more dramatically influenced by the type of graphite oxide used rather than the type of sulfur-containing gas used during exfoliation. Resulting sulfur-doped graphenes act as metal-free electrocatalysts for an oxygen reduction reaction.

Comparisons of Native Shiga Toxins (Stxs) Type 1 and 2 with Chimeric Toxins Indicate that the Source of the Binding Subunit Dictates Degree of Toxicity

PubMed Central

Russo, Lisa M.; Melton-Celsa, Angela R.; Smith, Michael J.; O'Brien, Alison D.

2014-01-01

Shiga toxin (Stx)-producing E. coli (STEC) cause food-borne outbreaks of hemorrhagic colitis. The main virulence factor expressed by STEC, Stx, is an AB5 toxin that has two antigenically distinct forms, Stx1a and Stx2a. Although Stx1a and Stx2a bind to the same receptor, globotriaosylceramide (Gb3), Stx2a is more potent than Stx1a in mice, whereas Stx1a is more cytotoxic than Stx2a in cell culture. In this study, we used chimeric toxins to ask what the relative contribution of individual Stx subunits is to the differential toxicity of Stx1a and Stx2a in vitro and in vivo. Chimeric stx1/stx2 operons were generated by PCR such that the coding regions for the A2 and B subunits of one toxin were combined with the coding region for the A1 subunit of the heterologous toxin. The toxicities of purified Stx1a, Stx2a, and the chimeric Stxs were determined on Vero and HCT-8 cell lines, while polarized HCT-8 cell monolayers grown on permeable supports were used to follow toxin translocation. In all in vitro assays, the activity of the chimeric toxin correlated with that of the parental toxin from which the B subunit originated. The origin of the native B subunit also dictated the 50% lethal dose of toxin after intraperitoneal intoxication of mice; however, the chimeric Stxs exhibited reduced oral toxicity and pH stability compared to Stx1a and Stx2a. Taken together, these data support the hypothesis that the differential toxicity of the chimeric toxins for cells and mice is determined by the origin of the B subunit. PMID:24671194

Effects of Clostridium perfringens iota toxin in the small intestine of mice.

PubMed

Redondo, Leandro M; Redondo, Enzo A; Dailoff, Gabriela C; Leiva, Carlos L; Díaz-Carrasco, Juan M; Bruzzone, Octavio A; Cangelosi, Adriana; Geoghegan, Patricia; Fernandez-Miyakawa, Mariano E

2017-12-01

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases. Published by Elsevier Ltd.

Two-dimensional materials from high-throughput computational exfoliation of experimentally known compounds.

PubMed

Mounet, Nicolas; Gibertini, Marco; Schwaller, Philippe; Campi, Davide; Merkys, Andrius; Marrazzo, Antimo; Sohier, Thibault; Castelli, Ivano Eligio; Cepellotti, Andrea; Pizzi, Giovanni; Marzari, Nicola

2018-03-01

Two-dimensional (2D) materials have emerged as promising candidates for next-generation electronic and optoelectronic applications. Yet, only a few dozen 2D materials have been successfully synthesized or exfoliated. Here, we search for 2D materials that can be easily exfoliated from their parent compounds. Starting from 108,423 unique, experimentally known 3D compounds, we identify a subset of 5,619 compounds that appear layered according to robust geometric and bonding criteria. High-throughput calculations using van der Waals density functional theory, validated against experimental structural data and calculated random phase approximation binding energies, further allowed the identification of 1,825 compounds that are either easily or potentially exfoliable. In particular, the subset of 1,036 easily exfoliable cases provides novel structural prototypes and simple ternary compounds as well as a large portfolio of materials to search from for optimal properties. For a subset of 258 compounds, we explore vibrational, electronic, magnetic and topological properties, identifying 56 ferromagnetic and antiferromagnetic systems, including half-metals and half-semiconductors.

Two-dimensional materials from high-throughput computational exfoliation of experimentally known compounds

NASA Astrophysics Data System (ADS)

Mounet, Nicolas; Gibertini, Marco; Schwaller, Philippe; Campi, Davide; Merkys, Andrius; Marrazzo, Antimo; Sohier, Thibault; Castelli, Ivano Eligio; Cepellotti, Andrea; Pizzi, Giovanni; Marzari, Nicola

2018-02-01

Two-dimensional (2D) materials have emerged as promising candidates for next-generation electronic and optoelectronic applications. Yet, only a few dozen 2D materials have been successfully synthesized or exfoliated. Here, we search for 2D materials that can be easily exfoliated from their parent compounds. Starting from 108,423 unique, experimentally known 3D compounds, we identify a subset of 5,619 compounds that appear layered according to robust geometric and bonding criteria. High-throughput calculations using van der Waals density functional theory, validated against experimental structural data and calculated random phase approximation binding energies, further allowed the identification of 1,825 compounds that are either easily or potentially exfoliable. In particular, the subset of 1,036 easily exfoliable cases provides novel structural prototypes and simple ternary compounds as well as a large portfolio of materials to search from for optimal properties. For a subset of 258 compounds, we explore vibrational, electronic, magnetic and topological properties, identifying 56 ferromagnetic and antiferromagnetic systems, including half-metals and half-semiconductors.

Epoxy based nanocomposites with fully exfoliated unmodified clay: mechanical and thermal properties.

PubMed

Li, Binghai; Zhang, Xiaohong; Gao, Jianming; Song, Zhihai; Qi, Guicun; Liu, Yiqun; Qiao, Jinliang

2010-09-01

The unmodified clay has been fully exfoliated in epoxy resin with the aid of a novel ultrafine full-vulcanized powdered rubber. Epoxy/rubber/clay nanocomposites with exfoliated morphology have been successfully prepared. The microstructures of the nanocomposites were characterized by means of X-ray diffraction and transmission electron microscopy. It was found that the unmodified clay was fully exfoliated and uniformly dispersed in the resulting nanocomposite. Characterizations of mechanical properties revealed that the impact strength of this special epoxy/rubber/clay nanocomposite increased up 107% over the neat epoxy resin. Thermal analyses showed that thermal stability of the nanocomposite was much better than that of epoxy nanocomposite based on organically modified clay.

Structural Insights into Clostridium perfringens Delta Toxin Pore Formation

PubMed Central

Huyet, Jessica; Naylor, Claire E.; Savva, Christos G.; Gibert, Maryse; Popoff, Michel R.; Basak, Ajit K.

2013-01-01

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins. PMID:23805259

Raman exfoliative cytology for oral precancer diagnosis

NASA Astrophysics Data System (ADS)

Sahu, Aditi; Gera, Poonam; Pai, Venkatesh; Dubey, Abhishek; Tyagi, Gunjan; Waghmare, Mandavi; Pagare, Sandeep; Mahimkar, Manoj; Murali Krishna, C.

2017-11-01

Oral premalignant lesions (OPLs) such as leukoplakia, erythroplakia, and oral submucous fibrosis, often precede oral cancer. Screening and management of these premalignant conditions can improve prognosis. Raman spectroscopy has previously demonstrated potential in the diagnosis of oral premalignant conditions (in vivo), detected viral infection, and identified cancer in both oral and cervical exfoliated cells (ex vivo). The potential of Raman exfoliative cytology (REC) in identifying premalignant conditions was investigated. Oral exfoliated samples were collected from healthy volunteers (n=20), healthy volunteers with tobacco habits (n=20), and oral premalignant conditions (n=27, OPL) using Cytobrush. Spectra were acquired using Raman microprobe. Spectral acquisition parameters were: λex: 785 nm, laser power: 40 mW, acquisition time: 15 s, and average: 3. Postspectral acquisition, cell pellet was subjected to Pap staining. Multivariate analysis was carried out using principal component analysis and principal component-linear discriminant analysis using both spectra- and patient-wise approaches in three- and two-group models. OPLs could be identified with ˜77% (spectra-wise) and ˜70% (patient-wise) sensitivity in the three-group model while with 86% (spectra-wise) and 83% (patient-wise) in the two-group model. Use of histopathologically confirmed premalignant cases and better sampling devices may help in development of improved standard models and also enhance the sensitivity of the method. Future longitudinal studies can help validate potential of REC in screening and monitoring high-risk populations and prognosis prediction of premalignant lesions.

Miscellaneous chemical toxins

USGS Publications Warehouse

Friend, M.

1999-01-01

The previous chapters provide information about some of the chemical toxins that have lethal effects on wild birds. The material presented in Section 7, Chemical Toxins, is far from comprehensive because wild birds are poisoned by a wide variety of toxic substances. Also, monitoring of wild bird mortality is not yet organized so that diagnostic findings can be extended to reflect the relative impacts among the types of toxins, within populations, or among species, geographic areas, and time. The data that are available are not collectively based on random sampling, nor do specimen collection and submission follow methodical assessment methods. Instead, most data simply document individual bird poisoning events. The inherent biases in this information include the species of birds observed dead (large birds in open areas are more likely to be observed dead than small forest birds); the species of birds likely to be submitted for analysis (bald eagles are more likely to be submitted than house sparrows); collection sites (agricultural fields are more likely to be observed than urban environments); geographic area of the country; season; reasons for submissions; and other variables. Nevertheless, findings from individual events reflect the causes of mortality associated with those events and collectively identify chemical toxins that repeatedly cause bird mortalities which result in carcass collection and sub

Mechanisms of nanoclay-enhanced plastic foaming processes: effects of nanoclay intercalation and exfoliation

NASA Astrophysics Data System (ADS)

Wong, Anson; Wijnands, Stephan F. L.; Kuboki, Takashi; Park, Chul B.

2013-08-01

The foaming behaviors of high-density polypropylene-nanoclay composites with intercalated and exfoliated nanoclay particles blown with carbon dioxide were examined via in situ observation of the foaming processes in a high-temperature/high-pressure view-cell. The intercalated nanoclay particles were 300-600 nm in length and 50-200 nm in thickness, while the exfoliated nanoclay particles were 100-200 nm in length and 1 nm in thickness. Contrary to common belief, it was discovered that intercalated nanoclay yielded higher cell density than exfoliated nanoclay despite its lower particle density. This was attributed to the higher tensile stresses generated around the larger and stiffer intercalated nanoclay particles, which led to increase in supersaturation level for cell nucleation. Also, the coupling agent used to exfoliate nanoclay would increase the affinity between polymer and surface of nanoclay particles. Consequently, the critical work needed for cell nucleation would be increased; pre-existing microvoids, which could act as seeds for cell nucleation, were also less likely to exist. Meanwhile, exfoliated nanoclay had better cell stabilization ability to prevent cell coalescence and cell coarsening. This investigation clarifies the roles of nanoclay in plastic foaming processes and provides guidance for the advancement of polymer nanocomposite foaming technology.

Loss of endothelial barrier antigen immunoreactivity as a marker of Clostridium perfringens type D epsilon toxin-induced microvascular damage in rat brain.

PubMed

Finnie, J W; Manavis, J; Chidlow, G

2014-01-01

The epsilon toxin elaborated by Clostridium perfringens type D in the intestine of domestic livestock is principally responsible for the neurological disease produced after its absorption in excessive quantities into the systemic circulation. The fundamental basis of the cerebral damage induced by epsilon toxin appears to be microvascular injury with ensuing severe, diffuse vasogenic oedema. Endothelial barrier antigen (EBA), which is normally expressed by virtually all capillaries and venules in the rat brain, was used in this study as a marker of blood-brain barrier (BBB) integrity. After exposure to high levels of circulating epsilon toxin, there was substantial loss of EBA in many brain microvessels, attended by widespread plasma albumin extravasation. These results support microvascular injury and subsequent BBB breakdown as a key factor in the pathogenesis of epsilon toxin-induced neurological disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Toshio; Tonozuka, Takashi; Kotani, Mao

2007-12-01

HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.6 Å resolution and the crystal belonged to the hexagonal space group P6{sub 3}. Matthews coefficient and self-rotation functionmore » calculations indicate that there is probably one molecule of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been undertaken.« less

On the exfoliating polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2016-06-01

The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative cheilitis.

PubMed

Bhatia, Bhavnit K; Bahr, Brooks A; Murase, Jenny E

2015-06-01

Exfoliative cheilitis is a condition of unknown etiology characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic desquamation. It remains largely refractory to treatment, including corticosteroid therapy, antibiotics, antifungals, and immunosuppressants. We sought to evaluate the safety and efficacy of excimer laser therapy and narrowband ultraviolet B therapy in female patients with refractory exfoliative cheilitis. We reviewed the medical records of two female patients who had been treated unsuccessfully for exfoliative cheilitis. We implemented excimer laser therapy, followed by hand-held narrowband UVB treatments for maintenance therapy, and followed them for clinical improvement and adverse effects. Both patients experienced significant clinical improvement with minimal adverse effects with excimer laser therapy 600-700 mJ/cm 2 twice weekly for several months. The most common adverse effects were bleeding and burning, which occurred at higher doses. The hand-held narrowband UVB unit was also an effective maintenance tool. Limitations include small sample size and lack of standardization of starting dose and dose increments. Excimer laser therapy is a well-tolerated and effective treatment for refractory exfoliative cheilitis with twice weekly laser treatments of up to 700 mJ/cm 2 . Transitioning to the hand-held narrowband UVB device was also an effective maintenance strategy.

Challenges in Liquid-Phase Exfoliation, Processing, and Assembly of Pristine Graphene.

PubMed

Parviz, Dorsa; Irin, Fahmida; Shah, Smit A; Das, Sriya; Sweeney, Charles B; Green, Micah J

2016-10-01

Recent developments in the exfoliation, dispersion, and processing of pristine graphene (i.e., non-oxidized graphene) are described. General metrics are outlined that can be used to assess the quality and processability of various "graphene" products, as well as metrics that determine the potential for industrial scale-up. The pristine graphene production process is categorized from a chemical engineering point of view with three key steps: i) pretreatment, ii) exfoliation, and iii) separation. How pristine graphene colloidal stability is distinct from the exfoliation step and is dependent upon graphene interactions with solvents and dispersants are extensively reviewed. Finally, the challenges and opportunities of using pristine graphene as nanofillers in polymer composites, as well as as building blocks for macrostructure assemblies are summarized in the context of large-scale production. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tire containing thermally exfoliated graphite oxide

NASA Technical Reports Server (NTRS)

Prud'homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor)

2011-01-01

A tire, tire lining or inner tube, containing a polymer composite, made of at least one rubber and/or at least one elastomer and a modified graphite oxide material, which is a thermally exfoliated graphite oxide with a surface area of from about 300 sq m/g to 2600 sq m/g.

Structure, temperature and frequency dependent electrical conductivity of oxidized and reduced electrochemically exfoliated graphite

NASA Astrophysics Data System (ADS)

Radoń, Adrian; Włodarczyk, Patryk; Łukowiec, Dariusz

2018-05-01

The article presents the influence of reduction by hydrogen in statu nascendi and modification by hydrogen peroxide on the structure and electrical conductivity of electrochemically exfoliated graphite. It was confirmed that the electrochemical exfoliation can be used to produce oxidized nanographite with an average number of 25 graphene layers. The modified electrochemical exfoliated graphite and reduced electrochemical exfoliated graphite were characterized by high thermal stability, what was associated with removing of labile oxygen-containing groups. The presence of oxygen-containing groups was confirmed using Fourier-transform infrared spectroscopy. Influence of chemical modification by hydrogen and hydrogen peroxide on the electrical conductivity was determined in wide frequency (0.1 Hz-10 kHz) and temperature range (-50 °C-100 °C). Material modified by hydrogen peroxide (0.29 mS/cm at 0 °C) had the lowest electrical conductivity. This can be associated with oxidation of unstable functional groups and was also confirmed by analysis of Raman spectra. The removal of oxygen-containing functional groups by hydrogen in statu nascendi resulted in a 1000-fold increase in the electrical conductivity compared to the electrochemical exfoliated graphite.

Lignin-assisted exfoliation of molybdenum disulfide in aqueous media and its application in lithium ion batteries.

PubMed

Liu, Wanshuang; Zhao, Chenyang; Zhou, Rui; Zhou, Dan; Liu, Zhaolin; Lu, Xuehong

2015-06-07

In this article, alkali lignin (AL)-assisted direct exfoliation of MoS2 mineral into single-layer and few-layer nanosheets in water is reported for the first time. Under optimized conditions, the concentration of MoS2 nanosheets in the obtained dispersion can be as high as 1.75 ± 0.08 mg mL(-1), which is much higher than the typical reported concentrations (<1.0 mg mL(-1)) using synthetic polymers or compounds as surfactants. The stabilizing mechanism primarily lies in the electrostatic repulsion between negative charged AL, as suggested by zeta-potential measurements. When the exfoliated MoS2 nanosheets are applied as electrode materials for lithium ion batteries, they show much improved electrochemical performance compared with the pristine MoS2 mineral because of the enhanced ion and electron transfer kinetics. This facile, scalable and eco-friendly aqueous-based process in combination with renewable and ultra-low-cost lignin opens up possibilities for large-scale fabrication of MoS2-based nanocomposites and devices. Moreover, herein we demonstrate that AL is also an excellent surfactant for exfoliation of many other types of layered materials, including graphene, tungsten disulfide and boron nitride, in water, providing rich opportunities for a wider range of applications.

Detecting hidden exfoliation corrosion in aircraft wing skins using thermography

NASA Astrophysics Data System (ADS)

Prati, John

2000-03-01

A thermal wave (pulse) thermography inspection technique demonstrated the ability to detect hidden subsurface exfoliation corrosion adjacent to countersunk fasteners in aircraft wing skins. In the wing skin, exfoliation corrosion is the result of the interaction between the steel fastener and the aluminum skin material in the presence of moisture. This interaction results in corrosion cracks that tend to grow parallel to the skin surface. The inspection technique developed allows rapid detection and evaluation of hidden (not visible on the surface) corrosion, which extends beyond the head of fastener countersinks in the aluminum skins.

Considerations for spectroscopy of liquid-exfoliated 2D materials: emerging photoluminescence of N-methyl-2-pyrrolidone.

PubMed

Ogilvie, Sean P; Large, Matthew J; Fratta, Giuseppe; Meloni, Manuela; Canton-Vitoria, Ruben; Tagmatarchis, Nikos; Massuyeau, Florian; Ewels, Christopher P; King, Alice A K; Dalton, Alan B

2017-12-01

N-methyl-2-pyrrolidone (NMP) has been shown to be the most effective solvent for liquid phase exfoliation and dispersion of a range of 2D materials including graphene, molybdenum disulphide (MoS 2 ) and black phosphorus. However, NMP is also known to be susceptible to sonochemical degradation during exfoliation. We report that this degradation gives rise to strong visible photoluminescence of NMP. Sonochemical modification is shown to influence exfoliation of layered materials in NMP and the optical absorbance of the solvent in the dispersion. The emerging optical properties of the degraded solvent present challenges for spectroscopy of nanomaterial dispersions; most notably the possibility of observing solvent photoluminescence in the spectra of 2D materials such as MoS 2 , highlighting the need for stable solvents and exfoliation processes to minimise the influence of solvent degradation on the properties of liquid-exfoliated 2D materials.

From poison to remedy: the chequered history of botulinum toxin.

PubMed

Erbguth, F J

2008-01-01

Botulinum toxin poisoning has afflicted mankind through the mists of time. However, the first incident of food-borne botulism was documented as late as the 18th century, when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The district medical officer Justinus Kerner (1786--1862), who was also a well-known German poet, published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822 and attributed the intoxication to a biological poison. Kerner also postulated that the toxin might be used for treatment purposes. In 1895, an outbreak of botulism in the small Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the type-A serotype was used in medicine to correct strabismus. Other preparations of the type-A toxin were developed and manufactured in the United Kingdom, Germany, and China, whereas a therapeutic type-B toxin was prepared in the United States. To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.

Botulinum toxin type-A (BOTOX) in the treatment of occipital neuralgia: a pilot study.

PubMed

Taylor, Martin; Silva, Sachin; Cottrell, Constance

2008-01-01

To determine the efficacy of occipital nerve blocks using reconstituted botulinum toxin type-A (BTX-A) in providing significant and prolonged pain relief in chronic occipital neuralgia. Occipital neuralgia is a unilateral or bilateral radiating pain with paresthesias commonly manifesting as paroxysmal episodes and involving the occipital and parietal regions. Common causes of occipital neuralgia include irritation or injury to the divisions of the occipital nerve, myofascial spasm, and focal entrapment of the occipital nerve. Treatment options include medication therapy, occipital nerve blocks, and surgical techniques. BTX-A, which has shown promise in relief of other headache types, may prove a viable therapeutic option for occipital neuralgia pain. Botulinum toxin type-A (reconstituted in 3 cc of saline) was injected into regions traversed by the greater and lesser occipital nerve in 6 subjects diagnosed with occipital neuralgia. Subjects were instructed to report their daily pain level (on a visual analog pain scale), their ability to perform daily activities (on several quality of life instruments) and their daily pain medication usage (based on a self-reported log), 2 weeks prior to the injection therapy and 12 weeks following injection therapy. Data were analyzed for significant variation from baseline values. The dull/aching and pin/needles types of pain reported by the subjects did not show a statistically significant improvement during the trial period. The sharp/shooting type of pain, however, showed improvement during most of the trial period except weeks 3-4 and 5-6. The quality of life measures exhibited some improvement. The headache-specific quality of life measure showed significant improvement by 6 weeks which continued through week 12. The general health- and depression-related measures showed no statistical improvement. No significant reduction in pain medication usage was demonstrated. Our results indicate that BTX-A improved the sharp

Lethal effects of Clostridium perfringens epsilon toxin are potentiated by alpha and perfringolysin-O toxins in a mouse model.

PubMed

Fernandez-Miyakawa, Mariano E; Jost, B Helen; Billington, Stephen J; Uzal, Francisco A

2008-03-18

Epsilon toxin (ETX) is the most important virulence factor of Clostridium perfringens type D. Two other important toxins, alpha toxin (CPA) and perfringolysin-O (PFO), are encoded and potentially produced by most C. perfringens type D isolates. The biological effects of these toxins are dissimilar although they are all lethal. Since the possible interaction of these toxins during infection is unknown, the effects of CPA and PFO on the lethal activity of ETX were studied in a mouse model. Mice were injected intravenously or intragastrically with CPA or PFO with or without ETX. Sublethal doses of CPA or PFO did not affect the lethality of ETX when either was injected together with the latter intravenously. However, sublethal or lethal doses of CPA or PFO resulted in reduction of the survival time of mice injected simultaneously with ETX when compared with the intravenous effect of ETX injected alone. When PFO was inoculated intragastrically with ETX, a reduction of the survival time was observed. CPA did not alter the survival time when inoculated intragastrically with ETX. The results of the present study suggest that both CPA and PFO have the potential to enhance the ETX lethal effects during enterotoxemia in natural hosts such as sheep and goats.

Multilocus Sequence Typing and Virulence-Associated Gene Profile Analysis of Staphylococcus aureus Isolates From Retail Ready-to-Eat Food in China.

PubMed

Yang, Xiaojuan; Yu, Shubo; Wu, Qingping; Zhang, Jumei; Wu, Shi; Rong, Dongli

2018-01-01

The aim of this study was to characterize the subtypes and virulence profiles of 69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in China. The isolates were analyzed using multilocus sequence typing (MLST) and polymerase chain reaction (PCR) analysis of important virulence factor genes, including the staphylococcal enterotoxin (SE) genes ( sea , seb , sec , sed , see , seg , seh , sei , sej ), the exfoliative toxin genes ( eta and etb ), the toxic shock syndrome toxin-1 gene ( tst ), and the Panton-Valentine leucocidin-encoding gene ( pvl ). The isolates encompassed 26 different sequence types (STs), including four new STs (ST3482, ST3484, ST3485, ST3504), clustered in three clonal complexes and 17 singletons. The most prevalent STs were ST1, ST6, and ST15, constituting 34.8% of all isolates. Most STs (15/26, 57.7%) detected have previously been associated with human infections. All 13 toxin genes examined were detected in the S. aureus isolates, with 84.1% of isolates containing toxin genes. The three most prevalent toxin genes were seb (36.2%), sea (33.3%), and seg (33.3%). The classical SE genes ( sea - see ), which contribute significantly to staphylococcal food poisoning (SFP), were detected in 72.5% of the S. aureus isolates. In addition, pvl , eta , etb , and tst were found in 11.6, 10.1, 10.1, and 7.2% of the S. aureus isolates, respectively. Strains ST6 carrying sea and ST1 harboring sec-seh enterotoxin profile, which are the two most common clones associated with SFP, were also frequently detected in the food samples in this study. This study indicates that these S. aureus isolates present in Chinese ready-to-eat food represents a potential public health risk. These data are valuable for epidemiological studies, risk management, and public health strategies.

Multilocus Sequence Typing and Virulence-Associated Gene Profile Analysis of Staphylococcus aureus Isolates From Retail Ready-to-Eat Food in China

PubMed Central

Yang, Xiaojuan; Yu, Shubo; Wu, Qingping; Zhang, Jumei; Wu, Shi; Rong, Dongli

2018-01-01

The aim of this study was to characterize the subtypes and virulence profiles of 69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in China. The isolates were analyzed using multilocus sequence typing (MLST) and polymerase chain reaction (PCR) analysis of important virulence factor genes, including the staphylococcal enterotoxin (SE) genes (sea, seb, sec, sed, see, seg, seh, sei, sej), the exfoliative toxin genes (eta and etb), the toxic shock syndrome toxin-1 gene (tst), and the Panton-Valentine leucocidin-encoding gene (pvl). The isolates encompassed 26 different sequence types (STs), including four new STs (ST3482, ST3484, ST3485, ST3504), clustered in three clonal complexes and 17 singletons. The most prevalent STs were ST1, ST6, and ST15, constituting 34.8% of all isolates. Most STs (15/26, 57.7%) detected have previously been associated with human infections. All 13 toxin genes examined were detected in the S. aureus isolates, with 84.1% of isolates containing toxin genes. The three most prevalent toxin genes were seb (36.2%), sea (33.3%), and seg (33.3%). The classical SE genes (sea–see), which contribute significantly to staphylococcal food poisoning (SFP), were detected in 72.5% of the S. aureus isolates. In addition, pvl, eta, etb, and tst were found in 11.6, 10.1, 10.1, and 7.2% of the S. aureus isolates, respectively. Strains ST6 carrying sea and ST1 harboring sec-seh enterotoxin profile, which are the two most common clones associated with SFP, were also frequently detected in the food samples in this study. This study indicates that these S. aureus isolates present in Chinese ready-to-eat food represents a potential public health risk. These data are valuable for epidemiological studies, risk management, and public health strategies. PMID:29662467

Epsilon-toxin production by Clostridium perfringens type D strain CN3718 is dependent upon the agr operon but not the VirS/VirR two-component regulatory system.

PubMed

Chen, Jianming; Rood, Julian I; McClane, Bruce A

2011-01-01

Clostridium perfringens type B and D strains cause enterotoxemias and enteritis in livestock after proliferating in the intestines and producing epsilon-toxin (ETX), alpha-toxin (CPA), and, usually, perfringolysin O (PFO). Although ETX is one of the most potent bacterial toxins, the regulation of ETX production by type B or D strains remains poorly understood. The present work determined that the type D strain CN3718 upregulates production of ETX upon close contact with enterocyte-like Caco-2 cells. This host cell-induced upregulation of ETX expression was mediated at the transcriptional level. Using an isogenic agrB null mutant and complemented strain, the agr operon was shown to be required when CN3718 produces ETX in broth culture or, via a secreted signal consistent with a quorum-sensing (QS) effect, upregulates ETX production upon contact with host cells. These findings provide the first insights into the regulation of ETX production, as well as additional evidence that the Agr-like QS system functions as a global regulator of C. perfringens toxin production. Since it was proposed previously that the Agr-like QS system regulates C. perfringens gene expression via the VirS/VirR two-component regulatory system, an isogenic virR null mutant of CN3718 was constructed to evaluate the importance of VirS/VirR for CN3718 toxin production. This mutation affected production of CPA and PFO, but not ETX, by CN3718. These results provide the first indication that C. perfringens toxin expression regulation by the Agr-like quorum-sensing system may not always act via the VirS/VirR two-component system. IMPORTANCE Mechanisms by which Clostridium perfringens type B and D strains regulate production of epsilon-toxin (ETX), a CDC class B select toxin, are poorly understood. Production of several other toxins expressed by C. perfringens is wholly or partially regulated by both the Agr-like quorum-sensing (QS) system and the VirS/VirR two-component regulatory system, so the

Development of a quail embryo model for the detection of botulinum toxin type A activity

USDA-ARS?s Scientific Manuscript database

Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

Orofacial pain and headaches associated with exfoliation glaucoma.

PubMed

Noma, Noboru; Iwasa, Mayumi; Young, Andrew; Ikeda, Mariko; Hsu, Yung-Chu; Yamamoto, Maasa; Inoue, Kenji; Imamura, Yoshiki

2017-12-01

Exfoliation syndrome is the most common identifiable cause of open-angle glaucoma. The authors report a case of exfoliation glaucoma in a patient who had orofacial pain. A 77-year-old woman was treated at the orofacial pain clinic for left-sided facial pain and headaches of 7 months' duration. Her cataracts and open-angle glaucoma had been diagnosed approximately 3 years earlier. Her main symptoms were orofacial pain, eye redness, inflammation of the eyelids, and eyelid edema. Magnetic resonance imaging showed no evidence of intracranial or extracranial pathology. Hemicrania continua was considered as a possible diagnosis. Indomethacin was prescribed but did not affect her headaches. She then went to an ophthalmologist to rule out secondary headaches. Intraocular pressure was 13 millimeters of mercury in the right eye and 67 mm Hg in the left eye. The ophthalmologist made a diagnosis of exfoliation glaucoma, and the patient underwent surgical treatment for the glaucoma and cataracts. After surgery, she was free of symptoms, and intraocular pressure was 15 mm Hg in the left eye. During differential diagnosis, dentists need to consider intraoral and systemic conditions that can mimic odontogenic or orofacial pain disorders in the patient's medical history and that have a higher incidence associated with the patient's age. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Comparison of extracorporeal shock wave therapy with botulinum toxin type A in the treatment of plantar fasciitis.

PubMed

Roca, Bernardino; Mendoza, María A; Roca, Manuel

2016-10-01

To compare the efficacy of extracorporeal shock wave therapy (ESWT) with botulinum toxin type A (BoNT-A) in the treatment of plantar fasciitis (PF). Open label, prospective, randomized study. A total of 72 patients were included. In all participants the median (and interquartile range) of the visual analog scale (VAS) of pain result, when taking the first steps, was 8 (6-9) points before treatment and 6 (4-8) points after treatment (p < 0.001). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the VAS of pain result, when taking the first steps, was 2 (1-4) points, and in the group of patients that received BoNT-A the same result was 1 (0-2) points (p = 0.009). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the Roles and Maudsley scale of pain result was 1 (0-1) points, and in the group of patients that received BoNT-A the same result was 0 (0-1) points (p = 0.006). In a multivariate analysis use of ESWT and lower weight were associated with improvement of pain with treatment in at least one of the three VAS of pain scales used in the study. ESWT was superior to BoNT-A in the control of pain in patients with PF. Implications for Rehabilitation Plantar fasciitis is characterized by pain at the calcaneal origin of the plantar fascia, exacerbated by weight bearing after prolonged periods of rest. Although studies comparing extracorporeal shock wave therapy or botulinum toxin type A to placebo suggest a superiority of the first one, no reliable data exist about it. Extracorporeal shock wave therapy was superior to botulinum toxin type A in the control of pain in patients with PF.

Large Area Atomically Flat Surfaces via Exfoliation of Bulk Bi 2Se 3 Single Crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melamed, Celeste L.; Ortiz, Brenden R.; Gorai, Prashun

In this paper, we present an exfoliation method that produces cm 2-area atomically flat surfaces from bulk layered single crystals, with broad applications such as for the formation of lateral heterostructures and for use as substrates for van der Waals epitaxy. Single crystals of Bi 2Se 3 were grown using the Bridgman method and examined with X-ray reciprocal space maps, Auger spectroscopy, low-energy electron diffraction, and X-ray photoelectron spectroscopy. An indium-bonding exfoliation technique was developed that produces multiple ~100 um thick atomically flat, macroscopic (>1 cm 2) slabs from each Bi 2Se 3 source crystal. Two-dimensional X-ray diffraction and reciprocalmore » space maps confirm the high crystalline quality of the exfoliated surfaces. Atomic force microscopy reveals that the exfoliated surfaces have an average root-mean-square (RMS) roughness of ~0.04 nm across 400 μm 2 scans and an average terrace width of 70 um between step edges. First-principles calculations reveal exfoliation energies of Bi 2Se 3 and a number of other layered compounds, which demonstrate relevance of our method across the field of 2D materials. While many potential applications exist, excellent lattice matching with the III-V alloy space suggests immediate potential for the use of these exfoliated layered materials as epitaxial substrates for photovoltaic development.« less

Large Area Atomically Flat Surfaces via Exfoliation of Bulk Bi 2Se 3 Single Crystals

DOE PAGES

Melamed, Celeste L.; Ortiz, Brenden R.; Gorai, Prashun; ...

2017-09-12

In this paper, we present an exfoliation method that produces cm 2-area atomically flat surfaces from bulk layered single crystals, with broad applications such as for the formation of lateral heterostructures and for use as substrates for van der Waals epitaxy. Single crystals of Bi 2Se 3 were grown using the Bridgman method and examined with X-ray reciprocal space maps, Auger spectroscopy, low-energy electron diffraction, and X-ray photoelectron spectroscopy. An indium-bonding exfoliation technique was developed that produces multiple ~100 um thick atomically flat, macroscopic (>1 cm 2) slabs from each Bi 2Se 3 source crystal. Two-dimensional X-ray diffraction and reciprocalmore » space maps confirm the high crystalline quality of the exfoliated surfaces. Atomic force microscopy reveals that the exfoliated surfaces have an average root-mean-square (RMS) roughness of ~0.04 nm across 400 μm 2 scans and an average terrace width of 70 um between step edges. First-principles calculations reveal exfoliation energies of Bi 2Se 3 and a number of other layered compounds, which demonstrate relevance of our method across the field of 2D materials. While many potential applications exist, excellent lattice matching with the III-V alloy space suggests immediate potential for the use of these exfoliated layered materials as epitaxial substrates for photovoltaic development.« less

Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus Group Type Strains and Dairy-Associated Isolates

PubMed Central

Jian, Jiahui; Beno, Sarah M.; Wiedmann, Martin

2018-01-01

ABSTRACT While some species in the Bacillus cereus group are well-characterized human pathogens (e.g., B. anthracis and B. cereus sensu stricto), the pathogenicity of other species (e.g., B. pseudomycoides) either has not been characterized or is presently not well understood. To provide an updated characterization of the pathogenic potential of species in the B. cereus group, we classified a set of 52 isolates, including 8 type strains and 44 isolates from dairy-associated sources, into 7 phylogenetic clades and characterized them for (i) the presence of toxin genes, (ii) phenotypic characteristics used for identification, and (iii) cytotoxicity to human epithelial cells. Overall, we found that B. cereus toxin genes are broadly distributed but are not consistently present within individual species and/or clades. After growth at 37°C, isolates within a clade did not typically show a consistent cytotoxicity phenotype, except for isolates in clade VI (B. weihenstephanensis/B. mycoides), where none of the isolates were cytotoxic, and isolates in clade I (B. pseudomycoides), which consistently displayed cytotoxic activity. Importantly, our study highlights that B. pseudomycoides is cytotoxic toward human cells. Our results indicate that the detection of toxin genes does not provide a reliable approach to predict the pathogenic potential of B. cereus group isolates, as the presence of toxin genes is not always consistent with cytotoxicity phenotype. Overall, our results suggest that isolates from multiple B. cereus group clades have the potential to cause foodborne illness, although cytotoxicity is not always consistently found among isolates within each clade. IMPORTANCE Despite the importance of the Bacillus cereus group as a foodborne pathogen, characterizations of the pathogenic potential of all B. cereus group species were lacking. We show here that B. pseudomycoides (clade I), which has been considered a harmless environmental microorganism, produces toxins and

Crystallization and preliminary X-ray diffraction studies of delta-toxin from Clostridium perfringens.

PubMed

Huyet, Jessica; Gilbert, Maryse; Popoff, Michel R; Basak, Ajit

2011-03-01

Clostridium perfringens is a Gram-positive anaerobic bacterium that is responsible for a wide range of diseases in humans and both wild and domesticated animals, including birds. C. perfringens is notable for its ability to produce a plethora of toxins, e.g. phospholipases C (alpha-toxin), pore-forming toxins (epsilon-toxin, beta-toxin and enterotoxin) and binary toxins (iota-toxin). Based on alpha-, beta-, epsilon- and iota-toxin production, the bacterium is classified into five different toxinotypes (A-E). Delta-toxin, which is a 32.6 kDa protein with 290 amino acids, is one of three haemolysins released by type C and possibly by type B strains of C. perfringens. This toxin is immunogenic and lytic to erythrocytes from the even-toed ungulates sheep, goats and pigs, and is cytotoxic to other cell types such as rabbit macrophages, human monocytes and blood platelets from goats, rabbits, guinea pigs and humans. The recombinant delta-toxin has been cloned, expressed, purified and crystallized in two different crystal forms by the hanging-drop vapour-diffusion method. Of these two different crystal forms, only the form II crystal diffracted to atomic resolution (dmin=2.4 Å), while the form I crystal diffracted to only 15 Å resolution. The form II crystals belonged to space group P2(1)2(1)2, with one molecule in the crystallographic asymmetric unit and unit-cell parameters a=49.66, b=58.48, c=112.93 Å.

Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins*

PubMed Central

Arévalo, Maria T.; Navarro, Ashley; Arico, Chenoa D.; Li, Junwei; Alkhatib, Omar; Chen, Shan; Diaz-Arévalo, Diana; Zeng, Mingtao

2014-01-01

Anthrax spores can be aerosolized and dispersed as a bioweapon. Current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. Anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2). We hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using RNA interference (RNAi) technology. Thus, anthrax toxin receptors in mouse and human macrophages were silenced using targeted siRNAs or blocked with specific antibody prior to challenge with anthrax lethal toxin. Viability assays were used to assess protection in macrophages treated with specific siRNA or antibody as compared with untreated cells. Silencing CMG2 using targeted siRNAs provided almost complete protection against anthrax lethal toxin-induced cytotoxicity and death in murine and human macrophages. The same results were obtained by prebinding cells with specific antibody prior to treatment with anthrax lethal toxin. In addition, TEM8-targeted siRNAs also offered significant protection against lethal toxin in human macrophage-like cells. Furthermore, silencing CMG2, TEM8, or both receptors in combination was also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase activity by edema toxin in human kidney cells. Thus, anthrax toxin receptor-targeted RNAi has the potential to be developed as a life-saving, postexposure therapy against anthrax. PMID:24742682

Naturally acquired antibodies against Clostridium perfringens epsilon toxin in goats.

PubMed

Veschi, Josir Laine A; Bruzzone, Octavio A; Losada-Eaton, Daniela M; Dutra, Iveraldo S; Fernandez-Miyakawa, Mariano E

2008-09-15

Clostridium perfringens type D-producing epsilon toxin is a common cause of death in sheep and goats worldwide. Although anti-epsilon toxin serum antibodies have been detected in healthy non-vaccinated sheep, the information regarding naturally acquired antibodies in ruminants is scanty. The objective of the present report was to characterize the development of naturally acquired antibodies against C. perfringens epsilon toxin in goats. The levels of anti-epsilon toxin antibodies in blood serum of goat kids from two different herds were examined continuously for 14 months. Goats were not vaccinated against any clostridial disease and received heterologous colostrums from cows that were not vaccinated against any clostridial disease. During the survey one of these flocks suffered an unexpectedly severe C. perfringens type D enterotoxemia outbreak. The results showed that natural acquired antibodies against C. perfringens epsilon toxin can appear as early as 6 weeks in young goats and increase with the age without evidence of clinical disease. The enterotoxemia outbreak was coincident with a significant increase in the level of anti-epsilon toxin antibodies.

Dysport: pharmacological properties and factors that influence toxin action.

PubMed

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.

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

PubMed Central

Frazão, Bárbara; Vasconcelos, Vitor; Antunes, Agostinho

2012-01-01

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

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

PubMed

Frazão, Bárbara; Vasconcelos, Vitor; Antunes, Agostinho

2012-08-01

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

Topology-Scaling Identification of Layered Solids and Stable Exfoliated 2D Materials.

PubMed

Ashton, Michael; Paul, Joshua; Sinnott, Susan B; Hennig, Richard G

2017-03-10

The Materials Project crystal structure database has been searched for materials possessing layered motifs in their crystal structures using a topology-scaling algorithm. The algorithm identifies and measures the sizes of bonded atomic clusters in a structure's unit cell, and determines their scaling with cell size. The search yielded 826 stable layered materials that are considered as candidates for the formation of two-dimensional monolayers via exfoliation. Density-functional theory was used to calculate the exfoliation energy of each material and 680 monolayers emerge with exfoliation energies below those of already-existent two-dimensional materials. The crystal structures of these two-dimensional materials provide templates for future theoretical searches of stable two-dimensional materials. The optimized structures and other calculated data for all 826 monolayers are provided at our database (https://materialsweb.org).

Indicators: Algal Toxins (microcystin)

EPA Pesticide Factsheets

Algal toxins are toxic substances released by some types of algae (phytoplankton) when they are present in large quantities (blooms) and decay or degrade. High nutrient levels and warm temperatures often result in favorable conditions for algae blooms.

THE PRODUCTION OF DIPHTHERIA TOXIN

PubMed Central

Park, W. H.; Williams, A. W.

1896-01-01

Toxin of sufficient strength to kill a 400-gramme guinea-pig in three days and a half in a dose of 0·cubic centimetre developed in suitable bouillon, contained in ordinary Erlenmeyer flasks, within a period of twenty-four hours. In such boullon the toxin reached its greatest strength in from four to seven days (0·005 cubic centimetre killing a 500-gramme guinea-pig in three days). This period of time covered that of the greatest growth of the bacilli, as shown both by the appearance of the culture and by the number of colonies developing an agar plates. The bodies of the diphtheria bacili did not at any time contain toxin in cosiderable amounts. The type of growth of the bacili and the rapidity and extent of the production of toxin depended more on the reaction of the bouillon than upon any other single factor. The best results were obtained in bouillon which, after being neutralized to litmus, had about seven cubic centimetres of normal soda solution added to each litre. An excessive amount of either acid or alkali prevented the development of toxin. Strong toxin was produced in bouillon containing peptone ranging from one to ten per cent. The strength of toxin averaged greater in the two and four-per-cent peptone solutions than in the one-percent. When the stage of acid reaction was brief and the degree of acidity probably slight, strong toxin developed while the culture bouillon was still acid; but when the stage of acid reaction was prolonged, little if any toxin was produced until just before the fluid became alkaline. Glucose is deleterious to the growth of the diphtheria bacillus and to the production of toxin when it is present in sufficient amounts to cause by its disintegration too great a degree of acidity in the fluid culture. When the acid resulting from decomposition of glucose is neutralized by the addition of alkali the diphtheria bacilus again grows abundantly. Glucose is not present, at least as a rule, in sufficient amounts in the meat as

Liquid-type Botulinum Toxin Type A in Adductor Spasmodic Dysphonia: A Prospective Pilot Study.

PubMed

Cha, Wonjae; Jang, Jeon Yeob; Wang, Soo-Geun; Kang, Ji-Heon; Jo, Min-Gyu

2017-05-01

Botulinum toxin (BTX) has been widely used to treat adductor spasmodic dysphonia (ADSD). Most commercially available forms of BTX require reconstitution before use, which may increase the risk of contamination and requires careful titration. Recently, a liquid-type BTX type A (BTX-A) has been developed, which should simplify the procedure and enhance its efficacy. Herein, we present a prospective pilot study to investigate the efficacy and safety of liquid-type BTX-A in the treatment of ADSD. Twenty-six consecutive liquid-type BTX-A injections were performed in 12 patients with ADSD. We included as a control group 34 consecutive patients with ADSD who had previously undergone 52 vocal fold injection procedures with freeze-dried-type BTX-A. All patients in both groups had improvement of symptoms related to ADSD and period of normal voice. Most patients experienced breathiness, and the onset time, the peak response time, and the duration of breathiness were similar in both groups. The duration of effect (days) was 96.96 ± 18.91 and 77.38 ± 18.97 in the freeze-dried-type and the liquid-type groups, and the duration of benefit (days) was 80.02 ± 18.24 and 62.69 ± 19.73 in the freeze-dried-type and the liquid-type groups. To compare the efficacy between the freeze-dried-type and the liquid-type BTX-A, the sessions of the unilateral vocal fold injection were included and were categorized as group A (1 ~ 2 units BTX-A) and group B (2 ~ 3 units BTX-A), according to the dose per vocal fold. There was no significant difference of effect time between freeze-dried-type and liquid-type BTX-A groups. No adverse events related to BTX or vocal fold injection were reported. Liquid-type BTX-A is safe and effective for the treatment of spasmodic dysphonia. With the advantages of simple preparation, storage, and reuse and animal protein-free constituents, liquid-type BTX-A may be a good option in the treatment of spasmodic dysphonia. Copyright © 2017 The

Raman spectroscopic studies on exfoliated cells of oral and cervix

NASA Astrophysics Data System (ADS)

Hole, Arti; Sahu, Aditi; Shaikh, Rubina; Tyagi, Gunjan; Murali Krishna, C.

2018-01-01

Visual inspection followed by biopsy is the standard procedure for cancer diagnosis. Due to invasive nature of the current diagnostic methods, patients are often non-compliant. Hence, it is necessary to explore less invasive and rapid methods for early detection. Exfoliative cytology is a simple, rapid, and less invasive technique. It is thus well accepted by patients and is suitable for routine applications in population screening programs. Raman spectroscopy (RS) has been increasingly explored for disease diagnosis in the recent past. In vivo RS has previously shown promise in management of both oral and cervix cancers. In vivo applications require on-site instrumentation and stringent experimental conditions. Hence, RS of less invasive samples like exfoliated cells has been explored, as this facilitates collection at multiple screening centers followed by analysis at a centralized facility. In the present study, efficacy of Raman spectroscopy in classification of 15 normal and 29 abnormal oral exfoliated cells specimens and 28 normal and 38 abnormal cervix specimens were explored. Spectra were acquired by Raman microprobe (HE 785, Horiba-Jobin-Yvon, France) from several areas to span the pellet. Spectral acquisition parameters were: microscopic objective: 40X, power: 40 mW, acquisition time: 15 s and average: 3. PCA and PC-LDA of pre-processed spectra was carried out on a 4-model system of normal and tumor of both cervix and oral specimens. Leave-one-out-cross-validation findings indicate 73 % correct classification. Findings suggest RS of exfoliated cells may serve as a patient-friendly, non-invasive, rapid and objective method for management of cervix and oral cancers.

Morphological and electrical properties of epoxy-based composites reinforced with exfoliated graphite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamberti, Patrizia; Spinelli, Giovanni, E-mail: gspinelli@unisa.it; Tucci, Vincenzo

An experimental study has been carried out to prepare and characterize epoxy/amine-based composites filled with different percentages of partially exfoliated graphite (i.e. pEG) particles having an exfoliation degree of 56% in order to analyze the effect of the filler amounts on the electrical properties of the resulting nanocomposites. Moreover, in order to fully investigate the direct relationship between the physical properties of the employed filler and the results of the electrical characterization, a structural and morphological characterization of the pEG samples is carried out by means of various type of analysis such as X-ray diffraction patterns, micro-Raman and Scanning Electronmore » Microscopy (SEM) images. The DC electrical characterization reveals a percolation thresholds (EPT) that falls in the range [2–3] wt% and an electrical conductivity of about 0.66 S/m at the highest filler loading (6.5 wt%). From the analysis of the percolative curve it is possible to derive the percolation law parameters and in particular the critical exponent t, whose value (i.e. 1.2) reflects an effective 2D organization of the percolating structure consistent with the type of filler used (2-dimensional). Finally, an extensive analysis concerning the electrical properties in the frequency domain has been carried out in order to evaluate the effectiveness of pEG-loaded composites in terms of electromagnetic interference compatibility (EMC) and their applicability as radar absorbers materials (RAMs).« less

Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin.

PubMed

Pelish, Teal M; McClain, Mark S

2009-10-23

The Clostridium perfringens epsilon-toxin is responsible for a severe, often lethal intoxication. In this study, we characterized dominant-negative inhibitors of the epsilon-toxin. Site-specific mutations were introduced into the gene encoding epsilon-toxin, and recombinant proteins were expressed in Escherichia coli. Paired cysteine substitutions were introduced at locations predicted to form a disulfide bond. One cysteine in each mutant was introduced into the membrane insertion domain of the toxin; the second cysteine was introduced into the protein backbone. Mutant proteins with cysteine substitutions at amino acid positions I51/A114 and at V56/F118 lacked detectable cytotoxic activity in a MDCK cell assay. Cytotoxic activity could be reconstituted in both mutant proteins by incubation with dithiothreitol, indicating that the lack of cytotoxic activity was attributable to the formation of a disulfide bond. Fluorescent labeling of the cysteines also indicated that the introduced cysteines participated in a disulfide bond. When equimolar mixtures of wild-type epsilon-toxin and mutant proteins were added to MDCK cells, the I51C/A114C and V56C/F118C mutant proteins each inhibited the activity of wild-type epsilon-toxin. Further analysis of the inhibitory activity of the I51C/A114C and V56C/F118C mutant proteins indicated that these proteins inhibit the ability of the active toxin to form stable oligomeric complexes in the context of MDCK cells. These results provide further insight into the properties of dominant-negative inhibitors of oligomeric pore-forming toxins and provide the basis for developing new therapeutics for treating intoxication by epsilon-toxin.

New insight of high temperature oxidation on self-exfoliation capability of graphene oxide.

PubMed

Liu, Yuhang; Zeng, Jie; Han, Di; Wu, Kai; Yu, Bowen; Chai, Songgang; Chen, Feng; Fu, Qiang

2018-05-04

The preparation of graphene oxide (GO) via Hummers method is usually divided into two steps: low temperature oxidation at 35 °C (step I oxidation) and high temperature oxidation at 98 °C (step II oxidation). However, the effects of these two steps on the exfoliation capability and chemical structure of graphite oxide remain unclear. In this study, both the functional group content of graphite oxide and the entire evolution of interlayer spacing were investigated during the two steps. Step I oxidation is a slowly inhomogeneous oxidation step to remove unoxidized graphite flakes. The prepared graphite oxide can be easily self-exfoliated but contains a lot of organic sulfur. During the first 20 min of step II oxidation, the majority of organic sulfur can be efficiently removed and graphite oxide still remains a good exfoliation capability due to sharp increasing of carboxyl groups. However, with a longer oxidation time at step II oxidation, the decrease of organic sulfur content is slowed down apparently but without any carboxyl groups forming, then graphite oxide finally loses self-exfoliation capability. It is concluded that a short time of step II oxidation can produce purer and ultralarge GO sheets via self-exfoliation. The pure GO is possessed with better thermal stability and liquid crystal behavior. Besides, reduced GO films prepared from step II oxidation show better mechanical and electric properties after reducing compared with that obtained only via step I oxidation.

New insight of high temperature oxidation on self-exfoliation capability of graphene oxide

NASA Astrophysics Data System (ADS)

Liu, Yuhang; Zeng, Jie; Han, Di; Wu, Kai; Yu, Bowen; Chai, Songgang; Chen, Feng; Fu, Qiang

2018-05-01

The preparation of graphene oxide (GO) via Hummers method is usually divided into two steps: low temperature oxidation at 35 °C (step I oxidation) and high temperature oxidation at 98 °C (step II oxidation). However, the effects of these two steps on the exfoliation capability and chemical structure of graphite oxide remain unclear. In this study, both the functional group content of graphite oxide and the entire evolution of interlayer spacing were investigated during the two steps. Step I oxidation is a slowly inhomogeneous oxidation step to remove unoxidized graphite flakes. The prepared graphite oxide can be easily self-exfoliated but contains a lot of organic sulfur. During the first 20 min of step II oxidation, the majority of organic sulfur can be efficiently removed and graphite oxide still remains a good exfoliation capability due to sharp increasing of carboxyl groups. However, with a longer oxidation time at step II oxidation, the decrease of organic sulfur content is slowed down apparently but without any carboxyl groups forming, then graphite oxide finally loses self-exfoliation capability. It is concluded that a short time of step II oxidation can produce purer and ultralarge GO sheets via self-exfoliation. The pure GO is possessed with better thermal stability and liquid crystal behavior. Besides, reduced GO films prepared from step II oxidation show better mechanical and electric properties after reducing compared with that obtained only via step I oxidation.

A Structure-Function Analysis of Shiga-Like Toxin Type 2 of Enterohemorrhagic Escherichia Coli

DTIC Science & Technology

1990-05-07

like toxins are summarized in Table 2. The genes coding for both SLT-I and SLT-II are borne on coliphage , and toxin expression by E. coli occurs as...A stock | | ’ • * suspension of toxin-converting W coliphage was prepared by inducing the phage from | "fif the E. coli C600(933W) lysogen with...mitomycin C as described previously (Marques et al., 1987). An appropriate amount of the W coliphage stock was added to an l| exponential culture of

Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells

PubMed Central

Tilley, Drew C.; Eum, Kenneth S.; Fletcher-Taylor, Sebastian; Austin, Daniel C.; Dupré, Christophe; Patrón, Lilian A.; Garcia, Rita L.; Lam, Kit; Yarov-Yarovoy, Vladimir; Cohen, Bruce E.; Sack, Jon T.

2014-01-01

Electrically excitable cells, such as neurons, exhibit tremendous diversity in their firing patterns, a consequence of the complex collection of ion channels present in any specific cell. Although numerous methods are capable of measuring cellular electrical signals, understanding which types of ion channels give rise to these signals remains a significant challenge. Here, we describe exogenous probes which use a novel mechanism to report activity of voltage-gated channels. We have synthesized chemoselective derivatives of the tarantula toxin guangxitoxin-1E (GxTX), an inhibitory cystine knot peptide that binds selectively to Kv2-type voltage gated potassium channels. We find that voltage activation of Kv2.1 channels triggers GxTX dissociation, and thus GxTX binding dynamically marks Kv2 activation. We identify GxTX residues that can be replaced by thiol- or alkyne-bearing amino acids, without disrupting toxin folding or activity, and chemoselectively ligate fluorophores or affinity probes to these sites. We find that GxTX–fluorophore conjugates colocalize with Kv2.1 clusters in live cells and are released from channels activated by voltage stimuli. Kv2.1 activation can be detected with concentrations of probe that have a trivial impact on cellular currents. Chemoselective GxTX mutants conjugated to dendrimeric beads likewise bind live cells expressing Kv2.1, and the beads are released by channel activation. These optical sensors of conformational change are prototype probes that can indicate when ion channels contribute to electrical signaling. PMID:25331865

Phenol-Soluble Modulin Toxins of Staphylococcus haemolyticus.

PubMed

Da, Fei; Joo, Hwang-Soo; Cheung, Gordon Y C; Villaruz, Amer E; Rohde, Holger; Luo, Xiaoxing; Otto, Michael

2017-01-01

Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, after Staphylococcus epidermidis , is Staphylococcus haemolyticus . However, we have a significant lack of knowledge about what causes virulence of S. haemolyticus , as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogen Staphylococcus aureus , toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs), amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other than S. epidermidis . Here, we identified, purified, and characterized PSMs of S. haemolyticus . We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed that S. haemolyticus does not produce a δ-toxin, as results from genome sequencing had indicated. All four S. haemolyticus PSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM, S. haemolyticus PSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis.

One-Pot Exfoliation of Graphite and Synthesis of Nanographene/Dimesitylporphyrin Hybrids

PubMed Central

Bernal, M. Mar; Pérez, Emilio M.

2015-01-01

A simple one-pot process to exfoliate graphite and synthesize nanographene-dimesitylporphyrin hybrids has been developed. Despite the bulky mesityl groups, which are expected to hinder the efficient π–π stacking between the porphyrin core and graphene, the liquid-phase exfoliation of graphite is significantly favored by the presence of the porphyrins. Metallation of the porphyrin further enhances this effect. The resulting graphene/porphyrin hybrids were characterized by spectroscopy (UV-visible, fluorescence, and Raman) and microscopy (STEM, scanning transmission electron microscopy). PMID:25984598

Stool C difficile toxin

MedlinePlus

... toxin; Colitis - toxin; Pseudomembranous - toxin; Necrotizing colitis - toxin; C difficile - toxin ... be analyzed. There are several ways to detect C difficile toxin in the stool sample. Enzyme immunoassay ( ...

Synthesis and Thermal Conductivity of Exfoliated Hexagonal Boron Nitride/Alumina Ceramic Composite

NASA Technical Reports Server (NTRS)

Hung, Ching-cheh; Hurst, Janet; Santiago, Diana; Lizcano, Maricela; Kelly, Marisabel

2017-01-01

Exfoliated hexagonal boron nitride (hBN)/alumina composite can be fabricated by following the process of (1) heating a mixture of hBN, AlCl3, and NaF in nitrogen for intercalation; (2) heating the intercalated product in air for exfoliation and at the same time converting the intercalate (AlCl3) into Al2O3, (3) rinsing the oxidized product, (4) coating individual exfoliated hBN platelets that contain Al2O3 with new layers of aluminum oxide, and finally, (5) hot pressing the product into the composite. The composite thus obtained has a composition of approximately 60 percent by weight hBN and 40 percent by weight alumina. Its in-plane and through-plane thermal conductivity were measured to be 86 and 18 watts per meter Kelvin, respectively, at room temperature.

Fabrication of single phase 2D homologous perovskite microplates by mechanical exfoliation

NASA Astrophysics Data System (ADS)

Li, Junze; Wang, Jun; Zhang, Yingjun; Wang, Haizhen; Lin, Gaoming; Xiong, Xuan; Zhou, Weihang; Luo, Hongmei; Li, Dehui

2018-04-01

The two-dimensional (2D) Ruddlesden-Popper type perovskites have attracted intensive interest for their great environmental stability and various potential optoelectronic applications. Fundamental understanding of the photophysical and electronic properties of the 2D perovskites with pure single phase is essential for improving the performance of the optoelectronic devices and designing devices with new architectures. Investigating the optical and electronic properties of these materials with pure single phase is required to obtain pure single phase 2D perovskites. Here, we report on an alternative approach to fabricate (C4H9NH3)2(CH3NH3) n-1Pb n I3n+1 microplates with pure single n-number perovskite phase for n  >  2 by mechanical exfoliation. Micro-photoluminescence and absorption spectroscopy studies reveal that the as-synthesized 2D perovskite plates for n  >  2 are comprised by dominant n-number phase and small inclusions of hybrid perovskite phases with different n values, which is supported by excitation power dependent photoluminescence. By mechanical exfoliation method, 2D perovskite microplates with the thickness of around 20 nm are obtained, which surprisingly have single n-number perovskite phase for n  =  2-5. In addition, we have demonstrated that the exfoliated 2D perovskite microplates can be integrated with other 2D layered materials such as boron nitride, and are able to be transferred to prefabricated electrodes for photodetections. Our studies not only provide a strategy to prepare 2D perovskites with a single n-number perovskite phase allowing us to extract the basic optical and electronic parameters of pure phase perovskites, but also demonstrate the possibility to integrate the 2D perovskites with other 2D layered materials to extend the device’s functionalities.

Ambipolar thermoelectric power of chemically-exfoliated RuO2 nanosheets

NASA Astrophysics Data System (ADS)

Kim, Jeongmin; Yoo, Somi; Moon, Hongjae; Kim, Se Yun; Ko, Dong-Su; Roh, Jong Wook; Lee, Wooyoung

2018-01-01

The electrical conductivity and Seebeck coefficient of RuO2 nanosheets are enhanced by metal nanoparticle doping using Ag-acetate solutions. In this study, RuO2 monolayer and bilayer nanosheets exfoliated from layered alkali metal ruthenates are transferred to Si substrates for device fabrication, and the temperature dependence of their conductivity and Seebeck coefficients is investigated. For pristine RuO2 nanosheets, the sign of the Seebeck coefficient changes with temperature from 350-450 K. This indicates that the dominant type of charge carrier is dependent on the temperature, and the RuO2 nanosheets show ambipolar carrier transport behavior. By contrast, the sign of the Seebeck coefficient for Ag nanoparticle-doped RuO2 nanosheets does not change with temperature, indicating that the extra charge carriers from metal nanoparticles promote n-type semiconductor behavior.

Targeting Metastasis with Snake Toxins: Molecular Mechanisms

PubMed Central

Urra, Félix A.

2017-01-01

Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network. PMID:29189742

Role of Botulinum Toxin in Depression.

PubMed

Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

2016-03-01

The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

Detecting thermally driven cyclic deformation of an exfoliation sheet with lidar and radar

USGS Publications Warehouse

Collins, Brian D.; Stock, Greg M.

2014-01-01

Rock falls from steep, exfoliating cliffs are common in many landscapes. Of the many mechanisms known to trigger rock falls, thermally driven deformation is among the least quantified, despite potentially being a prevalent trigger due to its occurrence at all times of year. Here we present the results of a field-based monitoring program using instrumentation, ground-based lidar, and ground-based radar to investigate the process of thermally driven deformation of an exfoliation sheet, and the ability of remote sensing tools to capture cyclic expansion and contraction patterns. Our results indicate that thermally driven exfoliation occurs on diurnal cycles and can be measured at the submillimeter to centimeter scale using high-resolution strain gauges, short-range (2 km) radar interfer-ometry.

Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation

PubMed Central

Nagahama, Masahiro; Morimitsu, Shinsuke; Kihara, Atsushi; Akita, Masahiko; Setsu, Koujun; Sakurai, Jun

2003-01-01

Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK1 receptor antagonists, [D-Pro2, D-Trp7,9]-SP, [D-Pro4, D-Trp7,9]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP8-37). The toxin-induced leakage was significantly inhibited by the N-type Ca2+ channel blocker, ω-conotoxin MVIIA, and the bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), but was not affected by the selective L-type Ca2+ channel blocker, verapamil, the P-type Ca2+ channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK1 receptors. PMID:12522069

Interaction of Type IV Toxin/Antitoxin Systems in Cryptic Prophages of Escherichia coli K-12.

PubMed

Wen, Zhongling; Wang, Pengxia; Sun, Chenglong; Guo, Yunxue; Wang, Xiaoxue

2017-03-01

Toxin/antitoxin (TA) systems are widespread in prokaryotic chromosomes and in mobile genetic elements including plasmids and prophages. The first characterized Type IV TA system CbtA/CbeA was found in cryptic prophage CP4-44 in Escherichia coli K-12. Two homologous TA loci of CbtA/CbeA also reside in cryptic prophages of E. coli K-12, YkfI/YafW in CP4-6 and YpjF/YfjZ in CP4-57. In this study, we demonstrated that YkfI and YpjF inhibited cell growth and led to the formation of "lemon-shaped" cells. Prolonged overproduction of YkfI led to the formation of "gourd-shaped" cells and immediate cell lysis. YafW and YfjZ can neutralize the toxicity of YkfI or YpjF. Furthermore, we found that YkfI and YpjF interacted with cell division protein FtsZ in E. coli , but ectopic expression in Pseudomonas and Shewanella did not cause the formation of "lemon-shaped" cells. Moreover, deletion of all of the three toxin genes together decreased resistance to oxidative stress and deletion of the antitoxin genes increased early biofilm formation. Collectively, these results demonstrated that the homologous Type IV TA systems in E. coli may target cell division protein FtsZ in E. coli and may have different physiological functions in E. coli .

Interaction of Type IV Toxin/Antitoxin Systems in Cryptic Prophages of Escherichia coli K-12

PubMed Central

Wen, Zhongling; Wang, Pengxia; Sun, Chenglong; Guo, Yunxue; Wang, Xiaoxue

2017-01-01

Toxin/antitoxin (TA) systems are widespread in prokaryotic chromosomes and in mobile genetic elements including plasmids and prophages. The first characterized Type IV TA system CbtA/CbeA was found in cryptic prophage CP4-44 in Escherichia coli K-12. Two homologous TA loci of CbtA/CbeA also reside in cryptic prophages of E. coli K-12, YkfI/YafW in CP4-6 and YpjF/YfjZ in CP4-57. In this study, we demonstrated that YkfI and YpjF inhibited cell growth and led to the formation of “lemon-shaped” cells. Prolonged overproduction of YkfI led to the formation of “gourd-shaped” cells and immediate cell lysis. YafW and YfjZ can neutralize the toxicity of YkfI or YpjF. Furthermore, we found that YkfI and YpjF interacted with cell division protein FtsZ in E. coli, but ectopic expression in Pseudomonas and Shewanella did not cause the formation of “lemon-shaped” cells. Moreover, deletion of all of the three toxin genes together decreased resistance to oxidative stress and deletion of the antitoxin genes increased early biofilm formation. Collectively, these results demonstrated that the homologous Type IV TA systems in E. coli may target cell division protein FtsZ in E. coli and may have different physiological functions in E. coli. PMID:28257056

Alpha-Toxin Promotes Staphylococcus aureus Mucosal Biofilm Formation

PubMed Central

Anderson, Michele J.; Lin, Ying-Chi; Gillman, Aaron N.; Parks, Patrick J.; Schlievert, Patrick M.; Peterson, Marnie L.

2012-01-01

Staphylococcus aureus causes many diseases in humans, ranging from mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS). S. aureus may be asymptomatically carried in the anterior nares or vagina or on the skin, serving as a reservoir for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and the leading cause of TSS. The cytolysin α-toxin (also known as α-hemolysin or Hla) is the major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. The current study aims to characterize the differences between TSS USA200 strains [high (hla+) and low (hla−) α-toxin producers] in their ability to disrupt vaginal mucosal tissue and to characterize the subsequent infection. Tissue viability post-infection and biofilm formation of TSS USA200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hla−), MNPE (hla+), and MNPE isogenic hla knockout (hlaKO), were observed via LIVE/DEAD® staining and confocal microscopy. All TSS strains grew to similar bacterial densities (1–5 × 108 CFU) on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587 (hla−), MN8 (hla−), nor MNPE hlaKO formed biofilms. The latter strains were also less cytotoxic than wild-type MNPE. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. We speculate that α-toxin affects S. aureus phenotypic growth on vaginal mucosa by promoting tissue disruption and biofilm formation. Further, α-toxin mutants (hla−) are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic variants (HDPV). PMID:22919655

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

PubMed

Omernik, Andrzej; Płusa, Tadeusz

2015-09-01

Clostridium perfringens is absolutely anaerobic rod-shaped, sporeforming bacterium. The morbidity is connected with producing toxins. Depending on the type of toxin produced Clostridium perfringens can be divided into five serotypes:A-E. Under natural conditions, this bacterium is responsible for local outbreaks of food poisoning associated with eating contaminated food which which was improperly heat treated. Some countries with lower economic level are endemic foci of necrotizing enteritis caused by Clostridium perfringens. The bacterium is also a major cause of gas gangrene. It is a disease, associated with wound infection, with potentially fatal prognosis in the case of treatment's delays. In the absence of early radical surgery, antibiotic therapy and (if available) hyperbaric treatment leads to the spread of toxins in the body causing shock, coma and death. Due to the force of produced toxins is a pathogen that poses a substrate for the production of biological weapons. It could potentially be used to induce outbreaks of food poisoning and by missiles contamination by spore lead to increased morbidity of gas gangrene in injured soldiers. C. perfringens types B and D produce epsilon toxin considered to be the third most powerful bacterial toxin. Because of the ability to disperse the toxin as an aerosol and a lack of methods of treatment and prevention of poisoning possible factors it is a potential tool for bioterrorism It is advisable to continue research into vaccines and treatments for poisoning toxins of C. perfringens. © 2015 MEDPRESS.

Analysis of the mechanisms that underlie absorption of botulinum toxin by the inhalation route.

PubMed

Al-Saleem, Fetweh H; Ancharski, Denise M; Joshi, Suresh G; Elias, M; Singh, Ajay; Nasser, Zidoon; Simpson, Lance L

2012-12-01

Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.

Ultrasound coupled with supercritical carbon dioxide for exfoliation of graphene: Simulation and experiment.

PubMed

Gai, Yanzhe; Wang, Wucong; Xiao, Ding; Zhao, Yaping

2018-03-01

Ultrasound coupled with supercritical CO 2 has become an important method for exfoliation of graphene, but behind which a peeling mechanism is unclear. In this work, CFD simulation and experiment were both investigated to elucidate the mechanism and the effects of the process parameters on the exfoliation yield. The experiments and the CFD simulation were conducted under pressure ranging from 8MPa to 16MPa, the ultrasonic power ranging from 12W to 240W and the frequency of 20kHz. The numerical analysis of fluid flow patterns and pressure distributions revealed that the fluid shear stress and the periodical pressure fluctuation generated by ultrasound were primary factors in exfoliating graphene. The distribution of the fluid shear stress decided the effective exfoliation area, which, in turn, affected the yield. The effective area increased from 5.339cm 3 to 8.074cm 3 with increasing ultrasonic power from 12W to 240W, corresponding to the yield increasing from 5.2% to 21.5%. The pressure fluctuation would cause the expansion of the interlayers of graphite. The degree of the expansion increased with the increase of the operating pressure but decreased beyond 12MPa. Thus, the maximum yield was obtained at 12MPa. The cavitation might be generated by ultrasound in supercritical CO 2 . But it is too weak to exfoliate graphite into graphene. These results provide a strategy in optimizing and scaling up the ultrasound-assisted supercritical CO 2 technique for producing graphene. Copyright © 2017 Elsevier B.V. All rights reserved.

Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation

PubMed Central

Yu, Qian; Lin, Brian; Qiu, Jessica; Stein, Daniel C.

2017-01-01

Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells. We found that GC colonization causes endocervical epithelial cells to shed. The shedding results from the disassembly of the apical junctions that seal the epithelial barrier. Apical junction disruption and epithelial exfoliation increase GC penetration into the endocervical epithelium without reducing bacterial adherence to and invasion into epithelial cells. Both epithelial exfoliation and junction disruption require the activation and accumulation of non-muscle myosin II (NMII) at the apical surface and GC adherent sites. GC inoculation activates NMII by elevating the levels of the cytoplasmic Ca2+ and NMII regulatory light chain phosphorylation. Piliation of GC promotes, but the expression of a GC opacity-associated protein variant, OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII activation and reorganization and Ca2+ flux. The inhibitory effects of OpaH lead to reductions in junction disruption, epithelial exfoliation, and GC penetration. Therefore, GC phase variation can modulate infection in the human endocervix by manipulating the activity of NMII and epithelial exfoliation. PMID:28406994

Decolorizing of azo dye Reactive red 24 aqueous solution using exfoliated graphite and H2O2 under ultrasound irradiation.

PubMed

Li, Mei; Li, Ji-Tai; Sun, Han-Wen

2008-07-01

At its natural pH (6.95), the decolorization of Reactive red 24 in ultrasound, ultrasound/H2O2, exfoliated graphite, ultrasound/exfoliated graphite, exfoliated graphite/H2O2 and ultrasound/exfoliated graphite/H2O2 systems were compared. An enhancement was observed for the decolorization in ultrasound/exfoliated graphite/H2O2 system. The effect of solution pH, H2O2 and exfoliated graphite dosages, and temperature on the decolorization of Reactive red 24 was investigated. The sonochemical treatment in combination with exfoliated graphite/H2O2 showed a synergistic effect for the decolorization of Reactive red 24. The results indicated that under proper conditions, there was a possibility to remove Reactive red 24 very efficient from aqueous solution. The decolorization of other azo dyes (Reactive red 2, Methyl orange, Acid red 1, Acid red 73, Acid red 249, Acid orange 7, Acid blue 113, Acid brown 75, Acid green 20, Acid yellow 42, Acid mordant brown 33, Acid mordant yellow 10 and Direct green 1) was also investigated, at their natural pH.

An Overview of Helicobacter pylori VacA Toxin Biology

PubMed Central

Foegeding, Nora J.; Caston, Rhonda R.; McClain, Mark S.; Ohi, Melanie D.; Cover, Timothy L.

2016-01-01

The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease. PMID:27271669

Evaluation of Efficacy and Toxicity of Exfoliated Silicate Nanoclays as a Feed Additive for Fumonisin Detoxification.

PubMed

Yuan, Chiao-Wei; Huang, Jie-Ting; Chen, Ching-Chin; Tang, Pin-Chi; Huang, Jenn-Wen; Lin, Jiang-Jen; Huang, San-Yuan; Chen, Shuen-Ei

2017-08-09

The efficacy of nanosilicate clay platelets (NSCP), exfoliated silicates from natural montmorillonites, as a feed additive for ameliorating fumonisin B1 (FB1) toxicosis was evaluated. Toxicological mechanisms by NSCP were examined through proteomic and biochemical analyses. Dietary supplementation with NSCP at a low level of 40 mg/kg of feed improved growth performances in chickens with respect to FB1 toxicosis. Other issues of ameliorated symptoms including serum and/or hepatic aspartate aminotransferase activity, oxidative stress indicators, and sphinganine/sphingosine ratio, a hallmark of FB1 toxicosis, were considered. Chickens with NSCP inclusion alone at 1000 mg/kg of feed exhibited no changes in hepatic histology, oxidative status, and serum parameters and even had a higher feed intake. Proteomic analysis with liver tissues identified 45 distinct proteins differentially affected by FB1 and/or NSCP, in which proteins involved in thiol metabolism and redox regulation, glycolysis, carcinogenesis, and detoxification by glutathione S-transferase were promoted by FB1, whereas NSCP caused differential changes of protein abundances related to methionine/cysteine and choline/glycine interconversion for glutathione synthesis, redox regulation by peroxiredoxin, toxin/metabolite delivery by albumin, glycolysis, tricarboxylic acid cycle, adenosine triphosphate (ATP) synthesis, and chaperon escort for endoplasmic reticulum stress relief. Functional analyses confirmed the enhancement of hepatic metabolic processes for ATP and NAD(P)H production to meet the need for detoxification, antioxidative defense, and toxin/metabolite clearance by FB1 or NSCP ingestion. On the basis of the amelioration of FB1 toxicosis, global profile of hepatic protein expressions, and validated toxicological mechanisms, NSCP were concluded as a safe and effective agent for FB1 detoxification.

Characterization of toxin III of the scorpion Leiurus quinquestriatus quinquestriatus: a new type of alpha-toxin highly toxic both to mammals and insects.

PubMed

Kopeyan, C; Mansuelle, P; Martin-Eauclaire, M F; Rochat, H; Miranda, F

1993-01-01

The primary structure of toxin III of Leiurus quinquestriatus quinquestriatus (Lqq III) was elucidated by automatic Edman degradation of the reduced and S-carboxymethylated protein and derived tryptic peptides. Like other scorpion toxins that are active on sodium channels, Lqq III, consisting of 64 amino acids, is a 7 kDa single-chain polypeptide crosslinked by four disulfide bridges. It belongs to the alpha-toxin group, as judged by competition experiments with 125I AaH II for binding to rat brain synaptosomes (K0.5 = 7 x 10(-7) M). Lqq III is the first alpha-toxin to be characterized that is highly toxic to mice [LD50 = 50 micrograms (7.1 nmol)/kg body wt], by subcutaneous injection, insects Blatella germanica [LD50 = 60 ng (8.5 pmol)/g body wt.] and Musca domestica [LD50 = 120 ng (17 pmol)/g body wt]. When tested via the intracerebroventricular route, the toxicity for mice [55 micrograms (8 nmol)/kg] was of the same order as that found by subcutaneous injection, indicating that Lqq III has a higher affinity for peripheral sodium channels that for those of the central nervous system. There are three differences between the sequences of Lqq III and Lqh alpha IT, an alpha-toxin isolated from the venom of Leiurus quinquestriatus hebraeus. These substitutions are found at positions 20, 24, and 64 (Ser-->Ala,Asp-->Glu and His-->Arg, respectively). Surprisingly Lqh alpha IT is only weakly active in mice [LD50 = 5 mg (0.7 mumol)/kg], while in insects its toxicity is similar to that of Lqq III [140 ng (20 pmol)/g body wt blowfly larvae]. These observations are relevant to the definition of scorpion toxin structure-activity relationships.

Attenuation of Ricin Toxin under Ambient Conditions and ...

EPA Pesticide Factsheets

Report This study focused on the attenuation of ricin toxin on six types of materials representative of a mail sorting facility and/or indoor building materials. Attenuation tests were conducted under various combinations of temperature, relative humidity (RH), and contact time, using two forms of ricin toxin: a commercially-available pure preparation and a crude preparation from castor beans.

Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin.

PubMed

Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

2009-01-30

The Clostridium botulinum type C 16S progenitor toxin contains a neurotoxin and several nontoxic components, designated nontoxic nonhemagglutinin (HA), HA1 (HA-33), HA2 (HA-17), HA3a (HA-22-23), and HA3b (HA-53). The HA3b subcomponent seems to play an important role cooperatively with HA1 in the internalization of the toxin by gastrointestinal epithelial cells via binding of these subcomponents to specific oligosaccharides. In this study, we investigated the sugar-binding specificity of the HA3b subcomponent using recombinant protein fused to glutathione S-transferase and determined the three-dimensional structure of the HA3a-HA3b complex based on X-ray crystallography. The crystal structure was determined at a resolution of 2.6 A. HA3b contains three domains, domains I to III, and the structure of domain I resembles HA3a. In crystal packing, three HA3a-HA3b molecules are assembled to form a three-leaved propeller-like structure. The three HA3b domain I and three HA3a alternate, forming a trimer of dimers. In a database search, no proteins with high structural homology to any of the domains (Z score >10) were found. Especially, HA3a and HA3b domain I, mainly composed of beta-sheets, reveal a unique fold. In binding assays, HA3b bound sialic acid with high affinity, but did not bind galactose, N-acetylgalactosamine, or N-acetylglucosamine. The electron density of liganded N-acetylneuraminic acid was determined by crystal soaking. In the sugar-complex structure, the N-acetylneuraminic acid-binding site was located in the cleft formed between domains II and III of HA3b. This report provides the first determination of the three-dimensional structure of the HA3a-HA3b complex and its sialic acid binding site. Our results will provide useful information for elucidating the mechanism of assembly of the C16S toxin and for understanding the interactions with oligosaccharides on epithelial cells and internalization of the botulinum toxin complex.

Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

2005-04-08

Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to lowmore » pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids.« less

Exfoliation of Hexagonal Boron Nitride via Ferric Chloride Intercalation

NASA Technical Reports Server (NTRS)

Hung, Ching-cheh; Hurst, Janet; Santiago, Diana; Rogers, Richard B.

2014-01-01

Sodium fluoride (NaF) was used as an activation agent to successfully intercalate ferric chloride (FeCl3) into hexagonal boron nitride (hBN). This reaction caused the hBN mass to increase by approx.100 percent, the lattice parameter c to decrease from 6.6585 to between 6.6565 and 6.6569 ?, the x-ray diffraction (XRD) (002) peak to widen from 0.01deg to 0.05deg of the full width half maximum value, the Fourier transform infrared (FTIR) spectrum's broad band (1277/cm peak) to change shape, and new FTIR bands to emerge at 3700 to 2700 and 1600/cm. This indicates hBN's structural and chemical properties are significantly changed. The intercalated product was hygroscopic and interacted with moisture in the air to cause further structural and chemical changes (from XRD and FTIR). During a 24-h hold at room temperature in air with 100 percent relative humidity, the mass increased another 141 percent. The intercalated product, hydrated or not, can be heated to 750 C in air to cause exfoliation. Exfoliation becomes significant after two intercalation-air heating cycles, when 20-nm nanosheets are commonly found. Structural and chemical changes indicated by XRD and FTIR data were nearly reversed after the product was placed in hydrochloric acid (HCl), resulting in purified, exfoliated, thin hBN products.

Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

ERIC Educational Resources Information Center

Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

2012-01-01

Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

High-yield production of graphene by liquid-phase exfoliation of graphite.

PubMed

Hernandez, Yenny; Nicolosi, Valeria; Lotya, Mustafa; Blighe, Fiona M; Sun, Zhenyu; De, Sukanta; McGovern, I T; Holland, Brendan; Byrne, Michele; Gun'Ko, Yurii K; Boland, John J; Niraj, Peter; Duesberg, Georg; Krishnamurthy, Satheesh; Goodhue, Robbie; Hutchison, John; Scardaci, Vittorio; Ferrari, Andrea C; Coleman, Jonathan N

2008-09-01

Fully exploiting the properties of graphene will require a method for the mass production of this remarkable material. Two main routes are possible: large-scale growth or large-scale exfoliation. Here, we demonstrate graphene dispersions with concentrations up to approximately 0.01 mg ml(-1), produced by dispersion and exfoliation of graphite in organic solvents such as N-methyl-pyrrolidone. This is possible because the energy required to exfoliate graphene is balanced by the solvent-graphene interaction for solvents whose surface energies match that of graphene. We confirm the presence of individual graphene sheets by Raman spectroscopy, transmission electron microscopy and electron diffraction. Our method results in a monolayer yield of approximately 1 wt%, which could potentially be improved to 7-12 wt% with further processing. The absence of defects or oxides is confirmed by X-ray photoelectron, infrared and Raman spectroscopies. We are able to produce semi-transparent conducting films and conducting composites. Solution processing of graphene opens up a range of potential large-area applications, from device and sensor fabrication to liquid-phase chemistry.

Phenol-Soluble Modulin Toxins of Staphylococcus haemolyticus

PubMed Central

Da, Fei; Joo, Hwang-Soo; Cheung, Gordon Y. C.; Villaruz, Amer E.; Rohde, Holger; Luo, Xiaoxing; Otto, Michael

2017-01-01

Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, after Staphylococcus epidermidis, is Staphylococcus haemolyticus. However, we have a significant lack of knowledge about what causes virulence of S. haemolyticus, as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogen Staphylococcus aureus, toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs), amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other than S. epidermidis. Here, we identified, purified, and characterized PSMs of S. haemolyticus. We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed that S. haemolyticus does not produce a δ-toxin, as results from genome sequencing had indicated. All four S. haemolyticus PSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM, S. haemolyticus PSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis. PMID:28596942

Molecular basis of toxicity of Clostridium perfringens epsilon toxin.

PubMed

Bokori-Brown, Monika; Savva, Christos G; Fernandes da Costa, Sérgio P; Naylor, Claire E; Basak, Ajit K; Titball, Richard W

2011-12-01

Clostridium perfringens ε-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive 32.9 kDa prototoxin is converted to active mature toxin by proteolytic cleavage, either by digestive proteases of the host, such as trypsin and chymotrypsin, or by C. perfringens λ-protease. In vivo, the toxin appears to target the brain and kidneys, but relatively few cell lines are susceptible to the toxin, and most work has been carried out using Madin-Darby canine kidney (MDCK) cells. The binding of ε-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable, high molecular weight complex. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells. © 2011 The Authors Journal compilation © 2011 FEBS.

Progress on Botulinum Toxin Type A-Induced Pain Relief in the Field of Plastics.

PubMed

Lu, Xiaona; Chen, Guocheng; Ren, Pengjie; Yang, Yan; Fan, Fei

2017-11-01

To retrospectively evaluate the effectiveness of Botulinum Toxin Type A (BTX-A) injections relieve pain in the field of plastic surgery and postoperative rehabilitation, and discuss the analgesic mechanism of BTX- A in plastics and related research progress. From appearance to September 1, 2016, PUBMED, EMBASE, and Web of Science were searched, using the key words related to "Botulinum Toxin Type A" and "Pain." Furtherly, nonplastic surgery-related literature was excluded by manual screening. Eleven literatures met the inclusion criteria, including 6 prospective controlled cohorts, 4 patient series, and 1 retrospective cohort. These studies involved Lower Limb, Breast, Hallux, Amputees, and Temporomandibular joint disk disfigurement and enrolled 402 patients. Among the patients, 360 received intraoperative BTX-A injection at the time of the main surgical procedure, 16 injected postoperatively and 26 did not undergo surgery. And 85.32% reported pain alleviation and 69.96% got favorable side effects and no one occurred major adverse effects. But 1.83% accepted injections more than once. Mechanism analysis explained these studies' results and demonstrated the analgesic effectiveness of BTX-A in plastics with nociceptive pain, inflammatory pain, and neuropathic pain. The results suggest that BTX-A may induce postoperative pain associated with plastic surgeries relief. But the available data of outcome assessment involved in this review are inconsistent and failed to meet methodological rigor. And pain alleviations are influenced by many factors. So further randomized controlled clinical trials with large sample sizes are needed to support this practice, determine standard usage methods, and establish corresponding specification systems.

Role of imprint/exfoliative cytology in ulcerated skin neoplasms.

PubMed

Ramakrishnaiah, Vishnu Prasad Nelamangala; Babu, Ravindra; Pai, Dinker; Verma, Surendra Kumar

2013-12-01

Imprint cytology is a method of studying cells by taking an imprint from the cut surface of a wedge biopsy specimen or from the resected margins of a surgical specimen. It is rapid, simple and fairly accurate. Exfoliative cytology is an offshoot from the imprint cytology where in cells obtained from the surface of ulcers, either by scrape or brush, are analyzed for the presence of malignant cells. We undertook this study to see the role of imprint/exfoliative cytology in the diagnosis of ulcerated skin neoplasm and to check the adequacy of resected margins intra-operatively. This was a prospective investigative study conducted from September 2003 to July 2005. All patients presenting to surgical clinic with ulcerated skin and soft tissue tumours were included in the study. A wedge biopsy obtained from the ulcer and imprint smears were taken from the cut surface. Exfoliative cytology was analyzed from the surface smears. Wedge biopsy specimen was sent for histopathological (HPE) examination. The cytology and HPE were analyzed by a separate pathologist. Imprint cytology was also used to check the adequacy of resected margins in case of wide excision. This was compared with final HPE. Total of 107 patients was included in the present study and 474 imprint smears were done, with an average of 4.43 slides per lesion. Out of 59 wide excision samples, 132 imprint smears were prepared for assessing resected margins accounting for an average of 2.24 slides per each excised lesion. On combining imprint cytology with exfoliative cytology the overall sensitivity, specificity and positive predictive value were 90.38 %, 100 % and 90.38 % respectively. Only one out of 59 cases had a positive resected margin which was not picked by imprint cytology. Imprint cytology can be used for rapid and accurate diagnosis of various skin malignancies. It can also be used to check the adequacy of the resected margin intraoperatively.

Tracing the metabolism of HT-2 toxin and T-2 toxin in barley by isotope-assisted untargeted screening and quantitative LC-HRMS analysis

USDA-ARS?s Scientific Manuscript database

An extensive study of the metabolism of the type-A trichothecene mycotoxins HT-2 toxin and T-2 toxin in barley using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) is reported. A recently developed untargeted approach based on stable isotopic labelling, LC-Orbitrap-MS a...

Exfoliation of graphene sheets via high energy wet milling of graphite in 2-ethylhexanol and kerosene.

PubMed

Al-Sherbini, Al-Sayed; Bakr, Mona; Ghoneim, Iman; Saad, Mohamed

2017-05-01

Graphene sheets have been exfoliated from bulk graphite using high energy wet milling in two different solvents that were 2-ethylhexanol and kerosene. The milling process was performed for 60 h using a planetary ball mill. Morphological characteristics were investigated using scanning electron microscope (SEM) and transmission electron microscope (TEM). On the other hand, the structural characterization was performed using X-ray diffraction technique (XRD) and Raman spectrometry. The exfoliated graphene sheets have represented good morphological and structural characteristics with a valuable amount of defects and a good graphitic structure. The graphene sheets exfoliated in the presence of 2-ethylhexanol have represented many layers, large crystal size and low level of defects, while the graphene sheets exfoliated in the presence of kerosene have represented fewer number of layers, smaller crystal size and higher level of defects.

Automotive body panel containing thermally exfoliated graphite oxide

NASA Technical Reports Server (NTRS)

Aksay, Ilhan A. (Inventor); Abdala, Ahmed (Inventor); Prud'Homme, Robert K. (Inventor); Adamson, Douglas (Inventor)

2011-01-01

An automotive body panel containing a polymer composite formed of at least one polymer and a modified graphite oxide material, which is a thermally exfoliated graphite oxide with a surface area of from about 300 m.sup.2/g to 2600 m.sup.2/g.

Botulinum Toxin for Rhinitis.

PubMed

Ozcan, Cengiz; Ismi, Onur

2016-08-01

Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.

Exfoliation Propensity of Oxide Scale in Heat Exchangers Used for Supercritical CO2 Power Cycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabau, Adrian S; Shingledecker, John P.; Kung, Steve

2016-01-01

Supercritical CO2 (sCO2) Brayton cycle systems offer the possibility of improved efficiency in future fossil energy power generation plants operating at temperatures of 650 C and above. As there are few data on the oxidation/corrosion behavior of structural alloys in sCO2 at these temperatures, modeling to predict the propensity for oxide exfoliation is not well developed, thus hindering materials selection for these novel cycles. The ultimate goal of this effort is to provide needed data on scale exfoliation behavior in sCO2 for confident alloy selection. To date, a model developed by ORNL and EPRI for the exfoliation of oxide scalesmore » formed on boiler tubes in high-temperature, high-pressure steam has proven useful for managing exfoliation in conventional steam plants. A major input provided by the model is the ability to predict the likelihood of scale failure and loss based on understanding of the evolution of the oxide morphologies and the conditions that result in susceptibility to exfoliation. This paper describes initial steps taken to extend the existing model for exfoliation of steam-side oxide scales to sCO2 conditions. The main differences between high-temperature, high-pressure steam and sCO2 that impact the model involve (i) significant geometrical differences in the heat exchangers, ranging from standard pressurized tubes seen typically in steam-producing boilers to designs for sCO2 that employ variously-curved thin walls to create shaped flow paths for extended heat transfer area and small channel cross-sections to promote thermal convection and support pressure loads; (ii) changed operating characteristics with sCO2 due to the differences in physical and thermal properties compared to steam; and (iii) possible modification of the scale morphologies, hence properties that influence exfoliation behavior, due to reaction with carbon species from sCO2. The numerical simulations conducted were based on an assumed sCO2 operating schedule and

Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology.

PubMed

Aboobakar, Inas F; Johnson, William M; Stamer, W Daniel; Hauser, Michael A; Allingham, R Rand

2017-01-01

Exfoliation syndrome (XFS) is a common age-related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worldwide. Recent developments in XFS genetics, cell biology and epidemiology have greatly improved our understanding of the etiology of this complex inherited disease. This review summarizes current knowledge of XFS pathogenesis, identifies gaps in knowledge, and discusses areas for future research. Copyright © 2016. Published by Elsevier Ltd.

Production of Two-Dimensional Nanomaterials via Liquid-Based Direct Exfoliation.

PubMed

Niu, Liyong; Coleman, Jonathan N; Zhang, Hua; Shin, Hyeonsuk; Chhowalla, Manish; Zheng, Zijian

2016-01-20

Tremendous efforts have been devoted to the synthesis and application of two-dimensional (2D) nanomaterials due to their extraordinary and unique properties in electronics, photonics, catalysis, etc., upon exfoliation from their bulk counterparts. One of the greatest challenges that scientists are confronted with is how to produce large quantities of 2D nanomaterials of high quality in a commercially viable way. This review summarizes the state-of-the-art of the production of 2D nanomaterials using liquid-based direct exfoliation (LBE), a very promising and highly scalable wet approach for synthesizing high quality 2D nanomaterials in mild conditions. LBE is a collection of methods that directly exfoliates bulk layered materials into thin flakes of 2D nanomaterials in liquid media without any, or with a minimum degree of, chemical reactions, so as to maintain the high crystallinity of 2D nanomaterials. Different synthetic methods are categorized in the following, in which material characteristics including dispersion concentration, flake thickness, flake size and some applications are discussed in detail. At the end, we provide an overview of the advantages and disadvantages of such synthetic methods of LBE and propose future perspectives. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atomically thin gallium layers from solid-melt exfoliation

PubMed Central

Kochat, Vidya; Samanta, Atanu; Zhang, Yuan; Bhowmick, Sanjit; Manimunda, Praveena; Asif, Syed Asif S.; Stender, Anthony S.; Vajtai, Robert; Singh, Abhishek K.; Tiwary, Chandra S.; Ajayan, Pulickel M.

2018-01-01

Among the large number of promising two-dimensional (2D) atomic layer crystals, true metallic layers are rare. Using combined theoretical and experimental approaches, we report on the stability and successful exfoliation of atomically thin “gallenene” sheets on a silicon substrate, which has two distinct atomic arrangements along crystallographic twin directions of the parent α-gallium. With a weak interface between solid and molten phases of gallium, a solid-melt interface exfoliation technique is developed to extract these layers. Phonon dispersion calculations show that gallenene can be stabilized with bulk gallium lattice parameters. The electronic band structure of gallenene shows a combination of partially filled Dirac cone and the nonlinear dispersive band near the Fermi level, suggesting that gallenene should behave as a metallic layer. Furthermore, it is observed that the strong interaction of gallenene with other 2D semiconductors induces semiconducting to metallic phase transitions in the latter, paving the way for using gallenene as promising metallic contacts in 2D devices. PMID:29536039

Glucosylation and Other Biotransformations of T-2 Toxin by Yeasts of the Trichomonascus Clade

PubMed Central

Price, Neil P. J.; Kurtzman, Cletus P.

2012-01-01

Trichothecenes are sesquiterpenoid toxins produced by Fusarium species. Since these mycotoxins are very stable, there is interest in microbial transformations that can remove toxins from contaminated grain or cereal products. Twenty-three yeast species assigned to the Trichomonascus clade (Saccharomycotina, Ascomycota), including four Trichomonascus species and 19 anamorphic species presently classified in Blastobotrys, were tested for their ability to convert the trichothecene T-2 toxin to less-toxic products. These species gave three types of biotransformations: acetylation to 3-acetyl T-2 toxin, glycosylation to T-2 toxin 3-glucoside, and removal of the isovaleryl group to form neosolaniol. Some species gave more than one type of biotransformation. Three Blastobotrys species converted T-2 toxin into T-2 toxin 3-glucoside, a compound that has been identified as a masked mycotoxin in Fusarium-infected grain. This is the first report of a microbial whole-cell method for producing trichothecene glycosides, and the potential large-scale availability of T-2 toxin 3-glucoside will facilitate toxicity testing and development of methods for detection of this compound in agricultural and other products. PMID:23042183

Novel toxic shock syndrome toxin-1 amino acids required for biological activity.

PubMed

Brosnahan, Amanda J; Schaefers, Matthew M; Amundson, William H; Mantz, Mary J; Squier, Christopher A; Peterson, Marnie L; Schlievert, Patrick M

2008-12-09

Superantigens interact with T lymphocytes and macrophages to cause T lymphocyte proliferation and overwhelming cytokine production, which lead to toxic shock syndrome. Staphylococcus aureus superantigen toxic shock syndrome toxin-1 is a major cause of menstrual toxic shock syndrome. In general, superantigen-secreting S. aureus remains localized at the vaginal surface, and the superantigen must therefore penetrate the vaginal mucosa to interact with underlying immune cells to cause toxic shock syndrome. A dodecapeptide region (toxic shock syndrome toxin-1 amino acids F119-D130), relatively conserved among superantigens, has been implicated in superantigen penetration of the epithelium. The purpose of this study was to determine amino acids within this dodecapeptide region that are required for interaction with vaginal epithelium. Alanine mutations were constructed in S. aureus toxic shock syndrome toxin-1 amino acids D120 to D130. All mutants maintained superantigenicity, and selected mutants were lethal when given intravenously to rabbits. Toxic shock syndrome toxin-1 induces interleukin-8 from immortalized human vaginal epithelial cells; however, three toxin mutants (S127A, T128A, and D130A) induced low levels of interleukin-8 compared to wild type toxin. When carboxy-terminal mutants (S127A to D130A) were administered vaginally to rabbits, D130A was nonlethal, while S127A and T128A demonstrated delayed lethality compared to wild type toxin. In a porcine ex vivo permeability model, mutant D130A penetrated the vaginal mucosa more quickly than wild type toxin. Toxic shock syndrome toxin-1 residue D130 may contribute to binding an epithelial receptor, which allows it to penetrate the vaginal mucosa, induce interleukin-8, and cause toxic shock syndrome.

Binding of ATP by pertussis toxin and isolated toxin subunits

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1990-07-03

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

Immunization with recombinant bivalent chimera r-Cpae confers protection against alpha toxin and enterotoxin of Clostridium perfringens type A in murine model.

PubMed

Shreya, Das; Uppalapati, Siva R; Kingston, Joseph J; Sripathy, Murali H; Batra, Harsh V

2015-05-01

Clostridium perfringens type A, an anaerobic pathogen is the most potent cause of soft tissue infections like gas gangrene and enteric diseases like food poisoning and enteritis. The disease manifestations are mediated via two important exotoxins, viz. myonecrotic alpha toxin (αC) and enterotoxin (CPE). In the present study, we synthesized a bivalent chimeric protein r-Cpae comprising C-terminal binding regions of αC and CPE using structural vaccinology rationale and assessed its protective efficacy against both alpha toxin (αC) and enterotoxin (CPE) respectively, in murine model. Active immunization of mice with r-Cpae generated high circulating serum IgG (systemic), significantly increased intestinal mucosal s-IgA antibody titres and resulted in substantial protection to the immunized animals (100% and 75% survival) with reduced tissue morbidity when administered with 5×LD(100) doses of αC (intramuscular) and CPE (intra-gastric gavage) respectively. Mouse RBCs and Caco-2 cells incubated with a mixture of anti-r-Cpae antibodies and αC and CPE respectively, illustrated significantly higher protection against the respective toxins. Passive immunization of mice with a similar mixture resulted in 91-100% survival at the end of the 15 days observation period while mice immunized with a concoction of sham sera and respective toxins died within 2-3 days. This work demonstrates the efficacy of the rationally designed r-Cpae chimeric protein as a potential sub unit vaccine candidate against αC and CPE of C. perfringens type A toxemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plastic changes in spinal synaptic transmission following botulinum toxin A in patients with post-stroke spasticity.

PubMed

Kerzoncuf, Marjorie; Bensoussan, Laurent; Delarque, Alain; Durand, Jacques; Viton, Jean-Michel; Rossi-Durand, Christiane

2015-11-01

The therapeutic effects of intramuscular injections of botulinum toxin-type A on spasticity can largely be explained by its blocking action at the neuromuscular junction. Botulinum toxin-type A is also thought to have a central action on the functional organization of the central nervous system. This study assessed the action of botulinum toxin-type A on spinal motor networks by investigating post-activation depression of the soleus H-reflex in post-stroke patients. Post-activation depression, a presynaptic mechanism controlling the synaptic efficacy of Ia-motoneuron transmission, is involved in the pathophysiology of spasticity. Eight patients with chronic hemiplegia post-stroke presenting with lower limb spasticity and requiring botulinum toxin-type A injection in the ankle extensor muscle. Post-activation depression of soleus H-reflex assessed as frequency-related depression of H-reflex was investigated before and 3, 6 and 12 weeks after botulinum toxin-type A injections in the triceps surae. Post-activation depression was quantified as the ratio between H-reflex amplitude at 0.5 and 0.1 Hz. Post-activation depression of soleus H-reflex, which is reduced on the paretic leg, was affected 3 weeks after botulinum toxin-type A injection. Depending on the residual motor capacity of the post-stroke patients, post-activation depression was either restored in patients with preserved voluntary motor control or further reduced in patients with no residual voluntary control. Botulinum toxin treatment induces synaptic plasticity at the Ia-motoneuron synapse in post-stroke paretic patients, which suggests that the effectiveness of botulinum toxin-type A in post-stroke rehabilitation might be partly due to its central effects.

Cellular Uptake of the Clostridium perfringens Binary Iota-Toxin

PubMed Central

Blöcker, Dagmar; Behlke, Joachim; Aktories, Klaus; Barth, Holger

2001-01-01

The binary iota-toxin is produced by Clostridium perfringens type E strains and consists of two separate proteins, the binding component iota b (98 kDa) and an actin-ADP-ribosylating enzyme component iota a (47 kDa). Iota b binds to the cell surface receptor and mediates the translocation of iota a into the cytosol. Here we studied the cellular uptake of iota-toxin into Vero cells. Bafilomycin A1, but not brefeldin A or nocodazole, inhibited the cytotoxic effects of iota-toxin, indicating that toxin is translocated from an endosomal compartment into the cytoplasm. Acidification (pH ≤ 5.0) of the extracellular medium enabled iota a to directly enter the cytosol in the presence of iota b. Activation by chymotrypsin induced oligomerization of iota b in solution. An average mass of 530 ± 28 kDa for oligomers was determined by analytical ultracentrifugation, indicating heptamer formation. The entry of iota-toxin into polarized CaCo-2 cells was studied by measuring the decrease in transepithelial resistance after toxin treatment. Iota-toxin led to a significant decrease in resistance when it was applied to the basolateral surface of the cells but not following application to the apical surface, indicating a polarized localization of the iota-toxin receptor. PMID:11292715

Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

PubMed

Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

2010-08-01

Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

Exfoliation and Reassembly of Cobalt Oxide Nanosheets into a Reversible Lithium-Ion Battery Cathode

DTIC Science & Technology

2012-01-01

REPORT Exfoliation and Reassembly of Cobalt Oxide Nanosheets into a Reversible Lithium-Ion Battery Cathode 14. ABSTRACT 16. SECURITY CLASSIFICATION OF...battery fabrication, cobalt oxide Owen C. Compton, Ali Abouimrane, Zhi An, Marc J. Palmeri, L. Catherine Brinson, Khalil Amine, SonBinh T. Nguyen...Exfoliation and Reassembly of Cobalt Oxide Nanosheets into a Reversible Lithium-Ion Battery Cathode Report Title ABSTRACT An exfoliation–reassembly

Identification of human-pathogenic strains of Shiga toxin-producing Escherichia coli from food by a combination of serotyping and molecular typing of Shiga toxin genes.

PubMed

Beutin, Lothar; Miko, Angelika; Krause, Gladys; Pries, Karin; Haby, Sabine; Steege, Katja; Albrecht, Nadine

2007-08-01

We examined 219 Shiga toxin-producing Escherichia coli (STEC) strains from meat, milk, and cheese samples collected in Germany between 2005 and 2006. All strains were investigated for their serotypes and for genetic variants of Shiga toxins 1 and 2 (Stx1 and Stx2). stx(1) or variant genes were detected in 88 (40.2%) strains and stx(2) and variants in 177 (80.8%) strains. Typing of stx genes was performed by stx-specific PCRs and by analysis of restriction fragment length polymorphisms (RFLP) of PCR products. Major genotypes of the Stx1 (stx(1), stx(1c), and stx(1d)) and the Stx2 (stx(2), stx(2d), stx(2-O118), stx(2e), and stx(2g)) families were detected, and multiple types of stx genes coexisted frequently in STEC strains. Only 1.8% of the STEC strains from food belonged to the classical enterohemorrhagic E. coli (EHEC) types O26:H11, O103:H2, and O157:H7, and only 5.0% of the STEC strains from food were positive for the eae gene, which is a virulence trait of classical EHEC. In contrast, 95 (43.4%) of the food-borne STEC strains carried stx(2) and/or mucus-activatable stx(2d) genes, an indicator for potential high virulence of STEC for humans. Most of these strains belonged to serotypes associated with severe illness in humans, such as O22:H8, O91:H21, O113:H21, O174:H2, and O174:H21. stx(2) and stx(2d) STEC strains were found frequently in milk and beef products. Other stx types were associated more frequently with pork (stx(2e)), lamb, and wildlife meat (stx(1c)). The combination of serotyping and stx genotyping was found useful for identification and for assignment of food-borne STEC to groups with potential lower and higher levels of virulence for humans.

Sensitive detection of active Shiga toxin using low cost CCD based optical detector

USDA-ARS?s Scientific Manuscript database

To reduce the sources and incidence of food-borne illness there is a need to develop inexpensive sensitive devices for detection of active toxin, such as Shiga toxin type 2 (Stx2). This approach increases the availability of foodborne bacterial toxin diagnostics in regions where there are limited r...

Properties of spray-deposited liquid-phase exfoliated graphene films

NASA Astrophysics Data System (ADS)

Sales, Maria Gabriela C.; Dela Vega, Ma. Shanlene D. C.; Vasquez, Magdaleno R., Jr.

2018-01-01

In this study, we demonstrate the feasibility of spray-depositing exfoliated graphene on flexible polyimide (PI) and rigid (soda lime glass) substrates for optoelectronic applications. The water contact angles of the substrates increased by 13% (for PI) and 49% (for glass) when the surfaces are pretreated with hexamethyldisiloxane, which significantly improved the adhesion of the films. Raman spectral analyses confirmed a minimum of 15 and a maximum of 23 layers of exfoliated graphene deposited on the substrates. After deposition, the films were exposed to 13.56 MHz radio-frequency plasma containing an admixture of argon and nitrogen gases. Plasma treatment modified the electrical properties with a response analogous to that of a rectifier. A 39% increase in transmittance in the visible region was also observed especially for glass substrates after plasma treatment without a significant change in film electrical conductivity.

Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

PubMed

Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

2008-02-22

Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

Toxin-Antitoxin Systems in the Mobile Genome of Acidithiobacillus ferrooxidans

PubMed Central

Bustamante, Paula; Tello, Mario; Orellana, Omar

2014-01-01

Toxin-antitoxin (TA) systems are genetic modules composed of a pair of genes encoding a stable toxin and an unstable antitoxin that inhibits toxin activity. They are widespread among plasmids and chromosomes of bacteria and archaea. TA systems are known to be involved in the stabilization of plasmids but there is no consensus about the function of chromosomal TA systems. To shed light on the role of chromosomally encoded TA systems we analyzed the distribution and functionality of type II TA systems in the chromosome of two strains from Acidithiobacillus ferrooxidans (ATCC 23270 and 53993), a Gram-negative, acidophilic, environmental bacterium that participates in the bioleaching of minerals. As in other environmental microorganisms, A. ferrooxidans has a high content of TA systems (28-29) and in twenty of them the toxin is a putative ribonuclease. According to the genetic context, some of these systems are encoded near or within mobile genetic elements. Although most TA systems are shared by both strains, four of them, which are encoded in the active mobile element ICEAfe1, are exclusive to the type strain ATCC 23270. We demostrated that two TA systems from ICEAfe1 are functional in E. coli cells, since the toxins inhibit growth and the antitoxins counteract the effect of their cognate toxins. All the toxins from ICEAfe1, including a novel toxin, are RNases with different ion requirements. The data indicate that some of the chromosomally encoded TA systems are actually part of the A. ferrooxidans mobile genome and we propose that could be involved in the maintenance of these integrated mobile genetic elements. PMID:25384039

The 5΄ UTR of the type I toxin ZorO can both inhibit and enhance translation

PubMed Central

Wen, Jia; Harp, John R.

2017-01-01

Abstract Many bacterial type I toxin mRNAs possess a long 5΄ untranslated region (UTR) that serves as the target site of the corresponding antitoxin sRNA. This is the case for the zorO-orzO type I system where the OrzO antitoxin base pairs to the 174-nucleotide zorO 5΄ UTR. Here, we demonstrate that the full-length 5΄ UTR of the zorO type I toxin hinders its own translation independent of the sRNA whereas a processed 5΄ UTR (zorO Δ28) promotes translation. The full-length zorO 5΄ UTR folds into an extensive secondary structure sequestering the ribosome binding site (RBS). Processing of the 5΄ UTR does not alter the RBS structure, but opens a large region (EAP region) located upstream of the RBS. Truncation of this EAP region impairs zorO translation, but this defect can be rescued upon exposing the RBS. Additionally, the region spanning +35 to +50 of the zorO mRNA is needed for optimal translation of zorO. Importantly, the positive and negative effects on translation imparted by the 5΄ UTR can be transferred onto a reporter gene, indicative that the 5΄ UTR can solely drive regulation. Moreover, we show that the OrzO sRNA can inhibit zorO translation via base pairing to the of the EAP region. PMID:27903909

Exfoliation of graphite into graphene in aqueous solutions of inorganic salts.

PubMed

Parvez, Khaled; Wu, Zhong-Shuai; Li, Rongjin; Liu, Xianjie; Graf, Robert; Feng, Xinliang; Müllen, Klaus

2014-04-23

Mass production of high-quality graphene sheets is essential for their practical application in electronics, optoelectronics, composite materials, and energy-storage devices. Here we report a prompt electrochemical exfoliation of graphene sheets into aqueous solutions of different inorganic salts ((NH4)2SO4, Na2SO4, K2SO4, etc.). Exfoliation in these electrolytes leads to graphene with a high yield (>85%, ≤3 layers), large lateral size (up to 44 μm), low oxidation degree (a C/O ratio of 17.2), and a remarkable hole mobility of 310 cm(2) V(-1) s(-1). Further, highly conductive graphene films (11 Ω sq(-1)) are readily fabricated on an A4-size paper by applying brush painting of a concentrated graphene ink (10 mg mL(-1), in N,N'-dimethylformamide). All-solid-state flexible supercapacitors manufactured on the basis of such graphene films deliver a high area capacitance of 11.3 mF cm(-2) and an excellent rate capability of 5000 mV s(-1). The described electrochemical exfoliation shows great promise for the industrial-scale synthesis of high-quality graphene for numerous advanced applications.

Crystal structure of the toxin Msmeg_6760, the structural homolog of Mycobacterium tuberculosis Rv2035, a novel type II toxin involved in the hypoxic response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajaj, R. Alexandra; Arbing, Mark A.; Shin, Annie

The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin–antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate–latch mechanism. The function of the Msmeg_6760 toxin is unknown, but structure-based predictions revealed that Msmeg_6760 and Msmeg_6762 are homologous to Rv2034 and Rv2035, a predicted novelmore » TA system involved inMycobacterium tuberculosislatency during macrophage infection. The Msmeg_6760 toxin fold has not been previously described for bacterial toxins and its unique structural features suggest that toxin activation is likely to be mediated by a novel mechanism.« less

Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle.

PubMed

James, Arlene N; Ryan, James P; Parkman, Henry P

2003-08-01

Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 microM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.

Topical Calendula officinalis L. successfully treated exfoliative cheilitis: a case report

PubMed Central

2009-01-01

Authors describe a case of recurrent exfoliative cheilitis that responded to treatment with a standardized topical preparation of Calendula officinalis L. An eighteen-year-old man was referred to UNESP - São Paulo State University, Department of Biosciences and Oral Diagnosis, São José dos Campos Dental School to investigate a chronic dry scaling lesion on his lips. The patient's main chief was aesthetic compromising. Corticoid therapy was suspended and Calendula officinalis ointment 10% for ad libitum use has been prescribed. The results presented allow the authors to consider Calendula officinalis L. as a potential therapy in cases of cheilitis exfoliative. PMID:20062714

Synthesis, characterization and photocatalytic performance of chemically exfoliated MoS2

NASA Astrophysics Data System (ADS)

Prabhakar Vattikuti, S. V.; Shim, Jaesool

2018-03-01

Two-dimensional (2D) layered structure transition metal dichalcogenides (TMDs) has gained huge attention and importance for photocatalytic energy conversion because of their unique properties. Molybdenum disulfide (MoS2) nanosheets were synthesized via one-pot method and exfoliated in (dimethylformamide) DMF solution. Subsequent exfoliated MoS2 nanosheets (e-MoS2) were used as photocatalysts for degradation of Rhodamine B (RhB) pollutant under solar light irradiation. The e-MoS2 nanosheets exhibited excellent photocatalytic activity than that of pristine MoS2, owing to high specific surface area with enormous active sites and light absorption capacity. In addition, e-MoS2 demonstrated remarkable photocatalytic stability.

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

PubMed

Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2015-12-01

To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

Molecular Typing and Virulence Characteristic of Methicillin-Resistant Staphylococcus Aureus Isolates from Pediatric Patients in Bucaramanga, Colombia

PubMed Central

Machuca, Mayra Alejandra; Sosa, Luis Miguel; González, Clara Isabel

2013-01-01

Background Staphylococcus aureus is among the most common global nosocomial pathogens. The emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide that causes nosocomial and community infections. The goals of this study were to establish the clonal complexes (CC) of the isolates of MRSA obtained from pediatric patients in a university hospital in Colombia and to investigate its molecular characteristics based on the virulence genes and the genes of staphylococcal toxins and adhesins. Methods A total of 53 MRSA isolates from pediatric patients with local or systemic infections were collected. The MRSA isolates were typed based on the SCCmec, MLST, spa and agr genes. The molecular characterization included the detection of Panton-Valentine Leukocidin, superantigenic and exfoliative toxins, and adhesin genes. The correlation between the molecular types identified and the profile of virulence factors was determined for all isolates. Results Four CC were identified, including CC8, CC5, CC80 and CC78. The ST8-MRSA-IVc-agrI was the predominant clone among the isolates, followed by the ST5-MRSA-I-agrII and ST5-MRSA-IVc-agrII clones. Twelve spa types were identified, of which t10796 and t10799 were new repeat sequences. The isolates were carriers of toxin genes, and hlg (100%), sek (92%) and pvl (88%) were the most frequent. Ten toxin gene profiles were observed, and the most frequent were seq-sek-hlg (22.6%), sek-hlg (22.6%), seb-seq-sek-hlg (18.9%) and seb-sek-hlg (15.1%). The adhesion genes were present in most of the MRSA isolates, including the following: clf-A (89%), clf-B (87%), fnb-A (83%) and ica (83%). The majority of the strains carried SCCmec-IVc and were identified as causing nosocomial infection. No significant association between a molecular type and the virulence factors was found. Conclusion Four major MRSA clone complexes were identified among the isolates. ST8-MRSA-IVc-agrI pvl+ (USA300-LV) was the

Treatment of proctalgia fugax with botulinum A toxin.

PubMed

Katsinelos, P; Kalomenopoulou, M; Christodoulou, K; Katsiba, D; Tsolkas, P; Pilpilidis, I; Papagiannis, A; Kapitsinis, I; Vasiliadis, I; Souparis, T

2001-11-01

Two recent studies described a temporal association between a high-amplitude and high-frequency myoelectrical activity of the anal sphincter and the occurrence of proctalgia, which suggest that paroxysmal hyperkinesis of the anus may cause proctalgia fugax. We describe a single case of proctalgia fugax responding to anal sphincter injection of Clostridium botulinum type A toxin. The presumed aetiology of proctalgia fugax is discussed and the possible mechanism of action of botulinum toxin (BTX) in this condition is outlined. Botulinum A toxin seems to be a promising treatment for patients with proctalgia fugax, and further trials appear to be worthwhile for this condition, which has been described as incurable.

Exfoliation and Air Stability of Germanane

DTIC Science & Technology

2013-01-01

Standard Form 298 (Rev 8/98) Prescribed by ANSI Std. Z39.18 614-247-7438 W911NF-12-1-0481 62249-MS.12 MS Thesis a . REPORT 14. ABSTRACT 16...Germanane Exfoliation of graphene has shown that it is not only possible to create stable, singleatom- thick sheets from a crystalline solid, but that...however, contains the sp3 hybridization needed for functionalization. This functionalization could lead to a tunable band gap necessary for

Climatic droplet keratopathy, exfoliation syndrome, and cataract.

PubMed Central

Resnikoff, S; Filliard, G; Dell'Aquila, B

1991-01-01

During a countrywide survey we assessed the prevalence of climatic droplet keratopathy (CDK) in a randomised sample of 2446 subjects representative of the population of the Republic of Djibouti. The investigation of the relationship between CDK and two diseases considered to be related to exposure to ultra-violet light--namely, exfoliation syndrome and cataract--was planned as a case control study. In the rural area prevalence of CDK was five times higher than in the urban one (2.8% vs 0.5%) and varied according to districts. The highest rates were observed where the inhabitants' activities were related to the sea. The case control study revealed that the opacification of the lens was about three times commoner in patients with CDK than in patients without CDK (p = 0.03) and that the exfoliation syndrome was about six times commoner in patients with CDK than in controls of similar age, sex, climatic conditions, and lens status (p = 0.02). Moreover, we noticed that the sequelae of corneal perforations were about 30 times commoner in patients with CDK than in controls of similar age (p less than 0.00001). PMID:1768663

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

USDA-ARS?s Scientific Manuscript database

Shiga toxin 1, exotoxin A, diphtheria toxin and ricin are all AB-type protein toxins that act within the host cytosol to kill the host cell through a pathway involving the inhibition of protein synthesis. It is thought that a single molecule of cytosolic toxin is sufficient to kill the host cell. In...

Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology.

PubMed

Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko; Gerdes, Kenn

2018-06-07

Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules. Copyright © 2018 Elsevier Inc. All rights reserved.

Detection, Characterization, and Typing of Shiga Toxin-Producing Escherichia coli.

PubMed

Parsons, Brendon D; Zelyas, Nathan; Berenger, Byron M; Chui, Linda

2016-01-01

Shiga toxin-producing Escherichia coli (STEC) are responsible for gastrointestinal diseases reported in numerous outbreaks around the world. Given the public health importance of STEC, effective detection, characterization and typing is critical to any medical laboratory system. While non-O157 serotypes account for the majority of STEC infections, frontline microbiology laboratories may only screen for STEC using O157-specific agar-based methods. As a result, non-O157 STEC infections are significantly under-reported. This review discusses recent advances on the detection, characterization and typing of STEC with emphasis on work performed at the Alberta Provincial Laboratory for Public Health (ProvLab). Candidates for the detection of all STEC serotypes include chromogenic agars, enzyme immunoassays (EIA) and quantitative real time polymerase chain reaction (qPCR). Culture methods allow further characterization of isolates, whereas qPCR provides the greatest sensitivity and specificity, followed by EIA. The virulence gene profiles using PCR arrays and stx gene subtypes can subsequently be determined. Different non-O157 serotypes exhibit markedly different virulence gene profiles and a greater prevalence of stx1 than stx2 subtypes compared to O157:H7 isolates. Finally, recent innovations in whole genome sequencing (WGS) have allowed it to emerge as a candidate for the characterization and typing of STEC in diagnostic surveillance isolates. Methods of whole genome analysis such as single nucleotide polymorphisms and k-mer analysis are concordant with epidemiological data and standard typing methods, such as pulsed-field gel electrophoresis and multiple-locus variable number tandem repeat analysis while offering additional strain differentiation. Together these findings highlight improved strategies for STEC detection using currently available systems and the development of novel approaches for future surveillance.

Detection, Characterization, and Typing of Shiga Toxin-Producing Escherichia coli

PubMed Central

Parsons, Brendon D.; Zelyas, Nathan; Berenger, Byron M.; Chui, Linda

2016-01-01

Shiga toxin-producing Escherichia coli (STEC) are responsible for gastrointestinal diseases reported in numerous outbreaks around the world. Given the public health importance of STEC, effective detection, characterization and typing is critical to any medical laboratory system. While non-O157 serotypes account for the majority of STEC infections, frontline microbiology laboratories may only screen for STEC using O157-specific agar-based methods. As a result, non-O157 STEC infections are significantly under-reported. This review discusses recent advances on the detection, characterization and typing of STEC with emphasis on work performed at the Alberta Provincial Laboratory for Public Health (ProvLab). Candidates for the detection of all STEC serotypes include chromogenic agars, enzyme immunoassays (EIA) and quantitative real time polymerase chain reaction (qPCR). Culture methods allow further characterization of isolates, whereas qPCR provides the greatest sensitivity and specificity, followed by EIA. The virulence gene profiles using PCR arrays and stx gene subtypes can subsequently be determined. Different non-O157 serotypes exhibit markedly different virulence gene profiles and a greater prevalence of stx1 than stx2 subtypes compared to O157:H7 isolates. Finally, recent innovations in whole genome sequencing (WGS) have allowed it to emerge as a candidate for the characterization and typing of STEC in diagnostic surveillance isolates. Methods of whole genome analysis such as single nucleotide polymorphisms and k-mer analysis are concordant with epidemiological data and standard typing methods, such as pulsed-field gel electrophoresis and multiple-locus variable number tandem repeat analysis while offering additional strain differentiation. Together these findings highlight improved strategies for STEC detection using currently available systems and the development of novel approaches for future surveillance. PMID:27148176

Toxins of filamentous fungi.

PubMed

Bhatnagar, Deepak; Yu, Jiujiang; Ehrlich, Kenneth C

2002-01-01

Mycotoxins are low-molecular-weight secondary metabolites of fungi. The most significant mycotoxins are contaminants of agricultural commodities, foods and feeds. Fungi that produce these toxins do so both prior to harvest and during storage. Although contamination of commodities by toxigenic fungi occurs frequently in areas with a hot and humid climate (i.e. conditions favorable for fungal growth), they can also be found in temperate conditions. Production of mycotoxins is dependent upon the type of producing fungus and environmental conditions such as the substrate, water activity (moisture and relative humidity), duration of exposure to stress conditions and microbial, insect or other animal interactions. Although outbreaks of mycotoxicoses in humans have been documented, several of these have not been well characterized, neither has a direct correlation between the mycotoxin and resulting toxic effect been well established in vivo. Even though the specific modes of action of most of the toxins are not well established, acute and chronic effects in prokaryotic and eukaryotic systems, including humans have been reported. The toxicity of the mycotoxins varies considerably with the toxin, the animal species exposed to it, and the extent of exposure, age and nutritional status. Most of the toxic effects of mycotoxins are limited to specific organs, but several mycotoxins affect many organs. Induction of cancer by some mycotoxins is a major concern as a chronic effect of these toxins. It is nearly impossible to eliminate mycotoxins from the foods and feed in spite of the regulatory efforts at the national and international levels to remove the contaminated commodities. This is because mycotoxins are highly stable compounds, the producing fungi are ubiquitous, and food contamination can occur both before and after harvest. Nevertheless, good farm management practices and adequate storage facilities minimize the toxin contamination problems. Current research is

Botulinic toxin detection by counterimmunoelectrophoresis.

PubMed

Nuñez, L; Amato de Lagarde, E A; d'Aquino, M

1990-03-01

A counterimmunoelectrophoretic (CIE) technique was developed to detect botulinic toxin type A, and the method was compared with the mouse bioassay. A 100 LD50 concentration was detected within 2 h. Crossed reactions were observed with antitoxins of types B and F. As regards other Clostridium species, precipitin lines were seen between C. sporogenes and antitoxin type A. Foodstuffs artificially contaminated with C. botulinum type A were assayed by means of CIE and mouse bioassay, without recording interference by substances normally contained in foodstuffs.

Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows

USGS Publications Warehouse

Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, T.E.; Smith, S.R.; Cullor, J.S.; Ardans, A.A.

2009-01-01

Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood–milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations.

Tetanus toxin interaction with human erythrocytes. II. Kinetic properties of toxin association and evidence for a ganglioside-toxin macromolecular complex formation.

PubMed

Lazarovici, P; Yavin, E

1985-01-25

The properties of tetanus toxin interaction with human erythrocytes supplemented with disialo- and trisialo-gangliosides have been investigated. Binding of toxin is linear with time for 1 h and is 3-4-fold higher at 37 degrees C than at 4 degrees C during incubation of long duration. It exhibits saturation at toxin concentrations between 0.1 and 1 microgram/ml; however, it is nonsaturable between 1 and up to 50 micrograms/ml. It is effectively prevented by free gangliosides and antibodies or by pretreatment with sialidase but is unaffected by a number of closely related ligands including toxoid and toxin fragments. NaCl (1 M) removes a great portion (86%) of cell-associated toxin while Triton X-100 extracts an additional fraction (30%) of the salt-resistant cell-bound toxin. The residual sequestred toxin after detergent extraction is sensitive to proteolytic degradation. The trypsin-stable fraction (1.5%) is biotoxic and may be indicative of internalization of toxin. A macromolecular complex of about 700 kDa containing toxin and gangliosides has been isolated and characterized by Sephacryl S-300 gel permeation chromatography, SDS-gel electrophoresis, immunoprecipitability and biotoxicity. This complex is obtained only in ganglioside-supplemented cells and not when free 3H-labeled GD1b is reacted with 125I-labeled toxin in solution in the absence of cells. The hydrophobicity properties acquired as a result of ganglioside-toxin interaction, presumably at the cell surface, suggest a conformational change of the toxin which may enable its penetration into the bilayer.

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

PubMed

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.

Urea-assisted liquid-phase exfoliation of natural graphite into few-layer graphene

NASA Astrophysics Data System (ADS)

Hou, Dandan; Liu, Qinfu; Wang, Xianshuai; Qiao, Zhichuan; Wu, Yingke; Xu, Bohui; Ding, Shuli

2018-05-01

The mass production of graphene with high quality is desirable for its wide applications. Here, we demonstrated a facile method to exfoliate natural graphite into graphene in organic solvent by assisting of urea. The exfoliation of graphite may originate from the "molecular wedge" effect of urea, which can intercalate into the edge of natural graphite, thus facilitating the production of graphene dispersion with a high concentration up to 1.2 mg/mL. The obtained graphene is non-oxidized with negligible defects. Therefore, this approach has great promise in bulk production of graphene with superior quality for a variety of applications.

Clostridium perfringens epsilon toxin: a malevolent molecule for animals and man?

PubMed

Stiles, Bradley G; Barth, Gillian; Barth, Holger; Popoff, Michel R

2013-11-12

Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein produced by Clostridium perfringens (types B and D) that induces fatal enteric disease of goats, sheep and cattle. Epsilon toxin (Etx) belongs to the aerolysin-like toxin family. It contains three distinct domains, is proteolytically-activated and forms oligomeric pores on cell surfaces via a lipid raft-associated protein(s). Vaccination controls Etx-induced disease in the field. However, therapeutic measures are currently lacking. This review initially introduces C. perfringens toxins, subsequently focusing upon the Etx and its biochemistry, disease characteristics in various animals that include laboratory models (in vitro and in vivo), and finally control mechanisms (vaccines and therapeutics).

Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.

PubMed

Peng, Lisheng; Berntsson, Ronnie P-A; Tepp, William H; Pitkin, Rose M; Johnson, Eric A; Stenmark, Pål; Dong, Min

2012-07-01

Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple subtype and mosaic toxins exist. These subtype and mosaic toxins share a high sequence identity, and presumably the same receptors and substrates with their parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C, binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its toxicity in vivo in mice. We also found that gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of the SytII luminal fragment to block BoNT/D-C entry into neurons. These data establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D-C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and G also bind, but utilizes a receptor-binding interface that is distinct from BoNT/B and G. Finally, we also report that human and chimpanzee SytII has diminished binding and function as the receptor for BoNT/B, D-C and G owing to a single residue change from rodent SytII within the toxin binding site, potentially reducing the potency of these BoNTs in humans and chimpanzees.

Occurrence and distribution of 13 trichothecene toxins in naturally contaminated maize plants in Germany.

PubMed

Schollenberger, Margit; Müller, Hans-Martin; Ernst, Katrin; Sondermann, Sarah; Liebscher, Melanie; Schlecker, Claudia; Wischer, Gerald; Drochner, Winfried; Hartung, Karin; Piepho, Hans-Peter

2012-10-01

The objective of the present study was to monitor the occurrence and distribution of a spectrum of trichothecene toxins in different parts of maize plants. Therefore maize plants were sampled randomly from 13 fields in southwest Germany and the fractions kernels, cobs, husks, stalks, leaves and rudimentary ears were analyzed for eight A-type and five B-type trichothecenes. Each of the toxins was found in at least three of the total of 78 samples. The study revealed that both A-type and B-type trichothecenes may be present in all parts of the maize plant but may be unevenly distributed. For the contents of deoxynivalenol, 3- and 15-acetyldeoxynivalenol, nivalenol, scirpentriol, 15-monoacetoxyscirpenol, HT-2 and T-2 toxin significant differences (p < 0.05) were found between different parts of the maize plants whereas no significant differences were observed for fusarenon-X, 4,15-diacetoxyscirpenol, neosolaniol, T-2 triol and T-2 tetraol. Up to twelve toxins co-occurring in one sample were detected. As a group B-type trichothecenes dominated over A-type trichothecenes concerning incidences and levels. Contamination was strongest with rudimentary ears based on incidence and mean and maximum contents; mean contents with few exceptions tended towards a higher level than in other fractions with significant (p < 0.05) differences compared to leaves for seven toxins.

Exfoliation restacking route to Au nanoparticle-clay nanohybrids

NASA Astrophysics Data System (ADS)

Paek, Seung-Min; Jang, Jae-Up; Hwang, Seong-Ju; Choy, Jin-Ho

2006-05-01

A novel gold-pillared aluminosilicate (Au-PILC) were synthesized with positively charged gold nanoparticles capped by mercaptoammonium and exfoliated silicate layers. Gold nanoparticles were synthesized by NaBH4 reduction of AuCl4- in the presence of N,N,N-Trimethyl (11-mercaptoundecyl)ammonium (HS(CH2)11NMe3+) protecting ligand in an aqueous solution, and purified by dialysis. The resulting positively charged and water-soluble gold nanoparticles were hybridized with exfoliated silicate sheets by electrostatic interaction. The formation of Au clay hybrids could be easily confirmed by the powder X-ray diffraction with the increased basal spacing of clay upon insertion of Au nanoparticles. TEM image clearly revealed that the Au particles with an average size of 4 nm maintain their structure even after intercalation. The Au nanoparticles supported by clay matrix were found to be thermally more stable, suggesting that the Au nanoparticles were homogeneously protected with clay nanoplates. The present synthetic route could be further applicable to various hybrid systems between metal nanoparticles and clays.

Anthrax Toxin

DTIC Science & Technology

1984-10-26

focused initially on EF because it seemed possible that this component, like cholera toxin, might cause edema in skin through elevation of cellular cAMP...behavior differed from that seen in cells exposed to cholera toxin, where cellular cAMP levels remain elevated upon toxin removal. Studies in CHO cell...LF, the rat bioassay is not likely to be an appropriate system for studying the cellular and molecular mechanisms of action of LF. Therefore, a survey

Detergent-Resistant Membrane Microdomains Facilitate Ib Oligomer Formation and Biological Activity of Clostridium perfringens Iota-Toxin

DTIC Science & Technology

2004-04-01

spore-forming bacilli such as Clostridium spiroforme (iota-like toxin), Clostridium botulinum (C2 toxin), Bacillus anthracis (lethal and edema toxins...ously (28). Goat C. spiroforme and C. perfringens type C antisera were purchased from TechLab, Inc. (Blacksburg, Va.). Mouse monoclonal antibodies...membrane preparations was specific. Previous studies showed that the binary C. spiroforme toxin shares common epitopes with iota-toxin, and antisera

Botulinum Toxin Type A as Preoperative Treatment for Immediately Loaded Dental Implants Placed in Fresh Extraction Sockets for Full-Arch Restoration of Patients With Bruxism.

PubMed

Mijiritsky, Eitan; Mortellaro, Carmen; Rudberg, Omri; Fahn, Miri; Basegmez, Cansu; Levin, Liran

2016-05-01

The aim of the present report was to describe the use of Botulinum toxin type A as preoperative treatment for immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration of patients with bruxism. Patients with bruxism who were scheduled to receive immediately loaded full-arch implant supported fixed restorations were included in this retrospective clinical report. To reduce the occlusal forces applied in patients with bruxism, Botulinum toxin type A was introduced prior to the implant placement procedure. Patients were followed and implant survival as well as peri-implant bone level was assessed in each periodic follow-up visit. Adverse effects were also recorded. A control group with no use of Botulinum toxin was evaluated as well. A total of 26 patients (13 test and 13 control), with bruxism, aged 59.15 ± 11.43 years on average were included in this retrospective report and received immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration. The test group treatment preceded by Botulinum toxin type A injection. Maxillary arches were supported by 8 to 10 implants while the mandibular arch was supported by 6 implants. All surgeries went uneventfully and no adverse effects were observed. The average follow-up time was 32.5 ± 10.4 months (range, 18-51). In the test group, no implant failures were recorded. One patient presented with 1 to 2 mm bone loss around 4 of the implants; the other implants presented with stable bone level. In the control group 1 patient lost 2 implants and another demonstrated 2 mm bone loss around 3 of the implants. The preoperative use of Botulinum toxin in patients with bruxism undergoing full-arch rehabilitation using immediately loaded dental implants placed in fresh extraction sockets seems to be a technique that deserves attention. Further long-term, large-scale randomized clinical trials will help to determine the additional benefit of this suggested

Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC).

PubMed

Rausch, Dana; Ruan, Xiaosai; Nandre, Rahul; Duan, Qiangde; Hashish, Emad; Casey, Thomas A; Zhang, Weiping

2017-04-01

Enterotoxigenic Escherichia coli (ETEC) strains are the main cause of diarrhea in pigs. Pig diarrhea especially post-weaning diarrhea remains one of the most important swine diseases. ETEC bacterial fimbriae including K88, F18, 987P, K99 and F41 promote bacterial attachment to intestinal epithelial cells and facilitate ETEC colonization in pig small intestine. ETEC enterotoxins including heat-labile toxin (LT) and heat-stable toxins type Ia (porcine-type STa) and type II (STb) stimulate fluid hyper-secretion, leading to watery diarrhea. Blocking bacteria colonization and/or neutralizing enterotoxicity of ETEC toxins are considered effective prevention against ETEC diarrhea. In this study, we applied the MEFA (multiepitope fusion antigen) strategy to create toxoid MEFAs that carried antigenic elements of ETEC toxins, and examined for broad antitoxin immunogenicity in a murine model. By embedding STa toxoid STa P12F (NTFYCCELCCNFACAGCY), a STb epitope (KKDLCEHY), and an epitope of Stx2e A subunit (QSYVSSLN) into the A1 peptide of a monomeric LT toxoid (LT R192G ), two toxoid MEFAs, 'LT R192G -STb-Stx2e-STa P12F ' and 'LT R192G -STb-Stx2e-3xSTa P12F ' which carried three copies of STa P12F , were constructed. Mice intraperitoneally immunized with each toxoid MEFA developed IgG antibodies to all four toxins. Induced antibodies showed in vitro neutralizing activities against LT, STa, STb and Stx2e toxins. Moreover, suckling piglets born by a gilt immunized with 'LT R192G -STb-Stx2e-3xSTa P12F ' were protected when challenged with ETEC strains, whereas piglets born by a control gilt developed diarrhea. Results from this study showed that the toxoid MEFA induced broadly antitoxin antibodies, and suggested potential application of the toxoid MEFA for developing a broad-spectrum vaccine against ETEC diarrhea in pigs. Copyright © 2016 Elsevier B.V. All rights reserved.

Mapping of the continuous epitopes displayed on the Clostridium perfringens type D epsilon-toxin.

PubMed

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

The epsilon toxin, produced by Clostridium perfringens, is responsible for enterotoxemia in ruminants and is a potential bioterrorism agent. In the present study, 15 regions of the toxin were recognized by antibodies present in the serum, with different immunodominance scales, and may be antigen determinants that can be used to formulate subunit vaccines. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Nanoimprint-Assisted Shear Exfoliation (NASE) for Producing Multilayer MoS2 Structures as Field-Effect Transistor Channel Arrays.

PubMed

Chen, Mikai; Nam, Hongsuk; Rokni, Hossein; Wi, Sungjin; Yoon, Jeong Seop; Chen, Pengyu; Kurabayashi, Katsuo; Lu, Wei; Liang, Xiaogan

2015-09-22

MoS2 and other semiconducting transition metal dichalcogenides (TMDCs) are of great interest due to their excellent physical properties and versatile chemistry. Although many recent research efforts have been directed to explore attractive properties associated with MoS2 monolayers, multilayer/few-layer MoS2 structures are indeed demanded by many practical scale-up device applications, because multilayer structures can provide sizable electronic/photonic state densities for driving upscalable electrical/optical signals. Currently there is a lack of processes capable of producing ordered, pristine multilayer structures of MoS2 (or other relevant TMDCs) with manufacturing-grade uniformity of thicknesses and electronic/photonic properties. In this article, we present a nanoimprint-based approach toward addressing this challenge. In this approach, termed as nanoimprint-assisted shear exfoliation (NASE), a prepatterned bulk MoS2 stamp is pressed into a polymeric fixing layer, and the imprinted MoS2 features are exfoliated along a shear direction. This shear exfoliation can significantly enhance the exfoliation efficiency and thickness uniformity of exfoliated flakes in comparison with previously reported exfoliation processes. Furthermore, we have preliminarily demonstrated the fabrication of multiple transistors and biosensors exhibiting excellent device-to-device performance consistency. Finally, we present a molecular dynamics modeling analysis of the scaling behavior of NASE. This work holds significant potential to leverage the superior properties of MoS2 and other emerging TMDCs for practical scale-up device applications.

Bioterrorism: toxins as weapons.

PubMed

Anderson, Peter D

2012-04-01

The potential for biological weapons to be used in terrorism is a real possibility. Biological weapons include infectious agents and toxins. Toxins are poisons produced by living organisms. Toxins relevant to bioterrorism include ricin, botulinum, Clostridium perfrigens epsilson toxin, conotoxins, shigatoxins, saxitoxins, tetrodotoxins, mycotoxins, and nicotine. Toxins have properties of biological and chemical weapons. Unlike pathogens, toxins do not produce an infection. Ricin causes multiorgan toxicity by blocking protein synthesis. Botulinum blocks acetylcholine in the peripheral nervous system leading to muscle paralysis. Epsilon toxin damages cell membranes. Conotoxins block potassium and sodium channels in neurons. Shigatoxins inhibit protein synthesis and induce apoptosis. Saxitoxin and tetrodotoxin inhibit sodium channels in neurons. Mycotoxins include aflatoxins and trichothecenes. Aflatoxins are carcinogens. Trichothecenes inhibit protein and nucleic acid synthesis. Nicotine produces numerous nicotinic effects in the nervous system.

Spatial, Temporal, and Matrix Variability of Clostridium botulinum Type E Toxin Gene Distribution at Great Lakes Beaches

PubMed Central

Oster, Ryan J.; Haack, Sheridan K.; Fogarty, Lisa R.; Tucker, Taaja R.; Riley, Stephen C.

2015-01-01

Clostridium botulinum type E toxin is responsible for extensive mortality of birds and fish in the Great Lakes. The C. botulinum bontE gene that produces the type E toxin was amplified with quantitative PCR from 150 sloughed algal samples (primarily Cladophora species) collected during summer 2012 from 10 Great Lakes beaches in five states; concurrently, 74 sediment and 37 water samples from four sites were also analyzed. The bontE gene concentration in algae was significantly higher than in water and sediment (P < 0.05), suggesting that algal mats provide a better microenvironment for C. botulinum. The bontE gene was detected most frequently in algae at Jeorse Park and Portage Lake Front beaches (Lake Michigan) and Bay City State Recreation Area beach on Saginaw Bay (Lake Huron), where 77, 100, and 83% of these algal samples contained the bontE gene, respectively. The highest concentration of bontE was detected at Bay City (1.98 × 105 gene copies/ml of algae or 5.21 × 106 g [dry weight]). This study revealed that the bontE gene is abundant in the Great Lakes but that it has spatial, temporal, and matrix variability. Further, embayed beaches, low wave height, low wind velocity, and greater average water temperature enhance the bontE occurrence. PMID:25888178

A rare case report and appraisal of the literature on spontaneous tooth exfoliation associated with trigeminal herpes zoster.

PubMed

Kaur, Rupinder; Rani, Pooja; Malhotra, Divye; Kaur, Rajwant; Dass, Praveen Kumar

2016-09-01

Reports of post herpetic maxillofacial complications have been very rarely documented in the literature that includes periapical lesions, calcified and devitalized pulps, resorption of roots, osteonecrosis, and spontaneous exfoliation of teeth. The atypical feature of the case of concern to the dental surgeon is the rare complication of spontaneous tooth exfoliation following herpes zoster. This case reports a male patient of age 47 years who reported to the Department of Periodontology with the chief complaint of mobility in the left upper central incisor. Patient history revealed herpes zoster infection that began 11 days earlier along with underlying diabetes mellitus condition. We hereby report a known diabetic patient with history of herpes zoster infection who presented with rare complication of spontaneous tooth exfoliation involving the maxillary division of the trigeminal nerve. Limited number of cases has been reported in the literature regarding spontaneous teeth exfoliation secondary to herpes zoster. The exact pathogenesis regarding the spontaneous exfoliation of teeth in herpes zoster patient is still controversial. Thus, an oral health care provider should be aware of this rare complication while managing a case of tooth mobility with the previous history of herpes zoster of trigeminal nerve.

Metabolism of HT-2 Toxin and T-2 Toxin in Oats

PubMed Central

Meng-Reiterer, Jacqueline; Bueschl, Christoph; Rechthaler, Justyna; Berthiller, Franz; Lemmens, Marc; Schuhmacher, Rainer

2016-01-01

The Fusarium mycotoxins HT-2 toxin (HT2) and T-2 toxin (T2) are frequent contaminants in oats. These toxins, but also their plant metabolites, may contribute to toxicological effects. This work describes the use of 13C-assisted liquid chromatography–high-resolution mass spectrometry for the first comprehensive study on the biotransformation of HT2 and T2 in oats. Using this approach, 16 HT2 and 17 T2 metabolites were annotated including novel glycosylated and hydroxylated forms of the toxins, hydrolysis products, and conjugates with acetic acid, putative malic acid, malonic acid, and ferulic acid. Further targeted quantitative analysis was performed to study toxin metabolism over time, as well as toxin and conjugate mobility within non-treated plant tissues. As a result, HT2-3-O-β-d-glucoside was identified as the major detoxification product of both parent toxins, which was rapidly formed (to an extent of 74% in HT2-treated and 48% in T2-treated oats within one day after treatment) and further metabolised. Mobility of the parent toxins appeared to be negligible, while HT2-3-O-β-d-glucoside was partly transported (up to approximately 4%) through panicle side branches and stem. Our findings demonstrate that the presented combination of untargeted and targeted analysis is well suited for the comprehensive elucidation of mycotoxin metabolism in plants. PMID:27929394

Preoperative preparation of «loss of domain» hernia. Progressive pneumoperitoneum and botulinum toxin type A.

PubMed

Bueno-Lledó, José; Torregrosa Gallud, Antonio; Jiménez Rosellón, Raquel; Carbonell Tatay, Fernando; García Pastor, Providencia; Bonafé Diana, Santiago; Iserte Hernández, José

2017-05-01

Preoperative progressive pneumoperitoneum and botulinum toxin type A are useful tools in the preparation of patients with loss of domain hernias. Both procedures are complementary in the surgical repair, especially with the use of prosthetic techniques without tension, that allow a integral management of these patients. The aim of this paper is to update concepts related to both procedures, emphasizing the advantages that take place in the preoperative management of loss of domain hernias. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of a quali embryo model for the detection of botulism toxin type A activity

USDA-ARS?s Scientific Manuscript database

The Japanese quail embryo (Coturnix japonica) was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving ...

Imaging surface plasmon resonance detection for T-2 toxin in wheat

USDA-ARS?s Scientific Manuscript database

T-2 toxin is a trichothecene (Type A) mycotoxin harmful to humans and animals. It is produced by mainly Fusarium species, particularly F. sporotrichoides. Fusarium species often contaminate grains such as corn, wheat, barley, oats, rice and rye. T-2 toxin contamination in grains has been observed mo...

Clostridium perfringens Epsilon Toxin: A Malevolent Molecule for Animals and Man?

PubMed Central

Stiles, Bradley G.; Barth, Gillian; Barth, Holger; Popoff, Michel R.

2013-01-01

Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein produced by Clostridium perfringens (types B and D) that induces fatal enteric disease of goats, sheep and cattle. Epsilon toxin (Etx) belongs to the aerolysin-like toxin family. It contains three distinct domains, is proteolytically-activated and forms oligomeric pores on cell surfaces via a lipid raft-associated protein(s). Vaccination controls Etx-induced disease in the field. However, therapeutic measures are currently lacking. This review initially introduces C. perfringens toxins, subsequently focusing upon the Etx and its biochemistry, disease characteristics in various animals that include laboratory models (in vitro and in vivo), and finally control mechanisms (vaccines and therapeutics). PMID:24284826

Identification of the cellular receptor for anthrax toxin

NASA Astrophysics Data System (ADS)

Bradley, Kenneth A.; Mogridge, Jeremy; Mourez, Michael; Collier, R. John; Young, John A. T.

2001-11-01

The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

Structure and Orientation of a Voltage-Sensor Toxin in Lipid Membranes

PubMed Central

Jung, Hyun Ho; Jung, Hoi Jong; Milescu, Mirela; Lee, Chul Won; Lee, Seungkyu; Lee, Ju Yeon; Eu, Young-Jae; Kim, Ha Hyung; Swartz, Kenton J.; Kim, Jae Il

2010-01-01

Abstract Amphipathic protein toxins from tarantula venom inhibit voltage-activated potassium (Kv) channels by binding to a critical helix-turn-helix motif termed the voltage sensor paddle. Although these toxins partition into membranes to bind the paddle motif, their structure and orientation within the membrane are unknown. We investigated the interaction of a tarantula toxin named SGTx with membranes using both fluorescence and NMR spectroscopy. Depth-dependent fluorescence-quenching experiments with brominated lipids suggest that Trp30 in SGTx is positioned ∼9 Å from the center of the bilayer. NMR spectra reveal that the inhibitor cystine knot structure of the toxin does not radically change upon membrane partitioning. Transferred cross-saturation NMR experiments indicate that the toxin's hydrophobic protrusion contacts the hydrophobic core of the membrane, whereas most surrounding polar residues remain at interfacial regions of the bilayer. The inferred orientation of the toxin reveals a twofold symmetry in the arrangement of basic and hydrophobic residues, a feature that is conserved among tarantula toxins. These results have important implications for regions of the toxin involved in recognizing membranes and voltage-sensor paddles, and for the mechanisms by which tarantula toxins alter the activity of different types of ion channels. PMID:20643084

Exfoliation of the tungsten fibreform nanostructure by unipolar arcing in the LHD divertor plasma

NASA Astrophysics Data System (ADS)

Tokitani, M.; Kajita, S.; Masuzaki, S.; Hirahata, Y.; Ohno, N.; Tanabe, T.; LHD Experiment Group

2011-10-01

The tungsten nanostructure (W-fuzz) created in the linear divertor simulator (NAGDIS) was exposed to the Large Helical Device (LHD) divertor plasma for only 2 s (1 shot) to study exfoliation/erosion and microscopic modifications due to the high heat/particle loading under high magnetic field conditions. Very fine and randomly moved unipolar arc trails were clearly observed on about half of the W-fuzz area (6 × 10 mm2). The fuzzy surface was exfoliated by continuously moving arc spots even for the very short exposure time. This is the first observation of unipolar arcing and exfoliation of some areas of the W-fuzz structure itself in a large plasma confinement device with a high magnetic field. The typical width and depth of each arc trail were about 8 µm and 1 µm, respectively, and the arc spots moved randomly on the micrometre scale. The fractality of the arc trails was analysed using a box-counting method, and the fractal dimension (D) of the arc trails was estimated to be D ≈ 1.922. This value indicated that the arc spots moved in Brownian motion, and were scarcely influenced by the magnetic field. One should note that such a large scale exfoliation due to unipolar arcing may enhance the surface erosion of the tungsten armour and act as a serious impurity source for fusion plasmas.

Cellular vacuolation induced by Clostridium perfringens epsilon-toxin.

PubMed

Nagahama, Masahiro; Itohayashi, Yukari; Hara, Hideki; Higashihara, Masahiro; Fukatani, Yusuke; Takagishi, Teruhisa; Oda, Masataka; Kobayashi, Keiko; Nakagawa, Ichiro; Sakurai, Jun

2011-09-01

The epsilon-toxin of Clostridium perfringens forms a heptamer in the membranes of Madin-Darby canine kidney cells, leading to cell death. Here, we report that it caused the vacuolation of Madin-Darby canine kidney cells. The toxin induced vacuolation in a dose-dependent and time-dependent manner. The monomer of the toxin formed oligomers on lipid rafts in membranes of the cells. Methyl-β-cyclodextrin and poly(ethylene glycol) 4000 inhibited the vacuolation. Epsilon-toxin was internalized into the cells. Confocal microscopy revealed that the internalized toxin was transported from early endosomes (early endosome antigen 1 staining) to late endosomes and lysosomes (lysosomal-associated membrane protein 2 staining) and then distributed to the membranes of vacuoles. Furthermore, the vacuolation was inhibited by bafilomycin A1, a V-type ATPase inhibitor, and colchicine and nocodazole, microtubule-depolymerizing agents. The early endosomal marker green fluorescent protein-Rab5 and early endosome antigen 1 did not localize to vacuolar membranes. In contrast, the vacuolar membranes were specifically stained by the late endosomal and lysosomal marker green fluorescent protein-Rab7 and lysosomal-associated membrane protein 2. The vacuoles in the toxin-treated cells were stained with LysoTracker Red DND-99, a marker for late endosomes and lysosomes. A dominant negative mutant of Rab7 prevented the vacuolization, whereas a mutant form of Rab5 was less effective. These results demonstrate, for the first time, that: (a) oligomers of epsilon-toxin formed in lipid rafts are endocytosed; and (b) the vacuoles originating from late endosomes and lysosomes are formed by an oligomer of epsilon-toxin. © 2011 The Authors Journal compilation © 2011 FEBS.

One-pot exfoliation, functionalization, and size manipulation of graphene sheets: efficient system for biomedical applications.

PubMed

Bani, Farhad; Bodaghi, Ali; Dadkhah, Abbas; Movahedi, Soodabeh; Bodaghabadi, Narges; Sadeghizadeh, Majid; Adeli, Mohsen

2018-05-01

In this work, we reported a facile method to produce stable aqueous graphene dispersion through direct exfoliation of graphite by modified hyperbranched polyglycerol. Size of graphene sheets was manipulated by simultaneous exfoliation and sonication of graphite, and functionalized graphene sheets with narrow size distribution were obtained. The polyglycerol-functionalized graphene sheets exhibited highly efficient cellular uptake and photothermal conversion, enabling it to serve as a photothermal agent for cancer therapy.

Applications of the oral scraped (exfoliative) cytology in oral cancer and precancer.

PubMed

Acha, Amelia; Ruesga, María T; Rodríguez, María J; Martínez de Pancorbo, María A; Aguirre, José M

2005-01-01

Scraped (exfoliative) cytology is a simple and harmless procedure, which has been a controversial technique according to its real validity in oral pathology. Lately it has re-emerged due to its application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. New diagnostic techniques have been developed, such as "brush biopsy" and multiple molecular studies using the cells collected. In this review we are going to analyse the more novel aspects related with the applications of the scraped or exfoliative cytology in oral precancerous and cancerous pathology, specially focusing on molecular studies and their diagnostic and prognostic implications.

Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye.

PubMed

Serna-Ojeda, Juan Carlos; Nava-Castaneda, Angel

2017-03-01

To evaluate the efficacy of botulinum toxin type A injection to cause orbicularis eyelid muscle paralysis to improve dry eye signs and symptoms. A prospective, randomized, comparative eye-to-eye and interventional study was performed. Patients with dry eye symptoms and positive fluorescein corneal staining were included. Randomly one eyelid received a subcutaneous injection of botulinum toxin in the medial orbicularis muscle portion of the lower eyelid, and the other eye received placebo. The subjective evaluation was achieved with a questionnaire assessing symptoms, quality of vision and ocular comfort level. The objective evaluation included the measurement of the tear film break-up time (TBUT), Schirmer's test and corneal and conjunctival staining. Twenty patients were included with a mean age of 59.5 years. Two weeks after the botulinum toxin injection, all patients showed a decrease in the horizontal movement of the lower eyelid when blinking. The eyes in the active treatment group showed better scores compared with the sham group in four symptoms 4 weeks after the treatment. The TBUT was higher at 1 and 3 months in the active treatment group. The corneal and conjunctival staining were significantly lower in the active treatment group at 1 and 3 months, and the Schirmer's test showed better measurements in the same group at 2 weeks, 1 month and 3 months. There were no adverse events reported. The injection of botulinum toxin A in the medial part of the lower eyelid is an effective and safe procedure that temporally improves some of the signs and symptoms of patients with dry eye. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

USDA-ARS?s Scientific Manuscript database

The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

PubMed

Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

2013-01-01

Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

Stabilization of antioxidant gallate in layered double hydroxide by exfoliation and reassembling reaction

NASA Astrophysics Data System (ADS)

Ansy, Kanakappan Mickel; Lee, Ji-Hee; Piao, Huiyan; Choi, Goeun; Choy, Jin-Ho

2018-06-01

As for the stabilization of chemically sensitive bioactive molecule in this study, gallic acid (GA) with antioxidant property was intercalated into interlayer space of layered double hydroxide (LDH), which was realized by exfoliation and reassembling reaction. At first, the pristine nitrate-type Zn2Al-LDH in solid state was synthesized via co-precipitation followed by the hydrothermal treatment at 80 °C for 6 h, and then exfoliated in formamide to form a colloidal solution of exfoliated LDH nanosheets, and finally reassembled in the presence of GA to prepare GA intercalated LDH (GA-LDH) desired, where the pH was adjusted to 8.0 in order to deprotonate GA to form gallate anion. According to the XRD analysis, GA-LDH showed well-developed (00l) diffraction peaks with a basal spacing of 1.15 nm, which was estimated to be larger than that of the pristine LDH (0.88 nm), indicating that gallate molecules were incorporated into LDH layers with perpendicular orientation. From the FT-IR spectra it was found that gallic acid was completely deprotonated into gallate, and stabilized in between LDH lattices via electrostatic interaction. The content of GA in GA-LDH was determined to be around 23 wt% by UV-vis spectroscopic study, which was also confirmed by HPLC analysis. According to the in-vitro release of GA out of GA-LDH in PBS solution (pH 7.4) at 4 °C, GA was sustainably released from GA-LDH nanohybrid up to 86% within 72 h. The antioxidant property of GA-LDH was almost the same with that of intact GA which was examined by DPPH. The photostability of GA-LDH under UV light irradiation was immensely enhanced compared to intact GA. It is, therefore, concluded that the present GA-LDH nanohybrid can be considered as an excellent antioxidant material with high chemical- and photo-stabilities, and controlled release property.

Strongly luminescent monolayered MoS2 prepared by effective ultrasound exfoliation.

PubMed

Štengl, Václav; Henych, Jiří

2013-04-21

Intense ultrasound in a pressurized batch reactor was used for preparation of monolayered MoS2 nanosheets from natural mineral molybdenite. Exfoliation of bulk MoS2 using ultrasound is an attractive route to large-scale preparation of monolayered crystals. To evaluate the quality of delamination, methods like X-ray diffraction, Raman spectroscopy and microscopic techniques (TEM and AFM) were employed. From single- or few-layered products obtained from intense sonication, MoS2 quantum dots (MoSQDs) were prepared by a one-pot reaction by refluxing exfoliated nanosheets of MoS2 in ethylene glycol under atmospheric pressure. The synthesised MoSQDs were characterised by photoluminescence spectroscopy and laser-scattering particle size analysis. Our easy preparation leads to very strongly green luminescing quantum dots.

Toxin yet not toxic: Botulinum toxin in dentistry.

PubMed

Archana, M S

2016-04-01

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

Trapping toxins within lipid droplets is a resistance mechanism in fungi

PubMed Central

Chang, Wenqiang; Zhang, Ming; Zheng, Sha; Li, Ying; Li, Xiaobin; Li, Wei; Li, Gang; Lin, Zhaomin; Xie, Zhiyu; Zhao, Zuntian; Lou, Hongxiang

2015-01-01

Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. However, the role of LDs in resistance to toxins in fungi remains largely unknown. Here, we show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. We found that an endolichenic fungus that generates phototoxic perylenequinones (PQs) trapped the PQs inside LDs. Using a model that incorporates the fungicidal action of hypocrellin A (HA), a PQ derivative, we showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery. PMID:26463663

Exfoliation of graphene with an industrial dye: teaching an old dog new tricks

NASA Astrophysics Data System (ADS)

Schlierf, Andrea; Cha, Kitty; Schwab, Matthias Georg; Samorı, Paolo; Palermo, Vincenzo

2014-12-01

We describe the exfoliation, processing and inclusion in polymer composites of few-layers graphene nanoplatelets (GNPs) by using the molecule indanthrone blue sulphonic acid sodium salt (IBS), a very common industrial dyestuff and intermediate for liquid crystal preparation. We show how IBS can be used to successfully exfoliate graphite into few-layers graphene yielding highly stable dispersions in water. To demonstrate that the method is suitable for applications in composites, these graphene-organic hybrids are processed into a commercial commodity polymer (polyvinyl alcohol, PVA), enhancing its electrical bulk conductivity by ten orders of magnitude by adding as few as 3% of GNP. We attribute the good performance of IBS in dispersing GNPs in water to its amphiphilic nature and the tendency to self-assemble through π-π interaction of its large aromatic core with the graphene surface. The molecule studied here, unlike many specialty organic surfactants or solvents commonly known to exfoliate graphene, is already used as a blue pigment dispersant additive in the industrial production of polymers and thus does not need to be removed from the final product.

Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin.

PubMed

Popoff, M R; Boquet, P

1988-05-16

We have purified from Clostridium spiroforme strain 246 an heterogeneous population of proteins (Sa) ranging from 43 to 47 kilodaltons exhibiting ADP-ribosyl transferase activity as do C. botulinum C2 toxin component I or the ia chain of C. perfringens E iota toxin. C. spiriforme Sa had alone no activity upon injection in mice or inoculated to Vero cells. When spiroforme ADP ribosyl transferase were mixed with a trypsin activated protein (Sb) separated from C. spiroforme bacterial supernatant, a lethal effect in mice and cytotoxicity on Vero cells were recorded. The Sa cross-reacted immunologically with either the light chain of C. perfringens E iota toxin or the ADP-ribosyl transferase from C. difficile 196 strain. No immunological relatedness was observed between Sa and C2 toxin component I. C. spiroforme toxin is thus another binary toxin close to iota.

Comparison of clinical marking and ultrasound-guided injection of Botulinum type A toxin into the masseter muscles for treating bruxism and its cosmetic effects.

PubMed

Quezada-Gaon, Natacha; Wortsman, Ximena; Peñaloza, Osvaldo; Carrasco, Juan Eduardo

2016-09-01

Botulinum toxin type A has been used for treating the hypertrophy of the masseter muscles and its cosmetic effects. Ultrasound is increasingly used in dermatology, along with the guidance of mini-invasive procedures. To evaluate the role of ultrasound for guiding the application of Botulinum A toxin in patients with cosmetic alterations due to bruxism, correlate the clinical landmarks with the ultrasound findings, and study the effect on the symptoms, cosmetics, and quality of life. Twenty individuals with bruxism and cosmetic alterations underwent an ultrasound-guided injection of Botulinum toxin type A in each masseter muscle. Clinical and ultrasound marking of the procedure was compared. Clinical and sonographic evaluation was performed at the time of injection and 3 months later. Ten normal individuals underwent ultrasound of the masseter muscles as a control group. Up to 65% of individuals showed anatomical variants of the salivary glands. The method for clinically marking the skin showed a frequently erroneous location of the anterior point (up to 40% of cases) that was proven by ultrasound to be out of the muscle. In 20% of cases, ultrasound showed that the needle should be longer to enter the muscle. After injection, most of the patients demonstrated a decrease of the symptoms and cosmetic and quality of life improvements. Ultrasound can be a potent tool for guiding the injection of Botulinum toxin into the masseter muscles. It may contribute to a more personalized procedure, better cosmetic results, and help to avoid potential complications. © 2016 Wiley Periodicals, Inc.

Atom-Thin SnS2-xSex with Adjustable Compositions by Direct Liquid Exfoliation from Single Crystals.

PubMed

Yang, Zhanhai; Liang, Hui; Wang, Xusheng; Ma, Xinlei; Zhang, Tao; Yang, Yanlian; Xie, Liming; Chen, Dong; Long, Yujia; Chen, Jitao; Chang, Yunjie; Yan, Chunhua; Zhang, Xinxiang; Zhang, Xueji; Ge, Binghui; Ren, Zhian; Xue, Mianqi; Chen, Genfu

2016-01-26

Two-dimensional (2D) chalcogenide materials are fundamentally and technologically fascinating for their suitable band gap energy and carrier type relevant to their adjustable composition, structure, and dimensionality. Here, we demonstrate the exfoliation of single-crystal SnS2-xSex (SSS) with S/Se vacancies into an atom-thin layer by simple sonication in ethanol without additive. The introduction of vacancies at the S/Se site, the conflicting atomic radius of sulfur in selenium layers, and easy incorporation with an ethanol molecule lead to high ion accessibility; therefore, atom-thin SSS flakes can be effectively prepared by exfoliating the single crystal via sonication. The in situ pyrolysis of such materials can further adjust their compositions, representing tunable activation energy, band gap, and also tunable response to analytes of such materials. As the most basic and crucial step of the 2D material field, the successful synthesis of an uncontaminated and atom-thin sample will further push ahead the large-scale applications of 2D materials, including, but not limited to, electronics, sensing, catalysis, and energy storage fields.

Stable aqueous dispersions of functionalized multi-layer graphene by pulsed underwater plasma exfoliation of graphite

NASA Astrophysics Data System (ADS)

Meyer-Plath, Asmus; Beckert, Fabian; Tölle, Folke J.; Sturm, Heinz; Mülhaupt, Rolf

2016-02-01

A process was developed for graphite particle exfoliation in water to stably dispersed multi-layer graphene. It uses electrohydraulic shockwaves and the functionalizing effect of solution plasma discharges in water. The discharges were excited by 100 ns high voltage pulsing of graphite particle chains that bridge an electrode gap. The underwater discharges allow simultaneous exfoliation and chemical functionalization of graphite particles to partially oxidized multi-layer graphene. Exfoliation is caused by shockwaves that result from rapid evaporation of carbon and water to plasma-excited gas species. Depending on discharge energy and locus of ignition, the shockwaves cause stirring, erosion, exfoliation and/or expansion of graphite flakes. The process was optimized to produce long-term stable aqueous dispersions of multi-layer graphene from graphite in a single process step without requiring addition of intercalants, surfactants, binders or special solvents. A setup was developed that allows continuous production of aqueous dispersions of flake size-selected multi-layer graphenes. Due to the well-preserved sp2-carbon structure, thin films made from the dispersed graphene exhibited high electrical conductivity. Underwater plasma discharge processing exhibits high innovation potential for morphological and chemical modifications of carbonaceous materials and surfaces, especially for the generation of stable dispersions of two-dimensional, layered materials.

Binding of epsilon-toxin from Clostridium perfringens in the nervous system.

PubMed

Dorca-Arévalo, Jonatan; Soler-Jover, Alex; Gibert, Maryse; Popoff, Michel R; Martín-Satué, Mireia; Blasi, Juan

2008-09-18

Epsilon-toxin (epsilon-toxin), produced by Clostridium perfringens type D, is the main agent responsible for enterotoxaemia in livestock. Neurological disorders are a characteristic of the onset of toxin poisoning. Epsilon-Toxin accumulates specifically in the central nervous system, where it produces a glutamatergic-mediated excitotoxic effect. However, no detailed study of putative binding structures in the nervous tissue has been carried out to date. Here we attempt to identify specific acceptor moieties and cell targets for epsilon-toxin, not only in the mouse nervous system but also in the brains of sheep and cattle. An epsilon-toxin-GFP fusion protein was produced and used to incubate brain sections, which were then analyzed by confocal microscopy. The results clearly show specific binding of epsilon-toxin to myelin structures. epsilon-Prototoxin-GFP and epsilon-toxin-GFP, the inactive and active forms of the toxin, respectively, showed identical results. By means of pronase E treatment, we found that the binding was mainly associated to a protein component of the myelin. Myelinated peripheral nerve fibres were also stained by epsilon-toxin. Moreover, the binding to myelin was not only restricted to rodents, but was also found in humans, sheep and cattle. Curiously, in the brains of both sheep and cattle, the toxin strongly stained the vascular endothelium, a result that may explain the differences in potency and effect between species. Although the binding of epsilon-toxin to myelin does not directly explain its neurotoxic effect, this feature opens up a new line of enquiry into its mechanism of toxicity and establishes the usefulness of this toxin for the study of the mammalian nervous system.

Nosocomial outbreak of staphyloccocal scalded skin syndrome in neonates in England, December 2012 to March 2013.

PubMed

Paranthaman, K; Bentley, A; Milne, L M; Kearns, A; Loader, S; Thomas, A; Thompson, F; Logan, M; Newitt, S; Puleston, R

2014-08-21

Staphylococcal scalded skin syndrome (SSSS) is a blistering skin condition caused by exfoliative toxin-producing strains of Staphylococcus aureus. Outbreaks of SSSS in maternity settings are rarely reported. We describe an outbreak of SSSS that occurred among neonates born at a maternity unit in England during December 2012 to March 2013. Detailed epidemiological and microbiological investigations were undertaken. Eight neonates were found to be infected with the outbreak strain of S. aureus, of spa type t346, representing a single pulsotype. All eight isolates contained genes encoding exfoliative toxin A (eta) and six of them contained genes encoding toxin B (etb). Nasal swabs taken during targeted staff screening yielded a staphylococcal carriage rate of 21% (17/80), but none contained the outbreak strain. Mass screening involving multi-site swabbing and pooled, enrichment culture identified a healthcare worker (HCW) with the outbreak strain. This HCW was known to have a chronic skin condition and their initial nasal screen was negative. The outbreak ended when they were excluded from work. This outbreak highlights the need for implementing robust swabbing and culture methodswhen conventional techniques are unsuccessful in identifying staff carrier(s). This study adds to the growing body of evidence on the role of HCWs in nosocomial transmission of S. aureus.

Millipede toxin

MedlinePlus

... The toxin that millipedes release keeps away most predators. Some large millipede species can spray these toxins ... Your local poison control center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from ...

Soft exfoliation of 2D SnO with size-dependent optical properties

NASA Astrophysics Data System (ADS)

Singh, Mandeep; Della Gaspera, Enrico; Ahmed, Taimur; Walia, Sumeet; Ramanathan, Rajesh; van Embden, Joel; Mayes, Edwin; Bansal, Vipul

2017-06-01

Two-dimensional (2D) materials have recently gained unprecedented attention as potential candidates for next-generation (opto)electronic devices due to their fascinating optical and electrical properties. Tin monoxide, SnO, is an important p-type semiconductor with applications across photocatalysis (water splitting) and electronics (transistors). However, despite its potential in several important technological applications, SnO remains underexplored in its 2D form. Here we present a soft exfoliation strategy to produce 2D SnO nanosheets with tunable optical and electrical properties. Our approach involves the initial synthesis of layered SnO microspheres, which are readily exfoliated through a low-power sonication step to form high quality SnO nanosheets. We demonstrate that the properties of 2D SnO are strongly dependent on its dimensions. As verified through optical absorption and photoluminescence studies, a strong size-dependent quantum confinement effect in 2D SnO leads to substantial variation in its optical and electrical properties. This results in a remarkable (>1 eV) band gap widening in atomically thin SnO. Through photoconductivity measurements, we further validate a strong correlation between the quantum-confined properties of 2D SnO and the selective photoresponse of atomically thin sheets in the high energy UV light. Such tunable semiconducting properties of 2D SnO could be exploited for a variety of applications including photocatalysis, photovoltaics and optoelectronics in general.

Treatment of anismus in intractable constipation with botulinum A toxin.

PubMed

Hallan, R I; Williams, N S; Melling, J; Waldron, D J; Womack, N R; Morrison, J F

1988-09-24

In seven patients with anismus the striated sphincter muscle complex was selectively weakened by local injection of Clostridium botulinum type A toxin. Symptom scores improved significantly and correlated with a significant reduction in the maximum voluntary and canal squeeze pressure and a significant increase in the anorectal angle on straining. Botulinum A toxin seems to be promising treatment for some patients with anismus.

Effect of Fill Temperature on Clostridium botulinum Type A Toxin Activity during the Hot Filling of Juice Bottles.

PubMed

Skinner, Guy E; Fleischman, Gregory J; Balster, Fran; Reineke, Karl; Reddy, N Rukma; Larkin, John W

2015-08-01

The potential threat of terrorist attacks against the United States food supply using neurotoxin produced by Clostridium botulinum (BoNT) has resulted in the need for studying the effect of various food process operations on the bioavailability of this toxin. The objective of this study was to evaluate C. botulinum type A neurotoxin bioavailability after a simulated hot fill juice bottling operation. C. botulinum type A acid mud toxin (∼10(6) mouse lethal dose [MLD50]/ml) was deposited into juice bottles at an experimentally determined fastest cooling spot. Bottles (12 or 20 oz [355 and 592 ml]) were filled with either apple juice or an orange drink, at 80 or 85°C, in either upright or inverted orientations. Toxicity of the juice was evaluated as a function of holding time (1 to 2 min) by the mouse bioassay. The fastest cooling point in the upright orientation was determined to be at a bottle's bottom rim. In the inverted orientation, the fastest cooling point was in the bottle cap region. With respect to these two points, the upright bottle cooled faster than the inverted bottle, which was reflected in a higher inactivation of BoNT in the latter. For the orange drink (pH 2.9) toxicity was reduced by 0.5 × 10(6) MLD50/ml to a nondetectable level after 1 min in all bottle sizes, orientations, and temperatures as measured by the mouse bioassay. This indicates that there was at least a 0.5 × 10(6) MLD50/ml reduction in activity. Inactivation in apple juice (pH 4.0), to the same degree as in the orange drink, was found only for the inverted orientation at 85°C. Complete inactivation in apple juice for all conditions was found at a lower added toxin level of 0.25 × 10(5) MLD50/ml. In general, bottle inversion and filling at 85°C provided complete inactivation of BoNT to the 0.5 × 10(6) MLD50/ml level. All experiments resulted in the inactivation of 2.5 × 10(4) MLD50/ml of BoNT regardless of juice type, fill temperature, or bottle orientation and size.

Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli.

PubMed Central

Perelle, S; Gibert, M; Boquet, P; Popoff, M R

1993-01-01

The iota toxin which is produced by Clostridium perfringens type E, is a binary toxin consisting of two independent polypeptides: Ia, which is an ADP-ribosyltransferase, and Ib, which is involved in the binding and internalization of the toxin into the cell. Two degenerate oligonucleotide probes deduced from partial amino acid sequence of each component of C. spiroforme toxin, which is closely related to the iota toxin, were used to clone three overlapping DNA fragments containing the iota-toxin genes from C. perfringens type E plasmid DNA. Two genes, in the same orientation, coding for Ia (387 amino acids) and Ib (875 amino acids) and separated by 243 noncoding nucleotides were identified. A predicted signal peptide was found for each component, and the secreted Ib displays two domains, the propeptide (172 amino acids) and the mature protein (664 amino acids). The Ia gene has been expressed in Escherichia coli and C. perfringens, under the control of its own promoter. The recombinant polypeptide obtained was recognized by Ia antibodies and ADP-ribosylated actin. The expression of the Ib gene was obtained in E. coli harboring a recombinant plasmid encompassing the putative promoter upstream of the Ia gene and the Ia and Ib genes. Two residues which have been found to be involved in the NAD+ binding site of diphtheria and pseudomonas toxins are conserved in the predicted Ia sequence (Glu-14 and Trp-19). The predicted amino acid Ib sequence shows 33.9% identity with and 54.4% similarity to the protective antigen of the anthrax toxin complex. In particular, the central region of Ib, which contains a predicted transmembrane segment (Leu-292 to Ser-308), presents 45% identity with the corresponding protective antigen sequence which is involved in the translocation of the toxin across the cell membrane. Images PMID:8225592

Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli.

PubMed

Perelle, S; Gibert, M; Boquet, P; Popoff, M R

1993-12-01

The iota toxin which is produced by Clostridium perfringens type E, is a binary toxin consisting of two independent polypeptides: Ia, which is an ADP-ribosyltransferase, and Ib, which is involved in the binding and internalization of the toxin into the cell. Two degenerate oligonucleotide probes deduced from partial amino acid sequence of each component of C. spiroforme toxin, which is closely related to the iota toxin, were used to clone three overlapping DNA fragments containing the iota-toxin genes from C. perfringens type E plasmid DNA. Two genes, in the same orientation, coding for Ia (387 amino acids) and Ib (875 amino acids) and separated by 243 noncoding nucleotides were identified. A predicted signal peptide was found for each component, and the secreted Ib displays two domains, the propeptide (172 amino acids) and the mature protein (664 amino acids). The Ia gene has been expressed in Escherichia coli and C. perfringens, under the control of its own promoter. The recombinant polypeptide obtained was recognized by Ia antibodies and ADP-ribosylated actin. The expression of the Ib gene was obtained in E. coli harboring a recombinant plasmid encompassing the putative promoter upstream of the Ia gene and the Ia and Ib genes. Two residues which have been found to be involved in the NAD+ binding site of diphtheria and pseudomonas toxins are conserved in the predicted Ia sequence (Glu-14 and Trp-19). The predicted amino acid Ib sequence shows 33.9% identity with and 54.4% similarity to the protective antigen of the anthrax toxin complex. In particular, the central region of Ib, which contains a predicted transmembrane segment (Leu-292 to Ser-308), presents 45% identity with the corresponding protective antigen sequence which is involved in the translocation of the toxin across the cell membrane.

Multilayer Black Phosphorus Exfoliated with the Aid of Sodium Hydroxide: An Improvement in Electrochemical Energy Storage

NASA Astrophysics Data System (ADS)

Liu, Wanying; Zhu, Yabo; Chen, Zhiyan; Lei, Jia; Feng, Peizhong

2018-05-01

We generated multilayer black phosphorus (MBP) as a precipitate in centrifugation under 3000 rpm for 25 min, preceded by liquid exfoliation, in which saturated sodium hydroxide (NaOH(s)) was added as an exfoliation auxiliary. The MBP exfoliated with NaOH(s) was characterized by scanning electron microscope, energy dispersive x-ray detector, x-ray diffraction, x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Its electrochemical performance was investigated by cyclic voltammetry, charge/discharge and electrochemical impedance spectroscopy. It was found that the appropriate amount of NaOH(s) can make MBP present a ladder-shaped structure or plackets on the layer edge, which may provide more active sites and channels for charge storage to improve its electrochemical performance. The specific capacitance of MBP samples exfoliated with appropriate amounts of NaOH(s) can quickly enter a relatively stable range of 110-90 F/g after the 75th cycle, and finally stabilize at about 90 F/g after thousands of cycles under the current density of 2 A/g, which demonstrates their good stability in the range of long charge/discharge cycles. MBP exhibits double-layer capacitance properties.

Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

PubMed

Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

2016-02-01

This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P < .001). These findings suggest that the combined use of botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria.

PubMed

Lee, Ki-Young; Lee, Bong-Jin

2016-10-22

Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

Determination of toxins involved in ciguatera fish poisoning in the Pacific by LC/MS.

PubMed

Yogi, Kentaro; Sakugawa, Satsuki; Oshiro, Naomasa; Ikehara, Tsuyoshi; Sugiyama, Kiminori; Yasumoto, Takeshi

2014-01-01

Ciguatera fish poisoning is the most extensive and difficult to control of the seafood poisonings. To facilitate monitoring of fish toxicity, toxin profiles were investigated by an LC/MS/MS method using 14 reference toxins on eight representative species of fish collected in four different areas of the Pacific. Snappers and groupers from Okinawa contained ciguatoxin-1B (CTX1B) and two deoxy congeners at variable but species-specific ratios, while red snapper, Lutjanus bohar, from Minamitorishima, and amberjack, Seriola dumerili, from Hawaii, contained both CTX1B-type and CTX3C-type toxins. Spotted knifejaw, Oplegnathus punctatus, from Okinawan waters, contained mainly CTX4A and CTX4B, but the same species caught at Miyazaki was contaminated primarily with the CTX3C-type toxins. Otherwise, the toxin profiles were consistently species-specific in fish collected from various locations around Okinawa over 20 years. The LC/MS/MS and mouse bioassay results agreed well, indicating the LC/MS/MS method is a promising alternative to the mouse bioassay. Pure CTX1B and CTX3C were prepared for use in future LC/MS/MS analysis.

Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

PubMed

Ochoa, Federico; Oltra, Gisela; Gerhardt, Elizabeth; Hermes, Ricardo; Cohen, Lilian; Damiano, Alicia E; Ibarra, Cristina; Lago, Nestor R; Zotta, Elsa

2012-01-01

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2%-4% of patients die during the acute phase, and one-third of the 96% who survive are at risk of chronic renal sequelae. Little information is available about the direct effect of Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. In this work, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 μg/kg body weight) to induce HUS. Functional, immunoblotting, and immunohistochemistry studies were carried out to determine alterations in slit diaphragm proteins and the proximal tubule endocytic system at 48 hours post-inoculation. We detected a significant increase in microalbuminuria, without changes in the proteinuria values compared to the control rats. In immunoperoxidase studies, the renal tubules and glomerular mesangium showed an increased expression of transforming growth factor β(1)(TGF-β(1)). The expression of megalin was decreased by immunoperoxidase and the cytoplasm showed a granular pattern of megalin expression by immunofluorescence techniques. Western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins. We suggest that the alterations in slit diaphragm proteins and megalin expression could be related to the development of microalbuminuria in response to lethal doses of Stx2.

Differential interaction of Escherichia coli heat-labile toxin and cholera toxin with pig intestinal brush border glycoproteins depending on their ABH and related blood group antigenic determinants.

PubMed

Balanzino, L E; Barra, J L; Monferran, C G; Cumar, F A

1994-04-01

The ability of glycoproteins from pig intestinal brush border membranes (BBM) to bind cholera toxin (CT) or heat-labile toxins from strains of Escherichia coli isolated from human (LTh) or pig (LTp) intestines was studied. Glycoproteins capable of binding the toxins are also recognized by antibodies or lectins specific for ABO(H) blood group and related antigens. Pigs expressing A, H, or I antigenic determinants were used for comparison. The toxin-binding capacity of a glycoprotein depends on the toxin type and the blood group epitope borne by the glycoprotein. LTh and LTp preferably bound to several blood group A-active glycoproteins rather than H-active glycoproteins. By contrast, CT practically did not recognize either blood group A- or blood group H-active glycoproteins, while glycoproteins from pigs expressing I antigenic determinants were able to interact with LTh, LTp, and CT. LTh, LTp, or CT glycoprotein binding was selectively inhibited by specific lectins or monosaccharides. Affinity purification of the toxin binding brush border glycoproteins on the basis of their blood group reactivity suggests that such glycoproteins are hydrolytic enzymes. BBM from A+ pigs contain about 27 times more LTh binding sites, in addition to those recognized by CT, than an equivalent membrane preparation from H+ pigs. The present findings may help clarify some previous unclear results on LTh binding to intestinal BBM glycoproteins obtained by use of animals not typed by their ABO(H) blood group phenotype.

The synergistic necrohemorrhagic action of Clostridium perfringens perfringolysin and alpha toxin in the bovine intestine and against bovine endothelial cells

PubMed Central

2013-01-01

Bovine necrohemorrhagic enteritis is a major cause of mortality in veal calves. Clostridium perfringens is considered as the causative agent, but there has been controversy on the toxins responsible for the disease. Recently, it has been demonstrated that a variety of C. perfringens type A strains can induce necrohemorrhagic lesions in a calf intestinal loop assay. These results put forward alpha toxin and perfringolysin as potential causative toxins, since both are produced by all C. perfringens type A strains. The importance of perfringolysin in the pathogenesis of bovine necrohemorrhagic enteritis has not been studied before. Therefore, the objective of the current study was to evaluate the role of perfringolysin in the development of necrohemorrhagic enteritis lesions in calves and its synergism with alpha toxin. A perfringolysin-deficient mutant, an alpha toxin-deficient mutant and a perfringolysin alpha toxin double mutant were less able to induce necrosis in a calf intestinal loop assay as compared to the wild-type strain. Only complementation with both toxins could restore the activity to that of the wild-type. In addition, perfringolysin and alpha toxin had a synergistic cytotoxic effect on bovine endothelial cells. This endothelial cell damage potentially explains why capillary hemorrhages are an initial step in the development of bovine necrohemorrhagic enteritis. Taken together, our results show that perfringolysin acts synergistically with alpha toxin in the development of necrohemorrhagic enteritis in a calf intestinal loop model and we hypothesize that both toxins act by targeting the endothelial cells. PMID:23782465

Electrolytic exfoliation of graphite in water with multifunctional electrolytes: en route towards high quality, oxide-free graphene flakes.

PubMed

Munuera, J M; Paredes, J I; Villar-Rodil, S; Ayán-Varela, M; Martínez-Alonso, A; Tascón, J M D

2016-02-07

Electrolytic--usually referred to as electrochemical--exfoliation of graphite in water under anodic potential holds enormous promise as a simple, green and high-yield method for the mass production of graphene, but currently suffers from several drawbacks that hinder its widespread adoption, one of the most critical being the oxidation and subsequent structural degradation of the carbon lattice that is usually associated with such a production process. To overcome this and other limitations, we introduce and implement the concept of multifunctional electrolytes. The latter are amphiphilic anions (mostly polyaromatic hydrocarbons appended with sulfonate groups) that play different relevant roles as (1) an intercalating electrolyte to trigger exfoliation of graphite into graphene flakes, (2) a dispersant to afford stable aqueous colloidal suspensions of the flakes suitable for further use, (3) a sacrificial agent to prevent graphene oxidation during exfoliation and (4) a linker to promote nanoparticle anchoring on the graphene flakes, yielding functional hybrids. The implementation of this strategy with some selected amphiphiles even furnishes anodically exfoliated graphenes of a quality similar to that of flakes produced by direct, ultrasound- or shear-induced exfoliation of graphite in the liquid phase (i.e., almost oxide- and defect-free). These high quality materials were used for the preparation of catalytically efficient graphene-Pt nanoparticle hybrids, as demonstrated by model reactions (reduction of nitroarenes). The multifunctional performance of these electrolytes is also discussed and rationalized, and a mechanistic picture of their oxidation-preventing ability is proposed. Overall, the present results open the prospect of anodic exfoliation as a competitive method for the production of very high quality graphene flakes.

Pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1985-01-01

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

A New Family of Secreted Toxins in Pathogenic Neisseria Species

PubMed Central

Jamet, Anne; Jousset, Agnès B.; Euphrasie, Daniel; Mukorako, Paulette; Boucharlat, Alix; Ducousso, Alexia; Charbit, Alain; Nassif, Xavier

2015-01-01

The genus Neisseria includes both commensal and pathogenic species which are genetically closely related. However, only meningococcus and gonococcus are important human pathogens. Very few toxins are known to be secreted by pathogenic Neisseria species. Recently, toxins secreted via type V secretion system and belonging to the widespread family of contact-dependent inhibition (CDI) toxins have been described in numerous species including meningococcus. In this study, we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We demonstrated that mafB genes encode secreted polymorphic toxins and that genes immediately downstream of mafB encode a specific immunity protein (MafI). We focused on a MafB toxin found in meningococcal strain NEM8013 and characterized its EndoU ribonuclease activity. maf genes represent 2% of the genome of pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus arguing for an important biological role. Indeed, we showed that overexpression of one of the four MafB toxins of strain NEM8013 provides an advantage in competition assays, suggesting a role of maf loci in niche adaptation. PMID:25569427

SNAKE VENOMICS OF Crotalus tigris: THE MINIMALIST TOXIN ARSENAL OF THE DEADLIEST NEARTIC RATTLESNAKE VENOM

PubMed Central

CALVETE, Juan J.; PÉREZ, Alicia; LOMONTE, Bruno; SÁNCHEZ, Elda E.; SANZ, Libia

2012-01-01

We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7–8 gene products from 6 toxin families: the presynaptic β-neurotoxic heterodimeric PLA2, Mojave toxin, and two serine proteinases comprise, respectively, 66% and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1–2 PIII-SVMPs, each represents 0.1–5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. catenatus catenatus, indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South American and North American Crotalus. PMID:22181673

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Won, JaeSeon; Nam, PilWon; Lee, YongChan

2009-04-24

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

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis.

PubMed

Cherubin, Patrick; Quiñones, Beatriz; Teter, Ken

2018-02-06

Ricin, Shiga toxin, exotoxin A, and diphtheria toxin are AB-type protein toxins that act within the host cytosol and kill the host cell through pathways involving the inhibition of protein synthesis. It is thought that a single molecule of cytosolic toxin is sufficient to kill the host cell. Intoxication is therefore viewed as an irreversible process. Using flow cytometry and a fluorescent reporter system to monitor protein synthesis, we show a single molecule of cytosolic toxin is not sufficient for complete inhibition of protein synthesis or cell death. Furthermore, cells can recover from intoxication: cells with a partial loss of protein synthesis will, upon removal of the toxin, increase the level of protein production and survive the toxin challenge. Thus, in contrast to the prevailing model, ongoing toxin delivery to the cytosol appears to be required for the death of cells exposed to sub-optimal toxin concentrations.

Rockfall triggering by cyclic thermal stressing of exfoliation fractures

USGS Publications Warehouse

Collins, Brian D.; Stock, Greg M.

2016-01-01

Exfoliation of rock deteriorates cliffs through the formation and subsequent opening of fractures, which in turn can lead to potentially hazardous rockfalls. Although a number of mechanisms are known to trigger rockfalls, many rockfalls occur during periods when likely triggers such as precipitation, seismic activity and freezing conditions are absent. It has been suggested that these enigmatic rockfalls may occur due to solar heating of rock surfaces, which can cause outward expansion. Here we use data from 3.5 years of field monitoring of an exfoliating granite cliff in Yosemite National Park in California, USA, to assess the magnitude and temporal pattern of thermally induced rock deformation. From a thermodynamic analysis, we find that daily, seasonal and annual temperature variations are sufficient to drive cyclic and cumulative opening of fractures. Application of fracture theory suggests that these changes can lead to further fracture propagation and the consequent detachment of rock. Our data indicate that the warmest times of the day and year are particularly conducive to triggering rockfalls, and that cyclic thermal forcing may enhance the efficacy of other, more typical rockfall triggers.

A retrospective study of a modified 1-minute formocresol pulpotomy technique part 2: effect on exfoliation times and successors.

PubMed

Kurji, Zahra A; Sigal, Michael J; Andrews, Paul; Titley, Keith

2011-01-01

The purposes of this study were to evaluate the: effect of a 1-minute application of full-strength Buckley's formocresol with concur- rent hemostasis using the medicated cotton pledget in human primary teeth on their successors; and exfoliation times compared to the contralateral nonpulpotomized tooth. Using a retrospective chart review, clinical and radiographic data were available for 557 primary molars in 320 patients. There was no difference between treated and control teeth in the number of enamel defects of succedaneous teeth (P<.45). Approximately 66% exfoliated at the same time as their contralateral counterpart and approximately 29% exfoliated earlier (P<.001). This 1-minute technique showed a tendency toward early exfoliation, but no effect on clinical management, and no increase in incidence of defects on succedaneous teeth was observed. The 1-minute full-strength formocresol technique may be considered an acceptable alternative to the 5-minute formocresol pulpotomy.

The resurgence of botulinum toxin injection for strabismus in children.

PubMed

Mahan, Marielle; Engel, J Mark

2017-09-01

The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.

Antibody-based bacterial toxin detection

NASA Astrophysics Data System (ADS)

Menking, Darrell E.; Heitz, Jonathon M.; Anis, Nabil A.; Thompson, Roy G.

1994-03-01

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

Toxin Plasmids of Clostridium perfringens

PubMed Central

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

2013-01-01

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

The Biology of Pichia membranifaciens Killer Toxins

PubMed Central

Belda, Ignacio; Ruiz, Javier; Alonso, Alejandro; Marquina, Domingo; Santos, Antonio

2017-01-01

The killer phenomenon is defined as the ability of some yeast to secrete toxins that are lethal to other sensitive yeasts and filamentous fungi. Since the discovery of strains of Saccharomyces cerevisiae capable of secreting killer toxins, much information has been gained regarding killer toxins and this fact has substantially contributed knowledge on fundamental aspects of cell biology and yeast genetics. The killer phenomenon has been studied in Pichia membranifaciens for several years, during which two toxins have been described. PMKT and PMKT2 are proteins of low molecular mass that bind to primary receptors located in the cell wall structure of sensitive yeast cells, linear (1→6)-β-d-glucans and mannoproteins for PMKT and PMKT2, respectively. Cwp2p also acts as a secondary receptor for PMKT. Killing of sensitive cells by PMKT is characterized by ionic movements across plasma membrane and an acidification of the intracellular pH triggering an activation of the High Osmolarity Glycerol (HOG) pathway. On the contrary, our investigations showed a mechanism of killing in which cells are arrested at an early S-phase by high concentrations of PMKT2. However, we concluded that induced mortality at low PMKT2 doses and also PMKT is indeed of an apoptotic nature. Killer yeasts and their toxins have found potential applications in several fields: in food and beverage production, as biocontrol agents, in yeast bio-typing, and as novel antimycotic agents. Accordingly, several applications have been found for P. membranifaciens killer toxins, ranging from pre- and post-harvest biocontrol of plant pathogens to applications during wine fermentation and ageing (inhibition of Botrytis cinerea, Brettanomyces bruxellensis, etc.). PMID:28333108

Comparison on exfoliated graphene nano-sheets and triturated graphite nano-particles for mode-locking the Erbium-doped fibre lasers

NASA Astrophysics Data System (ADS)

Yang, Chun-Yu; Lin, Yung-Hsiang; Wu, Chung-Lun; Cheng, Chih-Hsien; Tsai, Din-Ping; Lin, Gong-Ru

2018-06-01

Comparisons on exfoliated graphene nano-sheets and triturated graphite nano-particles for mode-locking the Erbium-doped fiber lasers (EDFLs) are performed. As opposed to the graphite nano-particles obtained by physically triturating the graphite foil, the tri-layer graphene nano-sheets is obtained by electrochemically exfoliating the graphite foil. To precisely control the size dispersion and the layer number of the exfoliated graphene nano-sheet, both the bias of electrochemical exfoliation and the speed of centrifugation are optimized. Under a threshold exfoliation bias of 3 volts and a centrifugation at 1000 rpm, graphene nano-sheets with an average diameter of 100  ±  40 nm can be obtained. The graphene nano-sheets with an area density of 15 #/µm2 are directly imprinted onto the end-face of a single-mode fiber made patchcord connector inside the EDFL cavity. Such electrochemically exfoliated graphene nano-sheets show comparable saturable absorption with standard single-graphene and perform the self-amplitude modulation better than physically triturated graphite nano-particles. The linear transmittance and modulation depth of the inserted graphene nano-sheets are 92.5% and 53%, respectively. Under the operation with a power gain of 21.5 dB, the EDFL can be passively mode-locked to deliver a pulsewidth of 454.5 fs with a spectral linewidth of 5.6 nm. The time-bandwidth product of 0.31 is close to the transform limit. The Kelly sideband frequency spacing of 1.34 THz is used to calculate the chirp coefficient as  ‑0.0015.

A cell-based fluorescent assay to detect the activity of AB toxins that inhibit protein synthesis

USDA-ARS?s Scientific Manuscript database

AB-type protein toxins, produced by numerous bacterial pathogens and some plants, elicit a cytotoxic effect involving the inhibition of protein synthesis. To develop an improved method to detect the inhibition of protein synthesis by AB-type toxins, the present study characterized a Vero cell line t...

The Profile of Patients and Current Practice of Treatment of Upper Limb Muscle Spasticity with Botulinum Toxin Type A: An International Survey

ERIC Educational Resources Information Center

Bakheit, Abdel Magid

2010-01-01

To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31…

The effect of the non-steroidal anti-inflammatory drug choline magnesium trisalicylate on gastric mucosal cell exfoliation.

PubMed Central

Mitchell, K G; Hearns, J; Crean, G P

1984-01-01

Gastric mucosal cell exfoliation was measured in 10 normal subjects taking choline magnesium trisalicylate (CMT), aspirin and placebo. Both drugs resulted in significantly elevated rates of exfoliation although the serum salicylate levels achieved with aspirin were lower than those achieved by CMT. Side-effects of tinnitus, nausea and increased faecal blood loss were more common while subjects were taking CMT. PMID:6691886

The effect of the non-steroidal anti-inflammatory drug choline magnesium trisalicylate on gastric mucosal cell exfoliation.

PubMed

Mitchell, K G; Hearns, J; Crean, G P

1984-01-01

Gastric mucosal cell exfoliation was measured in 10 normal subjects taking choline magnesium trisalicylate (CMT), aspirin and placebo. Both drugs resulted in significantly elevated rates of exfoliation although the serum salicylate levels achieved with aspirin were lower than those achieved by CMT. Side-effects of tinnitus, nausea and increased faecal blood loss were more common while subjects were taking CMT.

The primary and subunit structure of a novel type killer toxin produced by a halotolerant yeast, Pichia farinosa.

PubMed

Suzuki, C; Nikkuni, S

1994-01-28

A halotolerant yeast, Pichia farinosa KK1 strain, produces a unique killer toxin termed SMK toxin (salt-mediated killer toxin) which shows its maximum killer activity in the presence of 2 M NaCl. The toxin consists of two distinct subunits, alpha and beta, which are tightly linked without a disulfide bond under acidic conditions, even in the presence of 6 M urea. Under neutral conditions, however, the alpha subunit precipitates, resulting in the dissociation of the subunits and the loss of killer activity. The nucleotide sequence of the SMK1 gene predicts a 222 amino acid preprotoxin with a typical signal sequence, the hydrophobic alpha, an interstitial gamma polypeptide with a putative glycosylation site, and the hydrophilic beta. Amino acid sequence analyses of peptide fragments including the carboxyl-terminal peptides fragments including the carboxyl-terminal peptides from each subunit suggest that the alpha and beta subunits consist of amino acid residues 19-81 and 146-222 of the preprotoxin, respectively, and the molecular weight of the mature alpha beta dimer is 14,214. The KEX2-like endopeptidase and KEX1-like carboxypeptidase may be involved in the stepwise processing of the SMK preprotoxin. The maturation process and the functions of the SMK toxin are compared with the K1 toxin of Saccharomyces cerevisiae.

Black tea assisted exfoliation using a kitchen mixer allowing one-step production of graphene

NASA Astrophysics Data System (ADS)

Ismail, Zulhelmi; Farhana Abu Kassim, Nurul; Hannifa Abdullah, Abu; Sakinah Zainal Abidin, Anis; Sameha Ismail, Fadwa; Yusoh, Kamal

2017-07-01

A kitchen mixer is one of the possible tools for the exfoliation of graphene. While organic solvents such as NMP or DMF are suitable for the exfoliation of graphite, the majority are toxic and dangerously harmful when exposed to humans and the environment. Therefore, an alternative solvent must be proposed for green and sustainable production of graphene. In this initial work, we have developed a new synthesis method for graphene through the direct exfoliation of graphite in commercial black tea. We found that our maximum yield concentration of graphene is Y  =  0.032 mg ml-l after 15 min of mixing. From the data of Raman, the level of defects in our produced graphene is suggested as being very minor (I D/I G  =  0.17), despite possible graphene functionalization by oxygen groups in tea. Incorporation of our graphene into PMMA results in shifting the onset temperature from 300 °C to 326 °C, which impressively validates the potential of the produced graphene as a thermal reinforcement material for polymer composites.

Pluripotency of Stem Cells from Human Exfoliated Deciduous Teeth for Tissue Engineering

PubMed Central

Rosa, Vinicius; Dubey, Nileshkumar; Islam, Intekhab; Min, Kyung-San; Nör, Jacques E.

2016-01-01

Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative pluripotent cells that can be retrieved from primary teeth. Although SHED are isolated from the dental pulp, their differentiation potential is not limited to odontoblasts only. In fact, SHED can differentiate into several cell types including neurons, osteoblasts, adipocytes, and endothelial cells. The high plasticity makes SHED an interesting stem cell model for research in several biomedical areas. This review will discuss key findings about the characterization and differentiation of SHED into odontoblasts, neurons, and hormone secreting cells (e.g., hepatocytes and islet-like cell aggregates). The outcomes of the studies presented here support the multipotency of SHED and their potential to be used for tissue engineering-based therapies. PMID:27313627

Influence of laser wavelength on two-dimensional carbon nanosheet formation from laser-induced exfoliation of naphthalene

NASA Astrophysics Data System (ADS)

Qian, Min; Niu, Yue Ping; Gong, Shang Qing

2018-01-01

Pulsed Nd:YAG (532 nm) and Excimer (248 nm) lasers were employed to produce freestanding, two-dimensional (2D), carbon nanosheets (CNSs) from naphthalene, through laser-induced exfoliation. The polymer-to-carbon transition was investigated in terms of laser wavelengths, fluences, as well as target preparations. Continuous and porous CNSs of several nanometers in thickness and micrometers in size were obtained from 532 and 248 nm pulsed laser exfoliation of spin-coated naphthalene films, respectively. The porous morphology is ascribed to the photon-induced dissociation of chemical bonds dominated in 248 nm laser interaction with ablated naphthalene. With the increase of laser fluences from 1 to 5 J cm-2, amorphous carbon and ultrathin CNS structures were obtained in sequence. This work revealed a general mechanism of producing 2D structured carbon materials from pulsed laser exfoliation.

Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

PubMed

Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A

2008-05-01

The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

Sialidases affect the host cell adherence and epsilon toxin-induced cytotoxicity of Clostridium perfringens type D strain CN3718.

PubMed

Li, Jihong; Sayeed, Sameera; Robertson, Susan; Chen, Jianming; McClane, Bruce A

2011-12-01

Clostridium perfringens type B or D isolates, which cause enterotoxemias or enteritis in livestock, produce epsilon toxin (ETX). ETX is exceptionally potent, earning it a listing as a CDC class B select toxin. Most C. perfringens strains also express up to three different sialidases, although the possible contributions of those enzymes to type B or D pathogenesis remain unclear. Type D isolate CN3718 was found to carry two genes (nanI and nanJ) encoding secreted sialidases and one gene (nanH) encoding a cytoplasmic sialidase. Construction in CN3718 of single nanI, nanJ and nanH null mutants, as well as a nanI/nanJ double null mutant and a triple sialidase null mutant, identified NanI as the major secreted sialidase of this strain. Pretreating MDCK cells with NanI sialidase, or with culture supernatants of BMC206 (an isogenic CN3718 etx null mutant that still produces sialidases) enhanced the subsequent binding and cytotoxic effects of purified ETX. Complementation of BMC207 (an etx/nanH/nanI/nanJ null mutant) showed this effect is mainly attributable to NanI production. Contact between BMC206 and certain mammalian cells (e.g., enterocyte-like Caco-2 cells) resulted in more rapid sialidase production and this effect involved increased transcription of BMC206 nanI gene. BMC206 was shown to adhere to some (e.g. Caco-2 cells), but not all mammalian cells, and this effect was dependent upon sialidase, particularly NanI, expression. Finally, the sialidase activity of NanI (but not NanJ or NanH) could be enhanced by trypsin. Collectively these in vitro findings suggest that, during type D disease originating in the intestines, trypsin may activate NanI, which (in turn) could contribute to intestinal colonization by C. perfringens type D isolates and also increase ETX action.

Packaging material and flexible medical tubing containing thermally exfoliated graphite oxide

NASA Technical Reports Server (NTRS)

Prud'homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor)

2011-01-01

A packaging material or flexible medical tubing containing a modified graphite oxide material, which is a thermally exfoliated graphite oxide with a surface area of from about 300 m.sup.2/g to 2600 m.sup.2/g.

Luminescent monolayer MoS2 quantum dots produced by multi-exfoliation based on lithium intercalation

NASA Astrophysics Data System (ADS)

Qiao, Wen; Yan, Shiming; Song, Xueyin; Zhang, Xing; He, Xueming; Zhong, Wei; Du, Youwei

2015-12-01

An effective multi-exfoliation method based on lithium (Li) intercalation has been demonstrated for preparing monolayer molybdenum disulfide (MoS2) quantum dots (QDs). The cutting mechanism of MoS2 QDs may involve the complete breakup around the defects and edges during the reaction of LixMoS2 with water and its following ultrasonication process. The multiply exfoliation make the MoS2 fragile and easier to break up. After the third exfoliation, a large number of monolayer MoS2 QDs is formed. The as-prepared MoS2 QDs show photoluminescence (PL) inactive due to the existence of 1T phase. After heating treatment, the PL intensity excited at 300 nm is enhanced by five times. The MoS2 QDs solution has an excitation-dependent luminescence emission which shifts to longer wavelengths when the excitation wavelength changes from 280 nm to 370 nm. The optical properties are explored based on the quantum confinement and edge effect.

Effective NaBH4-exfoliated ultrathin multilayer Co(OH)2 nanosheets arrays and sulfidation for energy storage

NASA Astrophysics Data System (ADS)

Yang, Wanjun; Qu, Gan; Chen, Mingyue; Ma, Wenhao; Li, Wenhui; Tang, Yiwen

2018-07-01

Facile engineering ultrathin nano structural materials is still a huge challenge for material science. Thereinto, the strategy of exfoliating shows great advantages. In this work, we develop a convenient approach to exfoliate Co(OH)2 nanosheets into ultrathin Co(OH)2 nanoflakes through NaBH4-exfoliation method. Moreover, the microstructures of the Co(OH)2 nanosheets are conveniently controlled by varying the exfoliation time. As a result, the obtained ultrathin Co(OH)2-72 h nanosheets deliver the excellent electrochemical performance. In order to improve the energy storage properties, the obtained ultrathin Co(OH)2 nanosheets are further modified to enhance the conductivity via sulfidation. Consequently, the synthesized Co(OH)2-72 h/CoS2 composites exhibit a specific capacitance of 2536 F g‑1 at 1 A g‑1, which is more outstanding than that of Co(OH)2-72 h. What’s more, the Co(OH)2-72 h/CoS2 composites show a capacitance retention of 83.3% after 10 000 cycles. Besides, the assembled asymmetric supercapacitor displays a power density of 482 W kg‑1 at an energy density of 36 Wh kg‑1, demonstrating a large potential for application.

Effective NaBH4-exfoliated ultrathin multilayer Co(OH)2 nanosheets arrays and sulfidation for energy storage.

PubMed

Yang, Wanjun; Qu, Gan; Chen, Mingyue; Ma, Wenhao; Li, Wenhui; Tang, Yiwen

2018-07-20

Facile engineering ultrathin nano structural materials is still a huge challenge for material science. Thereinto, the strategy of exfoliating shows great advantages. In this work, we develop a convenient approach to exfoliate Co(OH) 2 nanosheets into ultrathin Co(OH) 2 nanoflakes through NaBH 4 -exfoliation method. Moreover, the microstructures of the Co(OH) 2 nanosheets are conveniently controlled by varying the exfoliation time. As a result, the obtained ultrathin Co(OH) 2 -72 h nanosheets deliver the excellent electrochemical performance. In order to improve the energy storage properties, the obtained ultrathin Co(OH) 2 nanosheets are further modified to enhance the conductivity via sulfidation. Consequently, the synthesized Co(OH) 2 -72 h/CoS 2 composites exhibit a specific capacitance of 2536 F g -1 at 1 A g -1 , which is more outstanding than that of Co(OH) 2 -72 h. What's more, the Co(OH) 2 -72 h/CoS 2 composites show a capacitance retention of 83.3% after 10 000 cycles. Besides, the assembled asymmetric supercapacitor displays a power density of 482 W kg -1 at an energy density of 36 Wh kg -1 , demonstrating a large potential for application.

Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels

PubMed Central

Salari, Autoosa; Vega, Benjamin S.; Milescu, Lorin S.; Milescu, Mirela

2016-01-01

Few gating-modifier toxins have been reported to target low-voltage-activated (LVA) calcium channels, and the structural basis of toxin sensitivity remains incompletely understood. Studies of voltage-gated potassium (Kv) channels have identified the S3b–S4 “paddle motif,” which moves at the protein-lipid interface to drive channel opening, as the target for these amphipathic neurotoxins. Voltage-gated calcium (Cav) channels contain four homologous voltage sensor domains, suggesting multiple toxin binding sites. We show here that the S3–S4 segments within Cav3.1 can be transplanted into Kv2.1 to examine their individual contributions to voltage sensing and pharmacology. With these results, we now have a more complete picture of the conserved nature of the paddle motif in all three major voltage-gated ion channel types (Kv, Nav, and Cav). When screened with tarantula toxins, the four paddle sequences display distinct toxin binding properties, demonstrating that gating-modifier toxins can bind to Cav channels in a domain specific fashion. Domain III was the most commonly and strongly targeted, and mutagenesis revealed an acidic residue that is important for toxin binding. We also measured the lipid partitioning strength of all toxins tested and observed a positive correlation with their inhibition of Cav3.1, suggesting a key role for membrane partitioning. PMID:27045173

Complete subunit structure of the Clostridium botulinum type D toxin complex via intermediate assembly with nontoxic components.

PubMed

Mutoh, Shingo; Kouguchi, Hirokazu; Sagane, Yoshimasa; Suzuki, Tomonori; Hasegawa, Kimiko; Watanabe, Toshihiro; Ohyama, Tohru

2003-09-23

Clostridium botulinum serotype D strains usually produce two types of stable toxin complex (TC), namely, the 300 kDa M (M-TC) and the 660 kDa L (L-TC) toxin complexes. We previously proposed assembly pathways for both TCs [Kouguchi, H., et al. (2002) J. Biol. Chem. 277, 2650-2656]: M-TC is composed by association of neurotoxin (NT) and nontoxic nonhemagglutinin (NTNHA); conjugation of M-TC with three auxiliary types of hemagglutinin subcomponents (HA-33, HA-17, and HA-70) leads to the formation of L-TC. In this study, we found three TC species, 410, 540, and 610 kDa TC species, in the culture supernatant of type D strain 4947. The 540 and 610 kDa TC species displayed banding patterns on SDS-PAGE similar to that of L-TC but with less staining intensity of the HA-33 and HA-17 bands than those of L-TC, indicating that these are intermediate species in the pathway to L-TC assembly. In contrast, the 410 kDa TC species consisted of M-TC and two molecules of HA-70. All of the TC species, except L-TC, demonstrated no hemagglutination activity. When the intermediate TC species were mixed with an isolated HA-33/17 complex, every TC species converted to 650 kDa L-TC with full hemagglutination activity and had the same molecular composition of L-TC. On the basis of titration analysis with the HA-33/17 complex, the stoichiometry of the HA-33/17 complex molecules in the L-TC, 610 kDa, and 540 kDa TC species was estimated as 4, 3, and 2, respectively. In conclusion, the complete subunit composition of mature L-TC is deduced to be a dodecamer assembled by a single NT, a single NTNHA, two HA-70, four HA-33, and four HA-17 molecules.

High-efficiency exfoliation of layered materials into 2D nanosheets in switchable CO2/Surfactant/H2O system.

PubMed

Wang, Nan; Xu, Qun; Xu, Shanshan; Qi, Yuhang; Chen, Meng; Li, Hongxiang; Han, Buxing

2015-11-16

Layered materials present attractive and important properties due to their two-dimensional (2D) structure, allowing potential applications including electronics, optoelectronics, and catalysis. However, fully exploiting the outstanding properties will require a method for their efficient exfoliation. Here we present that a series of layered materials can be successfully exfoliated into single- and few-layer nanosheets using the driving forces coming from the phase inversion, i.e., from micelles to reverse micelles in the emulsion microenvironment built by supercritical carbon dioxide (SC CO2). The effect of variable experimental parameters including CO2 pressure, ethanol/water ratio, and initial concentration of bulk materials on the exfoliation yield have been investigated. Moreover, we demonstrate that the exfoliated 2D nanosheets have their worthwhile applications, for example, graphene can be used to prepare conductive paper, MoS2 can be used as fluorescent label to perform cellular labelling, and BN can effectively reinforce polymers leading to the promising mechanical properties.

High-efficiency exfoliation of layered materials into 2D nanosheets in switchable CO2/Surfactant/H2O system

NASA Astrophysics Data System (ADS)

Wang, Nan; Xu, Qun; Xu, Shanshan; Qi, Yuhang; Chen, Meng; Li, Hongxiang; Han, Buxing

2015-11-01

Layered materials present attractive and important properties due to their two-dimensional (2D) structure, allowing potential applications including electronics, optoelectronics, and catalysis. However, fully exploiting the outstanding properties will require a method for their efficient exfoliation. Here we present that a series of layered materials can be successfully exfoliated into single- and few-layer nanosheets using the driving forces coming from the phase inversion, i.e., from micelles to reverse micelles in the emulsion microenvironment built by supercritical carbon dioxide (SC CO2). The effect of variable experimental parameters including CO2 pressure, ethanol/water ratio, and initial concentration of bulk materials on the exfoliation yield have been investigated. Moreover, we demonstrate that the exfoliated 2D nanosheets have their worthwhile applications, for example, graphene can be used to prepare conductive paper, MoS2 can be used as fluorescent label to perform cellular labelling, and BN can effectively reinforce polymers leading to the promising mechanical properties.

The role of exoproteases in governing intraneuronal metabolism of botulinum toxin.

PubMed

Simpson, Lance L; Maksymowych, Andrew B; Kouguchi, Hirokazu; Dubois, Garrett; Bora, Roop S; Joshi, Suresh

2005-04-01

Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases.

Toxin-Based Therapeutic Approaches

PubMed Central

Shapira, Assaf; Benhar, Itai

2010-01-01

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.

PubMed

Vance, David J; Greene, Christopher J; Rong, Yinghui; Mandell, Lorrie M; Connell, Terry D; Mantis, Nicholas J

2015-12-01

Type II heat-labile enterotoxins (HLTs) constitute a promising set of adjuvants that have been shown to enhance humoral and cellular immune responses when coadministered with an array of different proteins, including several pathogen-associated antigens. However, the adjuvant activities of the four best-studied HLTs, LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc, have never been compared side by side. We therefore conducted immunization studies in which LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc were coadministered by the intradermal route to mice with two clinically relevant protein subunit vaccine antigens derived from the enzymatic A subunit (RTA) of ricin toxin, RiVax and RVEc. The HLTs were tested with low and high doses of antigen and were assessed for their abilities to stimulate antigen-specific serum IgG titers, ricin toxin-neutralizing activity (TNA), and protective immunity. We found that all four HLTs tested were effective adjuvants when coadministered with RiVax or RVEc. LT-IIa was of particular interest because as little as 0.03 μg when coadministered with RiVax or RVEc proved effective at augmenting ricin toxin-specific serum antibody titers with nominal evidence of local inflammation. Collectively, these results justify the need for further studies into the mechanism(s) underlying LT-IIa adjuvant activity, with the long-term goal of evaluating LT-IIa's activity in humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Synthesis of ZnO Nanocrystal-Graphene Composite by Mechanical Milling and Sonication-Assisted Exfoliation

NASA Astrophysics Data System (ADS)

Arora, Sweety; Srivastava, Chandan

2017-02-01

A ZnO nanocrystal-graphene composite was synthesized by a two-step method involving mechanical milling and sonication-assisted exfoliation. Zn metal powder was first ball-milled with graphite powder for 30 h in water medium. This ball-milled mixture was then subjected to exfoliation by sonication in the presence of sodium lauryl sulfate surfactant to produce graphene decorated with spherical agglomerates of ultrafine nanocrystalline ZnO. The presence of a few layers of graphene was confirmed by Raman spectroscopy and atomic force microscopy measurements. The size, phase identity and composition of the ZnO nanocrystals was determined by transmission electron microscopy measurements.

Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

PubMed

Marston, Chung K; Ibrahim, Hisham; Lee, Philip; Churchwell, George; Gumke, Megan; Stanek, Danielle; Gee, Jay E; Boyer, Anne E; Gallegos-Candela, Maribel; Barr, John R; Li, Han; Boulay, Darbi; Cronin, Li; Quinn, Conrad P; Hoffmaster, Alex R

2016-01-01

Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity.

A flexible and transparent graphene/ZnO nanorod hybrid structure fabricated by exfoliating a graphite substrate

NASA Astrophysics Data System (ADS)

Nam, Gwang-Hee; Baek, Seong-Ho; Cho, Chang-Hee; Park, Il-Kyu

2014-09-01

We demonstrate the fabrication of a graphene/ZnO nanorod (NR) hybrid structure by mechanical exfoliation of ZnO NRs grown on a graphite substrate. We confirmed the existence of graphene sheets on the hybrid structure by analyzing the Raman spectra and current-voltage (I-V) characteristics. The Raman spectra of the exfoliated graphene/ZnO NR hybrid structure show G and 2D band peaks that are shifted to lower wavenumbers, indicating that the exfoliated graphene layer exists under a significant amount of strain. The I-V characteristics of the graphene/ZnO NR hybrid structure show current flow through the graphene layer, while no current flow is observed on the ZnO NR/polydimethylsiloxane (PDMS) composite without graphene, thereby indicating that the few-layer graphene was successfully transferred onto the hybrid structure. A piezoelectric nanogenerator is demonstrated by using the fabricated graphene/ZnO NR hybrid structure. The nanogenerator exhibits stable output voltage up to 3.04 V with alternating current output characteristics.We demonstrate the fabrication of a graphene/ZnO nanorod (NR) hybrid structure by mechanical exfoliation of ZnO NRs grown on a graphite substrate. We confirmed the existence of graphene sheets on the hybrid structure by analyzing the Raman spectra and current-voltage (I-V) characteristics. The Raman spectra of the exfoliated graphene/ZnO NR hybrid structure show G and 2D band peaks that are shifted to lower wavenumbers, indicating that the exfoliated graphene layer exists under a significant amount of strain. The I-V characteristics of the graphene/ZnO NR hybrid structure show current flow through the graphene layer, while no current flow is observed on the ZnO NR/polydimethylsiloxane (PDMS) composite without graphene, thereby indicating that the few-layer graphene was successfully transferred onto the hybrid structure. A piezoelectric nanogenerator is demonstrated by using the fabricated graphene/ZnO NR hybrid structure. The nanogenerator

Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity

PubMed Central

Masuda, Hisako; Inouye, Masayori

2017-01-01

Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes. Despite the prevalence of recognition sequences in many mRNA, preferential digestion seems to occur at specific positions within mRNA and also in certain reading frames. In this review, a variety of tools utilized to study the nuclease activities of toxins over the past 15 years will be reviewed. A recent adaptation of an RNA-seq-based technique to analyze entire sets of cellular RNA will be introduced with an emphasis on its strength in identifying novel targets and redefining recognition sequences. The differences in biochemical properties and postulated physiological roles will also be discussed. PMID:28420090

Improved purification process for cholera toxin and its application to the quantification of residual toxin in cholera vaccines.

PubMed

Jang, Hyun; Kim, Hyo Seung; Kim, Jeong Ah; Seo, Jin Ho; Carbis, Rodney

2009-01-01

A simplified method for the purification of cholera toxin was developed. The 569B strain of Vibrio cholerae, a recognized hyper-producer of cholera toxin, was propagated in a bioreactor under conditions that promote the production of the toxin. The toxin was separated from the bacterial cells using 0.2-microm crossflow microfiltration, the clarified toxin was passed through the membrane into the permeate, and the bacterial cells were retained in the retentate. The 0.2-microm permeate was then concentrated 3-fold and diafiltered against 10 mM phosphate buffer, pH 7.6, using 30-kDa crossflow ultrafiltration. The concentrated toxin was loaded onto a cation exchange column, the toxin was bound to the column, and most of the impurities were passed unimpeded through the column. The toxin was eluted with a salt gradient of phosphate buffer, pH7.0, containing 1.0M NaCl. The peak containing the toxin was assayed for cholera toxin and protein and the purity was determined to be 92%. The toxin peak had a low endotoxin level of 3.1 EU/microg of toxin. The purified toxin was used to prepare antiserum against whole toxin, which was used in a G(M1) ganglioside-binding ELISA to determine residual levels of toxin in an oral inactivated whole-cell cholera vaccine. The G(M1) ganglioside-binding ELISA was shown to be very sensitive and capable of detecting as little as 1 ng/ml of cholera toxin.

Large-area few-layer hexagonal boron nitride prepared by quadrupole field aided exfoliation

NASA Astrophysics Data System (ADS)

Lun Lu, Han; Zhi Rong, Min; Qiu Zhang, Ming

2018-03-01

A quadrupole electric field-mediated exfoliation method is proposed to convert micron-sized hexagonal boron nitride (h-BN) powder into few-layer hexagonal boron nitride nanosheets (h-BNNS). Under optimum conditions (400 Hz, 40 V, 32 μg ml-1, sodium deoxycholate, TAE medium), the h-BN powders (thickness >200 nm, horizontal scale ˜10 μm) are successfully exfoliated into 0.5-4 nm (1-10 layers) thick h-BNNS with the same horizontal scale. Dynamic laser scattering and atomic force microscope data show that the yield is 47.6% (for the portion with the thickness of 0.5-6 nm), and all of the vertical sizes are reduced to smaller than 18 nm (45 layers).

Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells.

PubMed

Girard, Magalí C; Sacerdoti, Flavia; Rivera, Fulton P; Repetto, Horacio A; Ibarra, Cristina; Amaral, María M

2015-10-01

Typical hemolytic uremic syndrome (HUS) is responsible for acute and chronic renal failure in children younger than 5 years old in Argentina. Renal damages have been associated with Shiga toxin type 1 and/or 2 (Stx1, Stx2) produced by Escherichia coli O157:H7, although strains expressing Stx2 are highly prevalent in Argentina. Human glomerular endothelial cells (HGEC) and proximal tubule epithelial cells are very Stx-sensitive since they express high levels of Stx receptor (Gb3). Nowadays, there is no available therapy to protect patients from acute toxin-mediated cellular injury. New strategies have been developed based on the Gb3 biosynthesis inhibition through blocking the enzyme glucosylceramide (GL1) synthase. We assayed the action of a GL1 inhibitor (Miglustat: MG), on the prevention of the renal damage induced by Stx2. HGEC primary cultures and HK-2 cell line were pre-treated with MG and then incubated with Stx2. HK- 2 and HGEC express Gb3 and MG was able to decrease the levels of this receptor. As a consequence, both types of cells were protected from Stx2 cytotoxicity and morphology damage. MG was able to avoid Stx2 effects in human renal cells and could be a feasible strategy to protect kidney tissues from the cytotoxic effects of Stx2 in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation of Graphene Sheets by Electrochemical Exfoliation of Graphite in Confined Space and Their Application in Transparent Conductive Films.

PubMed

Wang, Hui; Wei, Can; Zhu, Kaiyi; Zhang, Yu; Gong, Chunhong; Guo, Jianhui; Zhang, Jiwei; Yu, Laigui; Zhang, Jingwei

2017-10-04

A novel electrochemical exfoliation mode was established to prepare graphene sheets efficiently with potential applications in transparent conductive films. The graphite electrode was coated with paraffin to keep the electrochemical exfoliation in confined space in the presence of concentrated sodium hydroxide as the electrolyte, yielding ∼100% low-defect (the D band to G band intensity ratio, I D /I G = 0.26) graphene sheets. Furthermore, ozone was first detected with ozone test strips, and the effect of ozone on the exfoliation of graphite foil and the microstructure of the as-prepared graphene sheets was investigated. Findings indicate that upon applying a low voltage (3 V) on the graphite foil partially coated with paraffin wax that the coating can prevent the insufficiently intercalated graphite sheets from prematurely peeling off from the graphite electrode thereby affording few-layer (<5 layers) holey graphene sheets in a yield of as much as 60%. Besides, the ozone generated during the electrochemical exfoliation process plays a crucial role in the exfoliation of graphite, and the amount of defect in the as-prepared graphene sheets is dependent on electrolytic potential and electrode distance. Moreover, the graphene-based transparent conductive films prepared by simple modified vacuum filtration exhibit an excellent transparency and a low sheet resistance after being treated with NH 4 NO 3 and annealing (∼1.21 kΩ/□ at ∼72.4% transmittance).

Design of amine modified polymer dispersants for liquid-phase exfoliation of transition metal dichalcogenide nanosheets and their photodetective nanocomposites

NASA Astrophysics Data System (ADS)

Lee, Jinseong; Hahnkee Kim, Richard; Yu, Seunggun; Babu Velusamy, Dhinesh; Lee, Hyeokjung; Park, Chanho; Cho, Suk Man; Jeong, Beomjin; Sol Kang, Han; Park, Cheolmin

2017-12-01

Liquid-phase exfoliation (LPE) of transition metal dichalcogenide (TMD) nanosheets is a facile, cost-effective approach to large-area photoelectric devices including photodetectors and non-volatile memories. Non-destructive exfoliation of nanosheets using macromolecular dispersing agents is beneficial in rendering the TMD nanocomposite films suitable for mechanically flexible devices. Here, an efficient LPE of molybdenum disulfide (MoS2) with an amine modified poly(styrene-co-maleic anhydride) co-polymer (AM-PSMA) is demonstrated, wherein the maleic anhydrides were converted into maleic imides with primary amines using N-Boc-(CH2) n -NH2. The exfoliation of nanosheets was facilitated through Lewis acid-base interaction between the primary amine and transition metal. The results demonstrate that the exfoliation depends upon both the fraction of primary amines in the polymer chain and their distance from the polymer backbone. Under optimized conditions of primary amine content and its distance from the backbone, AM-PSMA gave rise to a highly concentrated MoS2 nanosheet suspension that was stable for over 10 d. Exfoliation of several other TMDs was also achieved using the optimized AM-PSMA, indicating the scope of AM-PSMA applications. Furthermore, a flexible composite film of AM-PSMA and MoS2 nanosheets fabricated by vacuum-assisted filtration showed excellent photoconductive performances including a high I on/I off ratio of 102 and a fast photocurrent switching of 300 ms.

Cytotoxicity assessment of polyhydroxybutyrate/chitosan/nano- bioglass nanofiber scaffolds by stem cells from human exfoliated deciduous teeth stem cells from dental pulp of exfoliated deciduous tooth.

PubMed

Hashemi-Beni, Batool; Khoroushi, Maryam; Foroughi, Mohammad Reza; Karbasi, Saeed; Khademi, Abbas Ali

2018-01-01

The aim of this study was to compare the cytotoxicity and the biocompatibility of three different nanofibers scaffolds after seeding of stem cells harvested from human deciduous dental pulp. Given the importance of scaffold and its features in tissue engineering, this study demonstrated the construction of polyhydroxybutyrate (PHB)/chitosan/nano-bioglass (nBG) nanocomposite scaffold using electrospinning method. This experimental study was conducted on normal exfoliated deciduous incisors obtained from 6-year-old to 11-year-old healthy children. The dental pulp was extracted from primary incisor teeth which are falling aseptically. After digesting the tissue with 4 mg/ml of type I collagenase, the cells were cultured in medium solution. Identification of stem cells from human exfoliated deciduous teeth was performed by flowcytometry using CD19, CD14, CD146, and CD90 markers. Then, 1 × 10 4 stem cells were seeded on the scaffold with a diameter of 10 mm × 0.3 mm. Cell viability was evaluated on days 3, 5, and 7 through methyl thiazol tetrazolium techniques ( P < 0.05) on different groups that they are groups included (1) PHB scaffold (G1), (2) PHB/chitosan scaffold (G2), (3) the optimal PHB/chitosan/nBG scaffold (G3), (4) mineral trioxide aggregate (MTA), and (5) the G3 + MTA scaffold (G3 + MTA). Data were analyzed with two-way ANOVA at significance level of P < 0.05. The results indicated that the PHB/chitosan/nBG scaffold and PHB/chitosan/nBG scaffold + MTA groups showed significant difference compared with the PHB/chitosan scaffold and PHB scaffold groups on the 7 th day ( P < 0.05). Thus, it can be concluded that the scaffold with nBG nanoparticles is more biocompatible than the other scaffolds and can be considered as a suitable scaffold for growth and proliferation of stem cells.

Ionic Liquid-Modified Thermosets and Their Nanocomposites: Dispersion, Exfoliation, Degradation, and Cure

NASA Astrophysics Data System (ADS)

Throckmorton, James A.

This dissertation explores the application of a room temperature ionic liquid (RTIL) to problems in the chemistry, processing, and modification of thermosetting polymers. In particular, the solution properties and reaction chemistry of 1-ethyl-3-methyl imidazolium dicyanamide (EMIM-DCN) are applied to problems of nanoparticle dispersion and processing, graphite exfoliation, cyanate ester (CE) cure, and the environmental degradation of CEs. Nanoparticle Dispersion: Nanocomposite processing can be simplified by using the same compound as both a nanoparticle solvent and an initiator for polymerization. This dual-function molecule can be designed both for solvent potential and reaction chemistry. EMIM-DCN, previously shown by our lab to act as an epoxy initiator, is used in the synthesis of silica and acid expanded graphite composites. These composites are then characterized for particle dispersion and physical properties. Individual particle dispersion of silica nanocomposites is shown, and silica nanocomposites at low loading show individual particle dispersion and improved modulus and fracture toughness. GNP nanocomposites show a 70% increase in modulus along with a 10-order of magnitude increase in electrical conductivity at 6.5 vol%, and an electrical percolation threshold of 1.7 vol%. Direct Graphite Exfoliation By Laminar Shear: This work presents a laminar-shear alternative to chemical processing and chaotic flow-fields for the direct exfoliation of graphite and the single-pot preparation of nanocomposites. Additionally, we develop the theory of laminar flow through a 3-roll mill, and apply that theory to the latest developments in the theory of graphite interlayer shear. The resulting nanocomposite shows low electrical percolation (0.5 vol%) and low thickness (1-3 layer) graphite/graphene flakes. Additionally, the effect of processing conditions by rheometry and comparison with solvent-free conditions reveal the interactions between processing and matrix

Clostridium difficile binary toxin CDT

PubMed Central

Gerding, Dale N; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus

2014-01-01

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed. PMID:24253566

Identification of the channel-forming domain of Clostridium perfringens Epsilon-toxin (ETX).

PubMed

Knapp, Oliver; Maier, Elke; Benz, Roland; Geny, Blandine; Popoff, Michel R

2009-12-01

Epsilon-toxin (ETX) is a potent toxin produced by Clostridium perfringens strains B and D. The bacteria are important pathogens in domestic animals and cause edema mediated by ETX. This toxin acts most likely by heptamer formation and rapid permeabilization of target cell membranes for monovalent anions and cations followed by a later entry of calcium. In this study, we compared the primary structure of ETX with that of the channel-forming stretches of a variety of binding components of A-B-types of toxins such as Anthrax protective antigen (PA), C2II of C2-toxin and Ib of Iota-toxin and found a remarkable homology to amino acids 151-180 of ETX. Site-directed mutagenesis of amino acids within the putative channel-forming domain resulted in changes of cytotoxicity and effects on channel characteristics in lipid bilayer experiments including changes of selectivity and partial channel block by methanethiosulfonate (MTS) reagents and antibodies against His(6)-tags from the trans-side of the lipid bilayer membranes.

A novel function of vitellogenin subdomain, vWF type D, as a toxin-binding protein in the pufferfish Takifugu pardalis ovary.

PubMed

Yin, Xianzhe; Kiriake, Aya; Ohta, Akira; Kitani, Yoichiro; Ishizaki, Shoichiro; Nagashima, Yuji

2017-09-15

Marine pufferfish of the Tetraodontidae family contain high levels of tetrodotoxin (TTX) in the liver and ovary. TTX is suggested to transfer from the liver to the ovary in female pufferfish during maturation. TTX in pufferfish eggs may act as a repellent against predators and as a sexual pheromone to attract male pufferfish. The toxification mechanism of the pufferfish ovary is poorly understood. Here we evaluated the chemical form of TTX and its related substances in the ovary of the panther pufferfish Takifugu pardalis by LC-ESI/MS. TTX and its analogs 4-epi-TTX, 4, 9-anhydroTTX, deoxyTTX, dideoxyTTX, and trideoxyTTX were detected in a low molecular weight fraction by Sephacryl S-400 column chromatography. The finding of an unknown TTX-related substance in a high molecular weight fraction from the Sephacryl S-400 column suggested the occurrence of toxin-binding protein in the ovary. The toxin-binding protein in the ovary was purified by ion-exchange HPLC, gel filtration HPLC, and SDS-PAGE. Amino acid sequencing and cDNA cloning revealed that the toxin-binding protein, TPOBP-10 (Takifugu pardalis ovary toxin-binding protein with a molecular mass of 10 kDa) was homologous with the predicted vitellogenin-1-like protein [Takifugu rubripes] subdomain, a von Willebrand factor type D domain. TPOBP-10 mRNA was highly expressed in the ovary and liver and less in other organs of female individuals based on RT-PCR. These findings reveal a novel function of the vitellogenin subdomain as binding with TTX-related substances, and its involvement in the toxification of the pufferfish ovary. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

PubMed Central

Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

2015-01-01

The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity. PMID:26485650

Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

PubMed

Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

2015-01-01

The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

Levels of salivary thiocyanate and its relation with occurrence of micronuclei using exfoliative cytology in smokers and nonsmokers.

PubMed

Baldawa, Prachi Shrigopal; Kulkarni, Venkatesh V; Koshy, Ajit V; Shaikh, Sabeer S; Varu, Rucha; Srivastava, Garima

2016-01-01

To evaluate the levels of salivary thiocyanate and its relation with the occurrence of micronuclei (MN) using exfoliative cytology in smokers and nonsmokers. One hundred and twenty patients were divided into 3 groups: nonsmoker group 1 (control), smokers group 2, and smokers group 3. Their saliva was collected and analyzed for thiocyanate levels, and exfoliative cytology was evaluated for the presence of MN. Fisher's exact test and ANOVA test were used. It was seen that as the grade of smoking increased, the levels of salivary thiocyanate and occurrence of MN increased. Detection and quantification of "biomarkers" such as salivary thiocyanate and MN in noninvasive and painless procedures such as oral exfoliative cytology can be an upcoming research domain in the field of cancer prevention and therapeutics.

Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles.

PubMed

Hong, Bin; Chen, Min; Hu, Xing-yue

2013-11-01

Botulinum toxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of a synaptosomal-associated protein of 25 kDa (SNAP-25). It has gained widespread use as a treatment for cerebral palsy and skeletal muscle hypertrophy. In China, Chinese botulinum toxin type A (CBTX-A), a type of BoNT/A, is in widespread clinical use. However, the changes in the morphological and biochemical properties of treated muscles and in remote muscles from the CBTX-A injection site are relatively unknown. Therefore, we investigated the changes in histomorphology and myosin heavy chain (MyHC) isoform composition and distribution in rat gastrocnemius muscles after intramuscular injection of CBTX-A. The weakness of the injected muscles was assessed periodically to identify their functional deficiency. Muscle slices were stained with hematoxylin-eosin (HE) and adenosine triphosphatase (ATPase). MyHC isoform composition was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to uncover changes in morphological and biochemical properties. Our findings demonstrate that following injection of CBTX-A 5 U into rat gastrocnemius muscles, shifts in MyHC isoform composition emerged on the third day after injection and peaked in the fourth week. The composition remained distinctly different from that of the control group after the twelfth week. More specifically, there was a decrease in the proportion of the type IIb isoform and an increase in the proportions of type IIx, type IIa, and type I isoforms. Data revealed that CBTX-A led to a shift in MyHC composition towards slower isoforms and that the MyHC composition remained far from normal six months after a single injection. However, no noticeable remote muscle weakness was induced.

Changes in intestinal fluid and mucosal immune responses to cholera toxin in Giardia muris infection and binding of cholera toxin to Giardia muris trophozoites.

PubMed

Ljungström, I; Holmgren, J; Svennerholm, A M; Ferrante, A

1985-10-01

The effect of Giardia muris infection on the diarrheal response and gut mucosal antibody response to cholera toxin was examined in mice. The results obtained showed that the fluid accumulation in intestinal loops exposed to cholera toxin was increased in mice infected with a low number (5 X 10(4) ) of G. muris cysts compared with the response in noninfected mice. This effect was associated with a marked reduction in absorption of oral rehydration fluid from the intestine. In contrast, mice infected with a high dose (2 X 10(5) ) of cysts showed a marked decrease in fluid accumulation in response to the toxin. This decrease might be related to the finding that both G. muris and Giardia lamblia trophozoites can bind significant amounts of cholera toxin. Evidence is presented which suggests that the gut mucosal antibody response, mainly immunoglobulin A but also immunoglobulin G, to an immunization course with perorally administered cholera toxin was depressed in mice infected with G. muris. The reduction in antibody levels was particularly evident when the primary immunization was made very early after infection. The serum antitoxin antibodies to the oral immunization with cholera toxin were, however, not affected. Likewise, the delayed-type hypersensitivity response against sheep erythrocytes in animals primed subcutaneously with sheep erythrocytes was not modified during the course of G. muris infection.

Behaviour of the surface hydroxide groups of exfoliated kaolinite in the gas phase and during water adsorption.

PubMed

Táborosi, Attila; Szilágyi, Róbert K

2016-02-14

The chemical and physical properties, and thus the reactivity of phylloaluminosilicates can be tailored by intercalation, delamination, and exfoliation processes. In going from the periodic crystalline to the molecular exfoliated phase, surface defects and modifications gain importance as each face of the phylloaluminosilicate comes in direct contact with the external chemical environment. In this work, we extend our earlier studies on the molecular cluster modelling of exfoliated kaolinite sheets by evaluating the positions and orientations of surface hydroxide groups and bridging oxide anions, as the sites of reactivity. The previous focus on the inner chemical environment of a single kaolinite layer is shifted to the surface exposed octahedral aluminium-hydroxide and tetrahedral silicon-oxide sheets. The combination of semi-empirical, ab initio wave function, and density functional calculations unanimously support the amphoteric nature of the surface hydroxide groups with respect to H-bonding donor/acceptor capabilities. To a lesser extent, we observe the same for the bridging oxide anions. This is in contrast to the crystalline phase, which manifests only donor orientation for maintaining an inter-layer H-bond network. These results suggest that both electrophilic and nucleophilic characteristics of the octahedral and tetrahedral sheets need to be considered during intercalation and concomitant exfoliation of the kaolinite sheets.

Electrochemical Exfoliation of Graphite in Aqueous Sodium Halide Electrolytes toward Low Oxygen Content Graphene for Energy and Environmental Applications.

PubMed

Munuera, J M; Paredes, J I; Enterría, M; Pagán, A; Villar-Rodil, S; Pereira, M F R; Martins, J I; Figueiredo, J L; Cenis, J L; Martínez-Alonso, A; Tascón, J M D

2017-07-19

Graphene and graphene-based materials have shown great promise in many technological applications, but their large-scale production and processing by simple and cost-effective means still constitute significant issues in the path of their widespread implementation. Here, we investigate a straightforward method for the preparation of a ready-to-use and low oxygen content graphene material that is based on electrochemical (anodic) delamination of graphite in aqueous medium with sodium halides as the electrolyte. Contrary to previous conflicting reports on the ability of halide anions to act as efficient exfoliating electrolytes in electrochemical graphene exfoliation, we show that proper choice of both graphite electrode (e.g., graphite foil) and sodium halide concentration readily leads to the generation of large quantities of single-/few-layer graphene nanosheets possessing a degree of oxidation (O/C ratio down to ∼0.06) lower than that typical of anodically exfoliated graphenes obtained with commonly used electrolytes. The halide anions are thought to play a role in mitigating the oxidation of the graphene lattice during exfoliation, which is also discussed and rationalized. The as-exfoliated graphene materials exhibited a three-dimensional morphology that was suitable for their practical use without the need to resort to any kind of postproduction processing. When tested as dye adsorbents, they outperformed many previously reported graphene-based materials (e.g., they adsorbed ∼920 mg g -1 for methyl orange) and were useful sorbents for oils and nonpolar organic solvents. Supercapacitor cells assembled directly from the as-exfoliated products delivered energy and power density values (up to 15.3 Wh kg -1 and 3220 W kg -1 , respectively) competitive with those of many other graphene-based devices but with the additional advantage of extreme simplicity of preparation.

Mechanism of endonuclease cleavage by the HigB toxin

PubMed Central

Schureck, Marc A.; Repack, Adrienne; Miles, Stacey J.; Marquez, Jhomar; Dunham, Christine M.

2016-01-01

Bacteria encode multiple type II toxin–antitoxin modules that cleave ribosome-bound mRNAs in response to stress. All ribosome-dependent toxin family members structurally characterized to date adopt similar microbial RNase architectures despite possessing low sequence identities. Therefore, determining which residues are catalytically important in this specialized RNase family has been a challenge in the field. Structural studies of RelE and YoeB toxins bound to the ribosome provided significant insights but biochemical experiments with RelE were required to clearly demonstrate which residues are critical for acid-base catalysis of mRNA cleavage. Here, we solved an X-ray crystal structure of the wild-type, ribosome-dependent toxin HigB bound to the ribosome revealing potential catalytic residues proximal to the mRNA substrate. Using cell-based and biochemical assays, we further determined that HigB residues His54, Asp90, Tyr91 and His92 are critical for activity in vivo, while HigB H54A and Y91A variants have the largest effect on mRNA cleavage in vitro. Comparison of X-ray crystal structures of two catalytically inactive HigB variants with 70S-HigB bound structures reveal that HigB active site residues undergo conformational rearrangements likely required for recognition of its mRNA substrate. These data support the emerging concept that ribosome-dependent toxins have diverse modes of mRNA recognition. PMID:27378776

Exfoliation of gastric pit-parietal cells into the gastric lumen associated with a stimulation of isolated rat gastric mucosa in vitro: a morphological study by the application of cryotechniques.

PubMed

Aoyama, Fumiyo; Sawaguchi, Akira; Ide, Soyuki; Kitamura, Kazuo; Suganuma, Tatsuo

2008-06-01

It is clinicopathologically important to elucidate the cell kinetics for the maintenance of normal gastric epithelium. In a rat gastric mucosa isolated after stimulation, a number of cells were exfoliated into the gastric lumen of the pit region. The present study was undertaken to clarify the origin of exfoliated cells and their histochemical profiles by taking the advantages of cryotechniques. As results, most of the exfoliated cells were identified as pit-parietal cells labeled with both peanut-lectin and anti-H+/K+-ATPase antibody. Quantitative analysis verified a time-dependent increase in the number of exfoliated cells in the gastric mucosa isolated after stimulation. The exfoliated cells exhibited a diffuse intracellular staining for E-cadherin, suggesting a dissociation of the adhesion molecule prior to the cell exfoliation. It should be noted that most of the exfoliated cells were negative to the apoptotic markers (TUNEL staining and caspase-3). Ultrastructurally, autophagosome-like structures consisting of H+/K+-ATPase positive membranes were frequently seen in the exfoliated pit-parietal cells. In addition, the pit-parietal cell exfoliation was accompanied by sealing of their basal portion with the cytoplasmic processes of adjacent surface mucous cells. The present morphological findings provide a new insight into the cell kinetics in the gastric epithelium in vitro.

Mechanistic examination of pre-exfoliating confinement of surface-active polystyrene nanobeads within pristine clay.

PubMed

Khvan, Svetlana; Kim, Junkyung; Lee, Sang-Soo

2007-02-01

Hydrophobic polymer (PS) nanoparticles preformed through an emulsifier-free emulsion polymerization method were successfully incorporated into a gallery of pristine sodium montmorillonite via interfacial cation exchange. The polymer beads confined between clay nanosheets were capable of (1) preventing the silicate layers from restacking and (2) maintaining the exfoliated state of clay. The increase in the abundance of surface groups promoted adsorption of the nanobeads onto the silicate surface and eventually led to the establishment of strong polymer-clay interactions. These findings suggest that, on the basis of the obtained pre-exfoliated clay masterbatch, the presence of strong polymer-clay interactions could improve the mechanical performance of nanocomposites.

Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A) in migraine.

PubMed

Robertson, Carrie E; Garza, Ivan

2012-01-01

OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days). The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution.

Dominant-Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax

NASA Astrophysics Data System (ADS)

Sellman, Bret R.; Mourez, Michael; John Collier, R.

2001-04-01

The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.

Supercritical fluid extraction of bi & multi-layer graphene sheets from graphite by using exfoliation technique

NASA Astrophysics Data System (ADS)

Xavier, Gauravi; Dave, Bhoomi; Khanna, Sakshum

2018-05-01

In recent times, researchers have turned to explore the possibility of using Supercritical Fluid (SCFs) system to penetrate into the inert-gaping of graphite and exfoliate it into a number of layer graphene sheets. The supercritical fluid holds excellent wetting surfaces with low interfacial tension and high diffusion coefficients. Although SCFs exfoliation approach looks promising to developed large scale & low-cost graphene sheet but has not received much attention. To arouse interest and reflection on this approach, this review is organized to summarize the recent progress in graphene production by SCF technology. Here we present the simplest route to obtained layers of graphene sheets by intercalating and exfoliating graphite using supercritical CO2 processing. The layers graphene nano-sheets were collected in dichloromethane (DCM) solution which prevents the restocking of sheets. The obtained graphene sheets show the desired characteristics and thus can be used in physical, chemical and biological sciences. Thus this method provides an effortless and eco-friendly approach for the synthesis of layers of graphene sheets.

Exfoliation and van der Waals heterostructure assembly of intercalated ferromagnet Cr1/3TaS2

NASA Astrophysics Data System (ADS)

Yamasaki, Yuji; Moriya, Rai; Arai, Miho; Masubuchi, Satoru; Pyon, Sunseng; Tamegai, Tsuyoshi; Ueno, Keiji; Machida, Tomoki

2017-12-01

Ferromagnetic van der Waals (vdW) materials are in demand for spintronic devices with all-two-dimensional-materials heterostructures. Here, we demonstrate mechanical exfoliation of magnetic-atom-intercalated transition metal dichalcogenide Cr1/3TaS2 from its bulk crystal; previously such intercalated materials were thought difficult to exfoliate. Magnetotransport in exfoliated tens-of-nanometres-thick flakes revealed ferromagnetic ordering below its Curie temperature T C ~ 110 K as well as strong in-plane magnetic anisotropy; these are identical to its bulk properties. Further, van der Waals heterostructure assembly of Cr1/3TaS2 with another intercalated ferromagnet Fe1/4TaS2 is demonstrated using a dry-transfer method. The fabricated heterojunction composed of Cr1/3TaS2 and Fe1/4TaS2 with a native Ta2O5 oxide tunnel barrier in between exhibits tunnel magnetoresistance (TMR), revealing possible spin injection and detection with these exfoliatable ferromagnetic materials through the vdW junction.

A flexible and transparent graphene/ZnO nanorod hybrid structure fabricated by exfoliating a graphite substrate.

PubMed

Nam, Gwang-Hee; Baek, Seong-Ho; Cho, Chang-Hee; Park, Il-Kyu

2014-10-21

We demonstrate the fabrication of a graphene/ZnO nanorod (NR) hybrid structure by mechanical exfoliation of ZnO NRs grown on a graphite substrate. We confirmed the existence of graphene sheets on the hybrid structure by analyzing the Raman spectra and current-voltage (I-V) characteristics. The Raman spectra of the exfoliated graphene/ZnO NR hybrid structure show G and 2D band peaks that are shifted to lower wavenumbers, indicating that the exfoliated graphene layer exists under a significant amount of strain. The I-V characteristics of the graphene/ZnO NR hybrid structure show current flow through the graphene layer, while no current flow is observed on the ZnO NR/polydimethylsiloxane (PDMS) composite without graphene, thereby indicating that the few-layer graphene was successfully transferred onto the hybrid structure. A piezoelectric nanogenerator is demonstrated by using the fabricated graphene/ZnO NR hybrid structure. The nanogenerator exhibits stable output voltage up to 3.04 V with alternating current output characteristics.

AdE-1, a new inotropic Na(+) channel toxin from Aiptasia diaphana, is similar to, yet distinct from, known anemone Na(+) channel toxins.

PubMed

Nesher, Nir; Shapira, Eli; Sher, Daniel; Moran, Yehu; Tsveyer, Liora; Turchetti-Maia, Ana Luiza; Horowitz, Michal; Hochner, Binyamin; Zlotkin, Eliahu

2013-04-01

Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na(+) channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (<36%). Physiologically, AdE-1 increases the amplitude of cardiomyocyte contraction and slows the late phase of the twitch relaxation velocity with no induction of spontaneous twitching. It increases action potential duration of cardiomyocytes with no effect on its threshold and on the cell's resting potential. Similar to other sea anemone Na(+) channel toxins such as Av2 (Anemonia viridis toxin II), AdE-1 markedly inhibits Na(+) current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED(50) value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure-function in sea anemone Na(+) channel toxins.

High-quality graphene flakes exfoliated on a flat hydrophobic polymer

NASA Astrophysics Data System (ADS)

Pedrinazzi, Paolo; Caridad, José M.; Mackenzie, David M. A.; Pizzocchero, Filippo; Gammelgaard, Lene; Jessen, Bjarke S.; Sordan, Roman; Booth, Timothy J.; Bøggild, Peter

2018-01-01

We show that graphene supported on a hydrophobic and flat polymer surface results in flakes with extremely low doping and strain as assessed by their Raman spectroscopic characteristics. We exemplify this technique by micromechanical exfoliation of graphene on flat poly(methylmethacrylate) layers and demonstrate Raman peak intensity ratios I(2D)/I(G) approaching 10, similar to pristine freestanding graphene. We verify that these features are not an artifact of optical interference effects occurring at the substrate: they are similarly observed when varying the substrate thickness and are maintained when the environment of the graphene flake is completely changed, by encapsulating preselected flakes between hexagonal boron nitride layers. The exfoliation of clean, pristine graphene layers directly on flat polymer substrates enables high performance, supported, and non-encapsulated graphene devices for flexible and transparent optoelectronic studies. We additionally show that the access to a clean and supported graphene source leads to high-quality van der Waals heterostructures and devices with reproducible carrier mobilities exceeding 50 000 cm2 V-1 s-1 at room temperature.

Genome Sequence of the Shiga Toxin-Producing Escherichia coli Strain NCCP15657

PubMed Central

Kim, Byung Kwon; Song, Geun Cheol; Hong, Gun Hyong; Seong, Won-Keun; Kim, Seon-Young; Jeong, Haeyoung; Kang, Sung Gyun; Kwon, Soon-Kyeong; Lee, Choong Hoon; Song, Ju Yeon; Yu, Dong Su; Park, Mi-Sun

2012-01-01

Shiga toxin-producing Escherichia coli causes bloody diarrhea and hemolytic-uremic syndrome and serious outbreaks worldwide. Here, we report the draft genome sequence of E. coli NCCP15657 isolated from a patient. The genome has virulence genes, many in the locus of enterocyte effacement (LEE) island, encoding a metalloprotease, the Shiga toxin, and constituents of type III secretion. PMID:22740674

Efficacy and Safety of Single Botulinum Toxin Type A (Botox®) Injection for Relief of Upper Trapezius Myofascial Trigger Point: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Kwanchuay, Photsawee; Petchnumsin, Thavatchai; Yiemsiri, Pichet; Pasuk, Nakkamol; Srikanok, Wannarat; Hathaiareerug, Chanasak

2015-12-01

Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox®) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0 ± 0.9 and 0.5 ± 0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox®) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However

Safety of Ultrasound-Guided Botulinum Toxin Injections for Sialorrhea as Performed by Pediatric Otolaryngologists.

PubMed

Shariat-Madar, Bahbak; Chun, Robert H; Sulman, Cecille G; Conley, Stephen F

2016-05-01

To evaluate incidence of complications and hospital readmission as a result of ultrasound-guided botulinum toxin injections to manage sialorrhea. Case series with chart review. Children's Hospital of Wisconsin. A case series with chart review was performed of all cases of ultrasound-guided injection of botulinum toxin by pediatric otolaryngologists from March 5, 2010, to September 26, 2014,. Primary outcomes included complications such as dysphagia, aspiration pneumonia, and motor paralysis. Secondary outcomes included hospitalization, intubation, and nasogastric tube placement. There were 48 patients, 111 interventions, and 306 intraglandular injections identified. Botulinum toxin type A and type B were utilized in 4 and 107 operative interventions, respectively. Type A was injected into 4 parotid and 4 submandibular glands, utilizing doses of 20 U per parotid and 30 U per submandibular gland. Type B was injected into 98 parotid and 200 submandibular glands, with average dosing of 923 U per parotid and 1170 U per submandibular gland, respectively. There were 2 instances of subjectively worsening of baseline dysphagia that self-resolved. No cases were complicated by aspiration pneumonia or motor paralysis. No patients required hospital readmission, intubation, or nasogastric tube placement. Prior published data indicated 16% complication incidence with ultrasound-guided injection of botulinum toxin. Our study found a low complication rate (0.6%) with ultrasound-guided injections of botulinum toxin to manage sialorrhea, without cases of aspiration pneumonia or motor paralysis. Of 306 intraglandular injections, there were 2 cases of worsening baseline subjective dysphagia that self-resolved. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Lymphocyte receptors for pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1990-12-01

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

Botulinum toxin: Bioweapon & magic drug

PubMed Central

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

2010-01-01

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

Botulinum toxin: bioweapon & magic drug.

PubMed

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

2010-11-01

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

Topical botulinum toxin.

PubMed

Collins, Ashley; Nasir, Adnan

2010-03-01

Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

Identification of a lambda toxin-negative Clostridium perfringens strain that processes and activates epsilon prototoxin intracellularly.

PubMed

Harkness, Justine M; Li, Jihong; McClane, Bruce A

2012-10-01

Clostridium perfringens type B and D strains produce epsilon toxin (ETX), which is one of the most potent clostridial toxins and is involved in enteritis and enterotoxemias of domestic animals. ETX is produced initially as an inactive prototoxin that is typically then secreted and processed by intestinal proteases or possibly, for some strains, lambda toxin. During the current work a unique C. perfringens strain was identified that intracellularly processes epsilon prototoxin to an active form capable of killing MDCK cells. This activated toxin is not secreted but instead is apparently released upon lysis of bacterial cells entering stationary phase. These findings broaden understanding of the pathogenesis of type B and D infections by identifying a new mechanism of ETX activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Large Area Few Layers Hexagonal Boron Nitride Prepared by Quadrupole Field Aided Exfoliation.

PubMed

Hanlun, Lu; Rong, Min Zhi; Zhang, Ming Qiu

2018-01-16

A quadrupole electric field mediated exfoliation method is proposed to convert micron sized hexagonal boron nitride (hBN) powders into few layers hexagonal boron nitride nano-sheets (h-BNNS). Under the optimum conditions (400 Hz, 40 V, 32μg/mL, sodium deoxycholate, TAE medium), the hBN powders (thickness > 200 nm, horizontal scale ~ 10 μm) are successfully exfoliated into 0.5-4 nm (1-10 layers) thick h-BNNS with the same horizontal scale. Dynamic laser scattering (DLS) and atomic force microscope (AFM) statistics show that the yield is 47.6 % (for the portion with the thickness of 0.5-6 nm), and all of the vertical sizes are reduced to smaller than 18 nm (45 layers). © 2018 IOP Publishing Ltd.

Sulfuric acid intercalated-mechanical exfoliation of reduced graphene oxide from old coconut shell

NASA Astrophysics Data System (ADS)

Islamiyah, Wildatun; Nashirudin, Luthfi; Baqiya, Malik A.; Cahyono, Yoyok; Darminto

2018-04-01

We report a fecile preparation of reduced grapheme oxide (rGO) from an old coconut shell by rapid reduction of heating at 400°C, chemical exfoliation using H2SO4 and HCl intercalating and mechanical exfoliation using ultrasonication. The produced samples consist of random stacks of nanometer-sized sheets. The dispersions prepared from H2SO4 had broader size distributions and larger particle sizes than the that from HCl. An average size of rGO in H2SO4 and HCl is respectively 23.62 nm and 570.4 nm. Furthermore, sample prepared in H2SO4 exhibited a high electronical conductivity of 1.1 × 10-3 S/m with a low energy gap of 0.11 eV.

Lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome.

PubMed

Thakur, B K; Verma, S; Mishra, J

2015-06-01

Human immunodeficiency virus-infected patients are at increased risk of drug reactions because of immune dysregulation and multiple drug intake. Lichenoid drug reactions to isoniazid have been reported previously in the literature. However, for lichenoid drug reaction to isoniazid to be so extensive to present as exfoliative dermatitis is rare. We report here a rare case of lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Thermal monitoring of a granitic exfoliation sheet and cliff in Yosemite Valley, California (USA)

NASA Astrophysics Data System (ADS)

Guerin, Antoine; Matasci, Battista; Collins, Brian D.; Stock, Greg M.; Derron, Marc-Henri; Jaboyedoff, Michel

2015-04-01

In recent years, new remote sensing techniques such as Terrestrial Laser Scanner (TLS) and Infrared Thermography (IRT) have been used in parallel for rock weathering and weakness detection in slope stability analysis. Nevertheless, the effects of thermal stresses on rock face deformation are still poorly quantified, especially for steep and inaccessible cliffs. To better understand how daily temperature fluctuations influence the behavior of exfoliation joints (i.e., fractures separating exfoliation sheets), we monitored a granitic exfoliation sheet in detail using TLS and IRT over a several day period and also compiled a single TLS-IRT thermal panorama of a larger nearby granitic cliff composed of hundreds to thousands of similar exfoliation sheets. The exfoliation sheet had been previously instrumented for 3.5 years beginning in May 2010 using crackmeters and temperature sensors (Collins and Stock, 2010 and 2012), thereby providing an important baseline to compare our IRT measurements. For several consecutive days, a series of infrared thermal images (collected every 20 min.) of the exfoliation flake (19 m by 4 m by 0.1 m) was taken with a long range IRISYS IRI 4040 thermal imager, as well as several ground-based LiDAR scans, collected at 4 mm point spacing. These pictures were draped on the TLS triangular meshes to quantify the lateral propagation of temperature during the warming and cooling periods. The evolution of vertical and horizontal temperature profiles was also investigated. Results show that the sheet edge undergoes the most significant temperature changes and that warming takes place from the inside part to the border of the flake; conversely cooling takes place from the outside-inwards. Furthermore, the comparison of point clouds indicates a maximum crack aperture of over 1 cm occurring in the afternoon (12:00 to 15:00), when temperatures are at their maximum. The thermal panoramic image of the cliff (600 m wide by 300 m tall) was created using over

Quantification of thickness and wrinkling of exfoliated two-dimensional zeolite nanosheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Prashant; Agrawal, Kumar Varoon; Tsapatsis, Michael

Some two-dimensional (2D) exfoliated zeolites are single- or near single-unit cell thick silicates that can function as molecular sieves. Although they have already found uses as catalysts, adsorbents and membranes precise determination of their thickness and wrinkling is critical as these properties influence their functionality. Here we demonstrate a method to accurately determine the thickness and wrinkles of a 2D zeolite nanosheet by comprehensive 3D mapping of its reciprocal lattice. Since the intensity modulation of a diffraction spot on tilting is a fingerprint of the thickness, and changes in the spot shape are a measure of wrinkling, this mapping ismore » achieved using a large-angle tilt-series of electron diffraction patterns. As a result, application of the method to a 2D zeolite with MFI structure reveals that the exfoliated MFI nanosheet is 1.5 unit cells (3.0 nm) thick and wrinkled anisotropically with up to 0.8 nm average surface roughness.« less

Quantification of thickness and wrinkling of exfoliated two-dimensional zeolite nanosheets

DOE PAGES

Kumar, Prashant; Agrawal, Kumar Varoon; Tsapatsis, Michael; ...

2015-05-11

Some two-dimensional (2D) exfoliated zeolites are single- or near single-unit cell thick silicates that can function as molecular sieves. Although they have already found uses as catalysts, adsorbents and membranes precise determination of their thickness and wrinkling is critical as these properties influence their functionality. Here we demonstrate a method to accurately determine the thickness and wrinkles of a 2D zeolite nanosheet by comprehensive 3D mapping of its reciprocal lattice. Since the intensity modulation of a diffraction spot on tilting is a fingerprint of the thickness, and changes in the spot shape are a measure of wrinkling, this mapping ismore » achieved using a large-angle tilt-series of electron diffraction patterns. As a result, application of the method to a 2D zeolite with MFI structure reveals that the exfoliated MFI nanosheet is 1.5 unit cells (3.0 nm) thick and wrinkled anisotropically with up to 0.8 nm average surface roughness.« less

Botulinum toxin for the treatment of strabismus.

PubMed

Rowe, Fiona J; Noonan, Carmel P

2017-03-02

The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further

Detecting and discriminating among Shiga toxins

USDA-ARS?s Scientific Manuscript database

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

Botulinum Toxin and Gastrointestinal Tract Disorders

PubMed Central

Weiser, Kirsten; Kennedy, Abigail

2008-01-01

The history of botulinum toxin is fascinating. First recognized as the cause of botulism nearly 200 years ago, it was originally feared as a deadly poison. Over the last 30 years, however, botulinum toxin has been transformed into a readily available medication used to treat a variety of medical disorders. Interest in the use of botulinum toxin has been particularly strong for patients with spastic smooth muscle disorders of the gastrointestinal tract. Patients with achalasia, diffuse esophageal spasm, gastroparesis, sphincter of Oddi dysfunction, and anal fissures have all been treated with botulinum toxin injections, often with impressive results. However, not all patients respond to botulinum toxin therapy, and large randomized controlled trials are lacking for many conditions commonly treated with botulinum toxin. This paper reviews the history, microbiology, and pharmacology of botulinum toxin, discusses its mechanism of action, and then presents recent evidence from the literature regarding the use of botulinum toxin for the treatment of a variety of gastrointestinal tract disorders. PMID:21960915

Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.

PubMed

Pavlik, Benjamin J; Hruska, Elizabeth J; Van Cott, Kevin E; Blum, Paul H

2016-03-30

Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.