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1

Cistrons encoding Escherichia coli heat-labile toxin.  

PubMed Central

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

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

1979-01-01

2

Activation of Cholera Toxin and E. Coli Heat-Labile Enterotoxin (LT) by Arf  

Microsoft Academic Search

Cholera (CT) and heat labile E. coli (LT) enterotoxins are members of the AB5 family of bacterial toxins that contain one catalytically active A subunit associated with a complex of five B subunits.\\u000a The B subunits of CT and LT bind the receptor, ganglioside GM1, at the cell surface as a required first step in entry of the\\u000a holotoxin into

G. Pacheco-Rodriguez; Naoko Morinaga; Masatoshi Noda; J. Moss; M. Vaughan

3

Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.  

PubMed Central

Cholera and the related Escherichia coli-associated diarrheal disease are important problems confronting Third World nations and any area where water supplies can become contaminated. The disease is extremely debilitating and may be fatal in the absence of treatment. Symptoms are caused by the action of cholera toxin, secreted by the bacterium Vibrio cholerae, or by a closely related heat-labile enterotoxin, produced by Escherichia coli, that causes a milder, more common traveler's diarrhea. Both toxins bind receptors in intestinal epithelial cells and insert an enzymatic subunit that modifies a G protein associated with the adenylate cyclase complex. The consequent stimulated production of cyclic AMP, or other factors such as increased synthesis of prostaglandins by intoxicated cells, initiates a metabolic cascade that results in the excessive secretion of fluid and electrolytes characteristic of the disease. The toxins have a very high degree of structural and functional homology and may be evolutionarily related. Several effective new vaccine formulations have been developed and tested, and a growing family of endogenous cofactors is being discovered in eukaryotic cells. The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins. This information may improve our understanding of the disease process itself, as well as illuminate the role of the toxin in studies of signal transduction and G-protein function. Images PMID:1480112

Spangler, B D

1992-01-01

4

Differential Biological and Adjuvant Activities of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin Hybrids  

PubMed Central

Two bacterial products that have been demonstrated to function as mucosal adjuvants are cholera toxin (CT), produced by various strains of Vibrio cholerae, and the heat-labile enterotoxin (LT) produced by some enterotoxigenic strains of Escherichia coli. Although LT and CT have many features in common, they are clearly distinct molecules with biochemical and immunologic differences which make them unique. The goal of this study was to determine the basis for these biological differences by constructing and characterizing chimeric CT-LT molecules. Toxin gene fragments were subcloned to create two constructs, each expressing the enzymatically active A subunit of one toxin and the receptor binding B subunit of the other toxin. These hybrid toxins were purified, and the composition and assembly of CT A subunit (CT-A)-LT B subunit (LT-B) and LT A subunit (LT-A)-CT B subunit (CT-B) were confirmed. Hybrids were evaluated for enzymatic activity, as measured by the accumulation of cyclic AMP in Caco-2 cells, and the enterotoxicity of each toxin was assessed in a patent-mouse assay. The results demonstrated that LT-A–CT-B induces the accumulation of lower levels of cyclic AMP and has less enterotoxicity than either wild-type toxin or the other hybrid. Nonetheless, this hybrid retains adjuvant activity equivalent to or greater than that of either wild-type toxin or the other hybrid when used in conjunction with tetanus toxoid for intranasal immunization of BALB/c mice. Importantly, the ability of LT to induce a type 1 cytokine response was found to be a function of LT-A. Specifically, LT-A–CT-B was able to augment the levels of antigen-specific gamma interferon (IFN-?) and interleukin 5 to levels comparable to those achieved with native LT, while CT-A–LT-B and native CT both produced lower levels of antigen-specific IFN-?. Thus, these toxin hybrids possess unique biological characteristics and provide information about the basis for differences in the biological activities observed for CT and LT. PMID:11179323

Bowman, Christal C.; Clements, John D.

2001-01-01

5

Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant  

PubMed Central

Native type I heat-labile toxins (LTs) produced by enterotoxigenic Escherichia coli (ETEC) strains exert strong adjuvant effects on both antibody and T cell responses to soluble and particulate antigens following co-administration via mucosal routes. However, inherent enterotoxicity and neurotoxicity (following intra-nasal delivery) had reduced the interest in the use of these toxins as mucosal adjuvants. LTs can also behave as powerful and safe adjuvants following delivery via parenteral routes, particularly for activation of cytotoxic lymphocytes. In the present study, we evaluated the adjuvant effects of a new natural LT polymorphic form (LT2), after delivery via intradermal (i.d.) and subcutaneous (s.c.) routes, with regard to both antibody and T cell responses. A recombinant HIV-1 p24 protein was employed as a model antigen for determination of antigen-specific immune responses while the reference LT (LT1), produced by the ETEC H10407 strain, and a non-toxigenic LT form (LTK63) were employed as previously characterized LT types. LT-treated mice submitted to a four dose-base immunization regimen elicited similar p24-specific serum IgG responses and CD4+ T cell activation. Nonetheless, mice immunized with LT1 or LT2 induced higher numbers of antigen-specific CD8+ T cells and in vivo cytotoxic responses compared to mice immunized with the non-toxic LT derivative. These effects were correlated with stronger activation of local dendritic cell populations. In addition, mice immunized with LT1 and LT2, but not with LTK63, via s.c. or i.d. routes developed local inflammatory reactions. Altogether, the present results confirmed that the two most prevalent natural polymorphic LT variants (LT1 or LT2) display similar and strong adjuvant effects for subunit vaccines administered via i.d. or s.c. routes. PMID:24432018

Braga, Catarina J. M.; Rodrigues, Juliana F.; Medina-Armenteros, Yordanka; Farinha-Arcieri, Luís E.; Ventura, Armando M.; Boscardin, Silvia B.; Sbrogio-Almeida, Maria E.; Ferreira, Luís C. S.

2014-01-01

6

Targeting of cholera toxin and Escherichia coli heat labile toxin in polarized epithelia: role of COOH-terminal KDEL  

Microsoft Academic Search

Vibrio cholerae and Escherichia coli heat la- bile toxins (CT and LT) elicit a secretory response from intestinal epithelia by binding apical receptors (ganglio- side GM1 ) and subsequently activating basolateral effec- tors (adenylate cyclase). We have recently proposed that signal transduction in polarized cells may require transcytosis of toxin-containing membranes (Lencer, W. I., G. Strohmeier, S. Moe, S. L.

W. I. Lencer; C. Constable; S. Moe; M. G. Jobling; H. M. Webb; S. Ruston; J. L. Madara; T. R. Hirst; R. K. Holmesll

1995-01-01

7

Multiplex PCR for detection of the heat-labile toxin gene and shiga-like toxin I and II genes in Escherichia coli isolated from natural waters.  

PubMed Central

A triplex PCR method was developed to simultaneously amplify a heat-labile toxin sequence (LT) of 258 bp, a shiga-like toxin I sequence (SLT I) of 130 bp, and a shiga-like toxin II sequence (SLT II) of 346 bp from toxigenic strains of Escherichia coli. This method was used to screen 377 environmental E. coli isolates from marine waters or estuaries located in Southern California and North Carolina for enterotoxigenic or enterohemorrhagic E. coli strains. Of the 377 E. coli screened, one isolate was found to belong to the enterotoxigenic group, since it contained a LT homologous sequence, and one isolate was found to belong to the enterohemorrhagic group, since it contained a SLT I homologous sequence. None was found to contain SLT II homologous sequences. The pathogenicity of the positive environmental E. coli isolates was confirmed by standard bioassays with Y-1 adrenal cells and Vero cells to confirm toxin production. Our results suggest that toxigenic E. coli occurs infrequently in environmental waters and that there is a low public health risk from toxigenic E. coli in coastal waters. Images PMID:7944359

Lang, A L; Tsai, Y L; Mayer, C L; Patton, K C; Palmer, C J

1994-01-01

8

Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin  

PubMed Central

Background An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. Methodology/Principal Findings Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. Conclusions/Significance While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT–derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes. PMID:19756141

Lewis, David J. M.; Huo, Zhiming; Barnett, Susan; Kromann, Ingrid; Giemza, Rafaela; Galiza, Eva; Woodrow, Maria; Thierry-Carstensen, Birgit; Andersen, Peter; Novicki, Deborah; Del Giudice, Giuseppe; Rappuoli, Rino

2009-01-01

9

Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies  

PubMed Central

A long-standing challenge in developing vaccines against enterotoxigenic Escherichia coli (ETEC), the most common bacteria causing diarrhea in children of developing countries and travelers to these countries, is to protect against heat-stable toxin type Ib (STa or hSTa). STa and heat-labile toxin (LT) are virulence determinants in ETEC diarrhea. LT antigens are often used in vaccine development, but STa has not been included because of its poor immunogenicity and potent toxicity. Toxic STa is not safe for vaccines, but only STa possessing toxicity is believed to be able to induce neutralizing antibodies. However, recent studies demonstrated that nontoxic STa derivatives (toxoids), after being fused to an LT protein, induced neutralizing antibodies and suggested that different STa toxoids fused to an LT protein might exhibit different STa antigenic propensity. In this study, we selected 14 STa toxoids from a mini-STa toxoid library based on toxicity reduction and reactivity to anti-native STa antibodies, and genetically fused each toxoid to a monomeric double mutant LT (dmLT) peptide for 14 STa-toxoid-dmLT toxoid fusions. These toxoid fusions were used to immunize mice and were characterized for induction of anti-STa antibody response. The results showed that different STa toxoids (in fusions) varied greatly in anti-STa antigenicity. Among them, STaN12S, STaN12T, and STaA14H were the top toxoids in inducing anti-STa antibodies. In vitro neutralization assays indicated that antibodies induced by the 3×STaN12S-dmLT fusion antigen exhibited the greatest neutralizing activity against STa toxin. These results suggested 3×STaN12S-dmLT is a preferred fusion antigen to induce an anti-STa antibody response and provided long-awaited information for effective ETEC vaccine development. PMID:24549325

Ruan, Xiaosai; Robertson, Donald C.; Nataro, James P.; Clements, John D.

2014-01-01

10

Intranasal immunization with live recombinant Lactococcus lactis combined with heat-labile toxin B subunit protects chickens from highly pathogenic avian influenza H5N1 virus.  

PubMed

Development of safe and effective vaccines to prevent highly pathogenic avian influenza H5N1 virus infection is a challenging goal. Lactococcus lactis (L. lactis) is an ideal delivery vector for vaccine development, and it has been shown previously that oral immunization of encapsulated secretory L. lactis-hemagglutinin (HA) could provide complete protection against homologous H5N1 virus challenge in the mice model. While intranasal immunization is an appealing approach, it is now reported that secretory L. lactis-HA combined with mucosal adjuvant heat-labile toxin B subunit (LTB) could provide protective immunity in the chicken model. As compared to intranasal immunization with L. lactis-HA alone, L. lactis-HA combined with LTB (L. lactis-HA?+?LTB) could elicit robust neutralizing antibody responses and mucosal IgA responses, as well as strong cellular immune responses in the vaccinated chickens. Importantly, intranasal immunization with L. lactis-HA?+?LTB could provide 100% protection against H5N1 virus challenge. Taken together, these results suggest that intranasal immunization with L. lactis-HA?+?LTB can be considered as an effective approach for preventing and controlling infection of H5N1 virus in poultry during an avian influenza A/H5N1 pandemic. J. Med. Virol. 87: 39-44, 2015. © 2014 Wiley Periodicals, Inc. PMID:24861477

Lei, Han; Peng, Xiaojue; Shu, Handing; Zhao, Daxian

2015-01-01

11

Cyclic AMP Receptor Protein-Dependent Repression of Heat-Labile Enterotoxin  

Microsoft Academic Search

Enterotoxigenic Escherichia coli is a major cause of acute diarrheal illness worldwide and is responsible for high infant and child mortality rates in developing nations. Two types of enterotoxins, one heat labile and the other heat stable, are known to cause diarrhea. The expression of soluble heat-labile toxin is subject to catabolite (glucose) activation, and three binding sites for cAMP

Maria D. Bodero; George P. Munson

2009-01-01

12

Safety and immunogenicity of bacterial and tobacco plant cell line derived recombinant native and mutant Escherichia coli heat-labile toxin in chickens.  

PubMed

The safety and immunogenicity of the mammalian mucosal adjuvants, Escherichia coli wild-type heat-labile holotoxin (LT) and E. coli mutant LT (LTA-K63/LTB), were examined in 1-day-old chicks and 10-day-old to 21-day-old broilers. Biologically active, E. coli recombinant wild-type LT and recombinant LTA-K63/LTB produced in a transgenic Nicotiana tabacum (NT-1) tobacco cell line (SLT102) were tested for safety and antigenicity following various routes of administration. Safety was assessed by clinical signs, body weight gain, gross organ pathology and wet organ weight, and histopathology. Antigenicity was assessed using LT-B-specific serum IgG enzyme-linked immunosorbent assay. Parenteral administration of E. coli recombinant wild-type LT did not have any discernible effect on bird health and was well tolerated at levels up to 400 µg per dose. Recombinant, SLT102-derived mutant LT derived from SLT102 cells retained in vitro ganglioside binding and was safe and antigenic following repeated mucosal administration to birds. The highest systemic LT-B-specific IgG titres were detected in birds that received three on-feed doses of SLT102-derived mutant LT. Among the various SLT102-derived mutant LT preparations tested, whole, wet cells or whole cell lysates were the most antigenic. These results demonstrate for the first time that E. coli-derived recombinant, wild-type LT holotoxin is well tolerated following multiple administrations to young birds at body weight doses previously reported to be enteropathogenic and toxic in mammalian species. Moreover, these data also demonstrate the feasibility of using recombinant wild-type and mutant LT produced in transgenic NT-1 tobacco cells as safe and potent vaccine adjuvants in poultry. PMID:22928883

Miller, Tim; Fanton, Matthew; Nickelson, Stephanie; Mason, Hugh; Webb, Steven

2012-10-01

13

Cloning and characterization of genes encoding homologues of the B subunit of cholera toxin and the Escherichia coli heat-labile enterotoxin from clinical isolates of Citrobacter freundii and E. coli.  

PubMed

We identified and characterized a gene encoding a homologue of the B subunits of cholera toxin (CTB) and heat-labile enterotoxin (LTB) of Escherichia coli from a clinical isolate of Citrobacter freundii that was found to produce a factor in the culture supernatant that cross-reacted with antibodies to CTB and LTB when assayed by enzyme-linked immunosorbent assay (ELISA). The gene encoding the ELISA-positive factor, cfxB, consisted of 375 nucleotides and was located downstream of an 852-nucleotide open reading frame, cfxA, with a 56-nucleotide intergenic space. The cfxB gene was predicted to encode a 125-amino-acid polypeptide, which had 73.8 and 72.8% identities with the amino acid sequences of LTB and CTB, respectively. However, the amino acid sequence of the deduced polypeptide CFXA had no homologies to those of the A subunits of CT or LT. DNA probes developed from the sequences of cfxA and cfxB were used to screen 67 C. freundii isolates and 152 E. coli isolates from diarrheal patients by colony blot hybridization. Two strains, C. freundii 48 and E. coli 176, reacted with both DNA probes under conditions of high stringency. We cloned homologues of the cfxA and cfxB genes from E. coli 176 and designated them ecxA and ecxB, respectively. The ecxA gene and the ecxB gene comprise 855 and 375 nucleotides, respectively, with a 50-nucleotide intergenic space, and encode a 285- and a 125-amino-acid residue polypeptides, respectively. The results of the present study may provide important clues to the origin and evolution of immunologically related factors sharing a common enterotoxin-like A and B subunit structures. PMID:12438400

Karasawa, Tadahiro; Ito, Hideaki; Tsukamoto, Teizo; Yamasaki, Shinji; Kurazono, Hisao; Faruque, Shah M; Nair, G Balakrish; Nishibuchi, Mitsuaki; Takeda, Yoshifumi

2002-12-01

14

Evaluation of the adjuvant effect of Salmonella-based Escherichia coli heat-labile toxin B subunits on the efficacy of a live Salmonella-delivered avian pathogenic Escherichia coli vaccine.  

PubMed

The present study evaluated the adjuvant effect of live attenuated salmonella organisms expressing the heat-labile toxin of Escherichia coli B subunit (LTB) on the efficacy of an avian pathogenic Escherichia coli (APEC) vaccine. The Asd(+) (aspartate semialdehyde dehydrogenase) plasmid pMMP906 containing the LTB gene was introduced into a Salmonella enterica Typhimurium strain lacking the lon, cpxR and asd genes to generate the adjuvant strain. Live recombinant Salmonella-delivered APEC vaccine candidates were used for this study. The birds were divided into three groups: group A, non-vaccinated controls; group B, immunized with vaccine candidates only; and group C, immunized with vaccine candidates and the LTB strain. The immune responses were measured and the birds were challenged at 21 days of age with a virulent APEC strain. Group C showed a significant increase in plasma IgG and intestinal IgA levels and a significantly higher lymphocyte proliferation response compared with the other groups. Upon challenge with the virulent APEC strain, group C showed effective protection whereas group B did not. We also attempted to optimize the effective dose of the adjuvant. The birds were immunized with the vaccine candidates together with 1×10? or 1×10? colony-forming units of the LTB strain and were subsequently challenged at 3 weeks of age. The 1×10? colony-forming units of the LTB strain showed a greater adjuvant effect with increased levels of serum IgG, intestinal IgA and a potent lymphocyte proliferation response, and yielded higher protection against challenge. Overall, the LTB strain increased the efficacy of the Salmonella -delivered APEC vaccine, indicating that vaccination for APEC along with the LTB strain appears to increase the efficacy for protection against colibacillosis in broiler chickens. PMID:23815619

Chaudhari, Atul A; Lee, John Hwa

2013-08-01

15

Toward the development of a stable, freeze-dried formulation of Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of Escherichia coli heat-labile toxin.  

PubMed

No vaccine exists for the prevention of infection with the ubiquitous gastric pathogen Helicobacter pylori, and drug therapy for the infection is complicated by poor patient compliance, the high cost of treatment, and ineffectiveness against drug-resistant strains. A new medical advancement is required to reduce the incidence of peptic ulcer disease and stomach cancer, two conditions caused by infection with H. pylori. Clinical trials have been performed with a formalin-inactivated H. pylori whole cell (HWC) vaccine, given orally in combination with the mucosal adjuvant mLT(R192G), a mutant of Escherichia coli heat-labile toxin. Following the initial dose of this vaccine, some subjects experienced gastrointestinal side effects. To reduce side effects and potentially further increase the amount of adjuvant that can safely be administered with the HWC vaccine, experiments were performed with a form of LT that carried two mutations in the A subunit, a substitution of G for R at position 192, and A for L at position 211. The double mutant LT (dmLT) adjuvant stimulated immune responses as effectively as the single mutant LT in mice. Additionally, following a challenge infection, the dmLT-adjuvanted vaccine was as effective as single mutant LT in reducing gastric urease levels (diagnostic for H. pylori infection), and H. pylori colonization in the stomach as assessed by quantitative analysis of stomach homogenates. A lyophilized formulation of HWC was developed to improve stability and to potentially reduce reliance on cold chain maintenance. It was observed that a dmLT-adjuvanted lyophilized vaccine was equally as protective in the mouse model as the liquid formulation as assessed by gastric urease analysis and analysis of stomach homogenates for viable H. pylori. No readily detectable effect of tonicity or moisture content was observed for the lyophilized vaccine within the formulation limits evaluated. In an accelerated stability study performed at 37 degrees C the lyophilized vaccine remained equally as protective as vaccine stored at 2-8 degrees C. The formulation selected for clinical development consisted of 2.5 x 10(10) formalin-inactivated cells per ml in 6.5% trehalose, 0.5% mannitol, and 10mM citrate buffer at pH 6.8. PMID:19897067

Summerton, Nancy A; Welch, Richard W; Bondoc, Laureano; Yang, Huei-Hsiung; Pleune, Brett; Ramachandran, Naryaswamy; Harris, Andrea M; Bland, Desiree; Jackson, W James; Park, Sukjoon; Clements, John D; Nabors, Gary S

2010-02-01

16

Effect of site-directed mutagenic alterations on ADP-ribosyltransferase activity of the A subunit of Escherichia coli heat-labile enterotoxin.  

PubMed Central

Previous studies of the S1 subunit of pertussis toxin, an NAD(+)-dependent ADP-ribosyltransferase, suggested that a small amino-terminal region of amino acid sequence similarity to the active fragments of both cholera toxin and Escherichia coli heat-labile enterotoxin represents a region containing critical active-site residues that might be involved in the binding of the substrate NAD+. Other studies of two other bacterial toxins possessing ADP-ribosyltransferase activity, diphtheria toxin and Pseudomonas exotoxin A, have revealed the presence of essential glutamic acid residues vicinal to the active site. To help determine the relevance of these observations to activities of the enterotoxins, the A-subunit gene of the E. coli heat-labile enterotoxin was subjected to site-specific mutagenesis in the region encoding the amino-terminal region of similarity to the S1 subunit of pertussis toxin delineated by residues 6 through 17 and at two glutamic acid residues, 110 and 112, that are conserved in the active domains of all of the heat-labile enterotoxin variants and in cholera toxin. Mutant proteins in which arginine 7 was either deleted or replaced with lysine exhibited undetectable levels of ADP-ribosyltransferase activity. However, limited trypsinolysis of the arginine 7 mutants yielded fragmentation kinetics that were different from that yielded by the wild-type recombinant subunit or the authentic A subunit. In contrast, mutant proteins in which glutamic acid residues at either position 110 or 112 were replaced with aspartic acid responded like the wild-type subunit upon limited trypsinolysis, while exhibiting severely depressed, but detectable, ADP-ribosyltransferase activity. The latter results may indicate that either glutamic acid 110 or glutamic acid 112 of the A subunit of heat-labile enterotoxin is analogous to those active-site glutamic acids identified in several other ADP-ribosylating toxins. Images PMID:1908825

Lobet, Y; Cluff, C W; Cieplak, W

1991-01-01

17

Transcutaneous Immunization Using Colonization Factor and Heat-Labile Enterotoxin Induces Correlates of Protective Immunity for Enterotoxigenic Escherichia coli  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) diarrheal disease is a worldwide problem that may be addressed by transcutaneous delivery of a vaccine. In several human settings, protective immunity has been associated with immune responses to E. coli colonization factors and to the heat-labile toxin that induces the diarrhea. In this set of animal studies, transcutaneous immunization (TCI) using recombinant colonization factor CS6 and cholera toxin (CT) or heat-labile enterotoxin (LT) as the adjuvant induced immunoglobulin G (IgG) and IgA anti-CS6 responses in sera and stools and antibody responses that recognized CS6 antigen in its native configuration. The antitoxin immunity induced by TCI was also shown to protect against enteric toxin challenge. Although immunization with LT via the skin induced mucosal secretory IgA responses to LT, protection could also be achieved by intravenous injection of the immune sera. Finally, a malaria vaccine antigen, merzoite surface protein 142 administered with CT as the adjuvant, induced both merzoite surface protein antibodies and T-cell responses while conferring protective antitoxin immunity, suggesting that both antiparasitic activity and antidiarrheal activity can be obtained with a single vaccine formulation. Overall, our results demonstrate that relevant colonization factor and antitoxin immunity can be induced by TCI and suggest that an ETEC traveler's diarrhea vaccine could be delivered by using a patch. PMID:11854183

Yu, Jianmei; Cassels, Frederick; Scharton-Kersten, Tanya; Hammond, Scott A.; Hartman, Antoinette; Angov, Evelina; Corthesy, Blaise; Alving, Carl; Glenn, Gregory

2002-01-01

18

Nutritional Requirements for Synthesis of Heat-Labile Enterotoxin by Enterotoxigenic Strains of Escherichia coli  

PubMed Central

Optimal growth conditions have been established for production of heat-labile enterotoxin (LT) by both porcine and human strains of enterotoxigenic (ENT+) Escherichia coli. There were no unusual growth factor requirements, and some strains produced fairly high levels of LT in a basal salts medium containing 0.5% glucose if the pH was carefully controlled. Several amino acids markedly stimulated LT synthesis when added to the basal salts-glucose medium. Methionine and lysine were the most stimulatory for both human and porcine strains. Either aspartic acid or glutamic acid further enhanced LT synthesis in the presence of methionine and lysine, with aspartic acid being more stimulatory for porcine strains and glutamic acid more stimulatory for human strains. There were no apparent vitamin requirements and no unusual cations needed for toxin synthesis except that Fe3+ was slightly stimulatory for porcine strains. The stimulation by Fe3+ was observed only in the presence of the three amino acids, suggesting that the effect was indirect rather than on toxin synthesis. The carbon source also influenced the yield of LT. Glucose supported maximal synthesis, but other carbon sources which exhibit a high degree of catabolite repression also supported high levels of synthesis. Little or no LT was released below pH 7.0; therefore, because the pH drops during growth from 7.5 to 6.8, even in highly buffered media, it was necessary to adjust the pH to 8.0 to effect complete release of cell-associated toxin. The defined medium containing three amino acids reduced the amount of UV-absorbing material in culture supernatants about fivefold and increased LT activity for various strains from two- to fivefold over a complex Casamino Acids-yeast extract medium. Conditions found to be optimal for synthesis of LT were inhibitory for the heat-stable enterotoxin. PMID:33900

Gilligan, Peter H.; Robertson, Donald C.

1979-01-01

19

Heat-labile Enterotoxins as Adjuvants or Anti-Inflammatory Agents  

PubMed Central

Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases. PMID:20461887

Liang, Shuang; Hajishengallis, George

2010-01-01

20

Heat-labile alkaline phosphatase from Antarctic bacteria: Rapid 5? end-labeling of nucleic acids  

PubMed Central

A heat-labile alkaline phosphatase has been purified to near homogeneity from HK47, a bacterial strain isolated from Antarctic seawater. The active form of the enzyme has a molecular weight of 68,000 and is uniquely monomeric. The optimal temperature for the enzymatic activity is 25°C. Complete and irreversible thermal inactivation of the enzyme occurs in 10 min at 55°C. By using this heat-labile enzyme for dephosphorylation followed by a 10-min heat treatment, rapid end-labeling of nucleic acids by T4 polynucleotide kinase has been achieved. Images PMID:16593525

Kobori, Hiromi; Sullivan, Cornelius W.; Shizuya, Hiroaki

1984-01-01

21

Radiation-induced heat-labile sites that convert into DNA double-strand breaks  

NASA Technical Reports Server (NTRS)

The yield of DNA double-strand breaks (DSBs) in SV40 DNA irradiated in aqueous solution was found to increase by more than a factor of two as a result of postirradiation incubation of the DNA at 50 degrees C and pH 8.0 for 24 h. This is in agreement with data from studies performed at 37 degrees C that were published previously. Importantly, similar results were also obtained from irradiation of mammalian DNA in agarose plugs. These results suggest that heat-labile sites within locally multiply damaged sites are produced by radiation and are subsequently transformed into DSBs. Since incubation at 50 degrees C is typically employed for lysis of cells in commonly used pulsed-field gel assays for detection of DSBs in mammalian cells, the possibility that heat-labile sites are present in irradiated cells was also studied. An increase in the apparent number of DSBs as a function of lysis time at 50 degrees C was found with kinetics that was similar to that for irradiated DNA, although the magnitude of the increase was smaller. This suggests that heat-labile sites are also formed in the cell. If this is the case, a proportion of DSBs measured by the pulsed-field gel assays may occur during the lysis step and may not be present in the cell as breaks but as heat-labile sites. It is suggested that such sites consist mainly of heat-labile sugar lesions within locally multiply damaged sites. Comparing rejoining of DSBs measured with short and long lysis procedure indicates that the heat-labile sites are repaired with fast kinetics in comparison with repair of the bulk of DSBs.

Rydberg, B.; Chatterjee, A. (Principal Investigator)

2000-01-01

22

Fall in the heat-labile alkaline phosphatase isoenzyme levels during pregnancy in healthy Nigerians.  

PubMed

Estimation of heat-labile alkaline phosphatase isoenzyme in the serum of 45 healthy non-pregnant women and 98 women in the second and third trimesters of pregnancy revealed a statistically significant reduction of this isoenzyme during pregnancy. Variations in normal activity were also more marked in the pregnant women compared with the non-pregnant control subjects. Now that normal serum levels of the heat-labile alkaline phosphatase isoenzyme in pregnancy have been established it is possible to use estimations of the enzyme as part of the assessment of maternal liver function in pregnancy. PMID:4063229

Okpere, E; Okorodudu, A O; Gbinigie, A O

1985-11-01

23

Rapid test for identification of heat-labile enterotoxin-producing Escherichia coli colonies.  

PubMed Central

A latex particle agglutination test is described which is suitable for the recognition of heat-labile enterotoxin-producing colonies of Escherichia coli immediately after primary culture on a variety of commonly used enteric diagnostic media. The test is simple and economical to perform, and the results are available in minutes. PMID:6350351

Finkelstein, R A; Yang, Z

1983-01-01

24

Simultaneous Exposure to Escherichia coli Heat-Labile and Heat-Stable Enterotoxins Increases Fluid Secretion and Alters Cyclic Nucleotide and Cytokine Production by Intestinal Epithelial Cells.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) is a significant cause of diarrheal disease and death, especially in children in developing countries. ETEC causes disease by colonizing the small intestine and producing heat-labile toxin (LT), heat-stable toxin (ST), or both LT and ST (LT+ST). The majority of ETEC strains produce both ST and LT. Despite the prevalence of LT+ST-producing organisms, few studies have examined the physiologic or immunologic consequences of simultaneous exposure to these two potent enterotoxins. In the current report, we demonstrate that when LT and ST are both present, they increase water movement into the intestinal lumen over and above the levels observed with either toxin alone. As expected, cultured intestinal epithelial cells increased their expression of intracellular cyclic GMP (cGMP) when treated with ST and their expression of intracellular cyclic AMP (cAMP) when treated with LT. When both toxins were present, cGMP levels but not cAMP levels were synergistically elevated compared with the levels of expression caused by the corresponding single-toxin treatment. Our data also demonstrate that the levels of inflammatory cytokines produced by intestinal epithelial cells in response to LT are significantly reduced in animals exposed to both enterotoxins. These findings suggest that there may be complex differences between the epithelial cell intoxication and, potentially, secretory outcomes induced by ETEC strains expressing LT+ST compared with strains that express LT or ST only. Our results also reveal a novel mechanism wherein ST production may reduce the hosts' ability to mount an effective innate or adaptive immune response to infecting organisms. PMID:25287923

Read, Lisa T; Hahn, Rachel W; Thompson, Carli C; Bauer, David L; Norton, Elizabeth B; Clements, John D

2014-12-01

25

Detection by a staphylococcal coagglutination test of heat-labile enterotoxin-producing enterotoxigenic Escherichia coli.  

PubMed Central

For detection of heat-labile enterotoxin-producing enterotoxigenic Escherichia coli, the staphylococcal coagglutination test reported by Brill et al. (J. Clin. Microbiol. 9:49-55, 1979) was modified to give better results. Staphylococcal cells were sensitized with anti-heat-labile enterotoxin antiserum and suspended in phosphate-buffered saline containing 0.5% bovine serum albumin, 0.05% Tween 80, 0.01% gelatin, and 0.02% NaN3. The test strain was cultured in 0.25 ml of Biken broth no. 2 in a test tube (12 by 100 mm) stood at an inclination of about 10 degrees to the horizontal. After incubation for 5 h at 37 degrees C, the cells were collected by centrifugation at 2,500 rpm for 15 min and suspended in 50 microliters of polymyxin B solution (20,000 IU/ml). The suspension was then incubated for 1 h at 37 degrees C and centrifuged at 2,500 rpm for 15 min, and 10 microliters of the supernatant was used for the test on a slide. The results of the modified test correlated completely with those obtained by the Biken test. The modifications of the staphylococcal coagglutination test described here allow for detection of heat-labile enterotoxin-producing enterotoxigenic E. coli within 6 to 7 h after inoculation of a test strain. Images PMID:6343418

Honda, T; Samakoses, R; Sornchai, C; Takeda, Y; Miwatani, T

1983-01-01

26

Type II Heat-Labile Enterotoxins from 50 Diverse Escherichia coli Isolates Belong Almost Exclusively to the LT-IIc Family and May Be Prophage Encoded  

PubMed Central

Some enterotoxigenic Escherichia coli (ETEC) produce a type II heat-labile enterotoxin (LT-II) that activates adenylate cyclase in susceptible cells but is not neutralized by antisera against cholera toxin or type I heat-labile enterotoxin (LT-I). LT-I variants encoded by plasmids in ETEC from humans and pigs have amino acid sequences that are ?95% identical. In contrast, LT-II toxins are chromosomally encoded and are much more diverse. Early studies characterized LT-IIa and LT-IIb variants, but a novel LT-IIc was reported recently. Here we characterized the LT-II encoding loci from 48 additional ETEC isolates. Two encoded LT-IIa, none encoded LT-IIb, and 46 encoded highly related variants of LT-IIc. Phylogenetic analysis indicated that the predicted LT-IIc toxins encoded by these loci could be assigned to 6 subgroups. The loci corresponding to individual toxins within each subgroup had DNA sequences that were more than 99% identical. The LT-IIc subgroups appear to have arisen by multiple recombinational events between progenitor loci encoding LT-IIc1- and LT-IIc3-like variants. All loci from representative isolates encoding the LT-IIa, LT-IIb, and each subgroup of LT-IIc enterotoxins are preceded by highly-related genes that are between 80 and 93% identical to predicted phage lysozyme genes. DNA sequences immediately following the B genes differ considerably between toxin subgroups, but all are most closely related to genomic sequences found in predicted prophages. Together these data suggest that the LT-II loci are inserted into lambdoid type prophages that may or may not be infectious. These findings raise the possibility that production of LT-II enterotoxins by ETEC may be determined by phage conversion and may be activated by induction of prophage, in a manner similar to control of production of Shiga-like toxins by converting phages in isolates of enterohemmorhagic E. coli. PMID:22242186

Jobling, Michael G.; Holmes, Randall K.

2012-01-01

27

Highly labile elements  

Microsoft Academic Search

Certain elements of high lability are very responsive to thermal processes, being either highly volatile during primary nebular condensation or highly mobile by postaccretionary metamorphic or shock heating. Data for highly labile elements indicate that different thermal processes were important in the genesis of each of the chondritic groups and a discussion of each is given. Contents of highly labile

Michael E. Lipschutz; Dorothy S. Woolum

1988-01-01

28

Induction of heat labile alkaline phosphatase by butyrate in differentiating endometrial cells.  

PubMed

The addition of 2 mM sodium butyrate to monolayers enhances differentiation of Ishikawa endometrial cells. Cells from this cell line have been shown to enlarge and lift off the dish into dome structures over a period of 24-48 h in response to a factor in fetal bovine serum (FBS) [Fleming, 1995 J Cell Biochem in press]. When butyrate is added to monolayers, together with FBS, three- to fourfold higher numbers of differentiated structures, domes and predomes, can be counted. It had previously been shown [Holinka et al., 1986b] that estradiol induces heat stable placental alkaline phosphatase in Ishikawa cells. The addition of butyrate, on the other hand, results in a significant increase in levels of a heat labile alkaline phosphatase isozyme. The heat labile isozyme is also increased to some extent in cells stimulated to differentiate in response to FBS in the absence of butyrate. Differential inhibition by homoarginine and phenylalanine indicates that butyrate is inducing the liver-bone kidney isozyme that is found in endometrial glands in vivo. PMID:7593273

Fleming, H; Begley, M; Campi, T; Condon, R; Dobyns, K; McDonagh, J; Wallace, S

1995-08-01

29

Serotype-related differences in production and type of heat-labile hemolysin and heat-labile cytotoxin of Actinobacillus (Haemophilus) pleuropneumoniae.  

PubMed

Reference strains of serotypes 1 to 12 of Actinobacillus (Haemophilus) pleuropneumoniae were cultured in Eagle minimal essential medium with 10% Serum Plus. Culture supernatants were examined for cytotoxicity to alveolar macrophages and for the ability to hemolyze sheep erythrocytes. All strains except the reference strain of serotype 6 produced cytotoxin, whereas only serotypes 1, 5, 9, 10, and 11 produced hemolysin. Both cytotoxin and hemolysin appeared to be heat labile. Antisera were raised against cytotoxin- and hemolysin-containing culture supernatants of serotypes 1 to 11. Cross-neutralization studies revealed that the hemolysins were serologically homogeneous. In contrast, four serologically different cytotoxins were distinguished. One cytotoxin was produced by serotypes 1, 5, 9, and 11, and a second was produced by serotypes 2, 3, 4, and 8. A third cytotoxin was produced by serotypes 7 and 12; this cytotoxin was related to the cytotoxins of serotypes 1, 2, 4, 5, 9, and 11. A fourth cytotoxin, produced by serotype 10, was related to the cytotoxin of serotypes 1, 5, 9, and 11. Seventy field strains belonging to serotypes 2, 3, 7, 8, 9, and 11 were also tested for production of cytotoxin and hemolysin. All strains belonging to serotypes 9 and 11 produced hemolysin and cytotoxin, whereas all strains of serotypes 2, 3, 7, and 8 produced only cytotoxin. Hemolysins and cytotoxins of both the field strains and the corresponding serotype reference strains were comparably neutralized. These findings strongly suggest that the observed differences in production and type of hemolysin and cytotoxin were related to serotype and not to strain. PMID:2526820

Kamp, E M; van Leengoed, L A

1989-06-01

30

Force relaxation, labile heat and parvalbumin content of skeletal muscle fibres of Xenopus laevis.  

PubMed

1. Measurements were made of stable (hb) and labile (ha) maintenance heat rate, slowing of relaxation as a function of tetanus duration, and parvalbumin (PA) content in intact single muscle fibres of types 1 and 2 from Xenopus laevis. The majority of experiments were performed at 20 degrees C. In addition, total and myofibrillar ATPase activity was measured in skinned Xenopus fibres, also of types 1 and 2; these studies were performed at 4 degrees C. 2. In agreement with a previous study hb was significantly higher in type 1 (175 +/- 13 mW (g wet wt)-1; n = 8) than in type 2 fibres (88 +/- 9 mW (g wet wt)-1; n = 7). The value of ha was 236 +/- 22 and 117 +/- 16 mW (g wet wt)-1, respectively (mean +/- S.E.M.). ha decayed with a time constant of 0.27 +/- 0.02 (n = 8) and 0.33 +/- 0.02 s (n = 7). 3. The early relaxation rate of tetanic force, extrapolated to the onset of stimulation (yo + yb; where yo is 'extra' rate of relaxation and yb steady rate) was 85.6 +/- 4.2 s-1 for type 1 fibres (n = 8) and 62.7 +/- 7.3 s-1 for type 2 fibres (n = 7). Relaxation rate at the end of a 1.8 s tetanus (yb) was 29.4 +/- 1.6 and 33.3 +/- 1.5 s-1, respectively; thus, there was more slowing with tetanus duration in type 1 fibres. The time constant for slowing of relaxation with tetanus duration was similar to that for decay of ha. 4. Parvalbumin concentration, [PA], was 0.45 +/- 0.04 mM in type 1 (n = 7) and 0.22 +/- 0.04 mM (n = 7) in type 2 fibres. 5. For individual fibres positive correlations were found between the 'extra' rate of relaxation (yo), labile heat (ha) and [PA]. Significantly more labile heat was liberated than can be accounted for by the enthalpy change of Ca2+ binding to PA. 6. For five fibres (type 1) studied both at 20 and 10 degrees C, the magnitude of slowing of relaxation, expressed as yo/(yo + yb), was 0.58 +/- 0.03 at 20 degrees C and 0.65 +/- 0.03 at 10 degrees C. 7. Both slowing of relaxation and labile heat were depressed in the second of two closely spaced tetani in type 1 fibres. Repriming of both effects followed similar, biphasic time courses and required more than 10 min for completion at 20 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8246178

Lännergren, J; Elzinga, G; Stienen, G J

1993-04-01

31

Force relaxation, labile heat and parvalbumin content of skeletal muscle fibres of Xenopus laevis.  

PubMed Central

1. Measurements were made of stable (hb) and labile (ha) maintenance heat rate, slowing of relaxation as a function of tetanus duration, and parvalbumin (PA) content in intact single muscle fibres of types 1 and 2 from Xenopus laevis. The majority of experiments were performed at 20 degrees C. In addition, total and myofibrillar ATPase activity was measured in skinned Xenopus fibres, also of types 1 and 2; these studies were performed at 4 degrees C. 2. In agreement with a previous study hb was significantly higher in type 1 (175 +/- 13 mW (g wet wt)-1; n = 8) than in type 2 fibres (88 +/- 9 mW (g wet wt)-1; n = 7). The value of ha was 236 +/- 22 and 117 +/- 16 mW (g wet wt)-1, respectively (mean +/- S.E.M.). ha decayed with a time constant of 0.27 +/- 0.02 (n = 8) and 0.33 +/- 0.02 s (n = 7). 3. The early relaxation rate of tetanic force, extrapolated to the onset of stimulation (yo + yb; where yo is 'extra' rate of relaxation and yb steady rate) was 85.6 +/- 4.2 s-1 for type 1 fibres (n = 8) and 62.7 +/- 7.3 s-1 for type 2 fibres (n = 7). Relaxation rate at the end of a 1.8 s tetanus (yb) was 29.4 +/- 1.6 and 33.3 +/- 1.5 s-1, respectively; thus, there was more slowing with tetanus duration in type 1 fibres. The time constant for slowing of relaxation with tetanus duration was similar to that for decay of ha. 4. Parvalbumin concentration, [PA], was 0.45 +/- 0.04 mM in type 1 (n = 7) and 0.22 +/- 0.04 mM (n = 7) in type 2 fibres. 5. For individual fibres positive correlations were found between the 'extra' rate of relaxation (yo), labile heat (ha) and [PA]. Significantly more labile heat was liberated than can be accounted for by the enthalpy change of Ca2+ binding to PA. 6. For five fibres (type 1) studied both at 20 and 10 degrees C, the magnitude of slowing of relaxation, expressed as yo/(yo + yb), was 0.58 +/- 0.03 at 20 degrees C and 0.65 +/- 0.03 at 10 degrees C. 7. Both slowing of relaxation and labile heat were depressed in the second of two closely spaced tetani in type 1 fibres. Repriming of both effects followed similar, biphasic time courses and required more than 10 min for completion at 20 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8246178

Lannergren, J; Elzinga, G; Stienen, G J

1993-01-01

32

Heat-labile enterotoxigenic Escherichia coli and intestinal protozoa in asymptomatic travellers.  

PubMed

Thirty-two asymptomatic travellers who had recently journeyed in the Near, Middle, and Far East and had experienced a high incidence of diarrhoeal disease were screened for heat-labile enterotoxigenic Escherichia coli (ent+ E. coli) and other bacterial and parasitic pathogens. Six percent were colonized with ent+ E. coli and while other bacterial pathogens were not found, the intestinal protozoa Giardia lamblia (13%), Entamoeba histolytica (6%), Entamoeba coli (6%), Endolimax nana (6%), and Entamoeba hartmanni (3%) were detected in the stools. Ent+ E. coli, G. lamblia and E. histolytica should be considered in the differential diagnosis of gastrointestinal disease in travellers returning from the Orient. Furthermore, these travellers may be a potential source for the introduction of ent+ E. coli into communities where such organisms are relatively rare. PMID:351820

Echeverria, P; Cross, J H

1977-12-01

33

Modulation of B lymphocyte signalling by the B subunit of Escherichia coli heat-labile enterotoxin.  

PubMed

The non-toxic B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a potent mucosal adjuvant and immunomodulator capable of blocking autoimmune disease. These effects are linked with its ability to modulate lymphocyte populations--a feature that is dependent on binding to ubiquitously expressed cell surface receptors. Here, we demonstrate that EtxB can trigger up-regulated expression of class II MHC and CD25 on purified populations of B lymphocytes, suggesting that EtxB can directly activate biochemical signalling pathways in these cells. The nature of the intracellular signalling events was investigated. B cells cultured with EtxB, but not a non-receptor binding mutant protein, EtxB(G33D), caused the activation of the extracellular signal-regulated kinase (Erk) forms of mitogen-activated protein (MAP) kinase in a process that was dependent on MAPK/Erk kinase (MEK), phosphoinositide 3-kinase (PI3-kinase) and protein kinase C (PKC), as determined by the use of specific inhibitors. PI3-kinase was critical not only in the activation of MAP kinase but also in the up-regulation of both class II and CD25. However, MEK inhibition only partially abrogated the EtxB-mediated up-regulation of MHC class II expression and did not affect CD25 expression--findings suggesting that additional pathways downstream of PI3-kinase are involved. A role for PKC in these processes was suggested by the finding that inhibitors of PKC completely blocked EtxB-mediated CD25 up-regulation. Thus, we have shown that receptor binding by EtxB triggers multiple signalling pathways in B cells that regulate the expression of key cell surface molecules. PMID:12039916

Bone, Heather; Eckholdt, Stephanie; Williams, Neil A

2002-06-01

34

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model  

PubMed Central

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea. PMID:24146989

Zhang, Chengxian; Knudsen, David E.; Liu, Mei; Robertson, Donald C.; Zhang, Weiping

2013-01-01

35

Expression of the B subunit of E. coli heat-labile enterotoxin in tobacco using a herbicide resistance gene as a selection marker  

Microsoft Academic Search

The B subunit of Escherichia coli heat-labile enterotoxin (LTB) has been transformed to plants for use as an edible vaccine. We have developed a simple and reliable Agrobacterium-mediated transformation method to express synthetic LTB gene in N. tabacum using a phosphinothricin acetyltransferase (bar) gene as a selectable marker. The synthetic LTB gene adapted to the coding sequence of tobacco plants

Tae-Jin Kang; So-Chon Han; Moon-Sik Yang

2005-01-01

36

Molecular comparison of plasmids encoding heat-labile enterotoxin isolated from Escherichia coli strains of human origin.  

PubMed

The molecular properties of enterotoxin (Ent) plasmids from 12 Escherichia coli strains of human origin were examined. Ten strains belonged to the O78 serogroup, and the remainder were of serogroup O7 or O159. Eleven plasmids coded for heat-labile enterotoxin (LT), and one coded for heat-stable enterotoxin (ST) and LT. The results of restriction enzyme digests and deoxyribonucleic acid reassociation experiments showed that all of the Ent plasmids were related, and supported the subdivision of the LT plasmids into three groups based on their genetic properties (M. M. McConnell et al., J. Bacteriol. 143: 158-167, 1980). Within group 1, two plasmids from South African strains were indistinguishable but differed in EcoRI and HindIII digests from the LT plasmid that originated from an Ethiopian strain. The three plasmids had >70% homology. The two non-autotransferring group 2 plasmids identified in O78.H11 strains from Bangladesh were indistinguishable. The group 3 plasmids were from strains belonging to serogroups O7 and O78 isolated in Bangladesh, India, and Thailand. They shared >95% homology but showed slight differences in fragment patterns when treated with EcoRI and HindIII. There was 60 to 70% homology between the plasmids of groups 1 and 3, and the group 2 plasmid had 40 to 50% homology with members of these two groups. The autotransferring Ent plasmids had up to 40% homology with R factors of incompatibility groups FI, FII, and FIV. PMID:6249787

Willshaw, G A; Barclay, E A; Smith, H R; McConnell, M M; Rowe, B

1980-07-01

37

The suppressive activities of six sources of medicinal ferns known as gusuibu on heat-labile enterotoxin-induced diarrhea.  

PubMed

Diarrheal disease is one of the most important worldwide health problems. Enterotoxigenic Escherichia coli (ETEC) is the most frequently isolated enteropathogen in diarrheal diseases. In developing countries, a very large number of people, especially children, suffer from diarrhea. To combat this problem, World Health Organization has constituted the Diarrhea Diseases Control Program which guides studies on traditional medicinal practices and preventive measures. Gusuibu, a traditional folk medicine, has been claimed to heal certain types of diarrhea. However, so far no scientific study has been carried out on the anti-diarrheal mechanism of Gusiubu. The present study was performed to examine the suppressive activities of ethanol extracts of six sources of folk medicinal ferns used as Gusuibu on heat-labile enterotoxin (LT)-induced diarrhea. Inhibitory effects of six sources were evaluated on the ETEC LT subunit B (LTB) and monosialotetrahexosylganglioside (GMI) interaction by GM1-enzyme linked immunosorbent assay and patent mouse gut assay. Our results indicated that Drynaria fortunei had no anti-diarrheal effect, while, among the remaining five folk medicinal ferns, four belonging to family Davalliaceae had significant abilities on both the blocking of LTB and GM1 interaction and the inhibition of LT-induced diarrhea. In conclusion, these findings suggested the potential application of Gusuibu as an anti-diarrheal remedy. PMID:24552982

Chang, Hung-Chi; Chen, Jaw-Chyun; Yang, Jiun-Long; Tsay, Hsin-Sheng; Hsiang, Chien-Yun; Ho, Tin-Yun

2014-01-01

38

Peracetic acid: a practical agent for sterilizing heat-labile polymeric tissue-engineering scaffolds.  

PubMed

Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering. PMID:24341350

Yoganarasimha, Suyog; Trahan, William R; Best, Al M; Bowlin, Gary L; Kitten, Todd O; Moon, Peter C; Madurantakam, Parthasarathy A

2014-09-01

39

Inhibition of Cronobacter sakazakii by heat labile bacteriocins produced by probiotic LAB isolated from healthy infants.  

PubMed

Cronobacter sakazakii is an opportunistic pathogen that can cause bacteremia, meningitis, and necrotizing enterocolitis, most often in neonates with case-fatality rates that may reach 80%. The antimicrobial activity of lactic acid bacteria against a wide range of foodborne pathogens is well-established in different types of food products. The objective of the current study was to investigate the antibacterial activity of Lactobacillus acidophilus and L. casei isolated from feces of healthy infants against different strains of C. sakazakii in agar and a rehydrated infant milk formula (RIMF) model. The inhibition zones of C. sakazakii around L. acidophilus or L. casei ranged from 22 to 32 mm on eMan Rogosa Sharpe (MRS) agar under aerobic conditions, while a slight reduction in antibacterial activity was noted on modified MRS (0.2% glucose) under anaerobic conditions. It was observed that pH-neutralized cell-free supernatant (CFS) of L. acidophilus or L. casei was inhibitory against tested C. sakazakii strains. The inhibition zones of neutralized CFS were lower than the antibacterial activities of live cultures. The antibacterial activity of CFS was abolished when CFS from L. acidophilus or L. casei was heated at 60 or 80 °C for either 10 min or 2 h, or treated with trypsin or pepsin. This was considered strong evidence that the inhibition was due to the production of bacteriocins by L. casei and L. acidophilus. Both the CFS and active growing cells of L. casei and L. acidophilus were able to reduce the viability of C. sakazakii in the RIMF model. The results may extend the use of natural antimicrobials instead of conventional preservation methods to improve the safety of RIMF. PMID:23924352

Awaisheh, Saddam S; Al-Nabulsi, Anas A; Osaili, Tareq M; Ibrahim, Salam; Holley, Richard

2013-09-01

40

Glucose Significantly Enhances Enterotoxigenic Escherichia coli Adherence to Intestinal Epithelial Cells through Its Effects on Heat-Labile Enterotoxin Production  

PubMed Central

The present study tested whether exposure of enterotoxigenic Escherichia coli (ETEC) to glucose at different concentrations in the media results in increased bacterial adherence to host cells through increased heat-labile enterotoxin (LT) production, thereby suggesting the effects are physiological. Porcine-origin ETEC strains grown in Casamino acid yeast extract medium containing different concentrations of glucose were washed and inoculated onto IPEC-J2 porcine intestinal epithelial cells to test for effects on adherence and host cell cAMP concentrations. Consistent with previous studies, all LT+ strains had higher ETEC adherence to IPEC-J2 cells than did LT? strains. Adherence of the LT? but not the LT+ strains was increased by pre-incubating the IPEC-J2 cells with LT and decreased by co-incubation with GM1 ganglioside in a dose-dependent manner (P<0.05). To determine whether the glucose concentration of the cell culture media has an effect on adherence, IPEC-J2 cells were inoculated with LT+ or LT? strains in cell culture media containing a final glucose concentration of 0, 0.25, 0.5, 1.0 or 2.0%, and incubated for 4 h. Only media containing 0.25% glucose resulted in increased adherence and cAMP levels, and this was limited to IPEC-J2 cells inoculated with LT+ strains. This study supports the hypothesis that glucose, at a concentration optimal for LT expression, enhances bacterial adherence through the promotion of LT production. Hence, these results establish the physiological relevance of the effects of glucose on LT production and provide a basis for how glucose intake may influence the severity of ETEC infection. PMID:25409235

Wijemanne, Prageeth; Moxley, Rodney A.

2014-01-01

41

Trivalent heat-labile- and heat-stable-enterotoxin probe conjugated with horseradish peroxidase for detection of enterotoxigenic Escherichia coli by hybridization.  

PubMed Central

A 1,268-bp polynucleotide probe for heat-labile and heat-stable enterotoxins (LTh, STIa, STIb) was conjugated with horseradish peroxidase (HRP). The HRP-conjugated trivalent probe was applied to the detection of enterotoxigenic Escherichia coli (ETEC) by colony and stool hybridizations. The binding of the probe to its targets was assayed by the addition of HRP substrates hydrogen peroxide and luminol in the presence of an enhancer, and the chemiluminescence was recorded by exposure to X-ray film. Slot blot hybridization demonstrated that the HRP-conjugated trivalent probe specifically hybridized with the DNA isolated from ETEC strains. The trivalent probe also specifically identified bacterial colonies of ETEC that produced LTh, STIa, STIb, LTh-STIa, or LTh-STIb. Treatment of targets with sodium dodecyl sulfate and proteinase K remarkably reduced nonspecific hybridization to DNAs of non-ETEC strains. Furthermore, this probe was able to detect stool specimens seeded with 10(2) original ETEC cells per 5 mg of feces. These results suggest that the HRP-conjugated trivalent probe is a candidate for use in the clinical laboratory to detect ETEC. Images PMID:2279991

Abe, A; Komase, K; Bangtrakulnonth, A; Ratchtrachenchat, O A; Kawahara, K; Danbara, H

1990-01-01

42

Functional Pentameric Formation via Coexpression of the Escherichia coli Heat-Labile Enterotoxin B Subunit and Its Fusion Protein Subunit with a Neutralizing Epitope of ApxIIA Exotoxin Improves the Mucosal Immunogenicity and Protection against Challenge by Actinobacillus pleuropneumoniae?  

PubMed Central

A coexpression strategy in Saccharomyces cerevisiae using episomal and integrative vectors for the Escherichia coli heat-labile enterotoxin B subunit (LTB) and a fusion protein of an ApxIIA toxin epitope produced by Actinobacillus pleuropneumoniae coupled to LTB, respectively, was adapted for the hetero-oligomerization of LTB and the LTB fusion construct. Enzyme-linked immunosorbent assay (ELISA) with GM1 ganglioside indicated that the LTB fusion construct, along with LTB, was oligomerized to make the functional heteropentameric form, which can bind to receptors on the mucosal epithelium. The antigen-specific antibody titer of mice orally administered antigen was increased when using recombinant yeast coexpressing the pentameric form instead of recombinant yeast expressing either the LTB fusion form or antigen alone. Better protection against challenge infection with A. pleuropneumoniae was also observed for coexpression in recombinant yeast compared with others. The present study clearly indicated that the coexpression strategy enabled the LTB fusion construct to participate in the pentameric formation, resulting in an improved induction of systemic and mucosal immune responses. PMID:22030372

Kim, Jung-Mi; Park, Seung-Moon; Kim, Jung-Ae; Park, Jin-Ah; Yi, Min-Hee; Kim, Nan-Sun; Bae, Jong-Lye; Park, Sung Goo; Jang, Yong-Suk; Yang, Moon-Sik; Kim, Dae-Hyuk

2011-01-01

43

Shiga toxin-2 enhances heat-shock-induced apoptotic cell death in cultured and primary glial cells.  

PubMed

The blood-brain barrier (BBB) selectively controls the homeostasis of the central nervous system (CNS) environment using specific structural and biochemical features of the endothelial cells, pericytes, and glial limitans. Glial cells, which represent the cellular components of the mature BBB, are the most numerous cells in the brain and are indispensable for neuronal functioning. We investigated the effects of Shiga toxin on glial cells in vitro. Shiga toxin failed to inhibit cell proliferation but attenuated expression of heat shock protein 70, which is one of the chaperone proteins, in cultured and primary glial cells. Furthermore, the combination of Shiga toxin and a heat shock procedure induced cell apoptosis and decreased cell proliferation in both cells. Thus, we speculate that glial cell death in response to the combination of Shiga toxin and heat shock might weaken the BBB and induce central nervous system complications. PMID:25200685

Sugimoto, Naotoshi; Toma, Tomoko; Shimizu, Masaki; Kuroda, Mondo; Wada, Taizo; Yachie, Akihiro

2014-10-01

44

Bacteria and their toxins tamed for immunotherapy.  

PubMed

Bacterial toxins share the ability to enter host cells to target various intracellular proteins and to modulate host immune responses. Over the last 20 years, toxins and their mutated variants, as well as live attenuated bacteria, have been exploited for vaccination and immunotherapy of various infectious, malignant and autoimmune diseases. The ability of Bordetella pertussis adenylate cyclase toxin to translocate its adenylate cyclase domain across the host cell membrane, as well as the pathways of intracellular trafficking of Bacillus anthracis lethal and edema toxins, Shigella dysenteriae shiga toxin or Escherichia coli shiga-like toxin, have been repeatedly exploited for the delivery of antigenic epitopes into host cells and for stimulation of antigen-specific T cell responses. Similarly, E. coli ?-hemolysin, or effector proteins of Yersinia and Salmonella secreted by the type III secretion systems, were used to facilitate the delivery of fused heterologous proteins or peptides for antigenic presentation. Vibrio cholerae cholera toxin, E. coli heat-labile enterotoxin, B. pertussis pertussis toxin or the Cry1A protein of Bacillus thuringiensis have shown a great potential to act as adjuvants and to stimulate mucosal as well as systemic immune responses. The immunotherapeutic potential of some toxins, like Clostridium perfringens perfringolysin O, Streptococcus intermedius intermedilysin, or Streptococcus pneumoniae pneumolysin needs to be evaluated further. The Bordetella adenylate cyclase toxoid used as a vaccine delivery tool, or Corynebacterium diphtheriae diphtheria toxin and Pseudomonas aeruginosa exotoxin A-based immunotoxins, are currently in various phases of clinical trials for cancer immunotherapy, as are some antigen-delivering Salmonella and Listeria monocytogenes strains. PMID:22339216

Adkins, Irena; Holubova, Jana; Kosova, Martina; Sadilkova, Lenka

2012-06-01

45

Partial purification of a toxin found in hamsters with antibiotic-associated colitis. Reversible binding of the toxin by cholestyramine.  

PubMed

A toxin with cytotoxic and enterotoxic activities was isolated from cecal contents of hamsters receiving lincomycin. The toxin was partially purified by ultracentrifugation, ultrafiltration, (NH4)2SO4 precipitation, and gel filtration. Cytotoxic activity, assayed on monolayers of HeLa cells, was restricted to material that eluted in the molecular weight range of 107,000 +/- 6,000 daltons. Cytotoxicity of crude AAC toxin could be demonstrated at concentrations as low as 0.04 microgram/ml. The toxin was heat labile (55 degrees-60 degrees C for 0.5 hr) and sensitive to trypsinization, acidification at pH 3, or alkalinization at pH 9. Cytotoxic activity was inhibited by Clostridium sordellii antitoxin. Enterotoxic activity of the crude toxin and the cytotoxic fraction from gel filtration was demonstrated by fluid secretion in ligated rabbit ileal loops. Studies were done in vitro with cholestyramine resin, vancomycin, or gentamicin to determine if the toxin was bound or denatured by these drugs. It was demonstrated that cholestyramine bound the toxin, significantly reducing its cytotoxicity. Reversible binding of the cytotoxic material was demonstrated by salt gradient elution. Neither vancomycin nor gentamicin had any effect on the in vitro cytotoxic activity of the toxin. PMID:34553

Humphrey, C D; Condon, C W; Cantey, J R; Pittman, F E

1979-03-01

46

Enhanced protective immune responses against Salmonella Enteritidis infection by Salmonella secreting an Escherichia coli heat-labile enterotoxin B subunit protein.  

PubMed

Escherichia coli heat-labile enterotoxin B subunit (LTB) protein is a potent mucosal adjuvant. In this study, the effect of an attenuated Salmonella secreting LTB protein as an adjuvant strain (JOL1228) for a live Salmonella Enteritidis (SE) vaccine candidate (JOL919) was evaluated. In a single immunization experiment, chickens immunized with a mixture of JOL919 (5 parts) and JOL1228 (1 part) showed enhanced mucosal and cellular immune responses and efficient protection against salmonellosis as compared to those unimmunized control chickens. In further analysis, chickens were primed at one day of age and were boosted at the fifth week of age to prolong immune responses and to maximize the protection efficacy against salmonellosis. The immunized groups B (prime and booster with JOL919), C (prime with JOL919-JOL1228 mixture and booster with JOL919), and D (prime and booster with JOL919-JOL1228 mixture) showed significantly higher humoral and cellular immune responses as compared to those in the unimmunized control group A. In addition, immunized groups C and D showed fewer gross lesions in the liver and spleen and a lower number of SE-positive organs, with the lowest bacterial counts in the SE challenge strain as compared to the control group. These results indicate that SE vaccination with the LTB strain can have an adjuvant effect on the vaccine candidate by enhancing immune responses, and that a prime-boost strategy with the addition of the adjuvant strain can efficiently protect birds against salmonellosis. PMID:23856155

Nandre, Rahul M; Jawale, Chetan V; Lee, John Hwa

2013-09-01

47

Analysis of Heat-Labile Sites Generated by Reactions of Depleted Uranium and Ascorbate in Plasmid DNA  

PubMed Central

The goal of this study was to characterize how depleted uranium (DU) causes DNA damage. Procedures were developed to assess the ability of organic and inorganic DNA adducts to convert to single strand breaks (SSB) in pBR322 plasmid DNA in the presence of heat or piperidine. DNA adducts formed by methyl methanesulfonate (MMS), cis-platin (cis-Pt), and chromic chloride were compared to those formed by reaction of uranyl acetate (UA) and ascorbate (Asc). Uranyl ion in the presence of Asc produced U-DNA adducts that converted to SSB upon heating. Piperidine, which acted on DNA methylated by MMS to convert methyl-DNA adducts to SSB, served in the opposite fashion with U-DNA adducts by decreasing SSB. The observation that piperidine also decreased the gel shift for metal-DNA adducts formed by monofunctional cis-Pt and chromic chloride was interpreted to suggest that piperidine served to remove U-DNA adducts. Radical scavengers did not affect formation of U-induced SSB, suggesting that SSB arose from the presence of U-DNA adducts and not from free radicals. A model is proposed to predict how U-DNA adducts may serve as initial lesions that convert to SSB or AP sites. Results suggest that DU can act as a chemical genotoxin that does not require radiation for its mode of action. Characterizing the DNA lesions formed by DU is necessary to assess the relative importance of different DNA lesions in the formation of DU-induced mutations. Understanding mechanisms of formation of DU-induced mutations may contribute to identification of biomarkers of DU exposures in humans. PMID:24218036

Wilson, Janice; Young, Ashley; Civitello, Edgar R.

2013-01-01

48

Salmonella enterica Serovar Enteritidis Ghosts Carrying the Escherichia coli Heat-Labile Enterotoxin B Subunit Are Capable of Inducing Enhanced Protective Immune Responses  

PubMed Central

The Escherichia coli heat-labile enterotoxin B subunit (LTB) is a potent vaccine adjuvant. Salmonella enterica serovar Enteritidis ghosts carrying LTB (S. Enteritidis-LTB ghosts) were genetically constructed using a novel plasmid, pJHL187-LTB, designed for the coexpression of the LTB and E lysis proteins. S. Enteritidis-LTB ghosts were characterized using scanning electron microscopy to visualize their transmembrane tunnel structures. The expression of LTB in S. Enteritidis-LTB ghost preparations was confirmed by immunoblot and enzyme-linked immunosorbent assays. The parenteral adjuvant activity of LTB was demonstrated by immunizing chickens with either S. Enteritidis-LTB ghosts or S. Enteritidis ghosts. Chickens were intramuscularly primed at 5 weeks of age and subsequently boosted at 8 weeks of age. In total, 60 chickens were equally divided into three groups (n = 20 for each): group A, nonvaccinated control; group B, immunized with S. Enteritidis-LTB ghosts; and group C, immunized with S. Enteritidis ghosts. Compared with the nonimmunized chickens (group A), the immunized chickens (groups B and C) exhibited increased titers of plasma IgG and intestinal secretory IgA antibodies. The CD3+ CD4+ subpopulation of T cells was also significantly increased in both immunized groups. Among the immunized chickens, those in group B exhibited significantly increased titers of specific plasma IgG and intestinal secretory IgA (sIgA) antibodies compared with those in group C, indicating the immunomodulatory effects of the LTB adjuvant. Furthermore, both immunized groups exhibited decreased bacterial loads in their feces and internal organs. These results indicate that parenteral immunization with S. Enteritidis-LTB ghosts can stimulate superior induction of systemic and mucosal immune responses compared to immunization with S. Enteritidis ghosts alone, thus conferring efficient protection against salmonellosis. PMID:24671556

Jawale, Chetan V.

2014-01-01

49

Antigenicity and immunogenicity of fused B-subunit of heat labile toxin of Escherichia coli and colonization factor antigen I polyepitopes.  

PubMed

Linear B-cell epitopes ((93)AKEFEAAAL(101) and (66)PQLTDVLN(73)) of CfaB were genetically fused to ltb-(gly)5-cfaB(1-25). Sera of rabbits immunized with fusion proteins reacted strongly with solid-phase bound ETEC bacteria bearing CFA/I fimbriae. Sera failed to agglutinate or inhibit hemagglutination promoted by CFA/I-positive strain which may be due to solvent inaccessibility of epitope residues on intact fimbriae. PMID:25108290

Savar, Nastaran Sadat; Dashti, Amir; Darzi Eslam, Elham; Jahanian-Najafabadi, Ali; Jafari, Anis

2014-11-01

50

Bacterial toxins: friends or foes?  

PubMed Central

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

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

1999-01-01

51

Epidemic of diarrhea caused by Vibrio cholerae non-O1 that produced heat-stable toxin among Khmers in a camp in Thailand.  

PubMed Central

An epidemic of a cholera-like disease occurred among Khmers in a camp in Aranyaprathet, Thailand, in May 1990. Of 215 patients with diarrhea, Vibrio cholerae O1 was isolated from 25 (12%) and V. cholerae non-O1 was isolated from 15 (7%). Five of 15 (33%) non-O1 V. cholerae isolates hybridized with two different oligonucleotide probes previously used to detect V. cholerae non-O1 that produces a heat-stable toxin. This is the first description of an epidemic of diarrhea caused by V. cholerae non-O1 that produces heat-stable toxin. PMID:8501234

Bagchi, K; Echeverria, P; Arthur, J D; Sethabutr, O; Serichantalergs, O; Hoge, C W

1993-01-01

52

A QUANTITATIVE STUDY OF HEAT LABILE SULFIDES OF MILK. I. METHOD OF DETERMINATION AND THE INFLU- ENCE OF TEMPERATURE AND TIME 1, 2  

Microsoft Academic Search

Studies on the heat volatile sulfides of milk have assumed especial impor- tance since relatively recent work has been reported indicating that the liberation of these sulfides and the formation of sulfhydryl groups may be closely allied with the production of the cooked flavor (6, 7, 11) ; with the heat prevention of the oxidized flavor in milk (5, 6,

I. A. GOULD

53

Purification and characterization of salmolysin, an extracellular hemolytic toxin from Aeromonas salmonicida.  

PubMed Central

An extracellular hemolytic toxin of Aeromonas salmonicida, termed salmolysin, was purified 945-fold by ammonium sulfate precipitation, anion-exchange chromatography on DEAE-cellulose, and gel filtration chromatography on Sephadex G-100 and Sepharose 2B. Salmolysin appeared homogeneous upon cellulose acetate membrane electrophoresis and immunodiffusion analysis. The molecular weight of the toxin was estimated to be approximately 200,000 by the sedimentation equilibrium method. The UV absorption spectrum showed a maximum at 275 nm and a minimum at 262 nm. The isoelectric point was found to be at pI 5.4. Carbohydrate and protein analyses and other biochemical data indicated that salmolysin is a glycoprotein, containing approximately 62% carbohydrates. The toxin is a heat-labile substance and is stable at a neutral pH value. Ferrous ion inhibited the activity, whereas metal-chelating agents did not affect the activity. Sulfhydryl reagents did not inhibit the toxin, whereas reducing agents, such as L-cysteine and reduced glutathione, inhibited the toxin to a certain extent. Salmolysin was inactivated by a nonionic detergent but was stimulated by an anionic detergent, sodium deoxycholate, at a low concentration. The toxin was also inactivated by subtilisin and trypsin but was not inhibited by papain and pepsin. Salmolysin, with a remarkable hemolytic activity against salmonid erythrocytes, was lethal to rainbow trout when it was injected intramuscularly. Images PMID:3136147

Nomura, S; Fujino, M; Yamakawa, M; Kawahara, E

1988-01-01

54

Immunogenicity of a Fusion Protein Comprising Coli Surface Antigen 3 and Labile B Subunit of Enterotoxigenic Escherichia coli  

PubMed Central

Background: Enterotoxigenic Escherichia coli (ETEC) strains are the major causes of diarrheal disease in humans and animals. Colonization factors and enterotoxins are the major virulence factors in ETEC pathogenesis. For the broad-spectrum protection against ETEC, one could focus on colonization factors and non-toxic heat labile as a vaccine candidate. Methods: A fusion protein is composed of a major fimbrial subunit of coli surface antigen 3, and the heat-labile B subunit (LTB) was constructed as a chimeric immunogen. For optimum level expression of protein, the gene was synthesized with codon bias of E. coli. Also, recombinant protein was expressed in E. coli BL21DE3. ELISA and Western tests were carried out for determination of antigen and specificity of antibody raised against recombinant protein in animals. The anti-toxicity and anti-adherence properties of the immune sera against ETEC were also evaluated. Results: Immunological analyses showed the production of high titer of specific antibody in immunized mice. The built-in LTB retains native toxin properties which were approved by GM1 binding assay. Pre-treatment of the ETEC cells with anti-sera significantly decreased their adhesion to Caco-2 cells. Conclusion: The results indicated the efficacy of the recombinant chimeric protein as an effective immunogen inducing strong humoral response. The designated chimer would be an interesting prototype for a vaccine and worthy of further investigation. PMID:25326019

Alerasol, Masoome; Mousavi Gargari, Seyed Latif; Nazarian, Shahram; Bagheri, Samane

2014-01-01

55

Virulence profiles of enterotoxigenic, shiga toxin and enteroaggregative Escherichia coli in South African pigs.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) and shiga toxin E. coli (STEC) are important causes of colibacillosis in piglets. Recently, enteroaggregative E. coli heat-stable enterotoxin 1 (EAST-1) has been implicated in pig diarrhoea. This study investigated the prevalence of enterotoxin [heat-labile toxins (LT), heat-stable toxin a (STa), heat-stable toxin b (STb)], shiga toxins (Stx1, Stx2, Stx2e), enteroaggregative heat-stable E. coli (EAST-1), associated fimbriae (F4, F5, F6, F41, F18ab, F18ac) and non-fimbrial adhesins [adhesin involved in diffuse adherence 1 (AIDA-1), attaching and effacing factor, porcine attaching- and effacing-associated factor] in South African pigs. A total of 263 E. coli strains were isolated from Landrace (n = 24), Large White (n = 126), Duroc (n = 28) and indigenous (n = 85) breeds of piglets aged between 9 and 136 days. PCR was used in the analysis. Virulent genes were detected in 40.3% of the isolates, of which 18.6, 0.4 and 17.5% were classified as ETEC, STEC and enteroaggregative E. coli (EAEC), respectively. Individual genes were found in the following proportions: STb (19.01%), LT (0.4%), STa (3.4%), St2xe (1.1%) and EAST-1 (20.2%) toxins. None of the tested fimbriae were detected in ETEC and STEC isolates. About one third of the ETEC and STEC isolates was tested negative for both fimbrial and non-fimbrial adhesins. Twenty-five pathotypes from ETEC-, EAEC- and STEC-positive strains were identified. Pathotypes EAST-1 (30.2%), STb (13.2%) and STb/AIDA-1 (10.4%) were most prevalent. The study provided insight on possible causes of colibacillosis in South African pigs. PMID:23417826

Mohlatlole, Ramadimetja Prescilla; Madoroba, Evelyn; Muchadeyi, Farai Catherine; Chimonyo, Michael; Kanengoni, Arnold Tapera; Dzomba, Edgar Farai

2013-08-01

56

Genetically detoxified mutants of heat-labile enterotoxin from Escherichia coli are effective adjuvants for induction of cytotoxic T-cell responses against HIV-1 gag-p55  

PubMed Central

There is an urgent need for prophylactic and therapeutic vaccines against human immunodeficiency virus (HIV). Mucosal immunization strategies have great potential to elicit both mucosal and systemic cellular immunity required to protect against HIV-induced aquired immune deficiency syndrome (AIDS). However, mucosal immunizations with soluble protein antigens generally require adjuvants. In this study, we tested two mutants of the heat-labile enterotoxin (LT) from Escherichia coli, LTK63: with no measurable ADP-ribosyltransferase activity, and LTR72: with residual ADP-ribosyltransferase activity, as mucosal adjuvants for induction of cytotoxic T lymphocyte (CTL) responses to coadministered HIV gag p55 protein. We found that intranasal (i.n.) immunizations with HIV gag p55 protein coadministered with LTK63 or LTR72 induced systemic CTL responses comparable to that obtained following intramuscular (i.m.) immunizations with the same adjuvants. Moreover, oral coadministration of LTR72, but not LTK63, resulted in local as well as systemic p55-specific CTL responses in mesenteric lymph nodes (MLN) and spleens (SP) of the immunized mice. These data have important implications for current efforts to develop a safe vaccine against HIV. PMID:11012767

Neidleman, J A; Vajdy, M; Ugozzoli, M; Ott, G; O'hagan, D

2000-01-01

57

Personality and Electrodermal Response Lability: An Interpretation  

Microsoft Academic Search

Electrodermal response (EDR) lability is a psychophysiological trait reflecting stable individual differences in electrodermal\\u000a activation as indexed by frequency measures of phasic EDR activity. There is no consistent evidence that EDR lability reflects\\u000a dispositional or clinical anxiety. However, EDR lability appears to be related to individual differences in the overt expression\\u000a of emotional and antagonistic impulses. Greater EDR lability is

Andrew Crider

2008-01-01

58

Treponema pallidum 3-phosphoglycerate mutase is a heat-labile enzyme that may limit the maximum growth temperature for the spirochete.  

PubMed

In the causative agent of syphilis, Treponema pallidum, the gene encoding 3-phosphoglycerate mutase, gpm, is part of a six-gene operon (tro operon) that is regulated by the Mn-dependent repressor TroR. Since substrate-level phosphorylation via the Embden-Meyerhof pathway is the principal way to generate ATP in T. pallidum and Gpm is a key enzyme in this pathway, Mn could exert a regulatory effect on central metabolism in this bacterium. To study this, T. pallidum gpm was cloned, Gpm was purified from Escherichia coli, and antiserum against the recombinant protein was raised. Immunoblots indicated that Gpm was expressed in freshly extracted infective T. pallidum. Enzyme assays indicated that Gpm did not require Mn(2+) while 2,3-diphosphoglycerate (DPG) was required for maximum activity. Consistent with these observations, Mn did not copurify with Gpm. The purified Gpm was stable for more than 4 h at 25 degrees C, retained only 50% activity after incubation for 20 min at 34 degrees C or 10 min at 37 degrees C, and was completely inactive after 10 min at 42 degrees C. The temperature effect was attenuated when 1 mM DPG was added to the assay mixture. The recombinant Gpm from pSLB2 complemented E. coli strain PL225 (gpm) and restored growth on minimal glucose medium in a temperature-dependent manner. Increasing the temperature of cultures of E. coli PL225 harboring pSLB2 from 34 to 42 degrees C resulted in a 7- to 11-h period in which no growth occurred (compared to wild-type E. coli). These data suggest that biochemical properties of Gpm could be one contributing factor to the heat sensitivity of T. pallidum. PMID:11466272

Benoit, S; Posey, J E; Chenoweth, M R; Gherardini, F C

2001-08-01

59

Treponema pallidum 3-Phosphoglycerate Mutase Is a Heat-Labile Enzyme That May Limit the Maximum Growth Temperature for the Spirochete  

PubMed Central

In the causative agent of syphilis, Treponema pallidum, the gene encoding 3-phosphoglycerate mutase, gpm, is part of a six-gene operon (tro operon) that is regulated by the Mn-dependent repressor TroR. Since substrate-level phosphorylation via the Embden-Meyerhof pathway is the principal way to generate ATP in T. pallidum and Gpm is a key enzyme in this pathway, Mn could exert a regulatory effect on central metabolism in this bacterium. To study this, T. pallidum gpm was cloned, Gpm was purified from Escherichia coli, and antiserum against the recombinant protein was raised. Immunoblots indicated that Gpm was expressed in freshly extracted infective T. pallidum. Enzyme assays indicated that Gpm did not require Mn2+ while 2,3-diphosphoglycerate (DPG) was required for maximum activity. Consistent with these observations, Mn did not copurify with Gpm. The purified Gpm was stable for more than 4 h at 25°C, retained only 50% activity after incubation for 20 min at 34°C or 10 min at 37°C, and was completely inactive after 10 min at 42°C. The temperature effect was attenuated when 1 mM DPG was added to the assay mixture. The recombinant Gpm from pSLB2 complemented E. coli strain PL225 (gpm) and restored growth on minimal glucose medium in a temperature-dependent manner. Increasing the temperature of cultures of E. coli PL225 harboring pSLB2 from 34 to 42°C resulted in a 7- to 11-h period in which no growth occurred (compared to wild-type E. coli). These data suggest that biochemical properties of Gpm could be one contributing factor to the heat sensitivity of T. pallidum. PMID:11466272

Benoit, Stéphane; Posey, James E.; Chenoweth, Matthew R.; Gherardini, Frank C.

2001-01-01

60

Labile neurotoxin in serum of calves with "nervous" coccidiosis.  

PubMed Central

Mouse inoculation was used to test for the presence of a toxin in the serum, cerebrospinal fluid, and intestinal contents collected from cases of bovine enteric coccidiosis, with and without neurological signs, and from control calves. Intravenous inoculation of mice with 10 mL/kg of serum from calves showing nervous signs caused effects significantly different from those caused by the inoculation of serum from calves not showing nervous signs and from control calves. The effect was particularly evident in female mice. At this dosage severe neurological signs such as loss of righting reflex, seizures and death occurred only with serum from calves with "nervous coccidiosis". The results suggest that serum from the calves with neurological signs contains a neurotoxin. This toxin appears to be highly labile. It was not present in the cerebrospinal fluid at levels comparable to those in the serum. The significance of this labile neurotoxin with respect to the pathogenesis of the neurological signs associated with bovine enteric coccidiosis is unknown. PMID:2955865

Isler, C M; Bellamy, J E; Wobeser, G A

1987-01-01

61

Oral immunization with an attenuated Salmonella Gallinarum mutant as a fowl typhoid vaccine with a live adjuvant strain secreting the B subunit of Escherichia coli heat-labile enterotoxin  

PubMed Central

Background The Salmonella Gallinarum (SG) lon/cpxR deletion mutant JOL916 was developed as a live vaccine candidate for fowl typhoid (FT), and a SG mutant secreting an Escherichia coli heat-labile enterotoxin B subunit (LTB), designated JOL1229, was recently constructed as an adjuvant strain for oral vaccination against FT. In this study, we evaluated the immunogenicity and protective properties of the SG mutant JOL916 and the LTB adjuvant strain JOL1229 in order to establish a prime and boost immunization strategy for each strain. In addition, we compared the increase in body weight, the immunogenicity, the egg production rates, and the bacteriological egg contamination of these strains with those of SG 9R, a widely used commercial vaccine. Results Plasma IgG, intestinal secretory IgA (sIgA), and cell-mediated responses were significantly induced after a boost inoculation with a mixture of JOL916 and JOL1229, and significant reductions in the mortality of chickens challenged with a wild-type SG strain were observed in the immunized groups. There were no significant differences in increases in body weight, cell-mediated immune responses, or systemic IgG responses between our vaccine mixture and the SG 9R vaccine groups. However, there was a significant elevation in intestinal sIgA in chickens immunized with our mixture at 3 weeks post-prime-immunization and at 3 weeks post-boost-immunization, while sIgA levels in SG 9R-immunized chickens were not significantly elevated compared to the control. In addition, the SG strain was not detected in the eggs of chickens immunized with our mixture. Conclusion Our results suggest that immunization with the LTB-adjuvant strain JOL1229 can significantly increase the immune response, and provide efficient protection against FT with no side effects on body weight, egg production, or egg contamination. PMID:23647814

2013-01-01

62

Detection of proteinous toxins using the BioThreat Alert system, part 3: effects of heat pretreatment and interfering substances  

Microsoft Academic Search

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 ?g\\/ml) staphylococcal\\u000a enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored\\u000a matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins\\u000a could

Yasuhiro Sano; Shigeharu Yamashiro; Asuka Komano; Hisashi Maruko; Hiroshi Sekiguchi; Yasuo Takayama; Ryoji Sekioka; Kouichiro Tsuge; Isaac Ohsawa; Mieko Kanamori-Kataoka; Yasuo Seto; Akiyoshi Satoh

2007-01-01

63

Lectin and toxin-like activities of Entamoeba histolytica: comparison of properties.  

PubMed

A comparison was made between properties of a recently discovered Entamoeba histolytica lectin which has a carbohydrate specificity for N-acetylglucosamine oligosaccharides and the previously found toxin-like principle of the ameba. A separation between these two activities was achieved upon subcellular fractionation by high speed centrifugation of freeze-thawed disrupted E. histolytica trophozoites (strain HM-1). Practically all of this lectin activity, as determined by hemagglutination of glutaraldehyde-fixed human erythrocytes, was found associated with the sedimented membrane fraction. This fraction did not affect monolayers of tissue-cultured mammalian cells. On the other hand, the soluble supernatant solution caused extensive damage to the tissue-cultured cells (change in morphology and detachment of cells). Both the lectin and toxin activities were heat-labile and their activities were preserved by the presence of reducing agents and proteolytic enzyme inhibitors. In contrast to the toxin, the isolated lectin was inactive at pH 7.2 and active only at pH 5.7-6.0. Both the lectin and toxin were inhibited by a number of macromolecular compounds such as chitin, peptidoglycan, bovine serum and an IgA fraction isolated from human colostrum. Only the lectin activity, however, was inhibited by low molecular weight chitin oligosaccharides (GlcNAc)n=2-6 or by lysozyme-digested peptidoglycan subunits. Moreover, fetuin and a ganglioside mixture extracted from ox brain were found to inhibit only the toxin-like activity. The IgG fraction of sera from patients with invasive amebiasis neutralized both lectin and toxin-like activities, while IgG from normal sera failed to neutralize either activity. Although our results indicate that in E. histolytica, lectin and toxin are two separate activities, both of them share a considerable number of properties which does not exclude the possibility that they may be related. PMID:6269446

Kobiler, D; Mirelman, D; Mattern, C F

1981-09-01

64

Pertussis toxin  

SciTech Connect

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.

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

1985-01-01

65

Aging effects on molybdate lability in soils.  

PubMed

Aging reactions in soils can influence the lability and hence bioavailability of added metals in soils through their removal from labile pools into pools from which desorption is slow (non-labile pools). The aims of this study were to examine the effect of aging reactions on the lability of soluble molybdate (MoO(4)(2-)) added into soils with varying physical and chemical properties and develop models to predict changes in the labile pool of MoO(4)(2-) in soils with incubation time. Soils were spiked with soluble MoO(4)(2-) at quantities sufficient to inhibit barley root growth by 10% (EC(10)) or 90% (EC(90)) and incubated for up to 18 months. The labile pool of MoO(4)(2-) (E value) was observed to decrease in soils with incubation time, particularly in soils with high clay content. A strong relationship was observed between measures of MoO(4)(2-) lability in soils determined using E and L value techniques (R(2)=0.98) suggesting E values provided a good measure of the potential plant available pool of MoO(4)(2-) in soils. A regression model was developed that indicates clay content and incubation time were the most important factors affecting the labile pool of MoO(4)(2-) in soils with time after addition (R(2)=0.70-0.75). The aging model developed suggests soluble MoO(4)(2-) will be removed into non-labile pools more rapidly with time in neutral to alkaline clay soils than in acidic sandy soils. Labile MoO(4)(2-) concentrations in molybdenum (Mo) contaminated soils was found to be <10% of the total Mo concentrations in soils. PMID:22704209

Kirby, Jason K; McLaughlin, Michael J; Ma, Yibing; Ajiboye, Babasola

2012-10-01

66

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

PubMed Central

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

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

1986-01-01

67

Botulinum Toxin.  

National Technical Information Service (NTIS)

Botulism is a disease caused by anaerobic, spore-forming bacteria found in soil. Disease results from the actions of chemical toxins produced by these bacteria. The most common forms of human botulism include foodborne, infant, and wound. The main etiolog...

A. M. Katos, J. Anderson, M. Krasna, P. T. Williams, W. Burrows

2009-01-01

68

Labile sulfide and sulfite in phytochelatin complexes  

SciTech Connect

Heavy metals such as cadmium induce tomato cell cultures to synthesize the metal binding polypeptides ({gamma}-Glu-Cys){sub 3} and ({gamma}-Glu-Cys){sub 4}-Gly (phytochelatins). Tomato cells selected for growth on normally lethal concentrations of CdCl{sub 2} synthesize higher quantities of these polypeptides. Cd{sup r} cells are not cross-resistant to other heavy metals, and recent work suggests that metal detoxification by these peptides may be Cd-specific. The occurrence of labile sulfur as a component of the metal complex raises questions concerning possible functions of phytochelatins besides that of Cd binding. The presence of acid-labile sulfide ion in phytochelatin complexes has been reported by several groups. We report the additional finding that labile sulfite is also present in these complexes and in higher amounts than sulfide. Sulfide and sulfite are both released from the metal binding complex by acidification or by treatment with EDTA.

Eannetta, N.T.; Steffens, J.C. (Cornell Univ., Ithaca, NY (USA))

1989-04-01

69

Storage stability of paralytic shellfish poisoning toxins  

Microsoft Academic Search

Variations in C toxins (C1- 2), GTX (gonyautoxin) 1-4, STX (saxitoxin) and NEO (neosaxitoxin) in scallop digestive glands and a mixture of purified paralytic shellfish poisoning (PSP) toxins were studied during storage at ?35, 5 and 25°C and at different pH levels. Heated and unheated samples of homogenates and purified toxin mixtures were stored for 1 year and 4 months,

W. M Indrasena; T. A Gill

2000-01-01

70

Thermal Inactivation of Botulinum Toxins in Canned Salmon  

Microsoft Academic Search

Canned salmon is a low acid food. If all C. botulinum spores are not destroyed by proper processing in home canning, a potential hazard of botulism exists. Boiling will destroy the toxin, but will also affect the palatability and appearance of the salmon. To determine the minimum temperature and heating time to destroy toxin, type A, B, or E toxin

Margy Woodburn; Edward J. Schantz; Jennifer Rodriguez

1979-01-01

71

Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.  

PubMed

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria. PMID:18227167

Stickings, Paul; Peyre, Marisa; Coombes, Laura; Muller, Sylviane; Rappuoli, Rino; Del Giudice, Giuseppe; Partidos, Charalambos D; Sesardic, Dorothea

2008-04-01

72

Rat Leukocyte Interferons: Productionof an Acid-LabileInterferonAfter InductionWith Newcastle Disease Virus  

Microsoft Academic Search

Rat leukocytes produce three interferon species after infection with Newcastle disease virus. Two of the three interferon species (22-24,000 and 30,000 daltons) were acid and heat stable, protected rat and mouse cells from virus-mediated cytopathic effect (CPE), and were neutralized by antisera to mouse L-cell (n\\/fl) interferon. The third, 30,000- dalton interferon species was heat and acid labile; protected rat,

Danny L. Wiedbrauk; Gary R. Burleson

73

Lability of leukosis virus enhancer-binding proteins in avian hematopoeitic cells.  

PubMed Central

Bursal lymphomas induced by avian leukosis virus (ALV) are characterized by integration of long terminal repeat (LTR) enhancer sequences next to the myc proto-oncogene and by subsequent myc hyperexpression. Nuclear runoff transcription analyses have shown that protein synthesis inhibition specifically decreases transcription of LTR-enhanced genes in bursal lymphoma cell lines (M. Linial, N. Gunderson, and M. Groudine, Science 230:1126-1132, 1985). Here, we show that LTR-enhanced transcription is also labile in nontransformed bursa, bone marrow, and spleen but not in other ALV-infected tissues from lymphoma-susceptible chickens. The bursal cells demonstrated this lability of LTR-enhanced transcription only at an early stage of development, when chickens are susceptible to ALV-induced lymphomagenesis. Mature bursal cells show stable LTR transcription enhancement (unaffected by inhibition of protein synthesis) and are not susceptible to lymphomagenesis. In lymphoma-resistant chicken strains, LTR-enhanced transcription was stable in all tissues during development. These data suggest that lability of LTR transcription enhancement in hematopoietic cells is involved in susceptibility to lymphomagenesis, and we propose a model for the action of these labile enhancing factors. Gel shift analysis of nuclear proteins from lymphoma cells indicated that four or more binding proteins specifically interact with the three LTR enhancer regions. These proteins can be separated by their differential sensitivity to heat treatment or protein synthesis inhibition. The lability of a subset of these binding proteins correlates with lability of LTR-enhanced transcription in certain lymphoid cell types, suggesting that these proteins are essential for LTR transcription enhancement. Images PMID:2839698

Ruddell, A; Linial, M; Schubach, W; Groudine, M

1988-01-01

74

T sub 84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin  

SciTech Connect

Escherichia coli heat-stable enterotoxin (STa) induces intestinal secretion by binding to enterocyte receptors and activating the guanylate cyclase-guanosine 3{prime},5{prime}-cyclic monophosphate (cGMP) system. The intermediate steps between binding of STa and secretion are poorly understood, due in part to the lack of a convenient system to study the effects of STa at the cellular level. To establish such a model, the authors investigated the binding of {sup 125}I-STa, STa activation of guanylate cyclase, and STa-induced increase in cGMP production in a well-characterized human colonic cell line, T{sub 84}. Binding was specific, linear with cell number, and time, temperature and pH dependent, and reversible. ST may also be internalized by these cells. Addition of unlabeled STa competitively inhibited binding of {sup 125}I-STa. These parameters closely resemble those described in intact rat enterocytes and cell-free membrane preparations. STa stimulated guanylate cyclase and cGMP production in a dose-related manner. The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors. These data, together with the fact that STa induces chloride secretion from T{sub 84} cells suggest that T{sub 84} cells are a suitable and convenient system to study the cellular mechanism of action of STa.

Guarino, A.; Cohen, M.; Thompson, M.; Dharmsathaphorn, K.; Giannella, R. (Veterans Administration Hospital, Cincinnati, OH (USA) Univ. of Cincinnati, OH (USA) Univ. of California, San Diego (USA))

1987-12-01

75

Development of an immunochromatographic test strip for detection of cholera toxin.  

PubMed

Because cholera toxin (CT) is responsible for most of the symptoms induced by Vibrio cholerae infection, detection of CT is critical for diagnosis of the disease. In this study, we constructed an immunochromatographic test strip for detection of CT (CT-IC) with polyclonal antibodies developed against purified recombinant whole CT protein. The detection limit of the CT-IC was 10 ng/mL of purified recombinant CT, and it could detect the CT in culture supernatant of all 15 toxigenic V. cholerae isolates examined, whereas no false-positive signal was detected in all 5 nontoxigenic V. cholerae isolates examined. The specificity of the CT-IC was examined with recombinant heat-labile toxin (LT), which shares high homology with CT, and it was revealed that the minimum detection limit for LT was 100 times higher than that for CT. In addition, lt gene-positive enterotoxigenic Escherichia coli (ETEC) was examined by CT-IC. The false-positive signals were observed in 3 out of 12 ETEC isolates, but these signals were considerably faint. The CT-IC did not develop false-positive signals with all 7 V. parahaemolyticus isolates. These results showed the high specificity of CT-IC and the feasible use of it for the detection and surveillance of toxigenic V. cholerae. PMID:24308002

Yamasaki, Eiki; Sakamoto, Ryuta; Matsumoto, Takashi; Morimatsu, Fumiki; Kurazono, Takayuki; Hiroi, Toyoko; Nair, G Balakrish; Kurazono, Hisao

2013-01-01

76

Development of an Immunochromatographic Test Strip for Detection of Cholera Toxin  

PubMed Central

Because cholera toxin (CT) is responsible for most of the symptoms induced by Vibrio cholerae infection, detection of CT is critical for diagnosis of the disease. In this study, we constructed an immunochromatographic test strip for detection of CT (CT-IC) with polyclonal antibodies developed against purified recombinant whole CT protein. The detection limit of the CT-IC was 10?ng/mL of purified recombinant CT, and it could detect the CT in culture supernatant of all 15 toxigenic V. cholerae isolates examined, whereas no false-positive signal was detected in all 5 nontoxigenic V. cholerae isolates examined. The specificity of the CT-IC was examined with recombinant heat-labile toxin (LT), which shares high homology with CT, and it was revealed that the minimum detection limit for LT was 100 times higher than that for CT. In addition, lt gene-positive enterotoxigenic Escherichia coli (ETEC) was examined by CT-IC. The false-positive signals were observed in 3 out of 12 ETEC isolates, but these signals were considerably faint. The CT-IC did not develop false-positive signals with all 7 V. parahaemolyticus isolates. These results showed the high specificity of CT-IC and the feasible use of it for the detection and surveillance of toxigenic V. cholerae. PMID:24308002

Yamasaki, Eiki; Sakamoto, Ryuta; Matsumoto, Takashi; Morimatsu, Fumiki; Kurazono, Takayuki; Hiroi, Toyoko; Nair, G. Balakrish; Kurazono, Hisao

2013-01-01

77

Vibrio cholerae: Cholera toxin  

Microsoft Academic Search

The bacterial protein toxin of Vibrio cholerae, cholera toxin, is a major agent involved in severe diarrhoeal disease. Cholera toxin is a member of the AB toxin family and is composed of a catalytically active heterodimeric A-subunit linked with a homopentameric B-subunit. Upon binding to its receptor, GM01, cholera toxin is internalized and transported in a retrograde manner through the

Davy Vanden Broeck; Caroline Horvath; Marc J. S. De Wolf

2007-01-01

78

Lability criteria in diffusive gradients in thin films.  

PubMed

The penetration of metal complexes into the resin layer of DGT (diffusive gradients in thin films) devices greatly influences the measured metal accumulation, unless the complexes are either totally inert or perfectly labile. Lability criteria to predict the contribution of complexes in DGT measurements are reported. The key role of the resin thickness is highlighted. For complexes that are partially labile to the DGT measurement, their dissociation inside the resin domain is the main source of metal accumulation. This phenomenon explains the practical independence of the lability degree of a complex in a DGT device with respect to the ligand concentration. Transient DGT regimes, reflecting the times required to replenish the gel and resin domains up to the steady-state profile of the complex, are also examined. Low lability complexes (lability degree between 0.1 and 0.2) exhibit the longest transient regimes and therefore require longer deployment times to ensure accurate DGT measurements. PMID:22404162

Puy, Jaume; Uribe, Ramiro; Mongin, Sandrine; Galceran, Josep; Cecília, Joan; Levy, Jacqueline; Zhang, Hao; Davison, William

2012-06-28

79

Serum Dihydrolipoamide Dehydrogenase Is a Labile Enzyme  

PubMed Central

Dihydrolipoamide dehydrogenase (DLDH) is a multifunctional oxidoreductase and is well known as an essential component of four mammalian mitochondrial multienzyme complexes: pyruvate dehydrogenase, ?-ketoglutarate dehydrogenase, branched chain ?-keto acid dehydrogenase, and the glycine cleavage system. However, existence of extracellular DLDH in mammals, if any, has not been clearly defined. The present article reports identification and biochemical characterization of serum DLDH. Proteomic analysis of rat serum using blue native polyacrylamide gel electrophoresis (BN-PAGE) and mass spectrometry peptide sequencing led to generation of 6 tryptic peptides in one band that matched to mitochondrial DLDH, indicating the existence of DLDH in rat serum. Measurement of enzymatic activity also indicated the existence of DLDH in human and mouse serum. Further biochemical analysis of rat serum DLDH revealed that this enzyme lacked diaphorase activity and could not be detected on Western blots probed with antibodies that recognized mitochondrial DLDH. Moreover, both ammonium sulfate fractioning and gel filtration of serum samples rendered a great loss in DLDH activity, indicating that the enzyme activity of this serum protein, unlike that of mitochondrial DLDH, is very labile. When DTT was supplemented in the buffer used for gel filtration, DLDH activity was found to be largely preserved; indicating that serum DLDH is susceptible to air-implicated inactivation. Results of the present study indicate that serum DLDH differs from mitochondrial DLDH in that it is a very labile enzyme. PMID:23646291

Yan, Liang-Jun; Thangthaeng, Nopporn; Sumien, Nathalie; Forster, Michael J.

2013-01-01

80

Toxines botuliques : utilisation pratique  

Microsoft Academic Search

Botulinum toxins (A and B) are neurotoxins derived from Clostridium botulinum. Clostridium are anaerobic bacteria. C. botulinum produces exotoxins (A to G) with distinct antigenicities. The neurotoxins inhibit the release of the neurotransmitter acetylcholine from the axon terminals of motor neurons. Botulinum toxin is officially used in clinic for the treatment of muscular hyperactivity (strabismus, blepharospam, cervical dystonia). Botulinum toxins

A Durand; G Serment

2003-01-01

81

Toxins of Amanita phalloides  

Microsoft Academic Search

The most poisonous mushroom toxins are produced by Amanita phalloides (death cap). The occurrence and chemistry of three groups of toxins (amatoxins, phallotoxins and virotoxins) are summarized. The concentration and distribution of toxins in certain species are variable, with the young fruit body containing lower, and the well-developed fungus higher concentrations, but there is a high variability among specimens collected

János Vetter

1998-01-01

82

Labile Soil Phosphorus as Influenced by Methods of  

E-print Network

Labile Soil Phosphorus as Influenced by Methods of Applying Radioactive Phosphorus Vilma V. Selvaratnam, Senay Siimer, A. J. Andersen, J. D. Thomsen and G. Gissel Nielsen #12;RISÃ?-R-409 LABILE SOIL barley, ijuckwheat, and rye grass for the L- value determination. The four soils differed greatly

83

Functional and Structural Insights of a Staphylococcus aureus Apoptotic-like Membrane Peptide from a Toxin-Antitoxin  

E-print Network

Functional and Structural Insights of a Staphylococcus aureus Apoptotic-like Membrane Peptide from of Staphylococcus aureus, has been solved. Conclusion: S. aureus has a functional type I TA system that induces, Staphylococcus aureus. TA sys- tems consist of stable toxins and labile antitoxins encoded within small genetic

Rennes, Université de

84

[Hemolysis of Scolopendra toxins].  

PubMed

The hemolysis of toxins from alive Scolopendra subspinipes mutilans, medicinal material of Scolopendra subspimipes mutilans and S. multidens have been compared. The result shows that all the toxins have hemolytic activity. The hemolytic activity of the toxin from the medicinal materials of S. subspinipes mutilans is obviously lower than that from alive ones, and that from fresh medicinal materials are twice as high that from old ones, and that from S. multidens is higher than that from S. subspinipes multilans. PMID:12572496

Deng, F; Fang, H; Wang, K

1997-01-01

85

Toxin-antitoxin systems  

PubMed Central

Toxin–antitoxin (TA) systems are small genetic elements composed of a toxin gene and its cognate antitoxin. The toxins of all known TA systems are proteins while the antitoxins are either proteins or non-coding RNAs. Based on the molecular nature of the antitoxin and its mode of interaction with the toxin the TA modules are currently grouped into five classes. In general, the toxin is more stable than the antitoxin but the latter is expressed to a higher level. If supply of the antitoxin stops, for instance under special growth conditions or by plasmid loss in case of plasmid encoded TA systems, the antitoxin is rapidly degraded and can no longer counteract the toxin. Consequently, the toxin becomes activated and can act on its cellular targets. Typically, TA toxins act on crucial cellular processes including translation, replication, cytoskeleton formation, membrane integrity, and cell wall biosynthesis. TA systems and their components are also versatile tools for a multitude of purposes in basic research and biotechnology. Currently, TA systems are frequently used for selection in cloning and for single protein expression in living bacterial cells. Since several TA toxins exhibit activity in yeast and mammalian cells they may be useful for applications in eukaryotic systems. TA modules are also considered as promising targets for the development of antibacterial drugs and their potential to combat viral infection may aid in controlling infectious diseases. PMID:24251069

Unterholzner, Simon J; Poppenberger, Brigitte; Rozhon, Wilfried

2013-01-01

86

Nanoparticle-detained toxins for safe and effective vaccination  

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

87

The Interaction between Sensation Seeking and Negative Affect Lability on Alcohol Involvement Kenny A. Karyadi1  

E-print Network

), the current study tested whether negative affect lability moderated the effect of sensation seeking on levelsThe Interaction between Sensation Seeking and Negative Affect Lability on Alcohol Involvement Kenny with negative affect and affect lability, negative affect lability might moderate the sensation seeking

Zhou, Yaoqi

88

Cell Motility by Labile Association of Molecules  

PubMed Central

This article summarizes our current views on the dynamic structure of the mitotic spindle and its relation to mitotic chromosome movements. The following statements are based on measurements of birefringence of spindle fibers in living cells, normally developing or experimentally modified by various physical and chemical agents, including high and low temperatures, antimitotic drugs, heavy water, and ultraviolet microbeam irradiation. Data were also obtained concomitantly with electron microscopy employing a new fixative and through measurements of isolated spindle protein. Spindle fibers in living cells are labile dynamic structures whose constituent filaments (microtubules) undergo cyclic breakdown and reformation. The dynamic state is maintained by an equilibrium between a pool of protein molecules and their linearly aggregated polymers, which constitute the microtubules or filaments. In living cells under physiological conditions, the association of the molecules into polymers is very weak (absolute value of ?F25°C < 1 kcal), and the equilibrium is readily shifted to dissociation by low temperature or by high hydrostatic pressure. The equilibrium is shifted toward formation of polymer by increase in temperature (with a large increase in entropy: ?S25°C ? 100 eu) or by the addition of heavy water. The spindle proteins tend to polymerize with orienting centers as their geometrical foci. The centrioles, kinetochores, and cell plate act as orienting centers successively during mitosis. Filaments are more concentrated adjacent to an orienting center and yield higher birefringence. Astral rays, continuous fibers, chromosomal fibers, and phragmoplast fibers are thus formed by successive reorganization of the same protein molecules. During late prophase and metaphase, polymerization takes place predominantly at the kinetochores; in metaphase and anaphase, depolymerization is prevalent near the spindle poles. When the concentration of spindle protein is high, fusiform bundles of polymer are precipitated out even in the absence of obvious orienting centers. The shift of equilibrium from free protein molecules to polymer increases the length and number of the spindle microtubules or filaments. Slow depolymerization of the polymers, which can be brought about by low concentrations of colchicine or by gradual cooling, allows the filaments to shorten and perform work. The dynamic equilibrium controlled by orienting centers and other factors provides a plasusible mechanism by which chromosomes and other organelles, as well as the cell surface, are deformed or moved by temporarily organized arrays of microtubules or filaments. PMID:6058222

Inoue, Shinya; Sato, Hidemi

1967-01-01

89

The response of gross nitrogen mineralization to labile carbon inputs  

NASA Astrophysics Data System (ADS)

Input of labile carbon sources to forest soils commonly result in priming, i.e. an increase in the microbial decomposition of soil organic matter. Efforts aimed at quantifying the extent of priming have, to date, largely focused on soil organic matter decomposition manifested as soil respiration. Less is known about how gross nitrogen mineralization responds to input of labile carbon. It is often assumed that increased priming results in decreased soil carbon stocks. However, microbial mineralization of organic nitrogen into plant available forms is a major factor limiting primary production in forests. If increased decomposition of soil organic matter in response to labile carbon is accompanied by a concurrent increased nitrogen mineralization, this could result in elevated primary production and higher rates of plant derived organic matter input to soils. Therefore, in order to fully understand the effect of priming on net ecosystem exchange and soil carbon stocks, it is vital to consider if increased decomposition of soil organic matter caused by priming also results in increased nitrogen mineralization. Here I present the results from a series of experiments aimed at determining if, and to which extent, gross nitrogen mineralization is stimulated by input of labile carbon. The results suggest that it is by no means uncommon to find an increase in gross N mineralization rates in response to labile carbon inputs. The magnitude of the increase seems dependent on the nitrogen status of the soil, as well as the concentration and rate of labile carbon inputs. However, continuous input of labile carbon sources that also contains nitrogen, e.g. amino acids, seems to inhibit rather than increase the mineralization of organic nitrogen. These findings suggest that there is a potential for a positive feedback between priming and primary production that needs to be considered in order to fully understand the influence of priming on net ecosystem exchange and soil carbon stocks.

Bengtson, Per

2014-05-01

90

ESBL-plasmids carrying toxin-antitoxin systems can be "cured" of wild-type Escherichia coli using a heat technique  

PubMed Central

Background Plasmid-encoded extended-spectrum beta-lactamase (ESBL)-enzymes are frequently produced by Escherichia coli. Several ESBL-plasmids contain genes for toxin-antitoxin (TA) systems, which assure the maintenance of plasmids in bacteria and prevent the cells from “post-segregational killing”. These systems limit options to “cure” plasmids of ESBL-wild-type strains due to the death of the bacterial cells. A helpful tool to understand the role of ESBL-plasmids in the dissemination of pandemic multi-resistant E. coli are ESBL-plasmid-“cured”-variants (PCVs) and their comparison to ESBL-wild-type strains. The purpose of this study was to construct PCVs of ESBL-wild-type E. coli strains despite the presence of genes for TA systems. Findings Using enhanced temperatures and brain-heart-infusion broth it was possible to construct viable PCVs of wild-type ESBL-E. coli strains. The occurrence of TA system-genes including hok/sok, srnB/C, vagC/D, pemI/K on ESBL-plasmids of replicon types FIA or FIB was demonstrated by bioinformatic analyses. The loss of the plasmid and the genetic identity of PCV and corresponding wild-type strain was confirmed via different methods including plasmid-profile-analysis, pulsed-field gel electrophoresis and bioinformatics using generated whole genome data of the strains. Conclusions This short report describes the successful construction of viable PCVs of ESBL-wild-type E. coli strains. The results are hence surprising due to the fact that all “cured” ESBL-plasmids contained at least one complete toxin-antitoxin system, whose loss would normally mean the death of bacterial cells. PMID:24245987

2013-01-01

91

Animal toxins and the kidney  

Microsoft Academic Search

Envenomation or poisoning by toxins from animals poses an important health hazard in the tropics. Animal toxins are complex mixtures of proteins, peptides, enzymes and chemicals. These toxins exert their effects through modulation of ion channels and receptors, and via direct enzyme action. Depolarization or hyperpolarization of ion channels—caused by most marine toxins, and some snake and insect venoms—results in

Visith Sitprija

2008-01-01

92

Using stimulants to treat ADHD-related emotional lability.  

PubMed

Emotional lability, or sudden strong shifts in emotion, commonly occurs in youth with attention-deficit/hyperactivity disorder. Although these symptoms are impairing and disruptive, relatively little research has addressed their treatment, likely due to the difficulty of reliable and valid assessment. Promising signals for symptom improvement have come from recent studies using stimulants in adults, children and adolescents. Similarly, neuroimaging studies have begun to identify neurobiological mechanisms underlying stimulants' impact on emotion regulation capacities. Here, we review these recent clinical and neuroimaging findings, as well as neurocognitive models for emotional lability in ADHD, issues of relevance to prescribers and the important role of psychiatric comorbidity with treatment choices. PMID:25135778

Posner, Jonathan; Kass, Erica; Hulvershorn, Leslie

2014-10-01

93

Contribution of partially labile complexes to the DGT metal flux.  

PubMed

Penetration of complexes into the resin layer can dramatically increase the contribution of complexes to the metal flux measured with a DGT (diffusive gradients in thin films) sensor, but equations to describe this phenomenon were not available. Here, simple approximate analytical expressions for the metal flux, the lability degree and the concentration profiles in a DGT experiment are reported. Together with the thickness of the reaction layer in the gel domain, the effective penetration distance into the resin layer that would be necessary for full dissociation of the complex (?(ML)) plays a key role in determining the metal flux. An increase in the resin-layer thickness (r) effectively increases the metal flux and the lability degree until r ? 3?(ML). For the usual DGT configuration, where the thickness of the gel layer exceeds that of the resin layer, the complex is labile if r > (D(ML)/k(d))½, where D(ML) is the diffusion coefficient of the metal complex and k(d) its dissociation rate constant. A general procedure for estimating the lability of any complex in a standard DGT configuration is provided. PMID:21608530

Uribe, Ramiro; Mongin, Sandrine; Puy, Jaume; Cecília, Joan; Galceran, Josep; Zhang, Hao; Davison, William

2011-06-15

94

Hydrolysis and Soil Adsorption of the Labile Herbicide Isoxaflutole  

E-print Network

Hydrolysis and Soil Adsorption of the Labile Herbicide Isoxaflutole S A R A H T A Y L O R - L O V E) is a new herbicide marketed for broadleaf and grass weed control in corn, but little information has been published on the soil behavior and environmental fate of the compound. The herbicide exhibits an unusual

Sims, Gerald K.

95

Neuropsychological Correlates of Emotional Lability in Children with ADHD  

ERIC Educational Resources Information Center

Background: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms…

Banaschewski, Tobias; Jennen-Steinmetz, Christine; Brandeis, Daniel; Buitelaar, Jan K.; Kuntsi, Jonna; Poustka, Luise; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.; Frazier-Wood, Alexis C.; Albrecht, Bjorn; Chen, Wai; Uebel, Henrik; Schlotz, Wolff; van der Meere, Jaap J.; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Asherson, Philip

2012-01-01

96

Free radical production and labile iron pool decrease triggered by subtoxic concentration of aclarubicin in human leukemia cell lines  

E-print Network

, iron regulatory protein; LIP, labile iron pool; NAC, N- acetylcysteine; NBT, nitroblue1 Free radical production and labile iron pool decrease triggered by subtoxic concentration, differentiation, HL-60, K562, labile iron pool, oxidative stress. Acknowledgements - This work was supported

Boyer, Edmond

97

Affective lability in patients with bipolar disorders is associated with high levels of childhood trauma.  

PubMed

This study aimed to investigate associations between a history of childhood trauma and levels of affective lability in bipolar patients compared to controls. Forty-two patients and 14 controls were assessed using the Affective Lability Scale (ALS) and the Childhood Trauma Questionnaire (CTQ). Affective Lability Score was significantly associated with scores on the Childhood Trauma Questionnaire. A multivariate regression model indicated a relationship between childhood trauma scores and differences in affective lability between patients and controls. PMID:24803185

Aas, Monica; Aminoff, Sofie R; Vik Lagerberg, Trine; Etain, Bruno; Agartz, Ingrid; Andreassen, Ole A; Melle, Ingrid

2014-08-15

98

Land Use Effects on the Distribution of Labile Organic Carbon Fractions through Soil Profiles  

Microsoft Academic Search

Labile fractions of organic matter can respond rapidly to changes in C supply and are considered to be important indicators of soil quality. However, much less is known on the impact of different land use systems and depth on labile organic matter fractions. The objective of this study was to estimate land use effects on a distribution of labile fraction

Zhang Jinbo; Song Changchun; Yang Wenyan

2006-01-01

99

Labile Organic Matter and Heavy Metals in Waters of Agricultural Landscape  

Microsoft Academic Search

This paper describes some characteristics and properties of low molecular compounds - labile fraction, isolated from dissolved organic matter in ground and surface waters on arable land. The differences in composition of labile fraction using IR spectroscopy were studied. Also, the ability of labile fraction to heavy metals complexation was analyzed.

B. Karlik; B. Szpakowska

2001-01-01

100

Valence Focus and Self-Esteem Lability: Reacting to Hedonic Cues in the Social Environment  

E-print Network

Valence Focus and Self-Esteem Lability: Reacting to Hedonic Cues in the Social Environment Paula R experience) demonstrated greater self-esteem lability (i.e., larger changes in self-esteem) to pleasant. Keywords: valence focus, emotion, self-esteem lability, experience sampling, social interactions Hedonic

Barrett, Lisa Feldman

101

Marine Neurotoxins: Ingestible Toxins.  

PubMed

Fish and shellfish account for a significant portion of food-borne illnesses throughout the world. In general, three classes of diseases result from seafood consumption--intoxication, allergies, and infections. In this review, the authors discuss several seafood-borne toxins, including domoic acid, which acts on the central nervous system. In addition, the authors discuss ciguatoxin-, brevetoxin-, saxitoxin-, tetrodotoxin-, and scombroid-related histamine toxicity, all of which act primarily on the peripheral nervous system. Fish has become a very popular food in the US mostly related to its potential health benefits. Fish is consumed to such a degree that fishing stocks are reportedly at an all time low from what seemed like an endless supply even 30 years ago. One of the most significant threats to human intoxication is the recreational harvest of shellfish, often times located in remote locations where the harvesters are subsistent on fishery resources and have no monitoring in place. The hazard to intoxication is not as common in purchased seafood, which is more stringently regulated, yet still is a serious problem. Most ingestible toxins are thermo-stable and therefore unaffected by cooking, freezing, or salting. Air transport of consumable products throughout the world makes it easy to obtain exotic edibles from far away countries. A seemingly unusual toxin can be more commonly encountered than previously thought and it is important to consider this when evaluating patients. Recognition and treatment of various neurologic symptoms related to seafood ingestion is paramount in today's mobile, gastronomic world. Specific treatments vary with each individual toxin and with the individual's specific reaction to the toxin. Generally, some degree of medical care is required with all ingestible toxin exposure, ranging from simple administration of medication and hydration to ventilatory and cardiovascular support. PMID:14759343

Stommel, Elijah W.; Watters, Michael R.

2004-03-01

102

Tracing the Toxins  

NSDL National Science Digital Library

This activity will help students understand that harmful algal blooms (HABs) can negatively impact organisms in a variety of ways, ranging from cell and tissue damage to death. Students will also realize that toxic blooms are caused by algae. The potent toxins produced by these algae can cause massive fish kills, marine mammal deaths, and human illness. Students will participate in a game based on an Antarctic food web in which their feeding decisions determine their survival in the environment. In follow-up activities, students will look for HABs reported in the media and attempt to trace the path of the toxins through the food chain.

103

Toxin Plasmids of Clostridium perfringens  

PubMed Central

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

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

2013-01-01

104

CYANOBACTERIA AND THEIR TOXINS.  

EPA Science Inventory

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

105

CYANOBACTERIA AND THEIR TOXINS  

EPA Science Inventory

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

106

The bacterial toxin toolkit  

Microsoft Academic Search

Pathogenic bacteria and higher eukaryotes have spent a long time together, leading to a precise understanding of one another's way of functioning. Through rapid evolution, bacteria have engineered increasingly sophisticated weapons to hit exactly where it hurts, interfering with fundamental host functions. However, toxins are not only useful to the bacteria — they have also become an essential asset for

Giampietro Schiavo; F. Gisou van der Goot

2001-01-01

107

Labile complexes facilitate cadmium uptake by Caco-2 cells.  

PubMed

The Free Ion Activity Model (FIAM) predicts that metal uptake in biota is related to the free ion activity in the external solution and that metal complexes do not contribute. However, studies with plants have shown that labile metal complexes enhance metal bioavailability when the uptake is rate-limited by transport of the free ion in solution to the uptake site. Here, the role of labile complexes of Cd on metal bioavailability was assessed using Caco-2 cells, the cell model for intestinal absorption. At low Cd(2+) concentration (1 nM), the CdCl(n)(2-n) complexes contributed to the uptake almost to the same extent as the free ion. At large Cd(2+) concentration (10 ?M), the contribution of the complexes was much smaller. At constant Cd(2+) concentration, Cd intake in the cells from solutions containing synthetic ligands such as EDTA increased as the dissociation rate of the cadmium complexes increased, and correlated well with the Cd diffusion flux in solution measured with the Diffusive Gradient in Thin Films technique (DGT). The Cd intake fluxes in the cells were well predicted assuming that the specific uptake is limited by diffusion of the free Cd(2+) ion to the cell surface. Our results underline that speciation of Cd has a major effect on its uptake by intestinal cells, but the availability is not simply related to the free ion concentration. Labile complexes of Cd enhance metal bioavailability in these cells, likely by alleviating diffusive limitations. PMID:22503671

Verheyen, L; Degryse, F; Niewold, T; Smolders, E

2012-06-01

108

Toxins of Amanita phalloides.  

PubMed

The most poisonous mushroom toxins are produced by Amanita phalloides (death cap). The occurrence and chemistry of three groups of toxins (amatoxins, phallotoxins and virotoxins) are summarized. The concentration and distribution of toxins in certain species are variable, with the young fruit body containing lower, and the well-developed fungus higher concentrations, but there is a high variability among specimens collected in the same region. Regarding phallotoxins, the volva (the ring) is the most poisonous. The most important biochemical effect of amatoxins is the inhibition of RNA polymerases (especially polymerase II). This interaction leads to a tight complex and the inhibition is of a non-competitive type. Non-mammalian polymerases show little sensitivity to amanitins. The amatoxins cause necrosis of the liver, also partly in the kidney, with the cellular changes causing the fragmentation and segregation of all nuclear components. Various groups of somatic cells of emanation resistance have been isolated, including from a mutant of Drosophila melanogaster. The phallotoxins stimulate the polymerization of G-actin and stabilize the F-actin filaments. The interaction of phallotoxins occurs via the small, 15-membered ring, on the left side of the spatial formula. The symptoms of human poisoning and the changes in toxin concentrations in different organs are summarized. Conventional therapy includes: (1) stabilization of patient's condition with the correction of hypoglycaemia and electrolytes; (2) decontamination; and (3) chemotherapy with different compounds. Finally, certain antagonists and protective compounds are reviewed, bearing in mind that today these have more of a theoretical than a practical role. PMID:9604278

Vetter, J

1998-01-01

109

Spinal cord injury: inductive lability can enhance and hasten recovery.  

PubMed

In spinal cord injury, recovery of function, if any, confirms the presence of survived neural tissue at the injury site. However, recovery several years after the injury remains unexplained. Body weight bearing locomotor exercises seem to bring these new outcomes. Developing locomotor system and computer simulation studies show that motor learning requires the presence of redundant sets of competing synapses within the spinal cord interneurons. The new exercise regimens have not addressed this essential prerequisite; this could perhaps explain the long delays in recovery. We recommend that inclusion of inductive lability procedure (Krishnan, 1983, 1991, 2003) will help hasten and enhance the recovery. PMID:12775341

Krishnan, R V

2003-06-01

110

Koilocytes are enriched for alkaline-labile sites  

PubMed Central

This study investigated possible variations in the chromatin structure of koilocytes resulting from human papillomavirus (HPV) infection. Alkaline-labile sites (ALS) were detected with the DNA breakage detection–fluorescence in situ hybridization (DBD-FISH) technique using a whole human genome DNA probe obtained from individuals without koilocytosis. The variable levels of ALS present were measured quantitatively using image analysis after whole-genome DNA hybridization. A significant increase in the number of ALS was observed in koilocytes compared with normal cells. We demonstrated that the presence of ALS could be an indicator of chromatin change in koilocytes caused by HPV infection. PMID:21337807

Cortés-Gutiérrez, E.I.; Dávila-Rodríguez, M.I.; Fernández, J.L.; López-Fernández, C.; Gosálvez, J.

2010-01-01

111

Pore formation by Cry toxins.  

PubMed

Bacillus thuringiensis (Bt) bacteria produce insecticidal Cry and Cyt proteins used in the biological control of different insect pests. In this review, we will focus on the 3d-Cry toxins that represent the biggest group of Cry proteins and also on Cyt toxins. The 3d-Cry toxins are pore-forming toxins that induce cell death by forming ionic pores into the membrane of the midgut epithelial cells in their target insect. The initial steps in the mode of action include ingestion of the protoxin, activation by midgut proteases to produce the toxin fragment and the interaction with the primary cadherin receptor. The interaction of the monomeric CrylA toxin with the cadherin receptor promotes an extra proteolytic cleavage, where helix alpha-1 of domain I is eliminated and the toxin oligomerization is induced, forming a structure of 250 kDa. The oligomeric structure binds to a secondary receptor, aminopeptidase N or alkaline phosphatase. The secondary receptor drives the toxin into detergent resistant membrane microdomains formingpores that cause osmotic shock, burst of the midgut cells and insect death. Regarding to Cyt toxins, these proteins have a synergistic effect on the toxicity of some Cry toxins. Cyt proteins are also proteolytic activated in the midgut lumen of their target, they bind to some phospholipids present in the mosquito midgut cells. The proposed mechanism of synergism between Cry and Cyt toxins is that Cyt1Aa function as a receptor for Cry toxins. The Cyt1A inserts into midgut epithelium membrane and exposes protein regions that are recognized by Cry11Aa. It was demonstrated that this interaction facilitates the oligomerization of Cry11Aa and also its pore formation activity. PMID:20687486

Soberón, Mario; Pardo, Liliana; Muñóz-Garay, Carlos; Sánchez, Jorge; Gómez, Isabel; Porta, Helena; Bravo, Alejandra

2010-01-01

112

Labile Cd complexes increase Cd availability to plants.  

PubMed

Dissolved trace metals are present in the environment as free ions and as complexes. Commonly used models to predict metal bioavailability consider the free ion as the major bioavailable species. However, increases in metal availability in the presence of metal complexes have repeatedly been found. We measured the uptake of cadmium (Cd) by spinach (Spinacia oleracea) from solution in absence or presence of synthetic ligands. At the same free ion concentration, the uptake of Cd ranged over almost 3 orders of magnitude and was largest in treatments with fast dissociating (i.e. labile) complexes. Similar results were found for the diffusional fluxes in these solutions, as measured with the DGT technique. The observed effect of Cd complexes on the plant uptake was in agreement with model calculations in which plant uptake was assumed to be governed by the diffusional flux. These results strongly suggest that Cd uptake is rate-limited by diffusion of the free ion to the root surface, even in stirred solutions. As a result, dissolved Cd complexes can increase Cd uptake, resulting in apparent exceptions from the free ion activity model. The magnitude of this increase depends both on the concentration and on the lability of the complexes. The free ion concept should therefore be reconsidered when transport limitations of the metal ion to the uptake site prevail. PMID:16509325

Degryse, Fien; Smolders, Erik; Merckx, Roel

2006-02-01

113

Acid-Labile Polyvinylamine Micro- and Nanogel Capsules  

PubMed Central

Hollow nanoparticles represent an emerging area of development for the encapsulation of active ingredients. Expanding the capabilities of these nanomaterials will require continued efforts to infill properties such as size control, biodegradability, and environmental responsiveness. Acid-labile poly(N-vinylformamide) (PNVF) nanocapsules were synthesized by free radical polymerization of N-vinylformamide on the surface of silica nanoparticles. Polymerization in the presence of a novel crosslinker that contains an acid-labile ketal facilitated stable etching of silica nanoparticle templates using sodium hydroxide and recovery of degradable PNVF nanocapsules. The formamido side group of PNVF was then hydrolyzed by extended exposure to sodium hydroxide to produce polyvinylamine (PVAm) micro- and nanocapsules. Both capsule types demonstrated an increasing dissolution rate as pH decreased. In addition, PVAm nanocapsules exhibited swelling in proportion to the relative charge density of the PVAm network (a function of the degree of formamide hydrolysis and pH), presumably due to the repulsion of positively charged amino groups within the elastic shell network. The synthetic approaches reported provide methods to endow nanocapsules with key attributes such as size control, pH sensitive degradation, swelling in response to pH, and amine functionality. PMID:18797513

Shi, Lianjun; Berkland, Cory

2008-01-01

114

Lymphocyte receptors for pertussis toxin  

SciTech Connect

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

Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

1990-12-01

115

Botulinum toxin: Bioweapon & magic drug  

PubMed Central

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

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

2010-01-01

116

Peptide antagonists of superantigen toxins  

Microsoft Academic Search

Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this large family trigger an excessive cellular immune response leading to toxic shock. Superantigens are secreted by the bacteria as diverse natural mixtures, a complexity that demands development of broad-spectrum countermeasures. We used a rational approach to design short peptides with homology to

Raymond Kaempfer

2004-01-01

117

Binding of ATP by pertussis toxin and isolated toxin subunits  

SciTech Connect

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

Hausman, S.Z.; Manclark, C.R.; Burns, D.L. (Center for Biologics Evaluation and Research, Bethesda, MD (USA))

1990-07-03

118

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

SciTech Connect

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

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

1982-04-01

119

The role of labile sulfur compounds in thermochemical sulfate reduction  

USGS Publications Warehouse

The reduction of sulfate to sulfide coupled with the oxidation of hydrocarbons to carbon dioxide, commonly referred to as thermochemical sulfate reduction (TSR), is an important abiotic alteration process that most commonly occurs in hot carbonate petroleum reservoirs. In the present study we focus on the role that organic labile sulfur compounds play in increasing the rate of TSR. A series of gold-tube hydrous pyrolysis experiments were conducted with n-octane and CaSO4 in the presence of reduced sulfur (e.g. H2S, S??, organic S) at temperatures of 330 and 356 ??C under a constant confining pressure. The in-situ pH was buffered to 3.5 (???6.3 at room temperature) with talc and silica. For comparison, three types of oil with different total S and labile S contents were reacted under similar conditions. The results show that the initial presence of organic or inorganic sulfur compounds increases the rate of TSR. However, organic sulfur compounds, such as 1-pentanethiol or diethyldisulfide, were significantly more effective in increasing the rate of TSR than H2S or elemental sulfur (on a mole S basis). The increase in rate is achieved at relatively low concentrations of 1-pentanethiol, less than 1 wt% of the total n-octane, which is comparable to the concentration of organic S that is common in many oils (???0.3 wt%). We examined several potential reaction mechanisms to explain the observed reactivity of organic LSC. First, the release of H2S from the thermal degradation of thiols was discounted as an important mechanism due to the significantly greater reactivity of thiol compared to an equivalent amount of H2S. Second, we considered the generation of olefines in association with the elimination of H2S during thermal degradation of thiols because olefines are much more reactive than n-alkanes during TSR. In our experiments, olefines increased the rate of TSR, but were less effective than 1-pentanethiol and other organic LSC. Third, the thermal decomposition of organic LSC creates free-radicals that in turn might initiate a radical chain-reaction that creates more reactive species. Experiments involving radical initiators, such as diethyldisulfide and benzyldisulfide, did not show an increase in reactivity compared to 1-pentanethiol. Therefore, we conclude that none of these can sufficiently explain our observations of the initial stages of TSR; they may, however, be important in the later stages. In order to gain greater insight into the potential mechanism for the observed reactivity of these organic sulfur compounds during TSR, we applied density functional theory-based molecular modeling techniques to our system. The results of these calculations indicate that 1-pentanethiol or its thermal degradation products may directly react with sulfate and reduce the activation energy required to rupture the first S-O bond through the formation of a sulfate ester. This study demonstrates the importance of labile sulfur compounds in reducing the onset timing and temperature of TSR. It is therefore essential that labile sulfur concentrations are taken into consideration when trying to make accurate predictions of TSR kinetics and the potential for H2S accumulation in petroleum reservoirs. ?? 2008.

Amrani, A.; Zhang, T.; Ma, Q.; Ellis, G. S.; Tang, Y.

2008-01-01

120

Chemical leaching methods and measurements of marine labile particulate Fe  

NASA Astrophysics Data System (ADS)

Iron (Fe) is an essential nutrient for life. Yet its low solubility and concentration in the ocean limits marine phytoplankton productivity in many regions of the world. Dissolved phase Fe (<0.4?m) has traditionally been considered the most biologically accessible form, however, the particulate phase (>0.4?m) may contain an important, labile reservoir of Fe that may also be available to phytoplankton. However, concentration data alone cannot elucidate the sources of particulate Fe to the ocean and to what extent particulate iron may support phytoplankton growth. Isotopic analysis of natural particles may help to elucidate the biogeochemical cycling of Fe, though it is important to find a leaching method which accesses bioavailable Fe. Thirty-three different chemical leaches were performed on a marine sediment reference material, MESS-3. The combinations included four different acids (25% acetic acid, 0.01M HCl, 0.5M HCl, 0.1M H2SO4 at pH2), various redox conditions (0.02M hydroxylamine hydrochloride or 0.02M H2O2), three temperatures (25°C, 60°C, 90°C), and three time points (10 minutes, 2 hours, 24 hours). Leached Fe concentrations varied from 1mg/g to 35mg/g, with longer treatment times, stronger acids, and hotter temperatures generally associated with an increase in leached Fe. ?56Fe in these leaches varied from -1.0‰ to +0.2‰. Interestingly, regardless of leaching method used, there was a very similar relationship between the amount of Fe leached from the particles and the ?56Fe of this iron. Isotopically lighter ?56Fe values were associated with smaller amounts of leached Fe whereas isotopically heavier ?56Fe values were associated with larger amounts of leached Fe. Two alternate hypotheses could explain these data. Either, the particles may contain pools of isotopically light Fe that are easily accessed early in dissolution, or isotopically light Fe may be preferentially leached from the particle due to a kinetic isotope effect during dissolution. To explore the first hypothesis, we modeled dissolution of Fe from particles assuming two separate pools, labile and refractory. The model produces a good fit to the data assuming 3mg/g of a labile Fe pool with ?56Fe = -0.9‰ and a refractory Fe pool with ?56Fe = +0.1‰. If the second hypothesis is true, and there is a kinetic isotope effect during dissolution, the similar relationship between amount of Fe leached and ?56Fe for both organic and mineral acids suggests that Fe is leached from particles via proton-promoted dissolution. Several of these leaching techniques will be employed on sediment trap material from the Cariaco Basin to further investigate the relationship between ?56Fe and the labile, bioavailable fraction of iron particles. A leach or series of leaches will be chosen to provide the most useful information about the bioavailability of iron from particles, and they will be applied to filtered particle samples from portions of the US GEOTRACES A10 (North Atlantic) transect. ?56Fe values from particulate material in these regions will provide a better understanding of the sources of particulate iron to the ocean, and may help to trace how particulate iron is involved in global biogeochemical cycles.

Revels, B. N.; John, S.

2012-12-01

121

The Effects of Moisture and Organic Matter Lability on Carbon Dioxide and Methane Production in an  

E-print Network

, global climate change, water table, organic matter lability #12;Introduction Wetlands as ecosystemsThe Effects of Moisture and Organic Matter Lability on Carbon Dioxide and Methane Production amounts of carbon in the form of peat and other undecomposed plant matter. Global climate change

Vallino, Joseph J.

122

Fast labile carbon turnover obscures sensitivity of heterotrophic respiration from soil to temperature: A model analysis  

Microsoft Academic Search

Labile carbon, although often a small fraction of soil organic carbon (SOC), significantly affects heterotrophic respiration at short timescales because of its rapid decomposition. However, in the current literature, most soil respiration measurements are interpreted without simultaneous information on labile carbon pool dynamics. Sensitivity of soil respiration to temperature is routinely derived directly from field observations, and such relationships have

Lianhong Gu; Wilfred M. Post; Anthony W. King

2004-01-01

123

B-cell epitope of beta toxin of Clostridium perfringens genetically conjugated to a carrier protein: expression, purification and characterization of the chimeric protein.  

PubMed

Beta toxin (btx) is the prime virulence factor for the pathogenesis of Clostridium perfringens type C strain, known to cause necrotic enteritis and enterotoxaemia in mammalian species. The existing vaccines targeting btx are formaldehyde inactivated culture filtrates of Clostridium. These filtrates raise antigenic load in the host leading to nonspecific and poor responses. The present study aimed to overcome these drawbacks and generate a chimeric protein carrying in silico identified B-cell epitope of btx fused with a carrier protein as a vaccine candidate. Using bioinformatic tools, three stretches of amino acids were predicted as putative B-cell epitopes. One of the epitopes spanning 140-156 amino acid residues was genetically conjugated with B-subunit of heat labile enterotoxin (LTB) of Escherichia coli and expressed as a translational fusion in Vibrio cholerae secretory expression system. High level expression of the recombinant fusion protein rLTB-Btx140-156 was obtained and the protein was successfully purified. The recombinant protein retained the native LTB property to pentamerize and bind to GM1 ganglioside receptor of LTB. The antigenicity of both the epitope and the carrier protein was maintained in fusion protein as indicated by immunoblotting against anti-LTB and anti-btx antibody. The rLTB-Btx140-156 fusion protein therefore can be evaluated as a potential vaccine candidate against C. perfringens. PMID:24996028

Bhatia, Bharti; Solanki, Amit Kumar; Kaushik, Himani; Dixit, Aparna; Garg, Lalit C

2014-10-01

124

Stoichiometric regulation of phytoplankton toxins.  

PubMed

Ecological Stoichiometry theory predicts that the production, elemental structure and cellular content of biomolecules should depend on the relative availability of resources and the elemental composition of their producer organism. We review the extent to which carbon- and nitrogen-rich phytoplankton toxins are regulated by nutrient limitation and cellular stoichiometry. Consistent with theory, we show that nitrogen limitation causes a reduction in the cellular quota of nitrogen-rich toxins, while phosphorus limitation causes an increase in the most nitrogen-rich paralytic shellfish poisoning toxin. In addition, we show that the cellular content of nitrogen-rich toxins increases with increasing cellular N : P ratios. Also consistent with theory, limitation by either nitrogen or phosphorus promotes the C-rich toxin cell quota or toxicity of phytoplankton cells. These observed relationships may assist in predicting and managing toxin-producing phytoplankton blooms. Such a stoichiometric regulation of toxins is likely not restricted to phytoplankton, and may well apply to carbon- and nitrogen-rich secondary metabolites produced by bacteria, fungi and plants. PMID:24712512

Van de Waal, Dedmer B; Smith, Val H; Declerck, Steven A J; Stam, Eva C M; Elser, James J

2014-06-01

125

Multiple Properties of Cl. Botulinum Toxin.  

National Technical Information Service (NTIS)

Testing Cl. botulinum toxin type A at various times after its preparation it was found that the toxin was not always toxic to the same degree for albino mice and guinea pigs. With the aging of toxin, the toxin's titer decreased to a greater extent for mic...

I. N. Morgunov, S. M. Minervin

1966-01-01

126

Translocation-Specific Conformation of Adenylate Cyclase Toxin from Bordetella pertussis Inhibits Toxin-Mediated Hemolysis  

Microsoft Academic Search

Bordetella pertussis adenylate cyclase (AC) toxin belongs to the RTX family of toxins but is the only member with a known catalytic domain. The principal pathophysiologic function of AC toxin appears to be rapid production of intracellular cyclic AMP (cAMP) by insertion of its catalytic domain into target cells (referred to as intoxication). Relative to other RTX toxins, AC toxin

MARY C. GRAY; SANG-JIN LEE; LLOYD S. GRAY; FRANCA R. ZARETZKY; ANGELA S. OTERO; GABOR SZABO; ERIK L. HEWLETT

2001-01-01

127

Chemical toxins that cause seizures.  

PubMed

Seizurogenic chemicals include a variety of toxic agents, including chemical warfare agents, toxic industrial chemicals, and natural toxins. Chemical weapons such as sarin and VX, and pesticides such as parathion and carbaryl cause hyperstimulation of cholinergic receptors and an increase in excitatory neurotransmission. Glutamatergic hyperstimulation can occur after exposure to excitatory amino acid toxins such as the marine toxin domoic acid. Other pesticides such as lindane and strychnine do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory GABA and glycine synapses. In this paper, chemicals that cause seizures by a variety of molecular mechanisms and pathways are discussed. PMID:23085523

Jett, David A

2012-12-01

128

Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo  

Microsoft Academic Search

Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in

Heather M. Scobie; Darran J. Wigelsworth; John M. Marlett; Diane Thomas; G. Jonah A. Rainey; D. Borden Lacy; Marianne Manchester; R. John Collier; John A. T. Young

2006-01-01

129

Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia.  

PubMed

Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A) was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required. PMID:23683264

Lin, Kuan-Hsiang; Wang, Shuu-Jiun; Fuh, Jong-Ling; Chen, Shih-Pin

2013-05-01

130

Cholera Toxin Mechanism of Action  

NSDL National Science Digital Library

This single image file shows the steps of action of cholera toxin, beginning at protein synthesis in the bacteria and proceeding through all of the major known steps of interaction with the host cell.

American Society For Microbiology;

2002-08-29

131

Botulinum toxin in clinical practice  

PubMed Central

Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications. PMID:15201348

Jankovic, J

2004-01-01

132

Transcytosis of Staphylococcal Superantigen Toxins  

PubMed Central

Staphylococcus aureus produces a set of proteins (e.g., staphylococcal enterotoxin A [SEA], SEB, toxic shock syndrome toxin 1 [TSST-1]) which act both as superantigens (SAgs) and toxins. Although their mode of action as SAgs is well understood, little is known about how they enter the body via the intestine and cause food poisoning. To examine this problem we used an in vitro culture system to study the capacity of class II MHC-negative human intestinal epithelial cells (Caco-2) to transcytose several staphylococcal toxins. We found that Caco-2 cells are capable of dosedependent, facilitated transcytosis of SEB and TSST-1, but not SEA. We extended these studies in vivo in mice by showing that ingested SEB appears in the blood more efficiently than SEA. Our data suggest that these toxins can cross the epithelium in an immunologically intact form. These results may have important implications for the pathogenesis of food poisoning. PMID:9126925

Hamad, Abdel Rahim A.; Marrack, Philippa; Kappler, John W.

1997-01-01

133

Lability of trace metals in submerged soils: a column study  

NASA Astrophysics Data System (ADS)

The reduction of Fe (III) and Mn (IV) and the decomposition of organic matter exert a great influence on the biogeochemical cycles of many trace metals and nutrients in the environment. In the particular case of intermittently submerged soils, metals associated with Fe and Mn oxides become readily available due to the reductive dissolution of Fe and Mn oxides. The effects of oxido-reductive conditions on the release of Cu and Zn from heavy metal contaminated soils and the changes in their chemical speciation were studied. Column experiments were performed, using Rhizon soil moisture samplers inserted at different heights to monitor the mobility and transport of metals in the submerged soil samples. Cu was released in solution immediately, in the first red-ox cycle, either due to the solubilization of Fe and Mn oxides, or to the oxidation of organic matter with which Cu is commonly complexed, or both. During the following reductive half-cycles, the amount of Cu extracted from the soil solution decreased. However, the concentration of Cu in the solution leached from the column, which was percolated in aerobic conditions, increased. Since in the successive red-ox cycles the Eh decreases faster and to lower values, it is possible that Cu might have been removed from pore water by sulfide precipitation during the anaerobic half-cycle and released during the aerobic half-cycle, due to the oxidation of sulfides to sulfates. The release of Zn was similar to the dissolution of Fe and Mn oxyhydroxydes, and the amount extracted by Rhizon and by leaching increased during the four red-ox cycles. The chemical fractionation of the soils was also studied and the results showed that the alternate oxidative-reductive conditions cause, in general, an increase in the lability of trace metals. While Zn speciation suffers little change, Cu showed a much higher exchangeable fraction in the submerged soils, as compared to the initial, not submerged ones. The results of this study indicate that intermittent submergence of contaminated soils not only causes the release of trace metals previously bound to Fe and Mn oxides and to organic matter, but also leads to an increase in their lability, rending them more readily available to be released into the environment.

Nimirciag, Ramona; Ajmone-Marsan, Franco

2013-04-01

134

NH3-Promoted Ligand Lability in Eleven-Vertex Rhodathiaboranes.  

PubMed

The reaction of the 11-vertex rhodathiaborane, [8,8-(PPh3)2-nido-8,7-RhSB9H10] (1), with NH3 affords inmediately the adduct, [8,8,8-(NH3)(PPh3)2-nido-8,7-RhSB9H10] (4). The NH3-Rh interaction induces the labilization of the PPh3 ligands leading to the dissociation product, [8,8-(NH3)(PPh3)-nido-8,7-RhSB9H10] (5), which can then react with another molecule of NH3 to give [8,8,8-(NH3)2(PPh3)-nido-8,7-RhSB9H10] (6). These clusters have been characterized in situ by multielement NMR spectroscopy at different temeperatures. The variable temperature behavior of the system demonstrates that the intermediates 4-6 are in equilibrium, involving ligand exchange processes. On the basis of low intensity signals present in the (1)H NMR spectra of the reaction mixture, some species are tentatively proposed to be the bis- and tris-NH3 ligated clusters, [8,8-(NH3)2-nido-8,7-RhSB9H10] (7) and [8,8,8-(NH3)3-nido-8,7-RhSB9H10] (8). After evaporation of the solvent and the excess of NH3, the system containing species 4-8 regenerates the starting reactant, 1, thus closing a stoichiometric cycle of ammonia addition and loss. After 40 h at room temperature, the reaction of 1 with NH3 gives the hydridorhodathiaborane, [8,8,8-(H)(PPh3)2-nido-8,7-RhSB9H9] (2), as a single product. The reported rhodathiaboranes show reversible H3N-promoted ligand lability, which implies weak Rh-N interactions, leading to a rare case of metal complexes that circumvent "classical" Werner chemistry. PMID:25382790

Calvo, Beatriz; Roy, Beatriz; Macías, Ramón; Artigas, Maria Jose; Lahoz, Fernando J; Oro, Luis A

2014-12-01

135

The three-dimensional crystal structure of cholera toxin  

SciTech Connect

The clinical manifestations of cholera are largely attributable to the actions of a secreted hexameric AB{sub 5} enterotoxin (choleragen). We have solved the three-dimensional structure of choleragen at 2.5 {Angstrom} resolution and compared the refined coordinates with those of choleragenoid (isolated B pentamer) and the heat-labile enterotoxin from Escherichia coli (LT). The crystalline coordinates provide a detailed view of the stereochemistry implicated in binding to GM1 gangliosides and in carrying out ADP-ribosylation. The A2 chain of choleragen, in contrast to that of LT, is a nearly continuous {alpha}-helix with an interpretable carboxyl tail.

Zhang, Rong-Guang; Westbrook, M.L.; Nance, S.; Spangler, B.D. [Argonne National Lab., IL (United States); Scott, D.L. [Yale Univ., New Haven, CT (United States). Dept. of Molecular Biophysics and Biochemistry; Westbrook, E.M. [Northwestern Univ., Evanston, IL (United States)

1996-02-01

136

Development and Application of Analytical Methods for Marine Toxins.  

E-print Network

??Shellfish accumulate marine toxins from their microalgal diet. The marine toxin tetrodotoxin (TTX) also accumulates in seafood, but via unknown mechanisms. Toxin determinations have traditionally… (more)

McNabb, Paul Simon

2014-01-01

137

Anticariogenic and phytochemical evaluation of Eucalyptus globules Labill.  

PubMed

In the present study, in vitro anticariogenic potential of ethyl acetate, hexane and methanol and aqueous extracts of plant leaves of Eucalyptus globules Labill. were evaluated by using four cariogenic bacteria, Lactobacillus acidophilus, Lactobacillus casei, Staphylococcus aureus and Streptococcus mutans. Agar well diffusion method and minimum inhibitory concentration (MIC) were used for this purpose. The ethyl acetate extracted fraction of plant leaves showed good inhibitory effects against all selected bacteria. In Eucalyptus globules, hexane and ethyl acetate extracts found highly effective against, Lactobacillus acidophilus with MIC value of 0.031 and 0.062 mg/mL, respectively. Qualitative phytochemical investigation of above extracts showed the presence of alkaloids, phenolic compounds, steroids, cardiac glycosides and terpenes. Based on the MIC value and bioautography, ethyl acetate of plant leaf was selected for further study. Further investigation on the structure elucidation of the bioactive compound using IR, GC-MS and NMR techniques revealed the presence of alpha-farnesene, a sesquiterpene. Eucalyptus globules plant leaf extracts have great potential as anticariogenic agents that may be useful in the treatment of oral disease. PMID:23961222

Ishnava, Kalpesh B; Chauhan, Jenabhai B; Barad, Mahesh B

2013-01-01

138

Anticariogenic and phytochemical evaluation of Eucalyptus globules Labill.  

PubMed Central

In the present study, in vitro anticariogenic potential of ethyl acetate, hexane and methanol and aqueous extracts of plant leaves of Eucalyptus globules Labill. were evaluated by using four cariogenic bacteria, Lactobacillus acidophilus, Lactobacillus casei, Staphylococcus aureus and Streptococcus mutans. Agar well diffusion method and minimum inhibitory concentration (MIC) were used for this purpose. The ethyl acetate extracted fraction of plant leaves showed good inhibitory effects against all selected bacteria. In Eucalyptus globules, hexane and ethyl acetate extracts found highly effective against, Lactobacillus acidophilus with MIC value of 0.031 and 0.062 mg/mL, respectively. Qualitative phytochemical investigation of above extracts showed the presence of alkaloids, phenolic compounds, steroids, cardiac glycosides and terpenes. Based on the MIC value and bioautography, ethyl acetate of plant leaf was selected for further study. Further investigation on the structure elucidation of the bioactive compound using IR, GC-MS and NMR techniques revealed the presence of alpha-farnesene, a sesquiterpene. Eucalyptus globules plant leaf extracts have great potential as anticariogenic agents that may be useful in the treatment of oral disease. PMID:23961222

Ishnava, Kalpesh B.; Chauhan, Jenabhai B.; Barad, Mahesh B.

2012-01-01

139

Antibody-based biological toxin detection  

SciTech Connect

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

Menking, D.E.; Goode, M.T. [Army Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, MD (United States)

1995-12-01

140

Ultrabright femtosecond electron sources: perspectives and challenges towards the study of structural dynamics in labile systems  

NASA Astrophysics Data System (ADS)

The advances made in femtosecond electron sources over the last thirty years have been remarkable. In particular, the development of ultrabright femtosecond electron sources has made possible the observation of molecular motion in labile organic materials and it is paving the way towards the study of complex protein systems. The principle of radio frequency (RF) rebunching cavities for the compression of ultrabright electron pulses is presented, alongside with a recent demonstration of its capabilities in capturing the relevant photoinduced dynamics in weakly scattering organic systems. Organic and biological systems can easily decompose or lose crystallinity as a consequence of cumulative heating effects or the formation of side reaction photoproducts. Hence, source brightness plays a crucial role in achieving sufficient signal-to-noise ratio before degradation effects become noticeable on the structural properties of the material. The current brightness of electron sources in addition to the high scattering cross section of keV-MeV electrons have made femtosecond electron diffraction a powerful tool for the study of materials composed by low-Z elements.

Gao, Meng; Jean-Ruel, H.; Lu, Cheng; Liu, L. C.; Marx, A.; Cooney, R. R.; Jiang, Y.; Kassier, G. H.; Moriena, G.; Sciaini, G.; Miller, R. J. D.

2014-09-01

141

Capturing Labile Sulfenamide and Sulfinamide Serum Albumin Adducts of Carcinogenic Arylamines by Chemical Oxidation  

PubMed Central

Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys34 residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

Peng, Lijuan; Turesky, Robert J.

2013-01-01

142

Stereochemical Lability of Azatitanacyclopropanes: Dynamic Kinetic Resolution in Reductive Cross-Coupling Reactions with Allylic Alcohols‡  

PubMed Central

Azatitanacyclopropanes (titanaziridines) are shown to be stereochemically labile under reaction conditions for reductive cross-coupling. This fundamental property has been employed to realize highly selective asymmetric coupling reactions with allylic alcohols that proceed by dynamic kinetic resolution. PMID:23963189

Yang, Dexi

2014-01-01

143

DETERMINATION OF APPARENT QUANTUM YIELD SPECTRA FOR THE FORMATION OF BIOLOGICALLY LABILE PHOTOPRODUCTS  

EPA Science Inventory

Quantum yield spectra for the photochemical formation of biologically labile photoproducts from dissolved organic matter (DOM) have not been available previously, although they would greatly facilitate attempts to model photoproduct formation rates across latitudinal, seasonal, a...

144

Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation  

NASA Astrophysics Data System (ADS)

Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

1984-02-01

145

Biogeochemical implications of labile phosphorus in forest soils determined by the Hedley fractionation procedure  

Microsoft Academic Search

Forest ecologists and biogeochemists have used a variety of extraction techniques to assess labile vs. non-labile soil P pools in chronosequences, the balance between biological vs. geochemical control of P transformations across a wide range of soil orders, the role of plants with either N-fixing or mycorrhizal symbionts in controlling soil P fractions, and to make inferences about plant-available P.

Arthur H. Johnson; Jaqueline Frizano; David R. Vann

2003-01-01

146

The effect of morphine and nalorphine on the level of labile phosphorous compounds in the brain  

Microsoft Academic Search

Summary The author studied the effect of morphine, administered in a dose of 40 mg\\/kg, and of its specific antagonist N-allylnormorphine (nalorphine) upon the contents of labile phosphorus compounds in the brain of white rats. As established, the administration of this analgesic provokes disturbances in the metabolism of high-energy compounds, manifested, in the statistically authentic reduction of the labile phosphate

É. B. Arushanyan

1961-01-01

147

The effect of the castor bean toxin, ricin, on rat IgE and IgG responses.  

PubMed Central

IgE responses are closely regulated in non-atopic humans and low IgE responder animals. After an initial period of IgE production following antigen exposure, IgE synthesis appears to be actively suppressed. Inhalation of the dust of castor beans induces persistent IgE responses in atopic and non-atopic humans alike. This phenomenon was investigated in animals. Hooded Lister rats were immunized intraperitoneally with different preparations of castor bean. These had been heated for different lengths of time, 60 and 15 mins, to inactivate the toxin ricin. Immunization with as much as 100 micrograms of the extract heated for 60 min failed to produce an IgE response, while injection of 100 micrograms of the extract heated for 15 min produced a marked IgE response to castor bean proteins. Thus the component of castor bean extract which induces the IgE response appears to be heat labile. The IgE potentiating component in castor bean was found to enhance IgE responses to other antigens such as ovalbumin and when 0.8 microgram of an unheated castor bean extract was administered together with an optimal dose of ovalbumin, there was a substantial increase in ovalbumin-specific IgE but not IgG in all animals. In addition, total serum IgE but not IgG increased up to 20-fold. The effect of castor bean was more sustainable than that of an established IgE-specific adjuvant, Bordetella pertussis, and was able to boost an IgE response that had diminished and maintain an ongoing IgE response when re-administered at weekly intervals. In addition, it was possible to reproduce the IgE potentiating effects with purified castor bean ricin at 25 ng/rat. The way that it produces this effect is not known but it is possible that ricin blocks the normal IgE suppressive mechanisms that regulate IgE responses. PMID:2592006

Thorpe, S C; Murdoch, R D; Kemeny, D M

1989-01-01

148

Spatial patterns of labile forms of phosphorus in a subtropical wetland.  

PubMed

Phosphorus (P) has been identified as the key constituent defining wetland productivity, structure, and function. Our goal was to investigate the spatial patterns of total P and three labile forms of P (labile organic, inorganic, and microbial biomass P) across a subtropical wetland located in east-central Florida, the Blue Cypress Marsh Conservation Area (BCMCA), and link spatial patterns to ecosystem processes. The wetland received a continual input of nutrients primarily from the south and intermittently from the west and east, respectively, which ceased in the mid-1990s. Since then the marsh system has been undergoing natural succession. We used (i) ordinary kriging to characterize the spatial patterns of total P and labile P forms across the wetland, (ii) local, moving spatial correlations to investigate relationships between total P and labile P forms, and (iii) a clustering technique to link the identified spatial patterns to biogeochemical processes. The spatially explicit analyses revealed patterns of total P and labile P forms as well as changing relationships between variables across the marsh. We were able to distinguish P-enriched areas from unaffected ("natural") areas and intermediate zones that are currently undergoing change as P is mobilized and translocated. We also identified areas that are at risk, showing a shift toward a more P-enriched status. Our results improve our understanding of P and its labile components within a spatially explicit context. PMID:16397113

Grunwald, S; Corstanje, R; Weinrich, B E; Reddy, K R

2006-01-01

149

Protein toxins: intracellular trafficking for targeted therapy  

Microsoft Academic Search

The immunotoxin approach is based on the use of tumor-targeting ligands or antibodies that are linked to the catalytic (toxic) moieties of bacterial or plant protein toxins. In this review, we first discuss the current state of clinical development of immunotoxin approaches describing the results obtained with the two toxins most frequently used: diphtheria and Pseudomonas toxin-derived proteins. In the

L Johannes; D Decaudin

2005-01-01

150

Shiga toxins induce autophagy leading to differential signaling pathways in toxin-sensitive and toxin-resistant human cells  

PubMed Central

Summary The bacterial virulence factors Shiga toxins (Stxs) are expressed by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. Stxs are protein synthesis inhibitors and induce apoptosis in many cell types. Stxs induce apoptosis via prolonged ER stress signaling to activate both extrinsic and intrinsic pathways in human myeloid cells. Studies have shown that autophagy, a lysosome-dependent catabolic process, may be associated with activation of pro-survival or death processes. It is currently unknown if autophagy contributes to apoptosis or protects cells from Stxs. To study cellular responses to Stxs, we intoxicated toxin-sensitive cells (THP-1 and HK-2 cells), and toxin-resistant cells (primary human monocyte-derived macrophages) and examined toxin intracellular trafficking and autophagosome formation. Stxs translocated to different cell compartments in toxin-resistant versus toxin-sensitive cells. Confocal microscopy revealed autophagosome formation in both toxin-resistant and toxin-sensitive cells. Proteolytic cleavage of Atg5 and Beclin-1 play pivotal roles in switching non-cytotoxic autophagy to cell death signaling. We detected cleaved forms of Atg5 and Beclin-1 in Stx-treated toxin-sensitive cells, while cleaved caspases, calpains, Atg5 and Beclin-1 were not detected in toxin-resistant primary human monocytes and macrophages. These findings suggest that toxin sensitivity correlates with caspase and calpain activation, leading to Atg5 and Beclin-1 cleavage. PMID:21722286

Lee, Moo-Seung; Cherla, Rama P.; Jenson, Matthew H.; Leyva-Illades, Dinorah; Martinez-Moczygemba, Margarita; Tesh, Vernon L.

2011-01-01

151

Whole-Ecosystem Labile Carbon Production in a North Temperate Deciduous Forest  

NASA Astrophysics Data System (ADS)

Management for forest carbon (C) sequestration requires knowledge of the fate of photosynthetic C. Labile C is an essential intermediary between C assimilation and growth in deciduous forests, accumulating when photosynthetic C supply exceeds demand and later depleting when reallocated to growth during periods of depressed photosynthesis. We developed a new approach that combined meteorological and biometric C cycling data for a mixed deciduous forest in Michigan, USA, to provide novel estimates of whole-ecosystem labile C production (PLC) and reallocation to growth inferred from the temporal imbalance between carbon supply from canopy net C assimilation (Ac) and C demand for net primary production (NPP). We substantiated these estimates with measurements of Populus grandidentata and Quercus rubra wood non-structural carbohydrate (NSC) concentration and mass over two years. Our analysis showed that half of annual Ac was allocated to PLC rather than to immediate growth. Labile C produced during the latter half of summer later supported dormant-season growth and respiration, with 35% of NPP in a given year requiring labile C stored during previous years. Seasonal changes in wood NSC concentration and mass generally corroborated patterns of labile C production and reallocation to growth. We observed a negative relationship between current-year PLC and NPP, indicating that disparities between same-year meteorological and biometric net ecosystem production (NEP) estimates can arise when C assimilated via photosynthesis, a flux incorporated into meteorological NEP estimates, is diverted away from NPP, a flux included in biometric NEP estimates, and instead allocated to PLC. A large, annually recharging pool of labile C also may buffer growth from climate conditions that immediately affect Ac. We conclude that a broader understanding of labile C production and reallocation across ecosystems may be important to interpreting lagged canopy C cycling and growth processes.

Gough, C. M.; Flower, C. E.; Vogel, C. S.; Dragoni, D.; Curtis, P. S.

2008-12-01

152

MCEARD - CYANOBACTERIA AND THEIR TOXINS  

EPA Science Inventory

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

153

Risk Assessment of Shellfish Toxins  

PubMed Central

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

Munday, Rex; Reeve, John

2013-01-01

154

Inactivation of allergens and toxins.  

PubMed

Plants are replete with thousands of proteins and small molecules, many of which are species-specific, poisonous or dangerous. Over time humans have learned to avoid dangerous plants or inactivate many toxic components in food plants, but there is still room for ameliorating food crops (and plants in general) in terms of their allergens and toxins content, especially in their edible parts. Inactivation at the genetic rather than physical or chemical level has many advantages and classical genetic approaches have resulted in significant reduction of toxin content. The capacity, offered by genetic engineering, of turning off (inactivating) specific genes has opened up the possibility of altering the plant content in a far more precise manner than previously available. Different levels of intervention (genes coding for toxins/allergens or for enzymes, transporters or regulators involved in their metabolism) are possible and there are several tools for inactivating genes, both direct (using chemical and physical mutagens, insertion of transposons and other genetic elements) and indirect (antisense RNA, RNA interference, microRNA, eventually leading to gene silencing). Each level/strategy has specific advantages and disadvantages (speed, costs, selectivity, stability, reversibility, frequency of desired genotype and regulatory regime). Paradigmatic examples from classical and transgenic approaches are discussed to emphasize the need to revise the present regulatory process. Reducing the content of natural toxins is a trade-off process: the lesser the content of natural toxins, the higher the susceptibility of a plant to pests and therefore the stronger the need to protect plants. As a consequence, more specific pesticides like Bt are needed to substitute for general pesticides. PMID:20601271

Morandini, Piero

2010-11-30

155

Differential priming of soil carbon driven by soil depth and root impacts on carbon lability  

NASA Astrophysics Data System (ADS)

An increase in root-derived labile soil carbon (C) inputs (e.g. exudates) can stimulate decomposition of more recalcitrant soil organic carbon (SOC) by priming microbial activity, which can lead to a net loss of soil C storage. This priming effect can be small or large and negative or positive, but the mechanisms by which root-C controls the magnitude and direction of SOC decomposition remain poorly understood. With this study we evaluated how small versus large differences in labile soil C availability affect microbial processing of simulated root exudate inputs and decomposition of SOC. We conducted a laboratory incubation experiment (60 days) with soils collected from under six switchgrass (Panicum virgatum) cultivars to a depth of 60 cm. Differences in specific root length among cultivars were expected to result in small differences in labile soil C availability, whereas differences associated with soil depth were expected to result in large differences in labile soil C availability. Soil cores were divided into 0-10 cm, 20-30 cm and 40-60 cm depth increments, and soils of all cultivars (no roots) across all three depths were incubated with addition of either: (1) water (60% water holding capacity), or (2) labile C provided as a 13C-labeled synthetic root exudate cocktail. We measured CO2 respiration throughout the experiment. The switchgrass was grown for three years in soils that formerly supported C3 pasture grasses, and the natural difference in 13C signature between C3 and C4 plants enabled quantification of differences in the lability of root-derived C among cultivars. Moreover the 13C labeled synthetic root-exudate cocktail amendment to soils allowed us to assess impacts of exudates-C addition on priming in soil derived from the different cultivars and from different depths. Our experiment led to three main results: (1) different cultivars of switchgrass regulate labile C availability across the soil profile differently; (2) small differences in labile C among the soils derived from different cultivars did not significantly mediate the impact of exudates-C additions on priming; (3) but, large differences in labile soil C contents among depths led to differences in priming effects, where greater priming effects were observed for shallow relative to deep soils across all days of the experiment. These results suggest that increased root-derived C inputs will have marginal impacts on decomposition of more stable SOC at depth and that their impact on priming will be similar in soils with small differences in available soil C.

De Graaff, M.; Jastrow, J. D.; Gilette, S.; Johns, A.; Wullschleger, S. D.

2012-12-01

156

Analysis of latex agglutination test for Clostridium difficile toxin A (D-1) and differentiation between C difficile toxins A and B and latex reactive protein.  

PubMed Central

Virulent toxigenic and avirulent non-toxigenic strains of Clostridium difficile gave a positive result in the latex agglutination test (LAT) for C difficile toxin A (D-1). Similar concentrations of latex agglutinating antigen were produced by these strains in vivo. Positive reactions were also given by C sporogenes, proteolytic C botulinum Types A, B, and A/F, and Bacteroides assaccharolyticus. The latex agglutinating antigen was denatured by boiling for 10 minutes, but not by heating at 56 degrees C for 30 minutes. The reaction was abolished by incubation of test material with crude C difficile antitoxin but not with other clostridial antitoxins or specific antitoxin to C difficile toxin A. The latex agglutinating antigen present in C difficile eluted between 0.39% and 0.47% M sodium chloride, and that produced by the other clostridia, between 0.35% and 0.43% M sodium chloride by fast protein liquid chromatography. The latex agglutinating antigen of C difficile was neither cytotoxic nor mouse lethal and was distinct from toxin A and toxin B. In the analysis of faecal specimens from patients with diarrhoea the latex agglutination test correlated better with the presence of C difficile than with toxin B and detected both toxigenic and non-toxigenic strains. The latex agglutination test should only be used in the laboratory as an alternative to culture for C difficile and not as a method for the detection of C difficile toxins. PMID:3108333

Borriello, S P; Barclay, F E; Reed, P J; Welch, A R; Brown, J D; Burdon, D W

1987-01-01

157

Analysis of latex agglutination test for Clostridium difficile toxin A (D-1) and differentiation between C difficile toxins A and B and latex reactive protein.  

PubMed

Virulent toxigenic and avirulent non-toxigenic strains of Clostridium difficile gave a positive result in the latex agglutination test (LAT) for C difficile toxin A (D-1). Similar concentrations of latex agglutinating antigen were produced by these strains in vivo. Positive reactions were also given by C sporogenes, proteolytic C botulinum Types A, B, and A/F, and Bacteroides assaccharolyticus. The latex agglutinating antigen was denatured by boiling for 10 minutes, but not by heating at 56 degrees C for 30 minutes. The reaction was abolished by incubation of test material with crude C difficile antitoxin but not with other clostridial antitoxins or specific antitoxin to C difficile toxin A. The latex agglutinating antigen present in C difficile eluted between 0.39% and 0.47% M sodium chloride, and that produced by the other clostridia, between 0.35% and 0.43% M sodium chloride by fast protein liquid chromatography. The latex agglutinating antigen of C difficile was neither cytotoxic nor mouse lethal and was distinct from toxin A and toxin B. In the analysis of faecal specimens from patients with diarrhoea the latex agglutination test correlated better with the presence of C difficile than with toxin B and detected both toxigenic and non-toxigenic strains. The latex agglutination test should only be used in the laboratory as an alternative to culture for C difficile and not as a method for the detection of C difficile toxins. PMID:3108333

Borriello, S P; Barclay, F E; Reed, P J; Welch, A R; Brown, J D; Burdon, D W

1987-05-01

158

Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery  

PubMed Central

Intracellular processes, including endosomal escape and intracellular release, are efficiency-determining steps in achieving successful gene delivery. It has been found that the presence of acid-labile units in polymers can facilitate endosomal escape and that the presence of reducible units in polymers can lead to intracellular release. In this study, poly(amido amine)s with both bioreducible and acid-labile properties were synthesized to improve gene delivery compared with single-responsive carriers. Transfection and cytotoxicity were evaluated in three cell lines. The complexes of DNA with dual-responsive polymers showed higher gene transfection efficiency than single-responsive polymers and polyethylenimine. At the same time, these polymers were tens of times less cytotoxic than polyethylenimine. Therefore, a polymer that is both reducible and acid-labile is a promising material for efficient and biocompatible gene delivery. PMID:23209367

Yu, Zhi-Qiang; Yan, Jun-Jie; You, Ye-Zi; Zhou, Qing-Hui

2012-01-01

159

The Interactive Effects of Affect Lability, Negative Urgency, and Sensation Seeking on Young Adult Problematic Drinking  

PubMed Central

Prior studies have suggested that affect lability might reduce the risk for problematic drinking among sensation seekers by compensating for their deficiencies in emotional reactivity and among individuals high on negative urgency by disrupting stable negative emotions. Due to the high prevalence of college drinking, this study examined whether affect lability interacted with sensation seeking and negative urgency to influence college student problematic drinking. 414 college drinkers (mean age: 20, 77% female, and 74% Caucasian) from a US Midwestern University completed self-administered questionnaires online. Consistent with our hypotheses, our results indicated that the effects of sensation seeking and negative urgency on problematic drinking weakened at higher levels of affect lability. These findings emphasize the importance of considering specific emotional contexts in understanding how negative urgency and sensation seeking create risk for problematic drinking among college students. These findings might also help us better understand how to reduce problematic drinking among sensation seekers and individuals high on negative urgency. PMID:24826366

Karyadi, Kenny; Coskunpinar, Ayca; Dir, Allyson L.; Cyders, Melissa A.

2013-01-01

160

Mood lability among offspring of parents with bipolar disorder and community controls  

PubMed Central

Objectives Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study. Methods Forty-one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of 174 BP parents, and 192 offspring of 117 control parents completed a scale that was developed to evaluate mood lability in youth, i.e., the Children’s Affective Lability Scale (CALS). Results A factor analysis of the parental CALS, and in part the child CALS, revealed Irritability, Mania, and Anxiety/Depression factors, with most of the variance explained by the Irritability factor. After adjusting for confounding factors (e.g., parental and offspring non-BP psychopathology), BP offspring of BP parents showed the highest parental and child total and factor scores, followed by the non-BP offspring of BP parents, and then the offspring of the controls. Conclusions Mood lability overall and mania-like, anxious/depressed, and particularly irritability symptoms may be a prodromal phenotype of BP among offspring of parents with BP. Prospective studies are warranted to clarify whether these symptoms will predict the development of BP and/or other psychopathology. If confirmed, these symptoms may become a target of treatment and biological studies before BP develops. PMID:23551755

Birmaher, Boris; Goldstein, Benjamin I; Axelson, David A; Monk, Kelly; Hickey, Mary Beth; Fan, Jieyu; Iyengar, Satish; Ha, Wonho; Diler, Rasim S; Goldstein, Tina; Brent, David; Ladouceur, Cecile D; Sakolsky, Dara; Kupfer, David J

2013-01-01

161

Labile iron in cells and body fluids: physiology, pathology, and pharmacology  

PubMed Central

In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI) composition varies with metal concentration and substances with chelating groups but also with pH and the medium redox potential. Although physiologically in the lower ?M range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS) formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (Tf; that renders iron essentially non-labile), in systemic iron overload (IO), the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma Tf approaches iron saturation, labile plasma iron (LPI) emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in intravenous iron formulations per se as well as in plasma (LPI) following parenteral iron administration. PMID:24659969

Cabantchik, Zvi Ioav

2014-01-01

162

The toxin and antidote puzzle  

PubMed Central

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

2011-01-01

163

An update on uremic toxins.  

PubMed

In the last decade, uremic toxicity as a potential cause for the excess of cardiovascular disease and mortality observed in chronic kidney disease gained more and more interest. This review focuses on uremic toxins with known cardiovascular effects and their removal. For protein-bound solutes, for example, indoxylsulfate and the conjugates of p-cresol, and for small water-soluble solutes, for example, guanidines, such as ADMA and SDMA, there is a growing evidence for a role in cardiovascular toxicity in vitro (e.g., affecting leukocyte, endothelial, vascular smooth muscle cell function) and/or in vivo. Several middle molecules (e.g., beta-2-microglobulin, interleukin-6, TNF-alpha and FGF-23) were shown to be predictors for cardiovascular disease and/or mortality. Most of these solutes, however, are difficult to remove during dialysis, which is traditionally assessed by studying the removal of urea, which can be considered as a relatively inert uremic retention solute. However, even the effective removal of other small water-soluble toxins than urea can be hampered by their larger distribution volumes. Middle molecules (beta-2-microglobulin as prototype, but not necessarily representative for others) are cleared more efficiently when the pore size of the dialyzer membrane increases, convection is applied and dialysis time is prolonged. Only adding convection to diffusion improves the removal of protein-bound toxins. Therefore, alternative removal strategies, such as intestinal adsorption, drugs interfering with toxic biochemical pathways or decreasing toxin concentration, and extracorporeal plasma adsorption, as well as kinetic behavior during dialysis need further investigation. Even more importantly, randomized clinical studies are required to demonstrate a survival advantage through these strategies. PMID:22893494

Neirynck, N; Vanholder, R; Schepers, E; Eloot, S; Pletinck, A; Glorieux, G

2013-02-01

164

Labile carbon concentrations are strongly linked to plant production in Arctic tussock tundra soils  

NASA Astrophysics Data System (ADS)

The exchange of carbon and nutrients between plants and microbes is a key determinant of carbon balance in Arctic soils. Microbes rely on labile plant carbon for the energy they need to produce enzymes that can release nutrients and less energetically favorable carbon from soil organic matter. One of the main mechanisms of carbon transfer is rhizodeposition, the exudation of labile plant carbon such as sugars from roots into the rhizosphere. Despite the importance of this flow of energy and materials from plants to microbes, there have been few attempts to quantify labile carbon pools or fluxes in Arctic soils. To improve our knowledge of labile carbon dynamics in Arctic soils, we address two basic questions: (1) What are the seasonal patterns of labile carbon concentrations? and (2) How do seasonal patterns in labile carbon correlate with plant production, microbial biomass, and soil nutrients? We measured concentrations of total reducing sugars (TRS) in the soil solution of moist acidic tussock tundra on 28 dates during the 2012 growing season in 20 plots of an early snowmelt × warming experiment. We evaluated these total reducing sugar concentrations in the context of eddy flux carbon exchange data, plant NDVI, total dissolved carbon in soils, microbial biomass, and soil nutrients. Though we did not see treatment effects of the snowmelt × warming experiment, we did observe a clear seasonal pattern in TRS concentrations in which they started low at the time of thaw, then built to a maximum value around the time of peak plant physiology in July, followed by a decline as plants senesced. We observed a clear correlation between TRS and gross primary production (GPP). NDVI values also increased with TRS concentrations during the first half of the season and then leveled off as TRS began its decline. These relationships were in contrast to labile N concentrations, which remained at low concentrations all season. Our data suggest that rhizodeposition of labile carbon compounds in Arctic tundra ecosystems has a strong seasonal pattern that closely tracks plant production. This connection suggests that if plant production increases in a warmer Arctic, plants may ease carbon limitation to summer microbial activity.

Darrouzet-Nardi, A.; Weintraub, M. N.; Euskirchen, E. S.; Steltzer, H.; Sullivan, P.

2013-12-01

165

Proteolytic regulation of toxin-antitoxin systems by ClpPC in Staphylococcus aureus.  

PubMed

Bacterial toxin-antitoxin (TA) systems typically consist of a small, labile antitoxin that inactivates a specific longer-lived toxin. In Escherichia coli, such antitoxins are proteolytically regulated by the ATP-dependent proteases Lon and ClpP. Under normal conditions, antitoxin synthesis is sufficient to replace this loss from proteolysis, and the bacterium remains protected from the toxin. However, if TA production is interrupted, antitoxin levels decrease, and the cognate toxin is free to inhibit the specific cellular component, such as mRNA, DnaB, or gyrase. To date, antitoxin degradation has been studied only in E. coli, so it remains unclear whether similar mechanisms of regulation exist in other organisms. To address this, we followed antitoxin levels over time for the three known TA systems of the major human pathogen Staphylococcus aureus, mazEF, axe1-txe1, and axe2-txe2. We observed that the antitoxins of these systems, MazE(sa), Axe1, and Axe2, respectively, were all degraded rapidly (half-life [t(1/2)], approximately 18 min) at rates notably higher than those of their E. coli counterparts, such as MazE (t(1/2), approximately 30 to 60 min). Furthermore, when S. aureus strains deficient for various proteolytic systems were examined for changes in the half-lives of these antitoxins, only strains with clpC or clpP deletions showed increased stability of the molecules. From these studies, we concluded that ClpPC serves as the functional unit for the degradation of all known antitoxins in S. aureus. PMID:20038589

Donegan, Niles P; Thompson, Earl T; Fu, Zhibiao; Cheung, Ambrose L

2010-03-01

166

Bt Toxin Modification for Enhanced Efficacy  

PubMed Central

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

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

2014-01-01

167

Bt toxin modification for enhanced efficacy.  

PubMed

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

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

2014-10-01

168

Prokaryotic toxin–antitoxin stress response loci  

Microsoft Academic Search

Although toxin–antitoxin gene cassettes were first found in plasmids, recent database mining has shown that these loci are abundant in free-living prokaryotes, including many pathogenic bacteria. For example, Mycobacterium tuberculosis has 38 chromosomal toxin–antitoxin loci, including 3 relBE and 9 mazEF loci. RelE and MazF are toxins that cleave mRNA in response to nutritional stress. RelE cleaves mRNAs that are

Susanne K. Christensen; Anders Løbner-Olesen; Kenn Gerdes

2005-01-01

169

Cellular and Systemic Effects of Anthrax Lethal Toxin and Edema Toxin  

PubMed Central

Anthrax lethal toxin (LT) and edema toxin (ET) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. This review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by LT in different cells. A brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented. PMID:19638283

Moayeri, Mahtab; Leppla, Stephen H.

2009-01-01

170

Long-term effects of soil warming on labile carbon availability and microbial community respiration and composition  

E-print Network

in soil composition in temperate forests as a result of decade- length warming. Keywords: climate change the control plots. I looked at what happened to carbon composition in mineral soil, both labile and ligninLong-term effects of soil warming on labile carbon availability and microbial community respiration

Vallino, Joseph J.

171

Toxin Detection by Surface Plasmon Resonance  

PubMed Central

Significant efforts have been invested in the past years for the development of analytical methods for fast toxin detection in food and water. Immunochemical methods like ELISA, spectroscopy and chromatography are the most used in toxin detection. Different methods have been linked, e.g. liquid chromatography and mass spectrometry (LC-MS), in order to detect as low concentrations as possible. Surface plasmon resonance (SPR) is one of the new biophysical methods which enables rapid toxin detection. Moreover, this method was already included in portable sensors for on-site determinations. In this paper we describe some of the most common methods for toxin detection, with an emphasis on SPR. PMID:22573957

Hodnik, Vesna; Anderluh, Gregor

2009-01-01

172

Toxins 2011, 3, 1502-1517; doi:10.3390/toxins3121502 ISSN 2072-6651  

E-print Network

Toxins 2011, 3, 1502-1517; doi:10.3390/toxins3121502 toxins ISSN 2072-6651 www.mdpi.com/journal common cause of refusal of grain deliveries to the food industry due to non-compliance with health regulations. Hence, it is imperative to find new molecules with less impact on the environment. One

Boyer, Edmond

173

TOXINS IN BIOTECHNOLOGY / 1 Animal Toxins in the World of Modern  

E-print Network

TOXINS IN BIOTECHNOLOGY / 1 Animal Toxins in the World of Modern Biotechnology JEAN-MARC SABATIER1 Biotechnologies, Bâtiment Biopolis, 5, avenue du Grand Sablon, 38700 La Tronche, France. Tel.: +33-4-56520563; Fax: +33-4-56520637; E-mail address: michel.dewaard@ujf-grenoble.fr Running title: Toxins in Biotechnology

Paris-Sud XI, Université de

174

2,3,7,8-Tetrachlorodibenzo-p-dioxin impairs iron homeostasis by modulating iron-related proteins expression and increasing the labile iron pool in mammalian cells.  

PubMed

Cellular iron metabolism is essentially controlled by the binding of cytosolic iron regulatory proteins (IRP1 or IRP2) to iron-responsive elements (IREs) located on mRNAs coding for proteins involved in iron acquisition, utilization and storage. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent toxins of current interest that occurs as poisonous chemical in the environment. TCDD exposure has been reported to induce a broad spectrum of toxic and biological responses, including significant changes in gene expression for heme and iron metabolism associated with liver injury. Here, we have investigated the molecular effects of TCDD on the iron metabolism providing the first evidence that administration of the toxin TCDD to mammalian cells affects the maintenance of iron homeostasis. We found that exposure of Madin-Darby Bovine Kidney cell to TCDD caused a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Interestingly, we observed a concomitant IRP1 down-regulation and IRP2 up-regulation thus determining a marked enhancement of transferrin receptor 1 (TfR-1) expression and a biphasic response in ferritin content. The changed ferritin content coupled to TfR-1 induction after TCDD exposure impairs the cellular iron homeostasis, ultimately leading to significant changes in the labile iron pool (LIP) extent. Since important iron requirement changes occur during the regulation of cell growth, it is not surprising that the dioxin-dependent iron metabolism dysregulation herein described may be linked to cell-fate decision, supporting the hypothesis of a central connection among exposure to dioxins and the regulation of critical cellular processes. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:21333694

Santamaria, Rita; Fiorito, Filomena; Irace, Carlo; De Martino, Luisa; Maffettone, Carmen; Granato, Giovanna Elvira; Di Pascale, Antonio; Iovane, Valentina; Pagnini, Ugo; Colonna, Alfredo

2011-05-01

175

A Longitudinal Study of Emotion Regulation, Emotion Lability/Negativity, and Internalizing Symptomatology in Maltreated and Nonmaltreated Children  

PubMed Central

The longitudinal contributions of emotion regulation and emotion lability/negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that, for both maltreated and nonmaltreated children, emotion regulation was a mediator between emotion lability/negativity and internalizing symptomatology, whereas emotion lability/negativity was not a mediator between emotion regulation and internalizing symptomatology. Early maltreatment was associated with high emotion lability/negativity (age 7) that contributed to poor emotion regulation (age 8), which in turn was predictive of increases in internalizing symptomatology (from age 8 to 9). The results imply important roles of emotion regulation in the development of internalizing symptomatology, especially for children with high emotion lability/negativity. PMID:23034132

Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.

2013-01-01

176

Research paper The determination of labile Fe in ferrihydrite by ascorbic acid extraction  

E-print Network

Research paper The determination of labile Fe in ferrihydrite by ascorbic acid extraction August 2010 Accepted 1 September 2010 Editor: J.D. Blum Keywords: Ferrihydrite Ascorbic acid Dissolution kinetics Aggregation Aging An ascorbic acid extraction at pH 7.5 has been examined to assess the influence

Benning, Liane G.

177

Multivariate Statistical Analysis of Labile Trace Elements in H Chondrites: Evidence for Meteoroid Streams  

Microsoft Academic Search

Differences have been observed between meteorite populations with vastly different terrestrial ages, i.e. Antarctic and non-Antarctic meteorite populations (Koeberl and Cassidy, 1991 and references therein). Comparisons of labile trace element contents (Wolf and Lipschutz, 1992) and induced TL parameters (Benoit and Sears, 1992) in samples from Victoria Land and Queen Maud Land, populations which also differ in mean terrestrial age

S. F. Wolf; M. E. Lipschutz

1992-01-01

178

Energy evaluation of forest residues originated from Eucalyptus globulus Labill in Galicia  

Microsoft Academic Search

The possibility of retrieving the energy contained in forest residues originating from wood exploitation in Galicia (Spain) is evaluated. This study was made on Eucalyptus globulus Labill occupying a forest surface of 240000 ha. This species plays an important role in the economical development of Galicia, as it is the main forest species for production of pulp. Sampling was made

L Núñez-Regueira; J Proup??n-Castiñeiras; J. A Rodr??guez-Añón

2002-01-01

179

Temperature effects on decomposition rates of soil organic matter with differing proportions of labile and  

E-print Network

soil carbon cycle models predict that climate warming will stimulate microbial decomposition of labile carbon cycle. Soil is this natural carbon sink because carbon is sequestered as biomass, such as plant disagreement regarding the effects of climate change on global soil carbon stocks. Soil carbon stocks

Vallino, Joseph J.

180

Key role of the resin layer thickness in the lability of complexes measured by DGT.  

PubMed

Analysis of the dynamic features of diffusion gradients in thin film devices (DGT) indicates that the penetration of complexes into the resin layer dramatically increases their lability. This should be taken into account when interpreting DGT measurements in terms of the dynamics of solution speciation. The experimental accumulation of Cd by DGT sensors in Cd-NTA systems confirmed these theoretical analyses. A computational code, which allows a rigorous digital simulation of the diffusion-reaction processes in the gel and resin layers, was used to model the results and to demonstrate the effect of the complex penetration into the resin layer on the lability degree. These findings suggest that DGT renders all complexes much more labile than if the resin-diffusive gel interface was considered as a perfect planar sink, explaining why DGT often measures a high proportion of the metal in a natural water. This information is relevant since some studies have stressed the importance of labile complexes as a source of bioaccumulated metal. PMID:21561131

Mongin, Sandrine; Uribe, Ramiro; Puy, Jaume; Cecília, Joan; Galceran, Josep; Zhang, Hao; Davison, William

2011-06-01

181

Synthesis of new maleimide derivatives of daunorubicin and biological activity of acid labile transferrin conjugates  

Microsoft Academic Search

Maleimide groups were bound to the 3?-amino position of daunorubicin through a benzamide bond or to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid labile transferrin conjugates prepared with the latter two derivatives exhibited high activity in human melanoma cells (MEXF 989) using a clonogenic cell assay comparable to or exceeding that of daunorubicin.

Felix Kratz; Ulrich Beyer; Peter Schumacher; Michael Krüger; Heike Zahn; Thomas Roth; Heinz H. Fiebig; Clemens Unger

1997-01-01

182

Labile proteins accumulated in damaged hair upon permanent waving and bleaching treatments  

Microsoft Academic Search

We previously found that certain hair proteins were soluble by means of a partial extraction method. In this study, we demonstrate that the amount of soluble proteins internally formed in permed and bleached hair, labile proteins, is a useful index for hair damage assessment. Compared to tensile property changes, this index rose in widely dynamic ranges as the time of

TAKAFUMI INOUE; MAYUMI ITO; KENJI KIZAWA

183

Mayolenes: Labile defensive lipids from the glandular hairs of a caterpillar (Pieris rapae)  

E-print Network

larvae of a laboratory population of P. rapae maintained on cabbage plants (Brassica oleraceaeMayolenes: Labile defensive lipids from the glandular hairs of a caterpillar (Pieris rapae) Scott R, Pieris rapae (Pieridae), are beset with glandular hairs, bearing droplets of a clear oily secretion

Rutowski, Ronald L.

184

Toxin-Antitoxin Genes of the Gram-Positive Pathogen Streptococcus pneumoniae: So Few and Yet So Many  

PubMed Central

Summary: Pneumococcal infections cause up to 2 million deaths annually and raise a large economic burden and thus constitute an important threat to mankind. Because of the increase in the antibiotic resistance of Streptococcus pneumoniae clinical isolates, there is an urgent need to find new antimicrobial approaches to triumph over pneumococcal infections. Toxin-antitoxin (TA) systems (TAS), which are present in most living bacteria but not in eukaryotes, have been proposed as an effective strategy to combat bacterial infections. Type II TAS comprise a stable toxin and a labile antitoxin that form an innocuous TA complex under normal conditions. Under stress conditions, TA synthesis will be triggered, resulting in the degradation of the labile antitoxin and the release of the toxin protein, which would poison the host cells. The three functional chromosomal TAS from S. pneumoniae that have been studied as well as their molecular characteristics are discussed in detail in this review. Furthermore, a meticulous bioinformatics search has been performed for 48 pneumococcal genomes that are found in public databases, and more putative TAS, homologous to well-characterized ones, have been revealed. Strikingly, several unusual putative TAS, in terms of components and genetic organizations previously not envisaged, have been discovered and are further discussed. Previously, we reported a novel finding in which a unique pneumococcal DNA signature, the BOX element, affected the regulation of the pneumococcal yefM-yoeB TAS. This BOX element has also been found in some of the other pneumococcal TAS. In this review, we also discuss possible relationships between some of the pneumococcal TAS with pathogenicity, competence, biofilm formation, persistence, and an interesting phenomenon called bistability. PMID:23204366

Chan, Wai Ting; Moreno-Córdoba, Inma

2012-01-01

185

Inputs of total and labile trace metals from wastewater treatment plants effluents to the Seine River  

NASA Astrophysics Data System (ADS)

The Seine river basin has long been impacted by metal inputs from the Paris area, but the water quality has been gradually improving for the last 20 years. Among all metal pollution sources (surface runoff, industries), urban wastewater discharge has been shown to significantly contribute, during low-flow periods, to metal fluxes of the River Seine. This paper assesses the current wastewater contribution to metal inputs in the Seine river basin, based on sampling of nine wastewater treatment plants (WWTPs). Seven metals were targeted (Al, Cd, Cr, Cu, Fe, Ni and Pb) during dry weather periods. Since total and dissolved concentrations alone are not relevant enough for an ecological risk assessment, labile metals (free + weekly complexed) were also measured by means of DGT (diffusive gradient in thin film technique). Results show that WWTPs greatly reduce total metal concentrations but reduce labile metal concentrations only slightly. Estimations made for direct total metal inputs in the River Seine via treated effluent discharge confirm the decrease observed for the 1994-1995 period. Labile metals released by WWTP were also considered by comparing fluxes in the effluent discharge of two different WWTPs to those flowing in the receiving river. Fluxes discharged by the largest plant were similar to those measured in the river during low-flow periods whereas they were negligible for the smaller one. Nevertheless, labile metal concentrations in both discharges were similar and the wastewater discharge’s contribution to labile fluxes in receiving waters seems to depend mostly on the relative significance of the discharge flow compared to the receiving water flow.

Buzier, Rémy; Tusseau-Vuillemin, Marie-Hélène; Keirsbulck, Marion; Mouchel, Jean-Marie

186

Biologic response to environmental toxins  

SciTech Connect

Biological response to environmental toxins results from the sum of natural, environmental, avocational, inapparent, and occupational exposures. These external exposures result in acceptable or unacceptable levels of absorption or internal exposure based on anticipated biological effects. There is no level of exposure which is in and of itself synonymous with intoxication. Biological effects may be classified as physiologic or pathologic, adaptive or nonadaptive, respectively. In each instance, the response may be acceptable or unacceptable. Intoxication requires the demonstration of a significant impairment of health. One may have an unacceptable pathologic response and still not have intoxication. Professional judgment is required.

Lerner, S.

1983-12-01

187

Botulinum toxin for axillary hyperhidrosis.  

PubMed

Botulinum toxin is a safe and effective treatment option for axillary hyperhidrosis. Although its pathophysiology is not clear and somewhat controversial, the beneficial effect of neuromodulators in inhibiting localized sweating temporarily is well known. Before the procedure, correct identification of the affected area is mandatory to avoid wastage of drug and neglect of target areas, and to enhance efficacy, as the hyperhidrotic location may not match the hairy axillary region. Utilization of this medication, such as dilution and injection techniques, depends on medical experience and may have some variations, including methods to make the procedure as painless as possible. PMID:25152343

de Almeida, Ada Regina Trindade; Montagner, Suelen

2014-10-01

188

The role of toxin A and toxin B in Clostridium difficile-associated disease  

PubMed Central

Recently, we constructed and characterized isogenic tcdA and tcdB mutants of a virulent Clostridium difficile strain and used a hamster model of disease to demonstrate that toxin B, not toxin A, is essential for virulence of this emerging pathogen. Earlier studies had shown that purified toxin A alone was able to induce C. difficile disease pathology and that purified toxin B was not effective unless it was co-administered with toxin A, suggesting that the toxins act synergistically. In this addendum we discuss this paradigm-shifting conclusion in the context of current strain epidemiology, particularly with respect to naturally occurring toxin A-negative, toxin B-positive isolates and the NAP1/027 epidemic isolates. The role of toxin receptors and how variant toxins might exert their effects is also discussed in relation to the published data. We conclude that it is critical to use the natural infection process to dissect the role of toxins in disease, and that future studies are contingent on such work. The impact and importance of animal models of C. difficile virulence are therefore considered within this frame of reference. PMID:20664812

Carter, Glen P; Rood, Julian I

2010-01-01

189

DNA probes for Shiga-like toxins I and II and for toxin-converting bacteriophages.  

PubMed Central

A set of DNA probes has been developed to study the genes for Shiga-like toxins (SLT) and the bacteriophage from which these toxin genes were isolated. Under stringent conditions of hybridization (80 to 90% homology), these probes detect strains containing (i) SLT I-related genes, (ii) SLT II-related genes, (iii) phage sequences from the SLT I-converting phage H19A/933J, and (iv) phage sequences from the SLT II-converting phage 933W. Strain characterization by hybridization with the toxin gene probes was as accurate as methods that used toxin-specific antibody to determine toxin synthesis. Screening of different gram-negative bacteria with the toxin probes revealed that only two species carry sequences related to the SLT genes, Escherichia coli and Shigella dysenteriae 1. These results indicated that the lower levels of toxin activity observed in shigellae other than S. dysenteriae 1 are due to a gene(s) that is genetically distinct from that which encodes Shiga toxin. Analysis of enterotoxigenic, enteroinvasive, enteropathogenic, and enterohemorrhagic E. coli indicated that SLT genes are found primarily in the enterohemorrhagic E. coli strain group. Use of both the toxin and the phage probes has identified a variety of genotypic combinations of phage and toxin sequences which differ from those observed for the original toxin-converting phage isolates, for E. coli O157:H7 strain 933, and for E. coli O26:H11 strain H19. Images PMID:2842369

Newland, J W; Neill, R J

1988-01-01

190

Botulinum Toxin and Gastrointestinal Tract Disorders  

PubMed Central

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

Weiser, Kirsten; Kennedy, Abigail

2008-01-01

191

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

PubMed

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

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

2012-06-01

192

The Enterotoxicity of Clostridium difficile Toxins  

PubMed Central

The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by acting directly on intestinal epithelial cells. Alternatively, the toxins may target immune cells and neurons once the intestinal epithelial barrier is disrupted. The toxins may also act indirectly by stimulating cells to produce chemokines, proinflammatory cytokines, neuropeptides and other neuroimmune signals. This review considers the mechanisms of TcdA- and TcdB-induced enterotoxicity, and recent developments in this field. PMID:22069662

Sun, Xingmin; Savidge, Tor; Feng, Hanping

2010-01-01

193

Protein toxins: intracellular trafficking for targeted therapy.  

PubMed

The immunotoxin approach is based on the use of tumor-targeting ligands or antibodies that are linked to the catalytic (toxic) moieties of bacterial or plant protein toxins. In this review, we first discuss the current state of clinical development of immunotoxin approaches describing the results obtained with the two toxins most frequently used: diphtheria and Pseudomonas toxin-derived proteins. In the second part of the review, a novel concept will be presented in which the roles are inverted: nontoxic receptor-binding toxin moieties are used for the targeting of therapeutic and diagnostic compounds to cancer or immune cells. The cell biological basis of these novel types of toxin-based therapeutics will be discussed, and we will summarize ongoing preclinical and clinical testing. PMID:15902276

Johannes, L; Decaudin, D

2005-09-01

194

Toxins  

MedlinePLUS

Ford MD. Acute poisoning. In: Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, Pa: Saunders ... trace metals and others. In: Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, Pa: Saunders ...

195

Lability and sorption of heavy metals as related to chemical, physical, and mineralogical characteristics of highly weathered soils  

Microsoft Academic Search

Purpose  Heavy metal lability, probably, is the most important isolated factor to cause toxicity in plants and organisms in soils.\\u000a Sorption of heavy metals, in turn, affects directly the amount of their labile forms in soils. Therefore, to assess sorption\\u000a and quantify labile forms of Cd, Cu, Ni, Pb, and Zn, adsorption and incubation studies were carried out.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and methods  The

Maurício Paulo Ferreira Fontes; Guilherme Cadinelli dos Santos

2010-01-01

196

Mechanism of CO displacement from an unusually labile rhenium complex: an experimental and theoretical investigation.  

PubMed

The displacement of a CO ligand from an unusually labile rhenium carbonyl complex containing a bidentate carboxyaldehyde pyrrolyl ligand by PPh(3) and pyridine has been investigated. The reaction is found to proceed by an associative, preequilibrium mechanism. Theoretical calculations support the experimental data and provide a complete energetic profile for the reaction. While the Re-CO bond is found to be intrinsically weak in these complexes, it is postulated that the unusual lability of this species is due to the presence of a weak aldehyde Re-O link that can easily dissociate to open a coordination site on the metal center and accommodate an incoming ligand prior to CO loss. The resulting intermediate complex has been identified by IR spectroscopy. The presence of the hemilabile pyrrolyl ligand provides a lower-energy reaction channel for the release of CO and may be of relevance in the design of CO-releasing molecules. PMID:23153281

Muhammad, Sohail; Yempally, Veeranna; Anas, Muhammad; Moncho, Salvador; Kyran, Samuel J; Brothers, Edward N; Darensbourg, Donald J; Bengali, Ashfaq A

2012-12-01

197

Clostridium difficile: its disease and toxins.  

PubMed Central

Clostridium difficile is the etiologic agent of pseudomembranous colitis, a severe, sometimes fatal disease that occurs in adults undergoing antimicrobial therapy. The disease, ironically, has been most effectively treated with antibiotics, although some of the newer methods of treatment such as the replacement of the bowel flora may prove more beneficial for patients who continue to relapse with pseudomembranous colitis. The organism produces two potent exotoxins designated toxin A and toxin B. Toxin A is an enterotoxin believed to be responsible for the diarrhea and mucosal tissue damage which occur during the disease. Toxin B is an extremely potent cytotoxin, but its role in the disease has not been as well studied. There appears to be a cascade of events which result in the expression of the activity of these toxins, and these events, ranging from the recognition of a trisaccharide receptor by toxin A to the synergistic action of the toxins and their possible dissemination in the body, are discussed in this review. The advantages and disadvantages of the various assays, including tissue culture assay, enzyme immunoassay, and latex agglutination, currently used in the clinical diagnosis of the disease also are discussed. PMID:3144429

Lyerly, D M; Krivan, H C; Wilkins, T D

1988-01-01

198

Effects on plant production after addition of labile carbon to arctic\\/alpine soils  

Microsoft Academic Search

Biomass production was analysed in Festuca vivipara, grown for 3 months in pots with non-sterilized or sterilized soil after factorial addition of three levels of labile carbon\\u000a combined with high and low levels of N and P. The soil was a nutrient-poor subarctic heath soil. In the non-sterilized soil\\u000a plant biomass production increased strongly only in the treatment with high

Inger K. Schmidt; Anders Michelsen; Sven Jonasson

1997-01-01

199

Lability of Drinking Water Treatment Residuals (WTR) Immobilized Phosphorus: Aging and pH Effects  

Microsoft Academic Search

Time constraints associated with conducting long-term (.20 yr) field experiments to test the stability of drinking water treatment resid- uals (WTR) sorbed phosphorus (P) inhibit improved understanding of the fate of sorbed P in soils when important soil properties (e.g., pH) change. We used artificially aged samples to evaluate aging and pH effects on lability of WTR-immobilized P. Artificial aging

Sampson Agyin-Birikorang; George A. O'Connor

2007-01-01

200

Protein degradation by ubiquitin-proteasome system in formation and labilization of contextual conditioning memory.  

PubMed

The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates. PMID:25135196

Sol Fustiñana, María; Federman, Noel; Freudenthal, Ramiro; Romano, Arturo

2014-09-01

201

Long-term time course of affective lability after subthalamic deep brain stimulation electrode implantation  

Microsoft Academic Search

The mechanism and time course of emotional side effects of subthalamic deep brain stimulation in Parkinson's disease are a matter for discussion. We report a 53-month follow-up of a patient with affective lability. Postoperative lesion plus bilateral stimulation strongly influenced mood in the first week in terms of laughing behavior, while voltage changes had only minor long-term impact up to

Lars Wojtecki; Lars Timmermann; Stefan Jun Groiss; Saskia Elben; Christiane Reck; Martin Südmeyer; Volker Sturm; Alfons Schnitzler

2011-01-01

202

Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences  

Microsoft Academic Search

The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3\\/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting

Horacio M. Domené; Vivian Hwa; Jesús Argente; Jan M. Wit; Cecilia Camacho-Hübner; Héctor G. Jasper; Jesús Pozo; Hermine A. van Duyvenvoorde; Shoshana Yakar; Olga V. Fofanova-Gambetti; Ron G. Rosenfeld; A. R. M. M. Hermus; T. B. Twickler; M. J. E. Kempers

2009-01-01

203

Behavioral Effects of Carbamazepine after Single and Repeated Administration in Emotionally Labile Subjects  

Microsoft Academic Search

The sample investigated consisted of two groups of emotionally labile healthy male subjects who were given either 100 mg\\/day of the antiepileptic drug carbamazepine (n = 16) or placebo (n = 16) for 8 days. Subjects were selected on the basis of their scores in the neuroticism scale of the Freiburg Personality Inventory (FPI-A: N score S⩾6). By means of

Wilhelm Janke; Jürgen Ehrhardt; Ulrich Münch

1983-01-01

204

Protection of Pyruvate,Pi Dikinase from Maize against Cold Lability by Compatible Solutes 1  

PubMed Central

Most C4 species are chilling sensitive and certain enzymes like pyruvate,Pi dikinase of the C4 pathway are also cold labile. The ability of cations and compatible solutes to protect maize (Zea mays) dikinase against cold lability was examined. The enzyme in desalted extracts at pH 8 from preilluminated leaves could be protected against cold lability (at 0°C) by the divalent cations Mn2+, Mg2+, and Ca2+. There was substantial protection by sulfate based salts but little protection by chloride based salts of potassium or ammonium (concentration 250 millimolar). The degree of protection against cold lability under limiting MgCl2 (5 millimolar) was pH sensitive (maximum protection at pH 8), but independent of ionic strength (up to 250 millimolar by addition of KCl). In catalysis Mg2+ is required and Mn2+ could not substitute as a cofactor. Several compatible solutes reduced or prevented the cold inactivation of dikinase (in desalted extracts and the partially purified enzyme), including glycerol, proline, glycinebetaine and trimethylamine-N-oxide (TMAO). TMAO and Mg2+ had an additive effect in protecting dikinase against cold inactivation. TMAO could largely substitute for the divalent cation and addition of TMAO during cold treatment prevented further inactivation. Cold inactivation was partially reversed by incubation at room temperature; with addition of TMAO reversal was complete. The temperature dependence of inactivation at pH 8 and 3 millimolar MgCl2 was evaluated by incubation at 2 to 17°C for 45 minutes, followed by assay at room temperature. At preincubation temperatures below 11°C there was a progressive inactivation which could be prevented by TMAO (450 millimolar). The results are discussed relative to possible effects of the solutes on the quaternary structure of this enzyme, which is known to dissociate at low temperatures. PMID:16666527

Krall, John P.; Edwards, Gerald E.; Andreo, Carlos S.

1989-01-01

205

Labile and stabilised fractions of soil organic carbon in some intensively cultivated alluvial soils.  

PubMed

The present investigation was undertaken in view of the limited information on the relative proportion of labile and stabilized fractions of soil organic carbon (SOC) in intensively cultivated lands, particularly under tropics. The specific objectives were i) to study the comparative recovery of SOC by different methods of labile carbon estimation under intensively cultivated lands and ii) to evaluate the impact of agricultural practices on carbon management index. For this purpose, in all, 105 surface soil samples were collected from intensively cultivated tube well and sewage irrigated agricultural lands. These samples were analysed for total as well as labile pools of SOC. Results indicated that Walkley and Black, KMnO4-oxidizable and microbial biomass carbon constituted the total SOC to the extent of 10.2 to 47.4, 1.66 to 23.2 and 0.30 to 5.49%, respectively with the corresponding mean values of 26.2, 9.16 and 2.15%. Lability of SOC was considerably higher in sewage irrigated soils than tube well irrigated soils under intensive cropping. Under soybean-wheat, the higher values of carbon management index (CMI) (279 and 286) were associated with the treatments where entire amount of nitrogen was supplied through FYM. Similar results were obtained under rice-wheat, whereas in case of maize-wheat the highest value of CMI was recorded under treatment receiving NPK through chemical fertilizer along with green manure. There was also a significant improvement in CMI under integrated (chemical fertilizer + organics) and chemical fertilizer-treated plots. The values of CMI ranged from 220 to 272 under cultivated lands receiving irrigation through sewage and industrial effluents. PMID:24555339

Verma, B C; Datta, S P; Rattan, R K; Singh, A K

2013-11-01

206

A biomimetic nanosponge that absorbs pore-forming toxins  

E-print Network

A biomimetic nanosponge that absorbs pore-forming toxins Che-Ming J. Hu, Ronnie H. Fang, Jonathan a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists virulence mechanism9. It has been demonstrated that the inhibition of the pore-forming a-toxin can reduce

Zhang, Liangfang

207

Toxin production by Bacillus pumilus.  

PubMed

Two strains of Bacillus pumilus (M11 and M38) and one strain each of Bacillus cereus (M27), Bacillus subtilis (M67), and Enterobacter agglomerans (M14) were identified from the air of Lancashire cotton mills. These strains were tested for cytopathic effects in Vero cells; B pumilus and B cereus strains were also examined for haemolytic activity, lecithinase production, and proteolytic action on casein. Rounding and clumping of the Vero cells occurred after the addition of supernatants prepared from B pumilus and B cereus strains; finger-like projections developed in the cells treated with B pumilus supernatants. Minimal effects occurred with B subtilis and E agglomerans. After two hours of exposure B pumilus (M11) produced the greatest effect, but treatment with trypan blue showed that most cells exposed to the M11 strain were still alive after 96 hours of exposure; those exposed to the supernatant prepared from the M38 strain of B pumilus were dead. Sheep erythrocytes were lysed more rapidly by B cereus than by B pumilus, B cereus (strongly positive) had a greater effect on lecithin than either of the B pumilus strains (M38 weakly positive, M11 negative). All hydrolised casein but the effect was more rapid with one of the B pumilus (M11) strains. It is concluded that not only do the toxins of B pumilus differ from those of B cereus, but there are also differences between the toxins produced by the two strains of B pumilus (M11 and M38). PMID:2066422

Hoult, B; Tuxford, A F

1991-06-01

208

Bacillithiol is a major buffer of the labile zinc pool in Bacillus subtilis.  

PubMed

Intracellular zinc levels are tightly regulated since zinc is an essential cofactor for numerous enzymes, yet can be toxic when present in excess. The majority of intracellular zinc is tightly associated with proteins and is incorporated during synthesis from a poorly defined pool of kinetically labile zinc. In Bacillus subtilis, this labile pool is sensed by equilibration with the metalloregulator Zur, as an indication of zinc sufficiency, and by CzrA, as an indication of zinc excess. Here, we demonstrate that the low-molecular-weight thiol bacillithiol (BSH) serves as a major buffer of the labile zinc pool. Upon shift to conditions of zinc excess, cells transiently accumulate zinc in a low-molecular-weight pool, and this accumulation is largely dependent on BSH. Cells lacking BSH are more sensitive to zinc stress, and they induce zinc efflux at lower external zinc concentrations. Thiol reactive agents such as diamide and cadmium induce zinc efflux by interfering with the Zn-buffering function of BSH. Our data provide new insights into intracellular zinc buffering and may have broad relevance given the presence of BSH in pathogens and the proposed role of zinc sequestration in innate immunity. PMID:25213752

Ma, Zhen; Chandrangsu, Pete; Helmann, Tyler C; Romsang, Adisak; Gaballa, Ahmed; Helmann, John D

2014-11-01

209

Labile synthetic cadmium complexes are not bioavailable to Pseudokirchneriella subcapitata in resin buffered solutions.  

PubMed

The Free Ion Activity Model (FIAM) predicts that cadmium (Cd) uptake by organisms is identical for solutions with the same free Cd(2+) concentration and inorganic composition. Clear exceptions to the FIAM have been shown for Cd uptake by plant roots, periphyton and human cells where labile Cd complexes increase bioavailability and which has been attributed to their role in enhancing Cd diffusion towards the uptake cells. Here, we assessed the role of labile Cd complexes on Cd uptake by algae, for which diffusion limitations should be less pronounced due to their smaller size. Long-term (3 days) Cd uptake by the green algae Pseudokirchneriella subcapitata was measured in resin buffered solutions with or without synthetic ligands and at three Cd(2+) ion activities (pCd 8.2-5.7). The free Cd(2+) activity was maintained during the test using a metal-selective resin located in the algal bottles. Total dissolved Cd increased up to 35-fold by adding the synthetic ligands at constant Cd(2+) activity. In contrast, Cd uptake by algae increased maximally 2.8 fold with increasing concentration of the synthetic ligands and the availability of the complexes were maximally 5.2% relative to Cd(2+) for NTA and CDTA complexes. It is concluded that labile Cd complexes do not greatly enhance Cd bioavailability to the unicellular algae and calculations suggest that Cd transport from solution to these small cells is not rate limiting. PMID:22903064

Verheyen, L; Merckx, R; Smolders, E

2012-11-15

210

Labile soil carbon inputs mediate the soil microbial community composition and plant residue decomposition rates  

SciTech Connect

Root carbon (C) inputs may regulate decomposition rates in soil, and in this study we ask: how do labile C inputs regulate decomposition of plant residues, and soil microbial communities? In a 14 d laboratory incubation, we added C compounds often found in root exudates in seven different concentrations (0, 0.7, 1.4, 3.6, 7.2, 14.4 and 21.7 mg C g{sup -1} soil) to soils amended with and without {sup 13}C-labeled plant residue. We measured CO{sub 2} respiration and shifts in relative fungal and bacterial rRNA gene copy numbers using quantitative polymerase chain reaction (qPCR). Increased labile C input enhanced total C respiration, but only addition of C at low concentrations (0.7 mg C g{sup -1}) stimulated plant residue decomposition (+2%). Intermediate concentrations (1.4, 3.6 mg C g{sup -1}) had no impact on plant residue decomposition, while greater concentrations of C (> 7.2 mg C g{sup -1}) reduced decomposition (-50%). Concurrently, high exudate concentrations (> 3.6 mg C g{sup -1}) increased fungal and bacterial gene copy numbers, whereas low exudate concentrations (< 3.6 mg C g{sup -1}) increased metabolic activity rather than gene copy numbers. These results underscore that labile soil C inputs can regulate decomposition of more recalcitrant soil C by controlling the activity and relative abundance of fungi and bacteria.

De Graaff, Marie-Anne [ORNL; Classen, Aimee T [University of Tennessee, Knoxville (UTK); Castro Gonzalez, Hector F [ORNL; Schadt, Christopher Warren [ORNL

2010-01-01

211

Difference in protein substrate specificity between hemorrhagic toxin and lethal toxin from Clostridium sordellii.  

PubMed

The hemorrhagic toxin (HT) from Clostridium sordellii is pharmacologically related to Clostridium difficile toxins A and B and Clostridium sordellii lethal toxin which have been recently identified as mono-glucosyl-transferases. Here we report that HT, which is coexpressed with lethal toxin, is also a glucosyltransferase. Whereas lethal toxin glucosylates the Rho subfamily proteins Rac and Cdc42 and the Ras subfamily proteins H-Ras and Rap, the substrate specificity of HT is strictly confined to the Rho subfamily proteins Rho, Rac and Cdc42. Comparable to lethal toxin, transferase activity of HT is stimulated by Mn2+. Acceptor amino acid in Rho was identified by mutagenesis as threonine-37. C. sordellii HT is a novel member of the family of clostridial mono-glucosyl-transferases, a family which modifies the Rho and Ras GTPases. PMID:8954906

Genth, H; Hofmann, F; Selzer, J; Rex, G; Aktories, K; Just, I

1996-12-13

212

Both, toxin A and toxin B, are important in Clostridium difficile infection  

PubMed Central

The bacterium Clostridium difficile is the leading cause of healthcare associated diarrhoea in the developed world and thus presents a major financial burden. The main virulence factors of C. difficile are two large toxins, A and B. Over the years there has been some debate over the respective roles and importance of these two toxins. To address this, we recently constructed stable toxin mutants of C. difficile and found that they were virulent if either toxin A or toxin B was functional. This underlined the importance of each toxin and the necessity to consider both when developing countermeasures against Clostridium difficile infection (CDI). In this article we discuss our findings in the context of previous work and outline some of the challenges which face the field as a result. PMID:21804353

Kuehne, Sarah A; Cartman, Stephen T

2011-01-01

213

The Toxins of Helminthosporium maydis (Race T) 1  

PubMed Central

Host-specific toxins produced by Helminthosporium maydis, race T, are measured quantitatively by a chemical assay procedure involving reaction of the toxins with a sulfuric acidacetic anhydride reagent and measurement of the absorbance of the product at 330 nm. The assay was shown to measure total toxin concentrations after only limited fractionation of the culture medium. Using the assay it was possible to show that the highest amount of toxin per gram of fungus mycelium occurs early in the growth cycle of H. maydis. Toxins I, II, and V are the predominant toxins at these early times both in culture and in infected corn and wheat varieties. Some chromatographic and spectral properties of toxin V, a previously unreported toxin, are described. Since toxin V appears in culture prior to toxins I, II, III and IV, a precursor-product relationship can be suggested. PMID:16659155

Karr, Dale B.; Karr, Arthur L.; Strobel, Gary A.

1975-01-01

214

Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin  

Microsoft Academic Search

1.The blocking effect of tetanus toxin on the neuromuscular junction of the mouse phrenic nervehemidiaphragm preparation exposed to the toxin (0.05–20 µg\\/ml) in the organ bath was studied and compared with the action of botulinum A toxin.2.The time course of the paralysis of the diaphragm could be divided into a latent and a manifest period. Still during the latent period

E. Habermann; F. Dreyer; H. Bigalke

1980-01-01

215

Lability of a mixture of metal complexes under steady-state planar diffusion in a finite domain.  

PubMed

The rigorous analytical solution for the fluxes from a mixture of 1:1 metal complexes toward an active surface under steady-state planar diffusion in a finite domain and excess ligand conditions allows for the computation of the global degree of lability of the system as well as particular degrees of lability of each complex in the mixture. This kind of system is found in a variety of fields ranging from electrochemical techniques (such as stripping chronopotentiometry at scanned deposition potential, SSCP) to analytical devices (such as diffusion gradients in thin-film gels, DGT). Among the specific effects arising from the presence of a mixture of ligands competing for the metal we highlight the following: (i) The degree of lability of a complex in the mixture differs from its degree of lability in an unmixed system with the same ligand concentration, and (ii) the degree of lability of one complex depends on (i.e., can be modified with) the concentrations of the ligands in the mixture. The impact of these characteristics on the metal flux crossing the active surface reaches the highest value when both complexes are partially labile. The complex contribution to the metal flux goes through a maximum when the thickness of the diffusion domain is varied. Thus, the thickness of the diffusion domain can be chosen to enhance the contribution of one particular complex. Lability criteria for each complex of the mixture within the reaction layer approximation are also reported. In particular, the reaction layer formulation for a complex is discussed in detail for two limiting cases: the rest of complexes are all nonlabile or the rest of complexes are all labile. PMID:16821895

Salvador, José; Garcés, José Luis; Galceran, Josep; Puy, Jaume

2006-07-13

216

CaMKII Activation State Underlies Synaptic Labile Phase of LTP and Short-Term Memory Formation  

Microsoft Academic Search

Summary Background: The labile state of short-term memory has been known for more than a century. It has been frequently reported that immediate postlearning intervention can readily disrupt newly formed memories. However, the molecular and cellular mechanisms underlying the labile state of new memory are not understood. Results: Using a bump-and-hole-based chemical-genetic method, we have rapidly and selectively manipulated aCaMKII

Huimin Wang; Ruiben Feng; L. Phillip Wang; Fei Li; Xiaohua Cao; Joe Z. Tsien

2008-01-01

217

Role of Heat-Stable Enterotoxins in the Induction of Early Immune Responses in Piglets after Infection with Enterotoxigenic Escherichia coli  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) strains that produce heat-stable (ST) and/or heat - labile (LT) enterotoxins are cause of post – weaning diarrhea in piglets. However, the relative importance of the different enterotoxins in host immune responses against ETEC infection has been poorly defined. In the present study, several isogenic mutant strains of an O149:F4ac+, LT+ STa+ STb+ ETEC strain were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). The small intestinal segment perfusion (SISP) technique and microarray analysis were used to study host early immune responses induced by these mutant strains 4 h after infection in comparison to the wild type strain and a PBS control. Simultaneously, net fluid absorption of pig small intestinal mucosa was measured 4 h after infection, allowing us to correlate enterotoxin secretion with gene regulation. Microarray analysis showed on the one hand a non-toxin related general antibacterial response comprising genes such as PAP, MMP1 and IL8. On the other hand, results suggest a dominant role for STb in small intestinal secretion early after post-weaning infection, as well as in the induced innate immune response through differential regulation of immune mediators like interleukin 1 and interleukin 17. PMID:22815904

Schauvliege, Stijn; Gasthuys, Frank; van der Meulen, Jan; Dubreuil, J. Daniel; Goddeeris, Bruno M.; Niewold, Theo; Cox, Eric

2012-01-01

218

Contributions to the bioassay of Gymnodinium breve toxin(s) with mosquito fish (Gambusia affinis  

E-print Network

which permitted rapid adsorption of the toxin. One of the major problems in developing a suitable fish bioassay of G. breve toxin(s) has been the matter of finding a non-toxic or slightly toxic solvent or emulsifying agent for quantitatively handling... is required, as compared with the chick assay. Also, mice have been employed to assay the potency of G. breve toxin (6, 14, 15, 17) . McFarren et al. (6) extracted toxic residues from shellfish with diethyl ether. The bioassay was based...

Russell, Melvin Curtis

2012-06-07

219

The Interactions of Human Neutrophils with Shiga Toxins and Related Plant Toxins: Danger or Safety?  

PubMed Central

Shiga toxins and ricin are well characterized similar toxins belonging to quite different biological kingdoms. Plant and bacteria have evolved the ability to produce these powerful toxins in parallel, while humans have evolved a defense system that recognizes molecular patterns common to foreign molecules through specific receptors expressed on the surface of the main actors of innate immunity, namely monocytes and neutrophils. The interactions between these toxins and neutrophils have been widely described and have stimulated intense debate. This paper is aimed at reviewing the topic, focusing particularly on implications for the pathogenesis and diagnosis of hemolytic uremic syndrome. PMID:22741061

Brigotti, Maurizio

2012-01-01

220

Requirements for anthrax toxin entry into cells  

E-print Network

Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response.response to nutrient deprivation and is considered a bacterial survival mechanism. Anthrax

Ryan, Patricia Lynn

2010-01-01

221

How Parkinsonian Toxins Dysregulate the Autophagy Machinery  

PubMed Central

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

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

2013-01-01

222

INVESTIGATOIN OF CYANOBACTERIA TOXINS IN WATER  

EPA Science Inventory

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

223

Bacillus cereus and its food poisoning toxins  

Microsoft Academic Search

Bacillus cereus is becoming one of the more important causes of food poisoning in the industrialised world. It produces one emetic toxin and three different enterotoxins. The emetic toxin is a ring-shaped structure of three repeats of four amino and\\/or oxy acids: [d-O-Leu-d-Ala-l-O-Val-l-Val]3. This ring structure has a molecular mass of 1.2 kDa, and is chemically closely related to the

Per Einar Granum; Terje Lund

1997-01-01

224

Sea Anemone Toxins Affecting Potassium Channels  

NASA Astrophysics Data System (ADS)

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

Diochot, Sylvie; Lazdunski, Michel

225

The Stable and Radio- Carbon Isotopic Content of Labile and Refractory Carbon in Atmospheric Particulate Matter  

NASA Astrophysics Data System (ADS)

Studies of the isotopic content of atmospheric particulate matter are hampered by difficulties in chemically defining the pools of carbon and analytically isolating the different pools. We are conducting studies on reference materials and atmospheric aerosol samples to develop a method to measure stable and radio- carbon isotopes on the labile and refractory carbon. We are using a flow-through combustion system that allows us to combust, collect and measure the isotopic content of the gases produced at all stages of heating/oxidizing. We compare our results to those measured using a chemothermal oxidation method (CTO) (Gustafsson et al., 2001). In this method, refractory carbon is defined as the material remaining after pre- combusting a sample at 375°C in the presence of oxygen for 24 hours. The reference materials are diesel soot, apple leaves and a hybrid of the two (DiesApple), all from NIST. These provide carbon with two well-defined fractions -- the soot provides refractory carbon that is radiocarbon dead and the apple leaves provide organic carbon that is radiocarbon modern. Radiocarbon results from DiesApple indicate that the "refractory" carbon defined by the CTO method is actually a mixture of old and modern carbon that contains over 25% modern carbon. This suggests that charred material formed from the apples leaves during the pre-combustion step is contributing to the fraction we identify as refractory carbon. We are studying this by analyzing the individual materials and the mixture using our flow-through system. First results with this system indicate that the refractory fraction trapped from the DiesApple contains much less modern carbon than the CTO method, less than 7%. We will present detailed concentration and isotopic results of the generation of carbon dioxide during programmed combustion of each of the reference materials. We studied the radiocarbon content of both the total carbon (TC) and refractory carbon in the fine particulate matter (PM2.5) collected on quartz fiber filters as part of the Southeastern Aerosol Research and Characterization (SEARCH) program. The five samples were collected at two sites (Birmingham, AL and Atlanta, GA) with very different sources of atmospheric particulate matter. In all instances, the refractory carbon contained significantly less radiocarbon than the TC suggesting, not unexpectedly, a source of particulate carbon from the combustion of fossil material. We will present results from the analysis of the same filters in the flow-through system. The implication of our results for the use of radiocarbon in the quantitative apportionment of atmospheric particulate matter sources will be discussed. Gustafsson O., T. Bucheli, Z. Kukulska, M. Andersson, C. Largeau, J-N. Rouzaud, C. Reddy and T. Eglinton (2001) Evaluation of a protocol for the quantification of black carbon in sediments. GBD 15, 881-890.

McNichol, A. P.; Rosenheim, B. E.; Gerlach, D. S.; Hayes, J. M.

2006-12-01

226

The chromosomal mazEF locus of Streptococcus mutans encodes a functional type II toxin-antitoxin addiction system.  

PubMed

Type II chromosomal toxin-antitoxin (TA) modules consist of a pair of genes that encode two components: a stable toxin and a labile antitoxin interfering with the lethal action of the toxin through protein complex formation. Bioinformatic analysis of Streptococcus mutans UA159 genome identified a pair of linked genes encoding a MazEF-like TA. Our results show that S. mutans mazEF genes form a bicistronic operon that is cotranscribed from a ?70-like promoter. Overproduction of S. mutans MazF toxin had a toxic effect on S. mutans which can be neutralized by coexpression of its cognate antitoxin, S. mutans MazE. Although mazF expression inhibited cell growth, no cell lysis of S. mutans cultures was observed under the conditions tested. The MazEF TA is also functional in E. coli, where S. mutans MazF did not kill the cells but rather caused reversible cell growth arrest. Recombinant S. mutans MazE and MazF proteins were purified and were shown to interact with each other in vivo, confirming the nature of this TA as a type II addiction system. Our data indicate that MazF is a toxic nuclease arresting cell growth through the mechanism of RNA cleavage and that MazE inhibits the RNase activity of MazF by forming a complex. Our results suggest that the MazEF TA module might represent a cell growth modulator facilitating the persistence of S. mutans under the harsh conditions of the oral cavity. PMID:21183668

Syed, Mohammad Adnan; Koyanagi, Stephanie; Sharma, Eesha; Jobin, Marie-Claude; Yakunin, Alexander F; Lévesque, Céline M

2011-03-01

227

[Botulinum toxin therapy for spasticity].  

PubMed

Abstract Botulinum toxin (BTX) administered as an adjunct to other interventions for spasticity can act as a useful and effective therapeutic tool for treating patients disabled by spasticity. Presence of other non-reflex motor disorders (muscle stiffness, shortness, and contracture) can complicate the clinical course and disturb rehabilitative process of patients with spasticity. Treatment of spasticity using BTX can improve paralysis by correcting muscular imbalance that follows these diseases. In patients with chronic severe spasticity, we also have to address unique and difficult-to-treat clinical conditions such as abnormal posture and movement disorders. The effectiveness of BTX in treating some of these conditions is discussed. Because patients with neurological disabilities can show complex dysfunctions, specific functional limitations, goals, and expected outcomes of treatment should be evaluated and discussed with the patient, family members, and caregivers, prior to initiating BTX therapy. BTX therapy might improve not only care, passive function, but also motor functions in these patients by supplementing intensive rehabilitation with repetitive transcranial magnetic stimulation, transcranial direct-current stimulation, peripheral electrical stimulation, muscle stretching, and other rehabilitation strategies. PMID:25200575

Masakado, Yoshihisa

2014-09-01

228

TRANSDUCTION OF THE SCORPION TOXIN MAUROCALCINE INTO CELLS EVIDENCE THAT THE TOXIN CROSSES THE  

E-print Network

of the endoplasmic reticulum, and induces long- lasting channel openings in a mode of smaller conductance. Here, we) is a 33 amino acid residue peptide toxin isolated from the scorpion Scorpio maurus palmatus. External that translocates into cells. Maurocalcine (MCa) is a 33-mer toxin isolated from the venom of the scorpion Scorpio

Paris-Sud XI, Université de

229

Mode of action of yeast toxins: energy requirement for Saccharomyces cerevisiae killer toxin.  

PubMed Central

The role of the energy status of the yeast cell in the sensitivity of cultures to two yeast toxins was examined by using 12K release from cells as a measure of toxin action. The Saccharomyces cerevisiae killer toxin bound to sensitive cells in the presence of drugs that interfered with the generation or use of energy, but it was unable to efflux 12K from the cells under these conditions. In direct contrast, the Torulopsis glabrata pool efflux-stimulating toxin induced efflux of the yeast 42K pool was insensitive to the presence of energy poisons in cultures. The results indicate that an energized state, maintained at the expense of adenosine 5'-triphosphate from either glycolytic or mitochondrial reactions, is required for the action of the killer toxin on the yeast cell. PMID:320190

Skipper, N; Bussey, H

1977-01-01

230

Core-Shell Hydrogel Particles Harvest, Concentrate and Preserve Labile Low Abundance Biomarkers  

PubMed Central

Background The blood proteome is thought to represent a rich source of biomarkers for early stage disease detection. Nevertheless, three major challenges have hindered biomarker discovery: a) candidate biomarkers exist at extremely low concentrations in blood; b) high abundance resident proteins such as albumin mask the rare biomarkers; c) biomarkers are rapidly degraded by endogenous and exogenous proteinases. Methodology and Principal Findings Hydrogel nanoparticles created with a N-isopropylacrylamide based core (365 nm)-shell (167 nm) and functionalized with a charged based bait (acrylic acid) were studied as a technology for addressing all these biomarker discovery problems, in one step, in solution. These harvesting core-shell nanoparticles are designed to simultaneously conduct size exclusion and affinity chromatography in solution. Platelet derived growth factor (PDGF), a clinically relevant, highly labile, and very low abundance biomarker, was chosen as a model. PDGF, spiked in human serum, was completely sequestered from its carrier protein albumin, concentrated, and fully preserved, within minutes by the particles. Particle sequestered PDGF was fully protected from exogenously added tryptic degradation. When the nanoparticles were added to a 1 mL dilute solution of PDGF at non detectable levels (less than 20 picograms per mL) the concentration of the PDGF released from the polymeric matrix of the particles increased within the detection range of ELISA and mass spectrometry. Beyond PDGF, the sequestration and protection from degradation for a series of additional very low abundance and very labile cytokines were verified. Conclusions and Significance We envision the application of harvesting core-shell nanoparticles to whole blood for concentration and immediate preservation of low abundance and labile analytes at the time of venipuncture. PMID:19274087

Longo, Caterina; Patanarut, Alexis; George, Tony; Bishop, Barney; Zhou, Weidong; Fredolini, Claudia; Ross, Mark M.; Espina, Virginia; Pellacani, Giovanni; Petricoin, Emanuel F.; Liotta, Lance A.; Luchini, Alessandra

2009-01-01

231

Interactions between recalcitrant and labile organic carbon in streams - Can stream biofilms mediate a priming effect?  

NASA Astrophysics Data System (ADS)

Inland waters - such as streams, rivers and lakes - are increasingly recognized as important components in the global carbon cycle. Dissolved organic carbon (DOC) in these systems is diverse in structure, origin and reactivity, and a fraction of it is regarded as recalcitrant to microbial degradation. In soils, degradation of recalcitrant carbon is often controlled by the availability of labile carbon sources. This is linked to the priming effect (PE). Mounting evidence suggests that PE is also important in aquatic ecosystems but there are so far very few studies addressing this topic. Biofilms are vital components of aquatic ecosystems. In stream biofilms, heterotrophic bacteria and algae coexist in close proximity, exposing the bacteria to both recalcitrant DOC of terrestrial origin and labile organic carbon from the algae. We hypothesize that this makes stream biofilms hotspots for PE. We used plug-flow bioreactors inoculated with natural stream biofilm bacterial communities to test the potential of a priming effect in aquatic ecosystems. The bioreactors were amended with an isotope-labeled plant extract serving as a model of recalcitrant DOC in streams. Labile carbon sources, in the form of glucose and an algal extract were added to induce PE. Nitrate and phosphate were also added to assess the role of these inorganic nutrients on carbon uptake. Microbial uptake of the different carbon sources was monitored by measuring the concentrations and isotopic ratios of respired CO2, biomass and DOC. Our results suggest that the priming effect plays a role in stream carbon cycling and that it is potentially an important process in other aquatic ecosystems.

Bengtsson, M. M.; Wagner, K.; Herberg, E. R.; Burns, N. R.; Wanek, W.; Battin, T. J.

2012-04-01

232

Nature of chiral-induced equilibrium shifts in racemic labile lanthanide complexes  

SciTech Connect

An analysis of the chiral-induced equilibrium shift of racemic D{sub 3} tris-terdendate complexes of lanthanides with 2,6-pyridinedicarboxylate is presented in terms of the associated/dissociated models of Schipper. Results are presented which indicate that the so-called Pfeiffer effect in these lanthanide complexes is best described by the dissociated model, as was determined for similar labile transition-metal complexes. The nature of the chiral discriminatory interaction is shown to be largely electrostatic by measurements in mixed solvents of varying dielectric constant.

Wu, Shuguang; Hilmes, G.L.; Riehl, J.P. (Univ. of Missouri, St. Louis (USA))

1989-03-23

233

Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite  

NASA Technical Reports Server (NTRS)

Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

Pizzarello, Sandra

1998-01-01

234

Essential oil composition of the fruits of Periploca laevigata Aiton subsp. angustifolia (Labill.) Markgraf (Apocynaceae - Periplocoideae).  

PubMed

The essential oil of the fruits of Periploca laevigata Aiton subsp. angustifolia (Labill.) Markgraf (Apocynaceae) from Lampedusa Island was obtained by hydrodistillation and its composition was analysed. The analyses allowed the identification and quantification of 64 volatile compounds belonging to different classes. The most abundant compounds were nonacosane, heptacosane, hentriacontane and ?-cadinene. Among the volatile compounds identified in the fruits of P. laevigata subsp. angustifolia, 31 are present in other taxa of Apocynaceae, 19 have antimicrobial activity and four are pheromones for the butterfly Danaus chrysippus. The possible ecological role of the volatile compounds found is briefly discussed. PMID:21859258

Zito, Pietro; Sajeva, Maurizio; Bruno, Maurizio; Maggio, Antonella; Rosselli, Sergio; Senatore, Felice; Formisano, Carmen

2011-08-01

235

Hybridoma Cell Lines amd Monoclonal Antibodies to Clostridium difficile Toxins A and B.  

National Technical Information Service (NTIS)

Clostridium difficile, the etiological agent of pseudomembranous colitis in humans and animals, produces two toxins, designated toxin A and toxin B, that are cytotoxic for tissue-cultured mammalian cells. Toxin B is approximately 1,000-fold more cytotoxic...

S. Rothman, M. K. Gentry

1986-01-01

236

Array biosensor for detection of toxins  

NASA Technical Reports Server (NTRS)

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

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

2003-01-01

237

A Truncated Diphtheria Toxin Based Recombinant Porcine CTLA-4 Fusion Toxin  

PubMed Central

Targeted cell therapies are possible through the generation of recombinant fusion proteins that combine a toxin, such as diphtheria toxin (DT), with an antibody or other molecule that confers specificity. Upon binding of the fusion protein to the cell of interest, the diphtheria toxin is internalized which results in protein synthesis inhibition and subsequent cell death. We have recently expressed and purified the recombinant soluble porcine CTLA-4 both with and without N-glycosylation in yeast Pichia Pastoris for in vivo use in our preclinical swine model. The glycosylated and non-N-glycosylated versions of this recombinant protein each bind to a porcine CD80 expressing B-cell lymphoma line (LCL13271) with equal affinity (KD = 13 nM). In this study we have linked each of the glycosylated and non-N-glycosylated soluble porcine CTLA-4 proteins to the truncated diphtheria toxin DT390 through genetic engineering yielding three versions of the porcine CTLA-4 fusion toxins: 1) monovalent glycosylated soluble porcine CTLA-4 fusion toxin; 2) monovalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin and 3) bivalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin. Protein synthesis inhibition analysis demonstrated that while all three fusion toxins are capable of inhibiting protein synthesis in vitro, the non-N-glycosylated porcine CTLA-4 isoforms function most efficiently. Binding analysis using flow cytometry of the porcine CTLA-4 fusion toxins to LCL13271 cells also demonstrated that the non-N-glycosylated porcine CTLA-4 isoforms bind to theses cells with higher affinity compared to the glycosylated fusion toxin. The monovalent non-N-glycosylated porcine CTLA-4 fusion toxin was tested in vivo. NSG (NOD/SCID IL-2 receptor ??/?) mice were injected with porcine CD80+ LCL13271 tumor cells. All animals succumbed to tumors and those treated with the monovalent non-N-glycosylated porcine CTLA-4 fusion toxin survived longer based on a symptomatic scoring system compared to the untreated controls. This recombinant protein may therefore provide a novel approach for in vivo depletion of porcine antigen presenting cells (APCs) for studies investigating the induction of transplantation tolerance, autoimmune disease and cancer treatment. PMID:23470981

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

2013-01-01

238

Toxoids of Pseudomonas aeruginosa exotoxin-A: photoaffinity inactivation of purified toxin and purified toxin derivatives.  

PubMed Central

For the preparation of greatly detoxified but highly immunogenic toxoids, two enzymatically active, low-toxicity derivatives of Pseudomonas aeruginosa exotoxin-A were further inactivated by photoaffinity labeling. These derivatives were formed during toxin purification, when a relatively crude toxin preparation was concentrated by ammonium sulfate precipitation and subsequently dialyzed. These derivatives, designated peak-1 protein (PK-1) and peak-2 protein (PK-2) were antigenically indistinguishable from native toxin, but had isoelectric points (5.00 and 4.90, respectively) that were different from that of the native toxin (4.95). Although the enzymatic activities and molecular weights of PK-1 and PK-2 were similar to those of native toxin, their toxicities were greatly reduced (ca. 500-fold). Photoaffinity labeling of fully active toxin-A, purified by a process which limits the formation of these derivatives, decreased its enzymatic activity (ca. 30-fold) and toxicity (ca. 100-fold). Likewise, photoaffinity labeling of purified PK-1 and PK-2 decreased their enzymatic activities and toxicities (ca. 30-fold and 100-fold, respectively) and, thus, yielded toxoids that were ca. 50,000-fold less toxic than unpurified native toxin. These toxoids were irreversibly detoxified and highly immunogenic during 9 months of storage at 4 degrees C. Images PMID:6321348

Callahan, L T; Martinez, D; Marburg, S; Tolman, R L; Galloway, D R

1984-01-01

239

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

PubMed Central

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

Rathore, D; Batra, J K

1997-01-01

240

Lack of correlation between non-labile iron parameters, total carbonyl and malondialdehyde in major thalassemia  

PubMed Central

Thalassemia patients are at high risk of iron-induced toxicity and oxidative stress consequences. The present cross-sectional study is conducted to determine whether or not lipid peroxidation or protein oxidation is correlated with iron parameters in patients with thalassemia major. To prove this hypothesis, malondialdehyde and total carbonyl were correlated with the degree of excess iron concentration in the patients. A total of 118 Arabic Iraqi patients and 30 healthy children were participated in the present study. Results showed a significant increase (p<0.05) in serum total carbonyls, malondialdehyde and the iron indices of patients as compared with the control group. Total iron binding capacity and transferrin concentrations decreased significantly (p<0.05) in patients with thalassemia compared with the control group. The results also showed a lack of a significant correlation between each serum malondialdehyde and total carbonyl with each component of iron status. In conclusion, total carbonyls and malondialdehyde were increased in thalassemia patients indicating the vulnerability of these patients to tissue injury caused by oxidative stress. The formation of total carbonyl and malondialdehyde are independent of excess non-labile iron concentration, indicating that different mechanisms are involved in injury caused by the labile iron and in the formation of oxidation end products. PMID:25411527

Al-Hakeim, Hussein Kadhem; Auda, Furqan Muein; Ali, Basim Muhammed

2014-01-01

241

Similar response of labile and resistant soil organic matter pools to changes in temperature.  

PubMed

Our understanding of the relationship between the decomposition of soil organic matter (SOM) and soil temperature affects our predictions of the impact of climate change on soil-stored carbon. One current opinion is that the decomposition of soil labile carbon is sensitive to temperature variation whereas resistant components are insensitive. The resistant carbon or organic matter in mineral soil is then assumed to be unresponsive to global warming. But the global pattern and magnitude of the predicted future soil carbon stock will mainly rely on the temperature sensitivity of these resistant carbon pools. To investigate this sensitivity, we have incubated soils under changing temperature. Here we report that SOM decomposition or soil basal respiration rate was significantly affected by changes in SOM components associated with soil depth, sampling method and incubation time. We find, however, that the temperature sensitivity for SOM decomposition was not affected, suggesting that the temperature sensitivity for resistant organic matter pools does not differ significantly from that of labile pools, and that both types of SOM will therefore respond similarly to global warming. PMID:15635408

Fang, Changming; Smith, Pete; Moncrieff, John B; Smith, Jo U

2005-01-01

242

Determination of the Labile Iron Pool of Human Lymphocytes using the Fluorescent Probe, CP655  

PubMed Central

The present study introduces a method for determining the labile iron pool (LIP) in human lymphocytes. It is measured using the probe CP655, the fluorescence of which is stoichiometrically quenched by the addition of iron. The intracellular CP655 fluorescence in lymphocytes was quenched by increasing intracellular iron concentrations using the highly lipophilic 8-hydroxyquinoline iron complex. Intracellular fluorescence quenching, mediated by the physiological intracellular labile iron, can be recovered on the addition of excess membrane-permeable iron chelator, CP94. The intracellular probe concentration was measured using laser scanning microscopy. An ex situ calibration was performed in a “cytosolic” medium based on the determined intracellular CP655 concentration and probe fluorescence quenching in the presence of iron. The concentration of the LIP of healthy human lymphocytes was determined to be 0.57 ± 0.27 ?M. The use of the fluorescent probe CP655 renders it possible to record the time course of iron uptake and iron chelation by CP94 in single intact lymphocytes. PMID:19662178

Ma, Yongmin; Liu, Zudong; Hider, Robert C; Petrat, Frank

2007-01-01

243

Validation of fluorouracil metabolite analysis in excised tumor. Lability of anabolites.  

PubMed

Rapid excision and freezing of tissue commonly is assumed to preserve the molecular composition of the tissue just prior to its removal from the host. We examined the lability of radiolabeled 5-fluorouracil (FUra) and its anabolites during excision and freeze-clamping in a rat tumor model. Acid-soluble metabolites were identified by HPLC. Two rats, each bearing multiple, subcutaneously-implanted colon tumors, were treated with eniluracil (an inactivator of dihydropyrimidine dehydrogenase) to prevent catabolism of FUra and then injected intravenously with [(3)H]FUra. After 2 hr, tumors were harvested sequentially and segmented. The tumor pieces were kept at room temperature for various times up to 4 min prior to freezing. These specimens showed a decrease (P < 0.01) in labeled nucleoside triphosphate content of 13 +/- 2%/min and commensurate increases (P < 0.005) in labeled nucleoside monophosphates and nucleosides with increasing time-to-freeze. The amounts of labeled macromolecules, nucleoside diphosphates, and FUra each remained approximately constant. The study indicates that substantial errors may occur in measured tissue concentrations of pyrimidine nucleosides and nucleotides due to lability during tissue excision and freeze-clamping. Such errors can be corrected using data of the type obtained in this study. PMID:10974205

Bading, J R; Shahinian, A H; Paff, M T; Yoo, P B; Hsia, D W

2000-10-01

244

Effects of lability of metal complex on free ion measurement using DMT.  

PubMed

Very low concentrations of free metal ion in natural samples can be measured using the Donnan membrane technique (DMT) based on ion transport kinetics. In this paper, the possible effects of slow dissociation of metal complexes on the interpretation of kinetic DMT are investigated both theoretically and experimentally. The expressions of the lability parameter, Lgrangian , were derived for DMT. Analysis of new experimental studies using synthetic solution containing NTA as the ligand and Cu(2+) ions shows that when the ionic strength is low (labile species measured using other dynamic sensors (DGT, GIME) in several freshwaters, it is concluded that in most waters ion transport in DMT is controlled by diffusion in the membrane. Only in very soft waters (<0.7 mM Ca+Mg), the dissociation rate of natural metal complex may influence ion transport in DMT. In this case, neglecting this effect may lead to an underestimation of the free metal ion concentration measured. PMID:20163175

Weng, Liping; Van Riemsdijk, Willem H; Temminghoff, Erwin J M

2010-04-01

245

Constraints on Transport and Emplacement Mechanisms of Labile Fractions in Lunar Cold Traps  

NASA Technical Reports Server (NTRS)

Sustaining the scientific exploration of the Solar System will require a significant proportion of the necessary fuels and propellants, as well as other bulk commodities, to be produced from local raw materials [1]. The viability of mineral production depends on the ability to locate and characterize mineable deposits of the necessary feedstocks. This requires, among other things, a workable understanding of the mechanisms by which such deposits form, which is the subject of Economic Geology. Multiple deposition scenarios are possible for labile materials on the Moon. This paper suggests labile fractions moved diffusely through space; deposits may grow richer with depth until low porosity rock; lateral transport is likely to have occurred with the regolith, at least for short distances; crystalline ice may not exist; the constituent phases could be extremely complex. At present we can constrain the sources only mildly; once on the Moon, the transport mechanisms inherently mix and therefore obscure the origins. However, the importance of expanding our understanding of ore-forming processes on the Moon behooves us to make the attempt. Thus begins a time of new inquiry for Economic Geology.

Rickman, D.; Gertsch, L.

2014-01-01

246

Localization of alkali-labile sites in donkey (Equus asinus) and stallion (Equus caballus) spermatozoa.  

PubMed

The presence of constitutive alkali-labile sites (ALS) has been investigated using a protocol of DNA breakage detection-fluorescence in situ hybridization and comet assay in spermatozoa of donkey (Equus asinus) and stallion (Equus caballus). These results were compared with those obtained using a similar experimental approach using somatic cells. The relative abundance of ALS was of the order of four times more in spermatozoa than in somatic cells. Alkali-labile sites showed a tendency to cluster localized at the equatorial-distal regions of the sperm. The amount of hybridized signal in the ALS in the sperm of donkey (Equus asinus) was 1.3 times greater than in stallion (Equus caballus), and the length of the comet tail obtained in donkey sperm was 1.6 times longer than that observed in stallion (P < 0.05); however, these differences were not appreciated in somatic cells. In conclusion, ALS localization in sperm is not a randomized event and a different pattern of ALS distribution occurs for each species. These results suggest that ALS represents a species-specific issue related to chromatin organization in sperm and somatic cells in mammalian species, and they might diverge even with very short phylogenetic distances. PMID:24182740

Cortés-Gutiérrez, Elva I; Dávila-Rodríguez, Martha I; López-Fernández, Carmen; Fernández, José Luis; Crespo, Francisco; Gosálvez, Jaime

2014-01-15

247

[Effects of land use change on soil labile organic carbon in Central Jiangxi of China].  

PubMed

Selecting the 15-year abandoned land (AL) and three forest lands [Phyllostachys edulis plantation (PE), Schima superba secondary forest (SS), and Cunninghamia Lanceolata plantation (CL)] in Anfu County of Jiangxi Province as test objects, this paper studied the effects of land use change on the soil organic carbon (SOC) pool and soil labile organic carbon (SLOC) contents. The soil organic carbon (SOC), microbial biomass carbon (MBC), hot- water extractable carbon (HWC), and readily oxidizable carbon (ROC) contents in the test lands were all in the order of PE>CL>SS>AL. As compared with those in AL, the SOC content, soil carbon stock, and soil labile organic carbon (SLOC) contents in the three forest lands all decreased with increasing soil depth, and had an obvious accumulation in surface soil. The proportions of different kinds of SLOC to soil total organic carbon differed markedly, among which, ROC had the highest proportion, while MBC had the smallest one. There existed significant relationships between SOC, MBC, HWC, and ROC. The MBC, HWC, and ROC contained higher content of active carbon, and were more sensitive to the land use change, being able to be used as the indicators for evaluating the soil quality and fertility in central Jiangxi Province. PMID:24483085

Du, Man-Yi; Fan, Shao-Hui; Liu, Guang-Lu; Qi, Liang-Hua; Guo, Bao-Hu; Tang, Xiao-Lu; Xiao, Fu-Ming

2013-10-01

248

Heterotrophic activity and biodegradation of labile and refractory compounds by groundwater and stream microbial populations.  

PubMed Central

The bacteriology and heterotrophic activity of a stream and of nearby groundwater in Marmot Basin, Alberta, Canada, were studied. Acridine orange direct counts indicated that bacterial populations in the groundwater were greater than in the stream. Bacteria that were isolated from the groundwater were similar to species associated with soils. Utilization of labile dissolved organic material as measured by the heterotrophic potential technique with glutamic acid, phenylalanine, and glycolic acid as substrates was generally greater in the groundwater. In addition, specific activity indices for the populations suggested greater metabolic activity per bacterium in the groundwater. 14C-labeled lignocellulose, preferentially labeled in the lignin fraction by feeding Picea engelmannii [14C]phenylalanine, was mineralized by microorganisms in both the groundwater and the stream, but no more than 4% of the added radioactivity was lost as 14CO2 within 960 h. Up to 20% of [3'-14C]cinnamic acid was mineralized by microorganisms in both environments within 500 h. Both microbial populations appear to influence the levels of labile and recalcitrant dissolved organic material in mountain streams. PMID:7125651

Ladd, T I; Ventullo, R M; Wallis, P M; Costerton, J W

1982-01-01

249

Novel bacterial ADP-ribosylating toxins: structure and function.  

PubMed

Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this Review, we use prototype bARTTs, such as diphtheria toxin and pertussis toxin, as references for the characterization of several new bARTTs from human, insect and plant pathogens, which were recently identified by bioinformatic analyses. Several of these toxins, including cholix toxin (ChxA) from Vibrio cholerae, SpyA from Streptococcus pyogenes, HopU1 from Pseudomonas syringae and the Tcc toxins from Photorhabdus luminescens, ADP-ribosylate novel substrates and have unique organizations, which distinguish them from the reference toxins. The characterization of these toxins increases our appreciation of the range of structural and functional properties that are possessed by bARTTs and their roles in bacterial pathogenesis. PMID:25023120

Simon, Nathan C; Aktories, Klaus; Barbieri, Joseph T

2014-09-01

250

Cu lability and bioavailability in an urban stream during baseflow versus stormflow  

NASA Astrophysics Data System (ADS)

Urban streams are dynamic systems with many anthropogenic inputs and stressors. Existing contaminant inputs are regulated through total maximum daily loads. Techniques for assessing that load are based on a combination of acute and chronic water quality criteria, biotic ligand models, and physical, chemical and biological assessments. In addition, the apportionment of reduction in load to different sources is based on total mass and not, for example, on bioavailable fraction. Our understanding of the impact of different metal inputs to stream impairment is limited. Free metal ions are understood to play a role in direct cellular uptake, but metal speciation (e.g. free metal, labile metals, or size fractionated) is relevant to more complex stream food webs. As part of an ongoing study, this work examines dissolved and particulate Cu concentrations in the Hockanum River, Vernon, CT situated in a developed watershed. Stream samples were taken during baseflow as well as stormflow upstream and downstream of wastewater treatment plant and stormwater runoff inputs. In addition, diffusive gradient in thin-film (DGT) devices which measure labile metal concentrations and cultured periphyton were used to examine bioavailable fractions. Total and filtered Cu concentrations ranged from about 1.3 to 10.7 ?g/L, and 0.9 to 5.1 ?g/L, respectively. Cu concentrations always increased downstream of the wastewater treatment plant by about 1.1-2 times, and effluent accounted for about 30% of baseflow. Generally, small increases (<10%) in concentration were observed in metals directly downstream of stormwater inlets, likely due to low volumes of runoff contributed from stormwater outfalls during these sampling periods. However, Cu concentrations were elevated (about 2-5 times higher) at all sites downstream from the wastewater treatment plant downstream sampling point, suggesting contributions from sediment resuspension. DGT measured concentrations represented 30 to 70% of dissolved Cu concentrations, and that percentage increased in the days following a storm, suggesting more labile Cu compounds remained in the water column longer. Whereas solution metal concentrations in stormwater influenced reaches did not largely change upstream versus downstream, concentrations of Cu in periphyton cultures increased 2-fold downstream of a stormwater input. This is likely due to differences in discrete sampling locations, but indicates the potential importance of resuspended sediment on enhancing metal bioavailability. These results suggest that legacy sediment contamination is contributing to water column Cu concentrations. Downstream Cu concentrations are elevated compared to near the wastewater treatment plant effluent but are mostly unchanged before and after stormwater inputs. In addition, DGT concentrations indicate a shift in percentage of labile metals, in part distinguished based on size exclusion by the DGT device, following a storm event. As total dissolved Cu concentration decreases, labile Cu increases likely due to settling or size dependent partitioning to the solid phases such as periphyton. Understanding the transport and bioavailability of size dependent Cu compounds in stream water is important to allocating resources to mitigate metal contamination.

Vadas, T.; Luan, H.

2012-12-01

251

Production, Purification, and Composition of Staphylococcal ? Toxin  

PubMed Central

Coulter, John R. (Institute of Medical and Veterinary Science, Adelaide, Australia). Production, purification, and composition of staphyloccocal ? toxin. J. Bacteriol. 92:1655–1662. 1966—Pure staphylococcal ? toxin has been prepared in quantities suitable for chemical, biological, and clinical characterization. Purification was achieved by acid-methanol precipitation, chromatography on G100 Sephadex, and electrophoresis in G100 Sephadex. We recovered 25% of the crude toxin in pure form, a yield of 12 mg/liter of crude culture supernatant fluid. The pure material gave a single line on gel diffusion and on immunoelectrophoresis and gave a single symmetrical peak in the ultracentrifuge. The ? toxin was highly unstable, with a half-life of 3 days at 0 C (pH 7.8); solutions of it could not be frozen, and we found no method to stabilize it. On standing, a thready precipitate appeared; it was inactive against rabbit red cells, was not lethal to rabbits, but was able to elicit specific anti-? antibody production in the rabbit. There is evidence that ? toxin is an associating molecule, with a mean sedimentation coefficient of approximately 3.0 and a molecular weight of approximately 30,000. The lowest molecular weight, found by equilibrium ultracentrifugation, was 21,200 ± 400. The amino acid composition was determined, and the high positive charge was explained by the presence of lysine, arginine, and histidine, and by amination of the aspartic and glutamic acid residues. Histidine and arginine were shown to be N-terminal amino acids, a fact which suggests the presence of two polypeptide chains. No carbohydrate was present. The ultraviolet absorption spectrum showed a maximum at 274.5 m?, a minimum at 251.5 m?, and a shoulder at 292 m?. The toxin was without proteolytic or phospholipase activity, and its highly specific action on cell membranes still remains unexplained. Images PMID:4959717

Coulter, John R.

1966-01-01

252

Swine atrophic rhinitis caused by pasteurella multocida toxin and bordetella dermonecrotic toxin.  

PubMed

Atrophic rhinitis is a widespread and economically important swine disease caused by Pasteurella multocida and Bordetella bronchiseptica. The disease is characterized by atrophy of the nasal turbinate bones, which results in a shortened and deformed snout in severe cases. P. multocida toxin and B. bronchiseptica dermonecrotic toxin have been considered to independently or cooperatively disturb the osteogenesis of the turbinate bone by inhibiting osteoblastic differentiation and/or stimulating bone resorption by osteoclasts. Recently, the intracellular targets and molecular actions of both toxins have been clarified, enabling speculation on the intracellular signals leading to the inhibition of osteogenesis. PMID:22411430

Horiguchi, Yasuhiko

2012-01-01

253

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

PubMed Central

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

Popoff, Michel R.; Poulain, Bernard

2010-01-01

254

Natural Toxins for Use in Pest Management  

PubMed Central

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

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

2010-01-01

255

MICROBIOLOGY: Arresting Features of Bacterial Toxins  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required: Bacteria produce an arsenal of sophisticated toxins that disrupt the normal processes of the host cell, usually by modifying or inactivating host cell proteins. Now, as Coburn and Leong discuss in their Perspective, members of the cytolethal distending toxin (CDT) family have been identified as enzymes that attack DNA (and not protein) within the host cell (Lara-Tejero and Galán). By attacking DNA, perhaps during chromosomal replication, CDTs cause the host cell to halt in G2 phase of the cell cycle.

Jenifer Coburn (Tufts-New England Medical Center;Division of Rheumatology and Immunology); John M. Leong (University of Massachusetts Medical School;Department of Molecular Genetics and Microbiology)

2000-10-13

256

Botulinum toxin type A in pregnancy  

PubMed Central

Abstract Question My patient received 62 units of botulinum toxin type A (BTX-A) for facial lines. Two weeks later, she found out that she was pregnant. Will this cause any harm to her fetus? Answer Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus. PMID:24235190

Tan, Michael; Kim, Eunji; Koren, Gideon; Bozzo, Pina

2013-01-01

257

High-throughput production of two disulphide-bridge toxins.  

PubMed

A quick and efficient production method compatible with high-throughput screening was developed using 36 toxins belonging to four different families of two disulphide-bridge toxins. Final toxins were characterized using HPLC co-elution, CD and pharmacological studies. PMID:24947561

Upert, Grégory; Mourier, Gilles; Pastor, Alexandra; Verdenaud, Marion; Alili, Doria; Servent, Denis; Gilles, Nicolas

2014-08-01

258

EFFECTS OF MARINE ALGAL TOXINS ON THERMOREGULATION IN MICE.  

EPA Science Inventory

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

259

Anthrax toxin-induced rupture of artificial lipid bilayer membranes  

PubMed Central

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

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

2013-01-01

260

Mutants of Pertussis Toxin Suitable for Vaccine Development  

Microsoft Academic Search

Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles

Mariagrazia Pizza; Antonio Covacci; Antonella Bartoloni; Maria Perugini; Luciano Nencioni; Maria Teresa de Magistris; Luigi Villa; Daniele Nucci; Roberto Manetti; Massimo Bugnoli; Franco Giovannoni; Roberto Olivieri; Joseph T. Barbieri; Hiroko Sato; Rino Rappuoli

1989-01-01

261

ArachnoServer: a database of protein toxins from spiders  

Microsoft Academic Search

BACKGROUND: Venomous animals incapacitate their prey using complex venoms that can contain hundreds of unique protein toxins. The realisation that many of these toxins may have pharmaceutical and insecticidal potential due to their remarkable potency and selectivity against target receptors has led to an explosion in the number of new toxins being discovered and characterised. From an evolutionary perspective, spiders

David LA Wood; Tomas Miljenovi?; Shuzhi Cai; Robert J Raven; Quentin Kaas; Pierre Escoubas; Volker Herzig; David Wilson; Glenn F King

2009-01-01

262

Amaninamide, a new toxin of Amanita virosa mushrooms  

Microsoft Academic Search

Summary Amaninamide, a toxin closely related to the family of amatoxins, was found exclusively inAmanita virosa mushrooms. It differs from the well known toxin ?-amanitin in that it lacks the 6?-hydroxyl group of the tryptophan unit, and from the toxin amanin found inAmanita phalloides by the presence of a carboxamide group instead of a carboxylic acid group.

A. Buku; Th. Wieland; H. Bodenmüller; H. Faulstich

1980-01-01

263

Staphylococcus aureus ?-Toxin: Nearly a Century of Intrigue  

PubMed Central

Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small ?-barrel pore-forming toxin ?-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of ?-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as ?-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for ?-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on ?-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of ?-toxin in modulation of the complex interaction of S. aureus with its human host. PMID:23888516

Berube, Bryan J.; Bubeck Wardenburg, Juliane

2013-01-01

264

Assessment of the labile fractions of copper and zinc in marinas and port areas in Southern Brazil.  

PubMed

The dissolved labile and labile particulate fractions (LPF) of Cu and Zn were analyzed during different seasons and salinity conditions in estuarine waters of marina, port, and shipyard areas in the southern region of the Patos Lagoon (RS, Brazil). The dissolved labile concentration was determined using the diffusive gradients in thin films technique (DGT). DGT devices were deployed in seven locations of the estuary for 72 h and the physicochemical parameters were also measured. The LPF of Cu and Zn was determined by daily filtering of water samples. Seasonal variation of DGT-Cu concentrations was only significant (p?labile Cu and Zn in both fractions. Strong relationship between DGT-Zn and LPF-Zn was found suggesting that the DGT-Zn fraction originates from the suspended particulate matter. Water salinity and suspended particulate matter content indicated their importance for the control of the labile concentrations of Cu and Zn in the water column. These parameters must be taken into consideration for comparison among labile metals in estuaries. PMID:23475526

Costa, Luiza Dy Fonseca; Wallner-Kersanach, Mônica

2013-08-01

265

Labile trace elements in basaltic achondrites: Can they distinguish between meteorites from the Moon, Mars, and V-type asteroids?  

NASA Astrophysics Data System (ADS)

We report data for 14 mainly labile trace elements (Ag, Au, Bi, Cd, Cs, Ga, In, Rb, Sb, Se, Te, Tl, U, and Zn) in eight whole-rock lunar meteorites (Asuka [A-] 881757, Dar al Gani [DaG] 262, Elephant Moraine [EET] 87521, Queen Alexandra Range [QUE] 93069, QUE 94269, QUE 94281, Yamato [Y-] 793169, and Y-981031), and Martian meteorite (DaG 476) and incorporate these into a comparative study of basaltic meteorites from the Moon, Mars, and V-type asteroids. Multivariate cluster analysis of data for these elements in 14 lunar, 13 Martian, and 34 howardite, eucrite, and diogenite (HED) meteorites demonstrate that materials from these three parents are distinguishable using these markers of late, low-temperature episodes. This distinguishability is essentially as complete as that based on markers of high-temperature igneous processes. Concentrations of these elements in 14 lunar meteorites are essentially lognormally distributed and generally more homogeneous than in Martian and HED meteorites. Mean siderophile and labile element concentrations in the 14 lunar meteorites indicate the presence of a CI-equivalent micrometeorite admixture of 2.6% When only feldspathic samples are considered, our data show a slightly higher value of 3.4% consistent with an increasing micrometeorite content in regolith samples of higher maturity. Concentrations of labile elements in the 8 feldspathic samples hint at the presence of a fractionated highly labile element component, possibly volcanic in origin, at a level comparable to the micrometeorite component. Apparently, the process(es) that contributed to establishing lunar meteorite siderophile and labile trace element contents occurred in a system open to highly labile element transport.

Wolf, Stephen F.; Wang, Ming-Sheng; Lipschutz, Michael E.

2009-06-01

266

Evolutionary lability of a complex life cycle in the aphid genus Brachycaudus  

PubMed Central

Background Most aphid species complete their life cycle on the same set of host-plant species, but some (heteroecious species) alternate between different hosts, migrating from primary (woody) to secondary (herbaceous) host plants. The evolutionary processes behind the evolution of this complex life cycle have often been debated. One widely accepted scenario is that heteroecy evolved from monoecy on woody host plants. Several shifts towards monoecy on herbaceous plants have subsequently occurred and resulted in the radiation of aphids. Host alternation would have persisted in some cases due to developmental constraints preventing aphids from shifting their entire life cycle to herbaceous hosts (which are thought to be more favourable). According to this scenario, if aphids lose their primary host during evolution they should not regain it. The genus Brachycaudus includes species with all the types of life cycle (monoecy on woody plants, heteroecy, monoecy on herbs). We used this genus to test hypotheses concerning the evolution of life cycles in aphids. Results Phylogenetic investigation and character reconstruction suggest that life cycle is evolutionary labile in the genus. Though ancestral character states can be ambiguous depending on optimization methods, all analyses suggest that transitions from monoecy on herbs towards heteroecy have occurred several times. Transitions from heteroecy towards monoecy, are also likely. There have been many shifts in feeding behaviour but we found no significant correlation between life cycle changes and changes in diet. Conclusions The transitions from monoecy on herbs towards heteroecy observed in this study go against a widely accepted evolutionary scenario: aphids in the genus Brachycaudus seem to be able to recapture their supposedly ancestral woody host. This suggests that the determinants of host alternation are probably not as complicated as previously thought. Definitive proofs of the lability of life cycle in Brachycaudus will necessitate investigation of these determinants. Life cycle changes, whether corresponding to the loss or acquisition of a primary host, necessarily promote speciation, by inducing shifts of the reproductive phase on different plants. We suggest that the evolutionary lability of life cycle may have driven speciation events in the Brachycaudus genus. PMID:20920188

2010-01-01

267

Paralytic shellfish toxin profiles and toxin variability of the genus Alexandrium (Dinophyceae) isolated from the Southeast China Sea.  

PubMed

Paralytic shellfish toxin (PST) profiles of 16 Alexandrium isolates from the Southeast China Sea were analyzed by high-pressure liquid chromatography. Toxin content and composition of three A. tamarense isolates, ATDH01, ATGX02 and ATMJ02, were also investigated at different growth phases and under various culture conditions. Our results showed that six strains of A. affine were non-toxic, while 10 strains of A. tamarense and A. catenella were toxic. These toxic isolates grown in the same culture conditions consistently produced an unusually high proportion of the N-sulfocarbamoyl toxin C1/2 (around 60-80% of total toxins) and medium amounts of gonyautoxin GTX5 (around 15-30% of total) with only trace quantities (<5% of total) of other saxitoxin derivatives (i.e. GTX1, GTX3, GTX4 and neoSTX). The toxin composition of three A. tamarense isolates did not vary with the growth phases, although higher toxin contents (Qt, fmolcell(-1)) were found in the exponential phase. Variations in temperature, salinity and nutrient levels affected toxin content of three A. tamarense isolates but they did not have pronounced effects on the toxin composition (mole %). These results indicate that toxin composition remained relatively constant under various culture conditions, suggesting that toxin composition could be used as a stable biomarker for the Alexandrium species in this region. However, comparison of toxin profiles between isolates from different localities require special caution since isolates even from the same region can have distinct toxin profiles. PMID:16859722

Wang, Da-Zhi; Zhang, Shu-Gang; Gu, Hai-Feng; Chan, Leo Lai; Hong, Hua-Sheng

2006-08-01

268

Escherichia coli toxin\\/antitoxin pair MqsR\\/MqsA regulate toxin CspD  

Microsoft Academic Search

Summary Previously we identified that the Escherichia coli protein MqsR (YgiU) functions as a toxin and that it is involved in the regulation of motility by quorum sensing signal autoinducer-2 (AI-2). Furthermore, MqsR is directly associated with biofilm develop- ment and is linked to the development of persister cells. Here we show that MqsR and MqsA (YgiT) are a toxin\\/antitoxin

Younghoon Kim; Xiaoxue Wang; Xue-Song Zhang; Simina Grigoriu; Rebecca Page; Wolfgang Peti; Thomas K. Wood

269

Botulinum toxin: clinical techniques, applications, and complications.  

PubMed

This article outlines practice routines, clinical techniques, applications, and complications of botulinum toxin type A treatment of mimetic facial and neck muscles. Detailed descriptions are provided for each clinical indication that maximize the treatment of the intended muscle groups while minimizing potential complications. PMID:22205526

Stephan, Scott; Wang, Tom D

2011-12-01

270

Diffusion, spread, and migration of botulinum toxin.  

PubMed

Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. PMID:23868503

Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

2013-11-01

271

Modulation of leukotriene generation by pertussis toxin.  

PubMed Central

The purpose of our study was to characterize the properties of the interaction of pertussis toxin with human polymorphonuclear leukocytes for the modulation of leukotriene generation and metabolism. The cells were stimulated with either the Ca ionophore A23187, opsonized zymosan, or the bacterial peptide formyl-methionyl-leucyl phenylalanine. Incubation of the cells with pertussis toxin led to a rapid inhibition of LTB4 generation when formyl-methionyl-leucyl phenylalanine was used as the stimulus, whereas there was no effect with the Ca ionophore and just a low effect with opsonized zymosan. The inhibition of leukotriene generation was dependent on the incubation time, temperature, and pertussis toxin concentration. The effect was not dependent on the presence of calcium. Incubation of the cells with guanosine 5'-O-(3-thiotriphosphate) the stable analog of GTP, led to a time-dependent increase in leukotriene generation induced by formyl-methionyl-leucyl phenylalanine which was abolished by the simultaneous addition of pertussis toxin. Our data suggest that the formyl-methionyl-leucyl phenylalanine-induced generation of leukotrienes is dependent on a GTP-binding protein. The participation of the various G proteins has yet to be elucidated. PMID:2550370

Hensler, T; Raulf, M; Megret, F; Alouf, J E; Konig, W

1989-01-01

272

Clostridium difficile and C. difficile Toxin Testing  

MedlinePLUS

... the Adult Patient with Fever of Unknown Origin. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20031201/2223.html through http://www.aafp.org . Clostridium difficile Toxins and Culture. ARUP's Guide to Clinical Laboratory Testing [On-line ...

273

[Botulinum toxin injection for production of ptosis].  

PubMed

Selective muscles can be paralysed or weakened for a limited time period using botulinum toxin type A. The upper eyelid muscles can be a target, leading to a temporary protective ptosis. In this report we discuss indications for this application, describe how to perform the injection, and present results. The procedure is safe and effective. PMID:17846779

Merté, R-L; Lanzl, I M

2007-09-01

274

The epidermolytic (exfoliative) toxins of Staphylococcus aureus  

Microsoft Academic Search

Two epidermolytic toxins, produced by different strains of Staphylococcus aureus, split human skin at a site in the upper epidermis. Clinical effects are most common in infants, but adults are susceptible. Epidermolysis may also be observed in the mouse, in vivo and in vitro, and in a few other mammals. Recent in vitro experiments have demonstrated an inhibition by chelators

Christopher J. Bailey; Brian P. Lockhart; Maria B. Redpath; Thomas P. Smith

1995-01-01

275

TOXINES D'ASPERGILLUS OCHRACEUS WILHELM II. —  

E-print Network

DE L'OCHRATOXINE A OBTENUE A PARTIR DE MILIEUX LIQUIDES FAIBLEMENT CONCENTR�S EN TOXINE P. GALTIER C, 31300 Toulouse R�SUM� En vue d'isoler l'ochratoxine A à partir d'extraits de cultures liquides d sur milieu solide. Les cristaux obtenus sont identifiés à l'ochratoxine A au moyen de tests physico

Paris-Sud XI, Université de

276

TOXINES D'ASPERGILLUS OCHRACEUS WILHELM III. —  

E-print Network

TOXINES D'ASPERGILLUS OCHRACEUS WILHELM III. — TOXICITÃ? AIGUÃ? DE L'OCHRATOXINE A CHEZ LE RAT aiguë de l'ochratoxine A est mesurée chez le Rat et la Souris adultes par les voies orale, intraveineuse importante transformation en ochratoxine ce. Par contre, on enregistre les pertes de poids les plus sensibles

Paris-Sud XI, Université de

277

Berberine in toxin-induced experimental cholera  

PubMed Central

1. Oral administration of berberine to infant rabbits 18-24 h before the intraintestinal administration of choleragenic toxins, arrests diarrhoea or significantly prolongs the survival time. 2. The use of berberine in the treatment of clinical cholera is further justified. 3. Berberine is an antidiarrhoeal drug and the host tissues play a major part in the control of diarrhoeal symptoms. PMID:5015035

Dutta, N. K.; Marker, P. H.; Rao, N. R.

1972-01-01

278

Rab12 localizes to Shiga toxin-induced plasma membrane invaginations and controls toxin transport.  

PubMed

Several exogenous and endogenous cargo proteins are internalized independently of clathrin, including the bacterial Shiga toxin. The mechanisms underlying early steps of clathrin-independent uptake remain largely unknown. In this study, we have designed a protocol to obtain gradient fractions containing Shiga toxin internalization intermediates. Using stable isotope labeling with amino acids in cell culture (SILAC) and quantitative mass spectrometry, Rab12 was found in association with these very early uptake carriers. The localization of the GTPase on Shiga toxin-induced plasma membrane invaginations was shown by fluorescence microscopy in cells transfected with GFP-Rab12. Furthermore, using a quantitative biochemical assay, it was found that the amount of receptor-binding B-subunit of Shiga toxin reaching the trans-Golgi/TGN membranes was decreased in Rab12-depleted cells, and that cells were partially protected against intoxication by Shiga-like toxin 1 under these conditions. These findings demonstrate the functional importance of Rab12 for retrograde toxin trafficking. Among several other intracellular transport pathways, only the steady-state localizations of TGN46 and cation-independent mannose-6-phosphate receptor were affected. These data thus strongly suggest that Rab12 functions in the retrograde transport route. PMID:24703428

Rydell, Gustaf E; Renard, Henri-François; Garcia-Castillo, Maria-Daniela; Dingli, Florent; Loew, Damarys; Lamaze, Christophe; Römer, Winfried; Johannes, Ludger

2014-07-01

279

A superior drug carrier - aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne  

PubMed Central

Background Neocarzinostatin is a potent antitumor drug consisting of an enediyne chromophore and a protein carrier. Methods We characterized an intermediate in the equilibrium unfolding pathway of aponeocarzinostatin, using a variety of biophysical techniques including 1-anilino-8-napthalene sulfonate binding studies, size-exclusion fast protein liquid chromatography, intrinsic tryptophan fluorescence, circular dichroism, and 1H-15N heteronuclear single quantum coherence spectroscopy. Results The partially unfolded protein is in molten globule-like state, in which ~60% and ~20% tertiary and secondary structure is disrupted respectively. Despite lacking a fully coordinated tertiary structure for assembling a functional binding cleft, the protein in molten globule-like state is still able to fully protect the labile chromophore. Titration of chromophore leads the partially denatured apoprotein to fold into its native state. Conclusion These findings bring insight into conserving mechanism of neocarzinostatin under harsh environment, where even the partially denatured apoprotein exhibits protective effect, confirming the superiority of the drug carrier. PMID:19463188

Shanmuganathan, Aranganathan; Kumar, Thallapuranam Krishnaswamy Suresh; Huang, Chiy-Mey; Yu, Chin; Chin, Der-Hang

2009-01-01

280

Isolation of labile Fcgamma-receptors from human peripheral blood lymphocytes and production of an antiserum.  

PubMed Central

In this study, we have isolated membranelabile Fcgamma-receptors (i.e. FcgammaR I) from normal human peripheral blood lymphocytes and have produced a rabbit antiserum to this protein. Using this antiserum, we have shown that membrane-labile and membrane-stable (i.e. FcgammaR II) Fcgamma-receptors are antigenically distinct and that these two forms of the receptors probably coexist on the same lymphocyte subpopulation. Moreover, it was apparent that lymphocyte FcgammaR Is are distinct from FcgammaRs expressed on other cell types (e.g. monocytes, polymorphs and spermatozoa). Preliminary evidence does suggest, however, that human platelets express an FcgammaR which is antigenically similar to human lymphocyte FcgammaR I. Images Figure 1 PMID:3158596

Sandilands, G P; Peel, M G; Froebel, K S; Belch, J J; MacSween, R N

1985-01-01

281

Developmental Change and Intraindividual Variability: Relating Cognitive Aging to Cognitive Plasticity, Cardiovascular Lability, and Emotional Diversity  

PubMed Central

Repeated assessments obtained over years can be used to measure individuals’ developmental change, whereas repeated assessments obtained over a few weeks can be used to measure individuals’ dynamic characteristics. Using data from a burst of measurement embedded in the Berlin Aging Study (BASE: Baltes & Mayer, 1999), we illustrate and examine how long-term changes in cognitive ability are related to short-term changes in cognitive performance, cardiovascular function, and emotional experience. Our findings suggest that “better” cognitive aging over approximately13 years was associated with greater cognitive plasticity, less cardiovascular lability, and less emotional diversity over approximately 2 weeks at age 90 years. The study highlights the potential benefits of multi-time scale longitudinal designs for the study of individual function and development. PMID:21443355

Ram, Nilam; Gerstorf, Denis; Lindenberger, Ulman; Smith, Jacqui

2010-01-01

282

Application of a chemical leach technique for estimating labile particulate aluminum, iron, and manganese in the Columbia River plume and coastal waters off Oregon and Washington  

Microsoft Academic Search

In order to determine the total concentration of bioavailable trace metals in seawater, measurement of both the dissolved and labile particulate fractions is necessary. Comparison of labile particulate metal concentrations from various researchers is limited because of differing definitions of the fraction that is potentially available to phytoplankton on a time frame of generations. A comparison experiment was conducted on

Carolyn J. M. Berger; Sherry M. Lippiatt; Michael G. Lawrence; Kenneth W. Bruland

2008-01-01

283

Poly(ortho ester amides): Acid-labile Temperature-responsive Copolymers for Potential Biomedical Applications  

PubMed Central

A new, convenient pathway is developed to synthesize highly hydrolytically labile poly(ortho ester amide) (POEA) copolymers that overcomes some of the major weaknesses of the traditional methods of synthesizing poly(ortho esters) and their derivatives. A diamine monomer containing a built-in, stabilized ortho ester group was synthesized and was used for polycondensation with diacid esters, giving rise to a series of POEA copolymers with unique stimuli-responsive properties. The POEA undergoes temperature-responsive, reversible sol-gel phase transition in water. Phase diagrams of the POEA/H2O mixture reveal the concentration-dependent existence of different phases, including hydrogel and opaque or clear solution. Such behavior may be attributed to the temperature-dependent hydrogen-bonding involving the amide groups in the POEA backbone and hydrophobic interactions between POEA chains, and it is tunable by selecting diacid monomers with different chemical structures. The kinetics of POEA mass loss in physiological aqueous buffers and release of a model macromolecular drug, fluorescently labeled dextran, are nearly zero-order, suggesting predominantly surface-restricted polymer erosion. The rates of polymer erosion and drug release are much faster at pH 5.0 than pH 7.4. No cytotoxicity was found for the polymer extracts and the polymer degradation products at concentrations as high as 1 mg/ml. The normal morphology of fibroblasts cultured directly in contact with POEA films was not altered. These novel acid-labile temperature-responsive POEA copolymers may be potentially useful for a wide range of biomedical applications such as minimal invasive delivery of controlled-release drug formulations that respond to biological temperature and acidic-pH environments in cells and tissues. PMID:19281150

Tang, Rupei; Palumbo, R. Noelle; Ji, Weihang; Wang, Chun

2009-01-01

284

Oxidative stress and labile plasmatic iron in anemic patients following blood therapy  

PubMed Central

AIM: To determine the plasmatic iron content and evaluate the oxidative stress (OS) markers in subjects receiving blood therapy. METHODS: Thirty-nine individuals with unspecified anemia receiving blood transfusions and 15 healthy subjects were included in the study. Anemic subjects were divided into three subgrouP: (1) those that received up to five blood transfusions (n = 14); (2) those that received from five to ten transfusions (n = 11); and (3) those that received more than ten transfusions (n = 14). Blood samples were collected by venous arm puncture and stored in tubes containing heparin. The plasma and cells were separated by centrifugation and subsequently used for analyses. Statistical analyses were performed using Kruskal-Wallis analysis of variance followed by Dunn’s multiple comparison tests when appropriate. RESULTS: The eletrophoretic hemoglobin profiles of the subjects included in this study indicated that no patients presented with hemoglobinopathy. Labile plasmatic iron, ferritin, protein carbonyl, thiobarbituric acid-reactive substances (TBARS) and dichlorofluorescein diacetate oxidation were significantly higher (P < 0.05), whereas total thiol levels were significantly lower (P < 0.05) in transfused subjects compared to controls. Additionally, the activity of catalase, superoxide dismutase and glutathione peroxidase were significantly lower in the transfused subjects (P < 0.05). Antioxidant enzyme activities and total thiol levels were positively correlated (P < 0.05), and negatively correlated with the levels of protein carbonyl and TBARS (P < 0.05). In contrast, protein carbonyl and TBARS were positively correlated (P < 0.05). Altogether, these data confirm the involvement of OS in patients following therapy with repeated blood transfusions. CONCLUSION: Our data reveal that changes in OS markers are correlated with levels of labile plasmatic iron and ferritin and the number of transfusions. PMID:25254188

Fernandes, Marilia Sabo; Rissi, Tatiana Tamborena; Zuravski, Luisa; Mezzomo, Juliana; Vargas, Carmen Regla; Folmer, Vanderlei; Soares, Felix Alexandre Antunes; Manfredini, Vanusa; Ahmed, Mushtaq; Puntel, Robson Luiz

2014-01-01

285

Labile and recalcitrant organic matter utilization by river biofilm under increasing water temperature.  

PubMed

Microbial biofilms in rivers contribute to the decomposition of the available organic matter which typically shows changes in composition and bioavailability due to their origin, seasonality, and watershed characteristics. In the context of global warming, enhanced biofilm organic matter decomposition would be expected but this effect could be specific when either a labile or a recalcitrant organic matter source would be available. A laboratory experiment was performed to mimic the effect of the predicted increase in river water temperature (+4 °C above an ambient temperature) on the microbial biofilm under differential organic matter sources. The biofilm microbial community responded to higher water temperature by increasing bacterial cell number, respiratory activity (electron transport system) and microbial extracellular enzymes (extracellular enzyme activity). At higher temperature, the phenol oxidase enzyme explained a large fraction of respiratory activity variation suggesting an enhanced microbial use of degradation products from humic substances. The decomposition of hemicellulose (?-xylosidase activity) seemed to be also favored by warmer conditions. However, at ambient temperature, the enzymes highly responsible for respiration activity variation were ?-glucosidase and leu-aminopeptidase, suggesting an enhanced microbial use of polysaccharides and peptides degradation products. The addition of labile dissolved organic carbon (DOC; dipeptide plus cellobiose) caused a further augmentation of heterotrophic biomass and respiratory activity. The changes in the fluorescence index and the ratio Abs(250)/total DOC indicated that higher temperature accelerated the rates of DOC degradation. The experiment showed that the more bioavailable organic matter was rapidly cycled irrespective of higher temperature while degradation of recalcitrant substances was enhanced by warming. Thus, pulses of carbon at higher water temperature might have consequences for DOC processing. PMID:22570120

Ylla, Irene; Romaní, Anna M; Sabater, Sergi

2012-10-01

286

Following The Money: Characterizing the Dynamics of Microbial Ecosystems and Labile Organic Matter in Grassland Soils  

NASA Astrophysics Data System (ADS)

The dynamics of soil microbial ecosystems and labile fractions of soil organic matter in grasslands have important implications for the response of these critical ecosystems to perturbations. Organic, inorganic and genetic biomarkers in the solid (e.g. lipids, microbial DNA), liquid (e.g. porewater ions) or gaseous phases (e.g. carbon dioxide) have been used to characterize carbon cycling and soil microbial ecology. These proxies are generally limited in the amount of temporal information that they can provide (i.e., solid-phase proxies) or the amount of specific information they can provide about carbon sources or microbial community processes (e.g. inorganic gases). It is the aim of this research to validate the use of soil volatile organic carbon emissions (VOCs) as useful indicators of subsurface microbial community shifts and processes as a function of ecosystem perturbations. We present results of method validation using laboratory microcosm, where VOC metabolites as characterized by gas chromatography and mass spectrometry (GC-MS), were related to other proxies including carbon dioxide (CO2) via infra-red technology, and microbial community shifts as measured by Biolog© and fatty acid methyl ester (FAME) techniques. Experiments with soil collected from grasslands along the coastal margin region in southern Texas were preformed where environmental factors such as soil water content, soil type, and charcoal content are manipulated. Results indicate that over fifty identifiable VOC metabolites are produced from the soils, where many (~15) can be direct indicators of microbial ecology. Principle component analysis (PCA) evidences these trends through similar cluster patterns for the VOC results, the Biolog© results, and FAME. Regression analysis further shows that VOCs are significant (p < 0.05) indicators of microbial stress. Our results are encouraging that characterizing VOCs production in grassland soils are easy to measure, relatively inexpensive method, and useful proxies of subsurface microbial ecosystems and the dynamics of labile carbon in these systems.

Herbert, B. E.; McNeal, K. S.

2006-12-01

287

High lability of sexual system over 250 million years of evolution in morphologically conservative tadpole shrimps  

PubMed Central

Background Sexual system is a key factor affecting the genetic diversity, population structure, genome structure and the evolutionary potential of species. The sexual system androdioecy – where males and hermaphrodites coexist in populations – is extremely rare, yet is found in three crustacean groups, barnacles, a genus of clam shrimps Eulimnadia, and in the order Notostraca, the tadpole shrimps. In the ancient crustacean order Notostraca, high morphological conservatism contrasts with a wide diversity of sexual systems, including androdioecy. An understanding of the evolution of sexual systems in this group has been hampered by poor phylogenetic resolution and confounded by the widespread occurrence of cryptic species. Here we use a multigene supermatrix for 30 taxa to produce a comprehensive phylogenetic reconstruction of Notostraca. Based on this phylogenetic reconstruction we use character mapping techniques to investigate the evolution of sexual systems. We also tested the hypothesis that reproductive assurance has driven the evolution of androdioecy in Notostraca. Results Character mapping analysis showed that sexual system is an extremely flexible trait within Notostraca, with repeated shifts between gonochorism and androdioecy, the latter having evolved a minimum of five times. In agreement with the reproductive assurance hypothesis androdioecious notostracans are found at significantly higher latitudes than gonochoric ones indicating that post glacial re-colonisation may have selected for the higher colonisation ability conferred by androdioecy. Conclusions In contrast to their conserved morphology, sexual system in Notostraca is highly labile and the rare reproductive mode androdioecy has evolved repeatedly within the order. Furthermore, we conclude that this lability of sexual system has been maintained for at least 250 million years and may have contributed to the long term evolutionary persistence of Notostraca. Our results further our understanding of the evolution of androdioecy and indicate that reproductive assurance is a recurrent theme involved in the evolution of this sexual system. PMID:23384124

2013-01-01

288

ReCLIP (Reversible Cross-Link Immuno-Precipitation): An Efficient Method for Interrogation of Labile Protein Complexes  

PubMed Central

The difficulty of maintaining intact protein complexes while minimizing non-specific background remains a significant limitation in proteomic studies. Labile interactions, such as the interaction between p120-catenin and the E-cadherin complex, are particularly challenging. Using the cadherin complex as a model-system, we have developed a procedure for efficient recovery of otherwise labile protein-protein interactions. We have named the procedure “ReCLIP” (Reversible Cross-Link Immuno-Precipitation) to reflect the primary elements of the method. Using cell-permeable, thiol-cleavable crosslinkers, normally labile interactions (i.e. p120 and E-cadherin) are stabilized in situ prior to isolation. After immunoprecipitation, crosslinked binding partners are selectively released and all other components of the procedure (i.e. beads, antibody, and p120 itself) are discarded. The end result is extremely efficient recovery with exceptionally low background. ReCLIP therefore appears to provide an excellent alternative to currently available affinity-purification approaches, particularly for studies of labile complexes. PMID:21283770

Smith, Andrew L.; Friedman, David B.; Yu, Huapeng; Carnahan, Robert H.; Reynolds, Albert B.

2011-01-01

289

Thermal Analysis of Labile Trace Elements in CM and CV Carbonaceous Chondrites Using Inductively Coupled Plasma-Mass Spectrometry  

NASA Technical Reports Server (NTRS)

We developed a technique to measure the thermal release profiles of a suite of labile elements (Zn, As, Se, Cd, In, Sn, Sb, Te, Pt, Hg, Au, Tl, Pb, Bi). Conclusions are reached about the behavior of each element during parent-body alteration. Additional information is contained in the original extended abstract.

Lauretta, D. S.; Klaue, B.; Blum, J. D.; Buseck, P. R.

2001-01-01

290

In situ measurements of labile Al and Mn in acid mine drainage using diffusive gradients in thin films.  

PubMed

The technique of diffusive gradients in thin films (DGT) can be used for in situ measurements of labile metal species in water, but the application for this method on acid mine drainage (AMD) is complicated due to reduced sampler adsorption of metals at low pH. This study evaluates the use of DGT on labile Al and Mn in AMD (pH 3.1-4.2). DGT measurements were performed both in standard solutions in the laboratory and in situ in the field. Laboratory results show that DGT can be used in water with pH as low as 3.0 for Al and 4.0 for Mn without correcting for reduced adsorption. Below pH 4.0, the adsorption of Mn showed a linearly decrease with pH to approximately 55% at pH 3.0. Taking this correction into account revealed that 84-100% of the total dissolved Al and Mn measured in the field was DGT-labile. Measurements using DGT agreed well with predictions using the speciation program WHAM VI. This study shows that the use of DGT can be extended below the previously reported pH working range for Al, and for Mn using a simple linear correction with respect to pH, and demonstrates that the technique can be applied for monitoring time-integrated labile metal concentrations at AMD sites. PMID:17620010

Søndergaard, Jens

2007-08-15

291

Soil Biology & Biochemistry 39 (2007) 22502263 Dynamics of labile and recalcitrant soil carbon pools in a sorghum  

E-print Network

-adequate (wet) and water-deficient (dry) treatments. We found that on average 53% of the final soil organic for the upper soil horizon (0­30 cm) where new carbon in recalcitrant soil pools of FACE wet and dry treatmentsSoil Biology & Biochemistry 39 (2007) 2250­2263 Dynamics of labile and recalcitrant soil carbon

Williams, David G.

292

A Longitudinal Study of Emotion Regulation, Emotion Lability-Negativity, and Internalizing Symptomatology in Maltreated and Nonmaltreated Children  

ERIC Educational Resources Information Center

The longitudinal contributions of emotion regulation and emotion lability-negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that for both maltreated and nonmaltreated children, emotion regulation was a…

Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.

2013-01-01

293

Methamphetamine and alcohol abuse and dependence symptoms: Associations with affect lability and impulsivity in a rural treatment population  

Microsoft Academic Search

The present study examined associations between impulsivity and affect lability and methamphetamine and alcohol abuse and dependence symptoms in a rural inpatient treatment population (N=235). Thirty-two percent of participants reported methamphetamine use in the past 90 days prior to admission. Amphetamine use disorders were found to be more common among younger participants whereas alcohol use disorders were more common among

Jeffrey S. Simons; Matthew N. I. Oliver; Raluca M. Gaher; Gerald Ebel; Patricia Brummels

2005-01-01

294

)Pieris rapaeMayolenes: Labile defensive lipids from the glandular hairs of a caterpillar ( Renwick, Ronald Rutowski, and Thomas Eisner  

E-print Network

of P. rapae maintained on cabbage plants (Brassica oleraceae). The larvae used in the ant bioassays)Pieris rapaeMayolenes: Labile defensive lipids from the glandular hairs of a caterpillar ( Renwick defensive lipids from the glandular hairs of a caterpillar (Pieris rapae) Scott R. Smedley*, Frank C

Weibel, Douglas B.

295

On the Labile Memory Buffer in the Attentional Blink: Masking the T2 Representation by Onset Transients Mediates the AB  

ERIC Educational Resources Information Center

Report of a second target (T2) is impaired when presented within 500 ms of the first (T1). This attentional blink (AB) is known to cause a delay in T2 processing during which T2 must be stored in a labile memory buffer. We explored the buffer's characteristics using different types of masks after T2. These characteristics were inferred by…

Jannati, Ali; Spalek, Thomas M.; Di Lollo, Vincent

2011-01-01

296

Bacterial RTX toxins allow acute ATP release from human erythrocytes directly through the toxin pore.  

PubMed

ATP is as an extracellular signaling molecule able to amplify the cell lysis inflicted by certain bacterial toxins including the two RTX toxins ?-hemolysin (HlyA) from Escherichia coli and leukotoxin A (LtxA) from Aggregatibacter actinomycetemcomitans. Inhibition of P2X receptors completely blocks the RTX toxin-induced hemolysis over a larger concentration range. It is, however, at present not known how the ATP that provides the amplification is released from the attacked cells. Here we show that both HlyA and LtxA trigger acute release of ATP from human erythrocytes that preceded and were not caused by cell lysis. This early ATP release did not occur via previously described ATP-release pathways in the erythrocyte. Both HlyA and LtxA were capable of triggering ATP release in the presence of the pannexin 1 blockers carbenoxolone and probenecid, and the HlyA-induced ATP release was found to be similar in erythrocytes from pannexin 1 wild type and knock-out mice. Moreover, the voltage-dependent anion channel antagonist TRO19622 had no effect on ATP release by either of the toxins. Finally, we showed that both HlyA and LtxA were able to release ATP from ATP-loaded lipid (1-palmitoyl-2-oleoyl-phosphatidylcholine) vesicles devoid of any erythrocyte channels or transporters. Again we were able to show that this happened in a non-lytic fashion, using calcein-containing vesicles as controls. These data show that both toxins incorporate into lipid vesicles and allow ATP to be released. We suggest that both toxins cause acute ATP release by letting ATP pass the toxin pores in both human erythrocytes and artificial membranes. PMID:24860098

Skals, Marianne; Bjaelde, Randi G; Reinholdt, Jesper; Poulsen, Knud; Vad, Brian S; Otzen, Daniel E; Leipziger, Jens; Praetorius, Helle A

2014-07-01

297

S. cerevisiae K28 toxin – a secreted virus toxin of the A\\/B family of protein toxins  

Microsoft Academic Search

Since the initial discovery of toxin-secreting killer strains in the yeast Saccharomyces cerevisiae more than 40 years ago, continuous research on this wide-spread phenomenon substantially strengthened our knowledge in different areas of modern biology, providing deeper insights into basic aspects of eukaryotic cell biology and virus-host cell interactions. This chapter will focus on the K28 killer system in S. cerevisiae,

Susanne Leis; Jenny Spindler; Jochen Reiter; Frank Breinig; Manfred Schmitt

298

Neutralization of Clostridium difficile toxin A using antibody combinations  

PubMed Central

The pathogenicity of Clostridium difficile (C. difficile) is mediated by the release of two toxins, A and B. Both toxins contain large clusters of repeats known as cell wall binding (CWB) domains responsible for binding epithelial cell surfaces. Several murine monoclonal antibodies were generated against the CWB domain of toxin A and screened for their ability to neutralize the toxin individually and in combination. Three antibodies capable of neutralizing toxin A all recognized multiple sites on toxin A, suggesting that the extent of surface coverage may contribute to neutralization. Combination of two noncompeting antibodies, denoted 3358 and 3359, enhanced toxin A neutralization over saturating levels of single antibodies. Antibody 3358 increased the level of detectable CWB domain on the surface of cells, while 3359 inhibited CWB domain cell surface association. These results suggest that antibody combinations that cover a broader epitope space on the CWB repeat domains of toxin A (and potentially toxin B) and utilize multiple mechanisms to reduce toxin internalization may provide enhanced protection against C. difficile-associated diarrhea. PMID:20150758

Hariharan, Mangala; Elia, Marikka; Salbato, Jared; Jin, Ping; Bird, Colin; Short, Jay M; Kimmel, Bruce E; Dudley, Michael; Woodnutt, Gary; Hansen, Genevieve

2010-01-01

299

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

PubMed Central

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

Frazao, Barbara; Vasconcelos, Vitor; Antunes, Agostinho

2012-01-01

300

Cholera toxin and the adenylate cyclase-activating signal.  

PubMed

Studies with chemically modified cholera toxin derivatives showed that all treatments that decreased the ability of toxin to bind to mouse thymus cells or to polystyrene-coupled GM1 ganglioside caused a concomitant reduction in the toxin's ability to increase adenosine 3':5'-cyclic phosphate (cyclic AMP) in thymus cells and skin vascular permeability in rabbits. Dissociation of the H (heavy) and L (light) subunits abolished the biologic activity without inhibiting receptor binding, as did treatment with arginyl-specific reagents (which did not change the aggregation state of the toxin). When thymus cells were incubated with 125I-labelled toxin at 37C,only about 1% of the total cell-bound radioactivity was recovered in the cytosol supernate. Similar values were found for cells incubated with toxin at 0C, and with 125I-labelled choleragenoid at 37C or 0C. Thymus cells rapidly bound less than or equal to equal to 5 X 10(4) cholera toxin molecules per cell at both 0C and 37C. Much less, however, of the radioactive toxin bound at 37C than of that bound at 0C was displaced by addition of unlabelled toxin or choleragenoid. Similar temperature-related irreversible binding was noted with 125I-labelled choleragenoid. The relative amounts of H and L subunits in the irreversibly cell-bound and in the displaced 125I-labelled toxin were indistinguishable. Treatment of thymus cells at 37C, but not at 0C, with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide caused a 10-fold reduction of adenylate cyclase stimulation by cholera toxin without inhibiting activation by epinephrine or prostaglandin E1, or appreciably altering the basal, unstimulated enzyme activity. The carbodiimide inhibited the cyclic AMP response to cholera toxin when added shortly after the toxin had bound to the cells (early in the lag phase). PMID:176282

Holmgren, J; Lönnroth, I

1976-03-01

301

Autopsy findings in botulinum toxin poisoning.  

PubMed

In the United States, foodborne botulism is most commonly associated with home-canned food products. Between 1950 and 2005, 405 separate outbreaks of botulism were reported to the Centers for Disease Control and Prevention (CDC). Approximately 8% of these outbreaks were attributed to commercially produced canned food products. Overall, 5-10% of persons ingesting botulinum toxin die. Few reports exist pertaining to autopsy findings in cases of foodborne botulism. Here, we report the autopsy findings of a man who died after a prolonged illness caused by botulinum toxin exposure likely attributable to a commercially prepared food source. Despite extensive testing, our histopathologic findings were nonspecific. We therefore conclude that the forensic pathologist must become familiar with the neurotoxicity syndrome associated with this illness. Maintaining vigilance for botulism by carefully reviewing the decedent's clinical history will aid in the early identification and control of outbreaks, either foodborne or terrorism-related. PMID:20533981

Devers, Kelly G; Nine, Jeffrey S

2010-11-01

302

Acid-labile sulfides in shallow marine bottom sediments: A review of the impact on ecosystems in the Azov Sea, the NE Black Sea shelf and NW Adriatic lagoons  

NASA Astrophysics Data System (ADS)

Acid-labile sulfides (LS) increase in bottom sediments at sites in the Azov Sea, at the NE Black Sea shelf and in the coastal lagoons of NW Adriatic Sea experiencing direct impacts of anthropogenic pollution. Fresh anthropogenic organic matter stimulates the bacterial sulfate reduction and here the rate of the LS production overcomes their loss during the oxidation and pyritization. This results in the expansion of reduced sediment layer up to the bottom surface. The LS concentration in the reduced sediments varies between 300 and 2000 mg S l -1 of wet silt depending on the size of pollution loading and on the rate of sedimentation. In the oxidized sediments away from the direct pollution impact, the LS concentration did not exceed 100-150 mg S l -1. Being a strong cytochrome toxin, the LS adversely affect the coastal ecosystems. The concentrations over 600 mg S l -1 result in quasi total benthic mortality whereas >300-400 mg S l -1 depletes the benthic faunal abundance and taxonomic diversity. Accumulation of the LS in sediments also induces nocturnal hypoxia and stimulates domination of toxic cyanobacteria in the pelagic phytocenoses.

Sorokin, Yu. I.; Zakuskina, O. Yu

2012-02-01

303

Mushroom toxins: a forensic toxicological review  

Microsoft Academic Search

Mushrooms are ubiquitous in the world. Amateur hunters harvest mushrooms growing in forests to enjoy eating them as seasonal\\u000a delicacies, and occasionally they cause poisonings and even deaths. In this review, mushroom toxins are tabulated according\\u000a to mushroom species, symptoms, toxicities and analytical methods on the basis of references. Second, because we constructed\\u000a a method for analysis of amatoxins, the

Kunio Gonmori; Hiroki Fujita; Kazumasa Yokoyama; Kanako Watanabe; Osamu Suzuki

2011-01-01

304

The Biology of the Cytolethal Distending Toxins  

PubMed Central

The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B2 toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered. PMID:22069704

Guerra, Lina; Cortes-Bratti, Ximena; Guidi, Riccardo; Frisan, Teresa

2011-01-01

305

Three controversial issues in extracorporeal toxin removal.  

PubMed

The optimal method of extracorporeal removal of many toxic compounds is often a matter of debate. Due to the lack of well-designed studies, we are often left with circumstantial evidence, and we must exercise our best clinical judgment as to whether extracorporeal drug removal is beneficial and if so, by what method. It is clear, however, that rapidity in toxin removal is beneficial. We present three issues dealing with extracorporeal removal of toxins for which there is no definitive answer but which may arise in clinical practice. The first is whether continuous renal replacement therapy (CRRT) is better at removing dialyzable toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is at all useful in treating paraquat poisoning. Finally, is any modality of extracorporeal treatment useful in the treatment of amatoxin poisoning? After a thorough literature review, it is evident that definitive answers are not strikingly apparent. However, extracorporeal treatment in the latter two instances may have potential benefit and may be the only hope for patient survival. Due to the urgent nature of treatment for poisoning, as well as the somewhat obscure nature of these issues, there may never be well-designed evidence-based studies to help guide us. In the meantime, we must continue to use less than ideal evidence and our own experience in dealing with these controversial issues to guide our decision-making process. PMID:16970731

Feinfeld, Donald A; Rosenberg, Jeffrey W; Winchester, James F

2006-01-01

306

Effect of toxin A and B of Clostridium difficile on rabbit ileum and colon  

Microsoft Academic Search

The effect of purified toxin A and partially purified toxin B on rabbit ileum and colon was investigated. Toxin A caused tissue damage which was followed by permeability changes and fluid accumulation in both tissues. Toxin A did not increase the permeability of the colon to the extent observed for ileum; secreted fluid contained less protein of plasma origin. Toxin

T J Mitchell; J M Ketley; S C Haslam; J Stephen; D W Burdon; D C Candy; R Daniel

1986-01-01

307

Enzyme-linked immunosorbent assay to detect Shiga toxin of Shigella dysenteriae and related toxins.  

PubMed Central

A sandwich enzyme-linked immunosorbent assay (ELISA) was developed for detection of Shiga toxin. Four species of Shigella, Escherichia coli, and Vibro parahaemolyticus were tested for production of Shiga or Shiga-like toxin by ELISA and Vero cell bioassay. In the ELISA, most strains of S. dysenteriae and some strains of E. coli isolated from traveler's diarrhea were positive. These ELISA-positive strains were positive by Vero cell bioassay without exception. Some E. coli strains and most V. parahaemolyticus strains were toxic to Vero cells, although they were negative in the ELISA. Much of the cytotoxic activity was not neutralized by anti-Shiga toxin antiserum. The newly developed sandwich ELISA is specific and can be a substitute for the cumbersome Vero cell bioassay. PMID:3539985

Kongmuang, U; Honda, T; Miwatani, T

1987-01-01

308

Toxin content, phallotoxin and amatoxin composition of Amanita phalloides tissues.  

PubMed

The toxin content and composition of Amanita phalloides tissues were determined in three specimens at two carpophore development stages. The carpophore was subdivided into six parts, namely, the cap, gills, ring, stipe, volva and bulb. To our knowledge, this is the first report of such an investigation on the ring and the bulb. Substantial differences in the tissue toxin content were revealed. The ring displayed a very high amount of toxins, whereas the bulb had the lowest toxin content. Compositional differences in relation to the nature of the tissue were also noted. The highest amatoxin content was found in the ring, gills and cap, whereas the bulb and volva were the richest in phallotoxins. Furthermore, variability in the toxin composition was observed. The differences in the distribution of individual toxins in the tissues might be related to the carpophore developmental stage. PMID:8342178

Enjalbert, F; Gallion, C; Jehl, F; Monteil, H

1993-06-01

309

Overview of Scorpion Species from China and Their Toxins  

PubMed Central

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

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

2014-01-01

310

Predicting the activity of Cd 2+ and Zn 2+ in soil pore water from the radio-labile metal fraction  

NASA Astrophysics Data System (ADS)

Cadmium and zinc were added at 3 and 300 mg kg -1, respectively, to 23 soils and incubated at 16°C and 80% field capacity for 818 d. Following addition of metal, changes in the radio-labile concentrations of both elements were examined on seven separate sampling occasions over 818 d. At each sample time, soil pore water was extracted using Rhizon soil solution samplers, and concentrations of Cd, Zn, dissolved organic carbon, and major cations and anions were determined. The chemical speciation program WHAM 6 was used to determine free metal ion activity, (M 2+). Similar measurements were made on a set of historically contaminated soils from old mining areas, sewage sludge disposal facilities, and industrial sources. The two data sets were combined to give a range of values for p(Cd 2+) and p(Zn 2+) that covered 5 and 4 log 10 units, respectively. A pH-dependent Freundlich model was used to predict Zn 2+ and Cd 2+ ion activity in soil pore water. Total and radio-labile metal ion concentration in the solid phase was assumed to be adsorbed on the "whole soil," humus, or free iron oxides to provide alternative model formats. The most successful models assumed that solubility was controlled by adsorption on soil humus. Inclusion of ionic strength as a model variable provided small improvements in model fit. Considering competition with Ca 2+ and between Zn 2+ and Cd 2+ produced no apparent improvement in model fit. Surprisingly, there was little difference between the use of total and labile adsorbed metal as a model determinant. However, this may have been due to a strong correlation between metal lability and pH in the data set used. Values of residual standard deviation for the parameterized models using labile metal adsorbed on humus were 0.26 and 0.28 for prediction of p(Cd 2+) and p(Zn 2+), respectively. Solubility control by pure Zn and Cd minerals was not indicated from saturation indices. However there may have been fixation of metals to non-radio-labile forms in CaCO 3 and Ca-phosphate compounds in the soils in the higher pH range. Independent validation of the Cd model was carried out using an unpublished data set that included measurements of isotopically exchangeable Cd. There was good agreement with the parameterized model.

Tye, A. M.; Young, S. D.; Crout, N. M. J.; Zhang, H.; Preston, S.; Barbosa-Jefferson, V. L.; Davison, W.; McGrath, S. P.; Paton, G. I.; Kilham, K.; Resende, L.

2003-02-01

311

Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks  

Microsoft Academic Search

Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS). HR is usually involved in the repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae implying that MMS somehow induces DSBs in vivo. Indeed there is evidence, based on pulsed-field gel electro- phoresis (PFGE), that MMS causes DNA fragmenta- tion. However, the mechanism through which MMS induces DSBs has

Cecilia Lundin; Matthew North; Klaus Erixon; Kevin Walters; Dag Jenssen; Alastair S. H. Goldman; Thomas Helleday

2005-01-01

312

Fusarial toxins: secondary metabolites of Fusarium fungi.  

PubMed

Exposure to mycotoxins occurs worldwide, even though there are geographic and climatic differences in the amounts produced and occurrence of these substances.Mycotoxins are secondary chemical metabolites of different fungi. They are natural contaminants of cereals, so their presence is often inevitable. Among many genera that produce mycotoxins, Fusarium fungi are the most widespread in cereal-growing areas of the planet. Fusarium fungi produce a diversity of mycotoxin types, whose distributions are also diverse. What is produced and where it is produced is influenced primarily by environmental conditions, and crop production and storage methods. The amount of toxin produced depends on physical (viz., moisture, relative humidity, temperature, and mechanical damage), chemical (viz., carbon dioxide,oxygen, composition of substrate, insecticides and fungicides), and biological factors (viz., plant variety, stress, insects, spore load, etc.). Moisture and temperature have a major influence on mold growth rate and mycotoxin production.Among the most toxic and prevalent fusaria) toxins are the following: zearalenone,fumonisins, moniliformin and trichothecenes (T-2/HT-2 toxin, deoxynivalenol,diacetoxyscirpenol, nivalenol). Zearalenone (ZEA; ZON, F-2 toxin) isaphy to estrogenic compound, primarily a field contaminant, which exhibits estrogenic activity and has been implicated in numerous mycotoxicoses of farm animals,especially pigs. Recently, evidence suggests that ZEA has potential to stimulate the growth of human breast cancer cells. Fumonisins are also cancer-promoting metabolites,of which Fumonisin 8 I (FBI) is the most important. Moniliformin (MON) isalso highly toxic to both animals and humans. Trichothecenes are classified as gastrointestinal toxins, dermatotoxins, immunotoxins, hematotoxins, and gene toxins.T-2 and HT-2 toxin, and diacetoxyscirpenol (DAS, anguidine) are the most toxic mycotoxins among the trichothecene group. Deoxynivalenol (DON, vomitoxin) and nivalenol although less toxic are important because they frequently occur at levels high enough to cause adverse effects.The presence of mycotoxins in the animal diet can produce significant production losses. Any considerable presence of mycotoxins, in major dietary components,confirms the need to adopt a continuous prevention and control program. Such programs are usually based on several common approaches to minimize mycotoxin contamination in the food chain. Major strategies include preventing fungal growth and therefore mycotoxin formation, reducing or eliminating mycotoxins from contaminated feedstuffs, or diverting contaminated products to low risk uses. Because of the complexity of their chemical structures, mycotoxins also present a major analytical challenge. They are also found in a vast array of feed matrices. Analysis is essential for determining the extent of mycotoxin contamination, for risk analysis, confirming the diagnosis of a mycotoxicosis and for monitoring mycotoxin mitigation strategies.For the future, adequately controlling the mycotoxin problem in the livestock economy will depend on implementing appropriate agricultural management policies,as well as augmenting production and storage systems and analysis methods.Only such policies offer the opportunity to bring solid and long-lasting economical results to the livestock industry that is afflicted with the mycotoxin problem. PMID:24162094

Nesic, Ksenija; Ivanovic, Snezana; Nesic, Vladimir

2014-01-01

313

Botulinum Toxin: Poisoning the Spastic Bladder and Urethra  

PubMed Central

Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine. PMID:16985657

Smith, Christopher P; Somogyi, George T; Chancellor, Michael B

2002-01-01

314

Organic Food Production and Its Influence on Naturally Occurring Toxins  

Microsoft Academic Search

The levels of natural plant toxins and mycotoxins in foods may be influenced by the methods used (organic vs. conventional)\\u000a for agricultural production. Research findings suggest that organic foods may possess higher levels of natural plant toxins\\u000a than conventional foods based upon mechanistic similarities between natural plant toxin production and the production of plant\\u000a secondary metabolites of nutritional interest. Specific

Carl K. Winter

315

Use of botulinum toxin in pediatric otolaryngology and laryngology.  

PubMed

The use of botulinum toxin in adult otolaryngology has been commonly used in conditions such as spasmodic dysphonia, cricopharyngeal spasm, palatal myoclonus, sialorrhea, and for cosmetic reasons. The current use of botulinum toxin in pediatric otolaryngology and laryngology has primarily been off label and in children older than 2 years of age. This review discusses the different applications of botulinum toxin in pediatric patients and its effectiveness in treating different pediatric conditions. PMID:25048857

Shogan, Andrea Nath; Rogers, Derek J; Hartnick, Christopher J; Kerschner, Joseph E

2014-09-01

316

Macrofragment localization of the toxin A and toxin B genes of Clostridium difficile.  

PubMed Central

We report the physical mapping of the toxin A and B genes to the bacterial chromosome of Clostridium difficile ATCC 43594 by pulsed-field gel electrophoresis. Single and double digestions with restriction endonucleases NruI and SacII allowed localization of the toxin genes to a specific 577-kb fragment and estimation of genome size to be approximately 3.8 megabases. This effort represents the initial step in the construction of a physical map of the whole genome. PMID:8914776

Norwood, D A; Sands, J A

1996-01-01

317

Development and fabrication of heat-sterilizable inhalation therapy equipment  

NASA Technical Reports Server (NTRS)

The development of a completely heat sterilizable intermittent positive pressure breathing (IPPB) ventilator in an effort to reduce the number of hospital acquired infections is reported. After appropriate changes in materials and design were made, six prototype units were fabricated and were successfully field tested in local hospitals. Most components of the modified ventilators are compatible with existing machines. In all but a few instances, such as installation of bacteria-retentive filters and a modified venturi, the change over from non-heat-sterilizable to sterilizable units was accomplished by replacement of heat labile materials with heat stable materials.

Irons, A. S.

1974-01-01

318

Shiga Toxin Pathogenesis: Kidney Complications and Renal Failure  

PubMed Central

The kidneys are the major organs affected in diarrhea-associated hemolytic uremic syndrome (D+HUS). The pathophysiology of renal disease in D+HUS is largely the result of the interaction between bacterial virulence factors such as Shiga toxin and lipopolysaccharide and host cells in the kidney and in the blood circulation. This chapter describes in detail the current knowledge of how these bacterial toxins may lead to kidney disease and renal failure. The toxin receptors expressed by specific blood and resident renal cell types are also discussed as are the actions of the toxins on these cells. PMID:21983749

Karpman, Diana

2013-01-01

319

Characterization of a transferrin-diphtheria toxin conjugate.  

PubMed

We report here the synthesis and properties of a hybrid toxin prepared by covalently coupling diphtheria toxin to transferrin. The purified material contained two major hybrid protein species and was highly cytotoxic to mouse LMTK- cells in culture, reducing protein synthesis by 50% in 24 h at a concentration of 1 ng/ml. Cytotoxic activity was completely abolished in the presence of exogenous transferrin or anti-transferrin or anti-diphtheria toxin, thus demonstrating that the hybrid toxin was intoxicating cells via their transferrin receptors and that both the diphtheria toxin and transferrin components of the conjugate were necessary for activity. NH4Cl, a drug that elevates the pH within acidic intracellular vesicles, also blocked cytotoxic activity, suggesting that a low intravesicular pH was required for activity. The inhibitory effect of NH4Cl could be abolished by exposing toxin-treated cells to acidic culture medium, further implicating an acid-dependent step in the mechanism of the hybrid toxin action. Studies on the kinetics of intoxication also implied that endocytosis and exposure to a low pH within vesicles were necessary for cytotoxicity. Altogether, the results suggest that the transferrin-diphtheria toxin conjugate binds to transferrin receptors and is internalized into acidic endocytic vesicles. The enzymatic moiety of diphtheria toxin then apparently enters the cytosol in response to the low pH and subsequently arrests protein synthesis. PMID:2981852

O'Keefe, D O; Draper, R K

1985-01-25

320

Purification and characterization of toxin B from Clostridium difficile.  

PubMed Central

Toxin B from Clostridium difficile was purified to homogeneity and characterized. Purification of toxin B was achieved by gel filtration, chromatography on two consecutive anion-exchange columns, and chromatography on a high-resolution anion-exchange column in the presence of 50 mM CaCl2. The molecular weight of toxin B was estimated to be 250,000 by denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 500,000 by gel filtration. No subunits were apparent when the toxin was reduced and analyzed by SDS-PAGE. The estimated molecular weight of native toxin B indicated that dimers may form in solution. Toxin B was homogeneous by SDS-PAGE, native PAGE, and high-resolution anion-exchange chromatography. No secondary sequences were detected when the amino terminus of the toxin was sequenced, which also indicated that contaminating peptides were absent from the preparation. The amino terminus of toxin B was determined to be NH3-Trp-Leu-Val-Asn-Arg-Lys-Gln-Leu-Glu-Lys-Met-Ala-Asn-Val-ARg-Phe-Arg. One cytotoxic unit of toxin B was estimated to be 0.2 to 0.8 pg. Images PMID:3384474

Meador, J; Tweten, R K

1988-01-01

321

ArachnoServer: a database of protein toxins from spiders  

PubMed Central

Background Venomous animals incapacitate their prey using complex venoms that can contain hundreds of unique protein toxins. The realisation that many of these toxins may have pharmaceutical and insecticidal potential due to their remarkable potency and selectivity against target receptors has led to an explosion in the number of new toxins being discovered and characterised. From an evolutionary perspective, spiders are the most successful venomous animals and they maintain by far the largest pool of toxic peptides. However, at present, there are no databases dedicated to spider toxins and hence it is difficult to realise their full potential as drugs, insecticides, and pharmacological probes. Description We have developed ArachnoServer, a manually curated database that provides detailed information about proteinaceous toxins from spiders. Key features of ArachnoServer include a new molecular target ontology designed especially for venom toxins, the most up-to-date taxonomic information available, and a powerful advanced search interface. Toxin information can be browsed through dynamic trees, and each toxin has a dedicated page summarising all available information about its sequence, structure, and biological activity. ArachnoServer currently manages 567 protein sequences, 334 nucleic acid sequences, and 51 protein structures. Conclusion ArachnoServer provides a single source of high-quality information about proteinaceous spider toxins that will be an invaluable resource for pharmacologists, neuroscientists, toxinologists, medicinal chemists, ion channel scientists, clinicians, and structural biologists. ArachnoServer is available online at http://www.arachnoserver.org. PMID:19674480

2009-01-01

322

Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine  

PubMed Central

Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd0-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd0-cleavable groups in positions that are mechanistically relevant for gemcitabine’s pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs’ cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry. PMID:24867590

2014-01-01

323

Labile Zn ions on octacalcium phosphate-derived Zn-containing hydroxyapatite surfaces  

NASA Astrophysics Data System (ADS)

We previously synthesized and characterized zinc-containing octacalcium phosphate (OCP) and its hydrolyzed Ca-deficient hydroxyapatite (HA). In the present report, we attempted to define the state of Zn in the OCP-derived Zn-calcium phosphates (CaPs) in relation to the presence of specific amino acids. Zn-containing OCPs were prepared in solutions that included Zn ions up to a concentration of 3.5 mM, and their hydrolyzates [hydrolyzed (hy)-Zn-CaP] were obtained in hot water. The materials were characterized by x-ray diffraction and scanning electron microscopy. The concentration of Ca and Zn ions at room temperature was determined by analyzing the supernatant after incubating the materials in ?-minimal essential medium (?-MEM) and HEPES buffer including cysteine, histidine, lysine, aspartic acid, and glutamic acid. Zn ions were more dissolved in ?-MEM than HEPES buffer in the absence of amino acids. The inclusion of the amino acids enhanced Zn dissolution by several hundred fold, even in HEPES buffer. Among the amino acids, both cysteine and histidine enhanced the release of Zn. The effect was particularly remarkable with cysteine even in the presence of the other amino acids tested. These results indicate that Zn ions are present as a surface labile pool, which tends to be preferentially desorbed by cysteine, a ubiquitous molecule present in serum.

Honda, Yoshitomo; Anada, Takahisa; Morimoto, Shinji; Suzuki, Osamu

2013-05-01

324

Interactive priming of biochar and labile organic matter mineralization in a smectite-rich soil.  

PubMed

Biochar is considered as an attractive tool for long-term carbon (C) storage in soil. However, there is limited knowledge about the effect of labile organic matter (LOM) on biochar-C mineralization in soil or the vice versa. An incubation experiment (20 °C) was conducted for 120 days to quantify the interactive priming effects of biochar-C and LOM-C mineralization in a smectitic clayey soil. Sugar cane residue (source of LOM) at a rate of 0, 1, 2, and 4% (w/w) in combination with two wood biochars (450 and 550 °C) at a rate of 2% (w/w) were applied to the soil. The use of biochars (~ -36‰) and LOM (-12.7‰) or soil (-14.3‰) with isotopically distinct ?(13)C values allowed the quantification of C mineralized from biochar and LOM/soil. A small fraction (0.4-1.1%) of the applied biochar-C was mineralized, and the mineralization of biochar-C increased significantly with increasing application rates of LOM, especially during the early stages of incubation. Concurrently, biochar application reduced the mineralization of LOM-C, and the magnitude of this effect increased with increasing rate of LOM addition. Over time, the interactive priming of biochar-C and LOM-C mineralization was stabilized. Biochar application possesses a considerable merit for long-term soil C-sequestration, and it has a stabilizing effect on LOM in soil. PMID:21950729

Keith, Alexandra; Singh, Balwant; Singh, Bhupinder Pal

2011-11-15

325

Energy evaluation of forest residues originated from Eucalyptus globulus Labill in Galicia.  

PubMed

The possibility of retrieving the energy contained in forest residues originating from wood exploitation in Galicia (Spain) is evaluated. This study was made on Eucalyptus globulus Labill occupying a forest surface of 240000 ha. This species plays an important role in the economical development of Galicia, as it is the main forest species for production of pulp. Sampling was made over 1999 in seven different zones, three main stations plus four selected for comparison, situated in Galicia. The residues originating from cutting were sorted into three different groups and their calorific values were measured by static bomb calorimetry. These calorific values, close to 7200 kJ kg(-1), make possible the use of this residual biomass as an energy source. Calorific values were measured by static bomb calorimeter in an oxygen atmosphere. Flammability was determined using a standard epiradiator. Simultaneously, some other parameters, elementary chemical composition, heavy metal contents, moisture, density, ash percentage after combustion in the bomb, and main bioclimatic characteristics, were also determined. PMID:11848377

Núñez-Regueira, L; Proupín-Castiñeiras, J; Rodríguez-Añón, J A

2002-03-01

326

Anatomical variation in Cactaceae and relatives: Trait lability and evolutionary innovation.  

PubMed

The cacti have undergone extensive specialization in their evolutionary history, providing an excellent system in which to address large-scale questions of morphological and physiological adaptation. Recent molecular phylogenetic studies suggest that (1) Pereskia, the leafy genus long interpreted as the sister group of all other cacti, is likely paraphyletic, and (2) Cactaceae are nested within a paraphyletic Portulacaceae as a member of the "ACPT" clade (Anacampseroteae, Cactaceae, Portulaca, and Talinum). We collected new data on the vegetative anatomy of the ACPT clade and relatives to evaluate whether patterns in the distributions of traits may provide insight into early events in the evolutionary transition to the cactus life form. Many traits had high levels of homoplasy and were mostly equivocal with regard to infraclade relationships of ACPT, although several characters do lend further support to a paraphyletic Pereskia. These include a thick stem cuticle, prominent stem mucilage cells, and hypodermal calcium oxalate druses, all of which are likely to be important traits for stem water storage and photosynthesis. We hypothesize that high lability of many putative "precursor" traits may have been critical in generating the organismal context necessary for the evolution of an efficient and integrated photosynthetic stem. PMID:21628195

Ogburn, R Matthew; Edwards, Erika J

2009-02-01

327

Detergent-labile, supramolecular assemblies of KcsA: relative abundance and interactions involved.  

PubMed

In this work, we illustrate the ability of the prokaryotic potassium channel KcsA to assemble into a variety of supramolecular clusters of defined sizes containing the tetrameric KcsA as the repeating unit. Such clusters, particularly the larger ones, are markedly detergent-labile and thus, disassemble readily upon exposure to the detergents commonly used in protein purification or conventional electrophoresis analysis. This is a reversible process, as cluster re-assembly occurs upon detergent removal and without the need of added membrane lipids. Interestingly, the dimeric ensemble between two tetrameric KcsA molecules are quite resistant to detergent disassembly to individual KcsA tetramers and along with the latter, are likely the basic building blocks through which the larger clusters are organized. As to the proteins domains involved in clustering, we have observed disassembly of KcsA clusters by SDS-like alkyl sulfates. As these amphiphiles bind to inter-subunit, "non-annular" sites on the protein, these observations suggest that such sites also mediate channel-channel interactions leading to cluster assembly. PMID:23022492

Giudici, A Marcela; Molina, M Luisa; Ayala, José L; Montoya, Estefanía; Renart, M Lourdes; Fernández, Asia M; Encinar, José A; Ferrer-Montiel, Antonio V; Poveda, José A; González-Ros, José M

2013-02-01

328

Nitric oxide is necessary for labilization of a consolidated context memory during reconsolidation in terrestrial snails.  

PubMed

Nitric oxide (NO) is known to be involved in associative memory formation. We investigated the influence of blocking NO function on the reconsolidation of context memory in terrestrial snails (Helix lucorum L.). After a 10 day session of electric shocks in one context only, context memory in snails was observed in test sessions as the significant difference of amplitudes of withdrawal responses to tactile stimuli in two different contexts. After a 1 day rest, a session of 'reminding' was performed, preceded by injection in different groups of the snails with either vehicle or combination of the protein synthesis blocker anisomycin (ANI) with one of the following drugs: the NO scavenger carboxy-PTIO, the NO-synthase inhibitors N-omega-nitro-L-arginin, nitroindazole and NG-nitro-L-arginine methyl ester hydrochloride, or the NO donor S-nitroso-N-acetyl-DL-penicillamine. Testing the context memory at different time intervals after the reminder under ANI injection showed that the context memory was impaired at 24 h and later, whereas the reminder under combined injection of ANI and each of the NO-synthase inhibitors used or the NO scavenger showed no impairment of long-term context memory. Injection of the NO donor S-nitroso-N-acetyl-DL-penicillamine with or without reminder had no effect on context memory. The results obtained demonstrated that NO is necessary for labilization of a consolidated context memory. PMID:24910164

Balaban, Pavel M; Roshchin, Matvey; Timoshenko, Alia K; Gainutdinov, Khalil L; Bogodvid, Tatiana K; Muranova, Lyudmila N; Zuzina, Alena B; Korshunova, Tatiana A

2014-09-01

329

On the synthesis and reactivity of highly labile pseudohalogen phosphenium ions.  

PubMed

The synthesis and characterization of salts bearing highly labile pseudohalogen-substituted aminophosphenium cations of the type [(Me3Si)2NPX][GaCl4] (X = NCO, NCS, O(SiMe3)) and their respective reactivity toward Lewis bases (4-dimethylaminopyridine, dmap) and dienes (2,3-dimethyl-1,3-butadiene, dmb; 1,3-cyclo-hexadiene, chd) are described. As ?-acidic species, aminophosphenium cations react with dmap at low temperatures to yield adduct salts of the type [(Me3Si)2NP(dmap)X][GaCl4] (X = Cl, N3, NCO) which were fully characterized. In the reaction with dienes at -50 °C, salts bearing phospholenium cations were obtained that could be structurally characterized. The crystal structures of novel 7-phosphanorbornenium cations of the type [(Me3Si)2NP(C6H8)X][GaCl4] (X = Cl, N3, NCO) are reported. All compounds were further investigated by means of density functional theory, and the bonding situation was accessed by Natural Bond Orbital (NBO) analysis. PMID:23614881

Hering, Christian; Schulz, Axel; Villinger, Alexander

2013-05-01

330

DGT-labile As, Cd, Cu and Ni monitoring in freshwater: toward a framework for interpretation of in situ deployment.  

PubMed

The use of the Diffusive Gradient in Thin Film sampler (DGT) as a monitoring tool for regulatory programs is currently evaluated. In this context, the impact of commonly followed procedures on the accuracy of DGT-labile As, Cd, Cu, and Ni quantification was studied. Initial sampler contamination yields to define quantification limits instead of using blank subtraction, thus avoiding artifact concentrations. Not considering the alteration of element diffusion by the filter membrane leads to significant underestimation. However, diffusion coefficients determined on a non-fouled membrane were found to be suitable for the studied site, making it possible to use data from the literature. When diffusive boundary layer formation is neglected, no loss of accuracy is recorded provided the layer is thinner than 0.5 mm. Finally, exploration of potential biases allowed initiating a framework that might help limit inaccuracies in DGT-labile concentration estimation and interpretation, especially in a low contamination context. PMID:24886969

Buzier, Rémy; Charriau, Adeline; Corona, David; Lenain, Jean-François; Fondanèche, Patrice; Joussein, Emmanuel; Poulier, Gaëlle; Lissalde, Sophie; Mazzella, Nicolas; Guibaud, Gilles

2014-09-01

331

Acute Toxin Registration All biological toxins with a mammalian LD50 of 100g/kg body weight, as well as the organisms (both natural and  

E-print Network

Acute Toxin Registration All biological toxins with a mammalian LD50 of 100�g/kg body weight_Edition.pdf. The use of acute toxins requires that each laboratory develop a standard operating procedure for the use stocks, are two people present in the lab? Acute Toxin Registration #AT - Yes Yes Yes Yes #12;2 EHS

Slatton, Clint

332

75 FR 20771 - Viruses, Serums, Toxins, and Analogous Products and Patent Term Restoration; Nonsubstantive...  

Federal Register 2010, 2011, 2012, 2013

...124 [Docket No. APHIS-2009-0069] Viruses, Serums, Toxins, and Analogous Products...SUMMARY: We are amending the Virus-Serum-Toxin Act regulations concerning...contain provisions implementing the Virus-Serum-Toxin Act, as amended...

2010-04-21

333

pH lability of myosin ATPase activity permits discrimination of different muscle fibre types in crustaceans.  

PubMed

Myofibrillar actomyosin ATPase activity has been studied histochemically in the closer muscle of the crab Eriphia spinifrons. Preincubation at pH 4.6 and 5.0 reveals differences in the lability of the ATPase. This permits the discrimination of four fibre types. Of these, three represent subgroups of rapidly contracting fibres. The histochemically defined fibre types correspond well with four groups defined according to electrophysiological criteria. PMID:6236181

Maier, L; Rathmayer, W; Pette, D

1984-01-01

334

A Comparison of Self-Esteem Lability and Low Trait Self-Esteem as Vulnerability Factors for Depression  

Microsoft Academic Search

Self-esteem lability (SEL), defined as daily event-related variability in state self-esteem, and low trait self-esteem (TSE) were assessed among 205 male and female undergraduates who were currently depressed (CD), previously depressed (PD), and never depressed (ND). SEL scores were derived for the effect of positive, negative, and combined events on state self-esteem over 30 days. Consistent with psychodynamic and cognitive

Andrew C. Butler; Jack E. Hokanson; Heather A. Flynn

1994-01-01

335

Monitoring of (bio)available labile metal fraction in a drinking water treatment plant by diffusive gradients in thin films  

Microsoft Academic Search

A performance study of diffusive gradients in thin films (DGT) and inductively coupled plasma optical emission spectrometry\\u000a (ICP-OES) was applied for the monitoring of the labile fraction of metals Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn, in Sant\\u000a Joan Despí Drinking Water Treatment Plant located in the South of Barcelona’s Metropolitan Area (Spain). The DWTP monitoring

Alfredo Díaz; Rebeca Arnedo; Raquel Céspedes-Sánchez; Ricard Devesa; Jordi Martin-Alonso

336

Visualization of Peroxynitrite-Induced Changes of Labile Zn2+ in the Endoplasmic Reticulum with Benzoresorufin-based Fluorescent Probes  

PubMed Central

Zn2+ plays essential roles in biology, and the homeostasis of Zn2+ is tightly regulated in all cells. Subcellular distribution and trafficking of labile Zn2+, and its interrelation with reactive nitrogen species, are poorly understood due to the scarcity of appropriate imaging tools. We report a new family of red-emitting fluorescent sensors for labile Zn2+, ZBR1-3, based on a benzoresorufin platform functionalized with dipicolylamine or picolylamine-derived metal binding groups. In combination, the pendant amines and fluorophore afford an [N3O] binding motif that resembles that of previously reported fluorescein-based sensors of the Zinpyr family, reproducing well their binding capabilities and yielding comparable Kd values in the subnanomolar and picomolar range. The ZBR sensors display up to 8.4-fold emission fluorescence enhancement upon Zn2+ binding in the cuvette, with similar responses obtained in live cells using standard wide-field fluorescence microscopy imaging. The new sensors localize spontaneously in the endoplasmic reticulum (ER) of various tested cell lines, allowing for organelle-specific monitoring of zinc levels in live cells. Study of ER zinc levels in neural stem cells (NSC) treated with a peroxynitrite generator, Sin-1, revealed an immediate decrease in labile Zn2+ thus providing evidence for a direct connection between ER stress and ER Zn2+ homeostasis. PMID:23902285

Lin, Wei; Buccella, Daniela; Lippard, Stephen J.

2013-01-01

337

Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker.  

PubMed

Polylysine dendrimers have potential as biodegradable vectors for the delivery of cytotoxic drugs to solid tumours. Here, the cytotoxicity, drug release and tumour targeting properties of Generation 5 PEGylated polylysine dendrimers comprising an outer generation of l-lysine or succinimyldipropyldiamine (SPN) and containing doxorubicin (DOX) linked through an acid labile 4-(hydrazinosulfonyl) benzoic acid (HSBA) linker have been characterised. Less than 10% of the DOX load was released from LYS or SPN dendrimers in pH 7.4 buffer over 3 days. In contrast approximately 100% release was evident at pH 5. The DOX-conjugated dendrimers also retained similar cytotoxic properties to free DOX in in vitro cell culture studies (presumably as a result of in situ liberation of free DOX). The clearance patterns of the DOX conjugated SPN and all-lysine dendrimers were similar to the equivalent non-DOX conjugated systems, however the SPN dendrimers showed reduced metabolic lability and increased uptake into RES organs when compared to the equivalent all-lysine dendrimers. In vivo assessment of the DOX-conjugated, PEGylated polylysine dendrimers (both SPN and LYS constructs) in rats bearing Walker 256 tumours revealed higher uptake into tumour tissue when compared with control tissue such as muscle (~8 fold) and heart (~3 fold). The data suggest that polylysine dendrimers containing DOX conjugated via an acid labile HSBA linker may provide a mechanism to target the delivery of DOX to tumours. PMID:21315119

Kaminskas, Lisa M; Kelly, Brian D; McLeod, Victoria M; Sberna, Gian; Owen, David J; Boyd, Ben J; Porter, Christopher J H

2011-06-10

338

Microwave-assisted extraction performed in low temperature and in vacuo for the extraction of labile compounds in food samples.  

PubMed

In this study, low temperature vacuum microwave-assisted extraction, which simultaneous performed microwave-assisted extraction (MAE) in low temperature and in vacuo environment, was proposed. The influencing parameters including solid/liquid ratio, extraction temperature, extraction time, degree of vacuum and microwave power were discussed. The predominance of low temperature vacuum microwave-assisted extraction was investigated by comparing the extraction yields of vitamin C, ?-carotene, aloin A and astaxanthin in different foods with that in MAE and solvent extraction, and 5.2-243% increments were obtained. On the other hand, the chemical kinetics of vitamin C and aloin A, which composed two different steps including the extraction step of analyte transferred from matrix into solvent and the decomposition step of analyte degraded in the extraction solvent, were proposed. All of the decomposition rates (K(2)) for the selected analyte in low temperature, in vacuo and in nitrogen atmosphere decreased significantly comparing with that in conventional MAE, which are in agreement with that obtained from experiments. Consequently, the present method was successfully applied to extract labile compound from different food samples. These results showed that low temperature and/or in vacuo environment in microwave-assisted extraction system was especially important to prevent the degradation of labile components and have good potential on the extraction of labile compound in foods, pharmaceutical and natural products. PMID:22177069

Xiao, Xiaohua; Song, Wei; Wang, Jiayue; Li, Gongke

2012-01-27

339

Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-On Fluorescent Probe  

PubMed Central

Iron is an essential metal for living organisms, but misregulation of its homeostasis at the cellular level can trigger detrimental oxidative and/or nitrosative stress and damage events. Motivated to help study the physiological and pathological consequences of biological iron regulation, we now report a reaction-based strategy for monitoring labile Fe2+ pools in aqueous solution and in living cells. Iron Probe 1 (IP1) exploits a bioinspired, iron-mediated oxidative C–O bond cleavage reaction to achieve a selective turn-on response to Fe2+ over a range of cellular metal ions in their bioavailable forms. We show that this first-generation chemical tool for fluorescence Fe2+ detection can visualize changes in exchangeable iron stores in living cells upon iron supplementation or depletion, including labile iron pools at endogenous, basal levels. Moreover, IP1 can be used to identify reversible expansion of labile iron pools by stimulation with vitamin C or the iron regulatory hormone hepcidin, providing a starting point for further investigations of iron signaling and stress events in living systems as well as future probe development. PMID:24063668

Au-Yeung, Ho Yu; Chan, Jefferson; Chantarojsiri, Teera; Chang, Christopher J.

2013-01-01

340

Effect of soluble calcium on the determination of the labile metal content of sediments with ion-exchangers.  

PubMed

Equilibration of sediments with cation-exchangers results in a transfer of loosely bound labile metal species to the exchanger phase. Dissolution of the matrix is also promoted and selectivity rules suggest that some of the cations released (particularly Ca) could effectively compete with metal ions for exchange sites. This potential source of error has been evaluated by studying synthetic mixtures of Ca(2+) and other metal ions (Cu(2+), Pb(2+), Cd(2+), Zn(2+)) and by analysis of two calcium-rich wastes (a calcine and a jarosite). The ion uptake most influenced by calcium competition was that of zinc; uptake of lead was least affected. For minimum error, i.e., optimum transfer of "available" or "labile" metal ion, the level of free Ca(2+) introduced into the solution should not exceed 300 mg/l., and the amount of exchanger added must provide an excess of exchange sites relative to the amount of cations released from the sample. By use of exchangers of different types it is possible to attempt some classification of the labile metal content, e.g., acid-displaced, exchangeable, salts of weak acids. PMID:18964894

Beveridge, A; Waller, P; Pickering, W F

1989-12-01

341

The ether lipid precursor hexadecylglycerol protects against Shiga toxins.  

PubMed

Shiga toxin-producing Escherichia coli bacteria cause hemorrhagic colitis and hemolytic uremic syndrome in humans. Currently, only supportive treatment is available for diagnosed patients. We show here that 24-h pretreatment with an ether lipid precursor, the alkylglycerol sn-1-O-hexadecylglycerol (HG), protects HEp-2 cells against Shiga toxin and Shiga toxin 2. Also the endothelial cell lines HMEC-1 and HBMEC are protected against Shiga toxins after HG pretreatment. In contrast, the corresponding acylglycerol, DL-?-palmitin, has no effect on Shiga toxicity. Although HG treatment provides a strong protection (~30 times higher IC50) against Shiga toxin, only a moderate reduction in toxin binding was observed, suggesting that retrograde transport of the toxin from the plasma membrane to the cytosol is perturbed. Furthermore, endocytosis of Shiga toxin and retrograde sorting from endosomes to the Golgi apparatus remain intact, but transport from the Golgi to the endoplasmic reticulum is inhibited by HG treatment. As previously described, HG reduces the total level of all quantified glycosphingolipids to 50-70 % of control, including the Shiga toxin receptor globotriaosylceramide (Gb3), in HEp-2 cells. In accordance with this, we find that interfering with Gb3 biosynthesis by siRNA-mediated knockdown of Gb3 synthase for 24 h causes a similar cytotoxic protection and only a moderate reduction in toxin binding (to 70 % of control cells). Alkylglycerols, including HG, have been administered to humans for investigation of therapeutic roles in disorders where ether lipid biosynthesis is deficient, as well as in cancer therapy. Further studies may reveal if HG can also have a therapeutic potential in Shiga toxin-producing E. coli infections. PMID:24740796

Bergan, Jonas; Skotland, Tore; Lingelem, Anne Berit Dyve; Simm, Roger; Spilsberg, Bjørn; Lindbäck, Toril; Sylvänne, Tuulia; Simolin, Helena; Ekroos, Kim; Sandvig, Kirsten

2014-11-01

342

Visualization of Peroxynitrite-Induced Changes of Labile Zn[superscript 2+] in the Endoplasmic Reticulum with Benzoresorufin-based Fluorescent Probes  

E-print Network

Zn[superscript 2+] plays essential roles in biology, and the homeostasis of Zn[superscript 2+] is tightly regulated in all cells. Subcellular distribution and trafficking of labile Zn[superscript 2+], and its inter-relation ...

Lin, Wei

343

Characterization of Toxin A-Negative, Toxin B-Positive Clostridium difficile Isolates from Outbreaks in Different Countries by Amplified Fragment Length Polymorphism and PCR Ribotyping  

Microsoft Academic Search

Clinical Clostridium difficile isolates of patients with diarrhea or pseudomembranous colitis usually produce both toxin A and toxin B, but an increasing number of reports mention infections due to toxin A-negative, toxin B-positive (A\\/B) strains. Thirty-nine clinical toxin A\\/B isolates, and 12 other unrelated isolates were obtained from Canada, the United States, Poland, the United Kingdom, France, Japan, and The

Renate J. van den Berg; Eric C. J. Claas; Duddy H. Oyib; W. Klaassen; Lenie Dijkshoorn; Jon S. Brazier; Ed J. Kuijper; Infectious Diseases

2004-01-01

344

Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum  

PubMed Central

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states. PMID:18988734

Spooner, Robert A.; Hart, Philip J.; Cook, Jonathan P.; Pietroni, Paola; Rogon, Christian; Höhfeld, Jörg; Roberts, Lynne M.; Lord, J. Michael

2008-01-01

345

Toxin-Resistant Sodium Channels: Parallel Adaptive Evolution across a Complete Gene Family  

E-print Network

species of pufferfishes (Tetraodontidae) each evolved resistance to the guanidinium toxins tetrodotoxin, naturally occurring guanidinium toxin tetrodotoxin (TTX), an extremely potent agent that, like STX, arrests

Hillis, David

346

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

PubMed Central

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

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

2013-01-01

347

DMA Alkali-labile Sites Induced by Incorporation of 5-Aza-2'-deoxycytidine into DMA of Mouse Leukemia L1210 Cells  

Microsoft Academic Search

The effects of 5-aza-2'-deoxycytidine on DMA in mouse L1210 leukemia cells were investigated using the alkaline elution tech nique. By comparing the DNA elution rate at pH 12.1 and 12.6, it was found that the drug produced DNA alkali-labile lesions. Alkali-labile sites were present only in DNA strands that were synthesized in the presence of the drug. They persisted for

Maurizio D'Incaici; Joseph M. Covey; Daniel S. Zaharko; Kurt W. Kohn

348

Possible importance of algal toxins in the Salton Sea, California  

Microsoft Academic Search

In response to wildlife mortality including unexplained eared grebe (Podiceps nigricollis) die-off events in 1992 and 1994 and other mortality events including large fish kills, a survey was conducted for the presence of algal toxins in the Salton Sea. Goals of this survey were to determine if and when algal toxins are present in the Salton Sea and to describe

Kristen M. Reifel; Michael P. McCoy; Tonie E. Rocke; Mary Ann Tiffany; Stuart H. Hurlbert; D. John Faulkner

2002-01-01

349

Using Modified Bacterial Toxins To Deliver Vaccine Antigens  

E-print Network

Using Modified Bacterial Toxins To Deliver Vaccine Antigens Researchers are using toxins to deliver protect them against many elements of the im- mune response. Once inside host cells, these organisms intracellular microbes, researchers are interested in develop- ing safe and effective vaccines that specifically

Starnbach, Michael

350

EFFECT OF MARINE TOXINS ON THERMOREGULATION IN MICE.  

EPA Science Inventory

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

351

Local botulinum toxin in the treatment of spastic drop foot  

Microsoft Academic Search

Ten patients with spastic drop foot were treated by local injections of botulinum toxin A (botulinum toxin A haemagglutinin complex). The purpose was to improve stance and gait and\\/or to facilitate physiotherapy and patient care. Various calf muscles were injected using EMG guidance. The average dose used was 23 ng. Prior to and 4 weeks after treatment, positions of the

R. Dengler; U. Neyer; K. Wohlfarth; U. Bettig; H. H. Janzik

1992-01-01

352

Clostridial Binary Toxins: Iota and C2 Family Portraits  

PubMed Central

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

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

2011-01-01

353

Pertussis Toxin Gene: Nucleotide Sequence and Genetic Organization  

Microsoft Academic Search

The current pertussis vaccines, although efficacious, in some instances produce undesirable side effects. Molecular engineering of pertussis toxin, the major protective antigen, could provide a safer, new generation of vaccines against whooping cough. As a first critical step in the development of such a vaccine, the complete nucleotide sequence of the pertussis toxin gene was determined and the amino acid

Camille Locht; Jerry M. Keith

1986-01-01

354

Molecular Characterization of an Operon Required for Pertussis Toxin Secretion  

Microsoft Academic Search

Mutants of Bordetella pertussis which are defective in secretion of pertussis toxin were isolated and characterized. The region of the B. pertussis chromosome identified by mutagenesis as playing a role in transport of pertussis toxin was sequenced. Analysis of this region revealed eight open reading frames, seven of which predict a protein exhibiting homology with one of the VirB proteins

Alison A. Weiss; Frederick D. Johnson; Drusilla L. Burns

1993-01-01

355

Original article Effects of a Bacillus thuringiensis toxin,  

E-print Network

Original article Effects of a Bacillus thuringiensis toxin, two Bacillus thuringiensis biopesticide and activated Cry1Ba ?-endotoxin, from Bacillus thuringien- sis Bt4412(Bt) (1, 0.25 and 0.025 % w/w), Bt as recommended. © Inra/DIB/AGIB/Elsevier, Paris honey bee / Bacillus thuringiensis / CrylBa toxin / Kunitz

Paris-Sud XI, Université de

356

Original article Effects of ingestion of a Bacillus thuringiensis toxin  

E-print Network

Original article Effects of ingestion of a Bacillus thuringiensis toxin and a trypsin inhibitor with 625 µg/g Cry1Ba Bacillus thuringiensis (Bt) toxin or 2.5 mg/g aprotinin proteinase inhibitor in pollen-plants on honey bees will thus depend on gene expression levels in pollen. Apis mellifera / Bacillus thuringiensis

Paris-Sud XI, Université de

357

IDENTIFICATION OF MICROCYSTIN TOXINS FROM A STRAIN OF MICROCYSTIS AERUGINOSA  

EPA Science Inventory

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

358

Spider toxins: A new group of potassium channel modulators  

Microsoft Academic Search

Spider toxins that target potassium channels constitute a new class of pharmacological tools that can be used to probe the structure and function of these channels at the molecular level. The limited studies performed to date indicate that these peptide toxins may facilitate the analysis of K+ channels that have proved insensitive to peptide inhibitors isolated from other animal sources.

Jamie I. Fletcher; Xiuhong Wang; Mark Connor; Macdonald J. Christie; Glenn F. King; Graham M. Nicholson

1999-01-01

359

Gangliosides as Receptors for Biological Toxins: Development of Sensitive Fluoroimmunoassays  

E-print Network

. Tetanus and botulinum toxins selectively bind gangliosides of the G1b series, namely, GT1b, GD1b, and GQ1b used in sandwich fluoroimmunoassays for tetanus, botulinum, and cholera toxins and as low as 1 n in 10-8 M range, indicating strong binding. This is the first report on detection of tetanus

Singh, Anup

360

Tetanus Toxin: Direct Evidence for Retrograde Intraaxonal Transport  

Microsoft Academic Search

The neurotoxin tetanospasmin causes tetanus when it reaches the central nervous system. In this autoradiographic study, 125I-labeled tetanospasmin was injected into the leg muscles of rodents, and the nerves supplying these muscles were crushed. The labeled toxin accumulated within axons on the distal side of the crush. This study provides direct evidence for retrograde axonal transport of a macromolecular toxin

Donald L. Price; Jack Griffin; Ann Young; Keith Peck; Adelaine Stocks

1975-01-01

361

Multiple receptors as targets of Cry toxins in mosquitoes.  

PubMed

Bacillus thuringiensis (Bt) produces inclusions that are composed of proteins known as crystal proteins or Cry toxins. Due to their high specificity and their safety to humans and the environment, these Cry toxins are considered to be valuable alternatives to chemical pesticides in insect control programs. It is believed that Cry toxin-induced membrane pore formation is responsible for insect toxicity. The molecular mechanism of pore formation involves recognition and subsequent binding of the toxin to membrane receptors. This binding is accompanied by toxin oligomerization and transfer of domain I helices of the toxin to the lipid-water interface. This toxin insertion creates pores that lyse the cells. Several receptors from lepidopteran, coleopteran, and dipteran insects have been well characterized. This paper provides an overview of the understanding of the interactions between Cry toxin and multiple receptors in mosquitoes, in particular Aedes aegypti and reviews the manner by which the receptors were identified and characterized, with a focus on three proteins, cadherin, alkaline phosphatase, and aminopeptidase-N. PMID:21210704

Likitvivatanavong, Supaporn; Chen, Jianwu; Evans, Amy M; Bravo, Alejandra; Soberon, Mario; Gill, Sarjeet S

2011-04-13

362

Preventing bacterial suicide: a novel toxin-antitoxin strategy.  

PubMed

In this issue of Molecular Cell, Aarke et al. (2013) identify a toxin-antitoxin system in Caulobacter crescentus that acts by a unique mechanism. The toxin, which blocks DNA replication, is constitutively degraded by ClpXP, and this degradation requires the antitoxin, a ClpXP adaptor. PMID:24332174

Markovski, Monica; Wickner, Sue

2013-12-12

363

T-2 toxin Analysis in Poultry and Cattle Feedstuff  

PubMed Central

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

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

2014-01-01

364

Interactions between Shiga toxins and human polymorphonuclear leukocytes  

Microsoft Academic Search

Human intestinal infections by Shiga toxin (Stx)-producing Escherichia coli cause hem- orrhagic colitis and hemolytic uremic syndrome (HUS), which represents the main cause of acute renal failure in early childhood. In HUS, Stx re- leased in the gut enter the bloodstream and are targeted to renal endothelium. The mechanism of toxin delivery is still a matter of debate, although the

Maurizio Brigotti; Domenica Carnicelli; Elisa Ravanelli; Stefania Barbieri; Francesca Ricci; Andrea Bontadini; Alberto E. Tozzi; Gaia Scavia; Alfredo Caprioli; Pier Luigi Tazzari

2008-01-01

365

Studies on the Mechanism of Action of Botulinum Toxin.  

National Technical Information Service (NTIS)

The thesis is divided into four sections. The first section presents a review of the literature on the mode of action of botulinum toxin. The second section considers the problem of whether botulinum toxin can act on the central nervous system. It is repo...

L. L. Simpson

1969-01-01

366

Construction of tumor-specific toxins using ubiquitin fusion technique.  

PubMed

The use of cytotoxic agents to eliminate cancer cells is limited because of their nonselective toxicity and unwanted side effects. One of the strategies to overcome these limitations is to use latent prodrugs that become toxic in situ after being enzymatically activated in target cells. In this work we describe a method for producing tumor-specific toxins by using a ubiquitin fusion technique. The method is illustrated by the production of recombinant toxins by in-frame fusion of ubiquitin to saporin, a toxin from the plant Saponaria officinalis. Ubiquitin-fused toxins were rapidly degraded via the ubiquitin-proteasome system, significantly reducing their nonspecific toxicity. The insertion of the protease-cleavage sequence between ubiquitin and saporin led to the removal of ubiquitin by the protease and resulted in protease-dependent stabilization of the toxin. We engineered toxins that can be stabilized by specific proteases such as deubiquitinating enzymes and prostate-specific antigen (PSA). Both constructs were activated in vitro and in cultured cells by the appropriate enzyme. Processing by the protease resulted in a greater than 10-fold increase in the toxicity of these constructs. Importantly, the PSA-cleavable toxin was able to kill specifically the PSA-producing prostate cancer cells. The ubiquitin fusion technique is thus a versatile and reliable method for obtaining selective cytotoxic agents and can easily be adapted for different kinds of toxins and activating proteases. PMID:15668131

Tcherniuk, Sergey O; Chroboczek, Jadwiga; Balakirev, Maxim Y

2005-02-01

367

The influence of labile dietary methyl donors on the arginine requirement of young broiler chicks.  

PubMed

Two experiments were conducted with Ross x Ross boiler chicks in battery brooders from 1 to 14 d of age to determine the influence of dietary methyl donors on the Arg requirement of young broiler chicks. Experiment 1 had a 6 x 2 factorial design, with six levels of Arg supplementation (0, 0.1, 0.2, 0.3, 0.4, and 0.5%) and two levels of DL-Met supplementation (0 and 0.2% of the diet). The design of Experiment 2 was identical to Experiment 1, except that a second source of labile methyl groups was added, 0.2% betaine (6 x 3 factorial arrangement). Both experiments had four replicate pens of 10 chicks each per treatment. The basal diet was based on corn (34.52%), whey (26.96%), corn gluten meal (16.53%), soybean meal (11.74%), and poultry fat (23% CP and 3.20 kcal/g of ME). At 14 d, three chicks per replicate were randomly killed, and breast muscle was collected and pooled for creatine analysis. The broken-line linear model was used to estimate the Arg requirements of the chicks. There were no differences in Arg requirements due to methyl source so the data were pooled. In Experiment 1, the Arg requirements were 1.17 +/- 0.04% for gain, 1.23 +/- 0.03% for feed conversion ratio (FCR), and 1.18 +/- 0.03% for muscle creatine, when the diet contained 0.45 or 0.65% Met. In Experiment 2, the Arg requirements were 1.20 +/- 0.05% for gain, 1.23 +/- 0.03% for FCR, and 1.26 +/- 0.02% for muscle creatine. There was no apparent difference in the Arg requirement of young broilers due to methyl donor supplementation. PMID:12211306

Chamruspollert, M; Pesti, G M; Bakalli, R I

2002-08-01

368

Labile carbon retention compensates for CO2 released by priming in forest soils.  

PubMed

Increase of belowground C allocation by plants under global warming or elevated CO2 may promote decomposition of soil organic carbon (SOC) by priming and strongly affects SOC dynamics. The specific effects by priming of SOC depend on the amount and frequency of C inputs. Most previous priming studies have investigated single C additions, but they are not very representative for litterfall and root exudation in many terrestrial ecosystems. We evaluated effects of (13)C-labeled glucose added to soil in three temporal patterns: single, repeated, and continuous on dynamics of CO2 and priming of SOC decomposition over 6 months. Total and (13)C labeled CO2 were monitored to analyze priming dynamics and net C balance between SOC loss caused by priming and the retention of added glucose-C. Cumulative priming ranged from 1.3 to 5.5 mg C g(-1) SOC in the subtropical, and from -0.6 to 5.5 mg C g(-1) SOC in the tropical soils. Single addition induced more priming than repeated and continuous inputs. Therefore, single additions of high substrate amounts may overestimate priming effects over the short term. The amount of added glucose C remaining in soil after 6 months (subtropical: 8.1-11.2 mg C g(-1) SOC or 41-56% of added glucose; tropical: 8.7-15.0 mg C g(-1) SOC or 43-75% of glucose) was substantially higher than the net C loss due to SOC decomposition including priming effect. This overcompensation of C losses was highest with continuous inputs and lowest with single inputs. Therefore, raised labile organic C input to soils by higher plant productivity will increase SOC content even though priming accelerates decomposition of native SOC. Consequently, higher continuous input of C belowground by plants under warming or elevated CO2 can increase C stocks in soil despite accelerated C cycling by priming in soils. PMID:24293210

Qiao, Na; Schaefer, Douglas; Blagodatskaya, Evgenia; Zou, Xiaoming; Xu, Xingliang; Kuzyakov, Yakov

2014-06-01

369

Accelerated junctional rhythm and non-alternans repolarization lability precede ventricular tachycardia in Casq2?/? mice  

PubMed Central

Background Calsequestrin-2 (CASQ2) is a Ca2+ buffering protein of myocardial sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated in Casq2?/? mice. Repolarization lability (RL) - beat-to-beat variability in the T wave morphology - has been reported in long-QT syndrome, but has not been evaluated in CPVT. Methods and Results ECG from Casq2?/? mice was evaluated with respect to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT) to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice (3-month-old males, 5 animals of each genotype) and ECG before and after isoproterenol administration in anesthetized mice was analyzed. Average HR in sinus rhythm (SR), occurrence of non-sinus rhythm and RL were quantified. HR was slower in Casq2?/? animals. Accelerated junctional rhythm (JR) occurred more frequently in Casq2?/? mice and often preceded VT. In Casq2?/? mice, HR increased prior to VT onset, prior to onset of JR and on transition from JR to VT. RL increased during progression from SR to VT and after isoproterenol administration in Casq2?/?, but not in Casq2+/+ animals. Isoproterenol did not increase repolarization alternans in either genotype. Conclusions Accelerated JR, likely caused by triggered activity in His/Purkinje system, occurs frequently in Casq2?/? mice. Absence of CASQ2 results in increased RL. Increase in HR and in RL precede onset of arrhythmias in this CPVT model. Non-alternans RL precedes ventricular arrhythmia in wider range of conditions than previously appreciated. PMID:22860618

Mezu, Ure; Singh, Prabhpreet; Shusterman, Vladimir; Hwang, Hyun Seok; Knollmann, Bjorn C.; Nemec, Jan

2012-01-01

370

Structure and Biological Activities of Beta Toxin from Staphylococcus aureus? †  

PubMed Central

Beta toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta toxin was determined at 2.4-Å resolution using crystals that were merohedrally twinned. This structure is similar to that of the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta toxin belongs to the DNase I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNase I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays demonstrated for the first time that beta toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme. PMID:17873030

Huseby, Medora; Shi, Ke; Brown, C. Kent; Digre, Jeff; Mengistu, Fikre; Seo, Keun Seok; Bohach, Gregory A.; Schlievert, Patrick M.; Ohlendorf, Douglas H.; Earhart, Cathleen A.

2007-01-01

371

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture  

SciTech Connect

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

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

1986-08-01

372

Discovery of a widely distributed toxin biosynthetic gene cluster  

PubMed Central

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

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

2008-01-01

373

Shiga toxin-producing Escherichia coli  

PubMed Central

Shiga toxin-producing Escherichia coli (STEC) cause hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) in humans. Outbreaks are linked to bovine food sources. STEC O157:H7 has been responsible for the most severe outbreaks worldwide. However, non-O157 serotypes have emerged as important enteric pathogens in several countries. The main virulence factor of STEC is the production of Shiga toxins 1 and 2. Additional virulence markers are a plasmid-encoded enterohemolysin (ehxA), an autoagglutinating adhesin (Saa), a catalase-peroxidase (katP), an extracellular serine protease (espP), a zinc metalloprotease (stcE), a subtilase cytotoxin (subAB), among others. Other virulence factors are intimin and adhesins that had a roll in the adherence of STEC to bovine colon. This review focuses on the virulence traits of STEC and especially on those related to the adhesion to bovine colon. The known of the interaction between STEC and the bovine host is crucial to develop strategies to control cattle colonization. PMID:23624795

Etcheverria, Analia Ines; Padola, Nora Lia

2013-01-01

374

Gene Therapy and Targeted Toxins for Glioma  

PubMed Central

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

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

2011-01-01

375

Gene Therapy and Targeted Toxins for Glioma  

PubMed Central

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

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

2006-01-01

376

Mass spectrometric detection of protein-based toxins.  

PubMed

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

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

2013-09-01

377

Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.  

PubMed

Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi alpha-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea and pseudomembraneous colitis. Lethal toxin is involved in toxic shock syndrome after abortion and alpha-toxin in gas gangrene development. CGTs enter cells via receptor-mediated endocytosis and require an acidified endosome for translocation of the catalytic domain into the cytosol. Here we studied the endocytic processes that mediate cell internalization of the CGTs. Intoxication of cells was monitored by analyzing cell morphology, status of Rac glucosylation in cell lysates and transepithelial resistance of cell monolayers. We found that the intoxication of cultured cells by CGTs was strongly delayed when cells were preincubated with dynasore, a cell-permeable inhibitor of dynamin, or chlorpromazine, an inhibitor of the clathrin-dependent endocytic pathway. Additional evidence about the role of clathrin in the uptake of the prototypical CGT family member toxin B was achieved by expression of a dominant-negative inhibitor of the clathrin-mediated endocytosis (Eps15 DN) or by siRNA against the clathrin heavy chain. Accordingly, cells that expressed dominant-negative caveolin-1 were not protected from toxin B-induced cell rounding. In addition, lipid rafts impairment by exogenous depletion of sphingomyelin did not decelerate intoxication of HeLa cells by CGTs. Taken together, our data indicate that the endocytic uptake of the CGTs involves a dynamin-dependent process that is mainly governed by clathrin. PMID:20498856

Papatheodorou, Panagiotis; Zamboglou, Constantinos; Genisyuerek, Selda; Guttenberg, Gregor; Aktories, Klaus

2010-01-01

378

Characterization of toxin plasmids in Clostridium perfringens type C isolates.  

PubMed

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

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

2010-11-01

379

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

PubMed Central

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

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

1985-01-01

380

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

PubMed Central

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

Hensler, T; Koller, M; Geoffroy, C; Alouf, J E; Konig, W

1993-01-01

381

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

PubMed Central

Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the SpiderP website. PMID:23894279

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

2013-01-01

382

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

PubMed

Paralytic shellfish poisoning (PSP) is one of the most lethal biotoxin-induced diseases worldwide, which may pose serious public health threat and potential devastating economic damage on fisheries industry in the affected region(s). To prevent the importation of PSP contaminated shellfish to a community, detailed documentation on the supply chain and routine surveillance systems are, in principle, crucial measures to protect people from this intoxication. However, difficulties have always been encountered on the traceability of the source/origin of contaminated shellfish. In the present study, we reported the potential application of PSP-toxins profiles with similarity analysis that can be used to identify epidemiological linkage between shellfish samples collected from markets and patients during a PSP outbreak. PSP-toxins were identified and quantified by ion-pair chromatographic separation followed by post-column oxidation to fluorescent imino purine derivatives. Samples from a PSP incident and other surveillance samples collected in our past 7-year record were also compared for their similarity in PSP-toxins profiles patterns. Molar distributions (nmol%) of 10 PSP-toxins were analyzed by Unweighted Pair Group Method with Arithmetric averages (UPGMA). Three prominent clusters emerged with similarity levels reaching over 80% for each, suggesting that each group of samples probably originated from a same source/batch. The PSP-toxins profiles and toxicities determined from surveillance samples could provide premonitory clues on the occurrences of PSP incident and outbreak with corresponding toxin profiles in the later time. Due to species-specific characteristics of PSP-toxins composition and profile in shellfish under varieties of environmental and physiological conditions, PSP-toxins profile can be a specific and useful biochemical indicator for tracing PSP contaminated shellfish provided that spatio-temporal occurrence patterns of toxins profiles are available in a databank for inter-laboratory comparison and standardized methodologies such as consentaneous toxins extraction and identification criteria are used for analysis and comparison. PMID:21777914

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

2011-11-01

383

Antimicrobial resistance and production of toxins in Escherichia coli strains from wild ruminants and the alpine marmot.  

PubMed

Escherichia coli strains isolated from 81 fecal samples from red deer (Cervus elaphus), roe deer (Capreoulus capreoulus), chamois (Rupicapra rupicapra) and alpine marmot (Marmota marmota) living in the Stelvio National Park, Italy, were examined for antimicrobial resistance and production of toxic factors. Direct plating of specimens on media containing antimicrobial drugs allowed us to isolate resistant strains of E. coli from 10 of 59 (17%) specimens examined by this technique. Nine of 31 specimens from red deer (29%) contained resistant strains. Different animals were likely colonized by the same resistant strain of E. coli. Conjugative R plasmids were found in four strains isolated from the marmot, roe deer and chamois. A strain from red deer produced heat-stable enterotoxin and another strain produced both hemolysin and cytotoxic necrotizing factor. A marmot isolate produced hemolysin alone. No strains were found to produce heat-labile enterotoxin or verotoxins. PMID:2067054

Caprioli, A; Donelli, G; Falbo, V; Passi, C; Pagano, A; Mantovani, A

1991-04-01

384

Stabilization of labile organic C along a chronosequence of soil development: mineralogical vs. biological controls  

NASA Astrophysics Data System (ADS)

Soil organic matter (SOM) represents an important reservoir for carbon (C), nitrogen (N), and other essential nutrients. Consequently, variation in SOM turnover rates regulates resource availability for soil microbial activity and plant growth. Long-term SOM stabilization generally involves restricted microbial access to SOM through a variety of processes including complexation with soil minerals. These organo-mineral interactions are influenced by mineral composition and texture, often related to soil age. Soil microorganisms also influence the stabilization of C inputs to the pedosphere through the production of refractory residues controlled in part by C allocation patterns during metabolism. In this study we examined, simultaneously, the contribution of these two C stabilizing mechanisms by ‘tracing’ the fate of two 13C-labeled substrates (glucose and p-hydroxybenzoic acid) along a 1600Kya chronosequence of soil development along the Cowlitz River in southwest Washington. Our objective was to evaluate the relationship between mineralogical and biological controls over C sequestration in soils. Mineralogical analyses were done using the selective dissolutions ammonium oxalate (AOD), and dithionite-citrate extraction (CBD). In this cool, humid environment, intermediate aged soils derived from the late Wisconsin Evans Creek drift (24ka) had the highest AOD extractable Al, Fe, and Si, indicating a higher concentration of poorly crystalline minerals relative to other terraces. Correspondingly, CBD extractable Fe increases with soil age, further supporting the idea that crystalline iron oxides are also more prevalent with weathering. Turnover of both 13C-labeled substrates was rapid (< 12.5 hrs) However, the proportion of substrate mineralized to CO2 varied among terraces. Mineralization to CO2 was significantly lower at 24ka than that for the other three age classes (0.25k, 220k, and 1,600k years bp), corresponding to higher recovery of 13C in bulk soil for this age class. In similar studies, soils containing a higher proportion of poorly crystalline minerals typically have a higher degree of hydration, surface area, and variable charge, which can increase microbial yield, reducing the amount of CO2 produced per unit biomass and increasing potential for soil C sequestration. Additionally, total flux of 13CO2 was significantly higher and recovery of 13C in microbial pools trended lower for the phenolic than for glucose for all soils types excluding the 24ka terrace. The broader implication, which may warrant consideration in models of terrestrial C flux, is that altering the constituency of labile C inputs to these soil environments could similarly influence the degree to which C is stabilized in soil mineral assemblages.

McFarland, J. W.; Waldrop, M. P.; Strawn, D.; Harden, J. W.

2010-12-01

385

Molybdenum(VI) speciation in sulfidic waters:. Stability and lability of thiomolybdates  

NASA Astrophysics Data System (ADS)

Molybdenum in sedimentary rocks and sediments has evoked interest as a paleo-environmental indicator of reducing conditions. This application demands better understanding of Mo deposition mechanisms and in turn, requires improved knowledge of Mo speciation in anaerobic natural waters. In sulfidic solution, molybdate undergoes sulfidation in four steps that conserve MoVI and lead to tetrathiomolybdate: MoOxS4-x2- + H2S(aq) ? MoOx-1S5-x2- + H2O(l), 1 ? x ? 4. Equilibrium constants (K(4-x)(5-x)) and rate constants (k(4-x)(5-x)) have been measured by UV-visible spectroscopy. At 25°C, I = 0.8-2.2 M, log K01 = 5.19 ± 0.03, log K12 = 4.80 ± 0.12, log K23 = 5.00 ± 0.13, log K34 = 4.88 ± 0.28. The monothio to trithio-intermediates have negligible stability fields. If H2S(aq) increases slowly enough to maintain near-equilibrium conditions, a sharp switch will occur from MoO42- to MoS42- at ?11 ?M H2S(aq) (298 K, 1 atm). Sulfide actuation of the switch depends on aH2S4, so a ?3-fold change in aH2S produces a ?100-fold change in MoO42-/MoS42-. Conversion of the predominant anion from a hard to a soft base alters Mo’s geochemical behavior, increasing its susceptibility to scavenging. Because each successive sulfidation reaction is ?1 order of magnitude slower than the previous one, dithio- ? trithio- and trithio- ? tetrathiomolybdate equilibria might not be achieved in seasonally or intermittently sulfidic waters. In such environments, unstable mixtures of intermediate thiomolybdates can predominate, contradicting thermodynamic predictions. The sulfidation reactions are acid catalyzed. Anoxic sediment porewaters, which are enriched relative to overlying waters in Brønsted acids, will promote conversion of molybdate to thiomolybdates. This may account for observations that Mo deposition in euxinic environments occurs often by diagenetic pathways rather than by water column scavenging. Slow hydrolysis and oxidation of MoS42- suggests that it could serve as a reservoir of fixed, but acid-labile sulfide in oxic waters.

Erickson, Britt E.; Helz, George R.

2000-04-01

386

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

PubMed Central

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

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

1982-01-01

387

Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins  

PubMed Central

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 ?-PFTs, Cyt toxin type ?-PFTs and aerolysin type ?-PFTs. Structures from each group are elucidated and discussed in relation to the latest data, respectively. PMID:25229189

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

2014-01-01

388

Toxin diversity revealed by a transcriptomic study of Ornithoctonus huwena.  

PubMed

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

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

2014-01-01

389

Structural insights into Bacillus thuringiensis Cry, Cyt and parasporin toxins.  

PubMed

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 ?-PFTs, Cyt toxin type ?-PFTs and aerolysin type ?-PFTs. Structures from each group are elucidated and discussed in relation to the latest data, respectively. PMID:25229189

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

2014-09-01

390

Identification and characterization of Clostridium sordellii toxin gene regulator.  

PubMed

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

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

2013-09-01

391

Identification and Characterization of Clostridium sordellii Toxin Gene Regulator  

PubMed Central

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

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

2013-01-01

392

Trace metals: essential nutrients or toxins  

SciTech Connect

Trace metals play important roles in biological processes, both as essential components and toxins. Monitoring body status of trace metals thus has become an important function of many clinical, industrial, and government laboratories. Deficiencies of some essential trace metals are seen occasionally, but of most importance is the area of metal toxicity resulting from environmental, occupational, accidental, or iatrogenic exposure. Major questions persist about which specimen best reflects body status, and in this regard each metal has different requirements. Blood is used most widely, urine has a few applications, and hair can be used, although external contamination is an ever-present problem. Tissue is by far the best specimen but is not easily obtained. Contamination of specimens during collection and processing must be controlled. Of the instrumental techniques available, atomic absorption spectrometry has been used most widely, particularly with electrothermal and atomization approaches.62 references.

Savory, J.; Wills, M.R. (Department of Pathology, University of Virginia, Charlottesville (United States))

1992-08-01

393

Acrylamide inhibits nerve sprouting induced by botulinum toxin type A  

PubMed Central

Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3–4 months, muscle strength usually recovers because functional recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3% acrylamide every 3 days for 21 days. Nerve sprouting appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction 1 week after intramuscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle fiber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in fiber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Additionally, the increase in tibial nerve fibers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.

Jiang, Hong; Xiang, Yi; Hu, Xingyue; Cai, Huaying

2014-01-01

394

Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin  

Microsoft Academic Search

MARTX toxins modulate the virulence of a number of Gram-negative Vibrio species. This family of toxins is defined by the presence of a cysteine protease domain (CPD), which proteolytically activates the Vibrio cholerae MARTX toxin. Although recent structural studies of the CPD have uncovered a new allosteric activation mechanism, the mechanism of CPD substrate recognition or toxin processing is unknown.

Patrick J Lupardus; Victoria E Albrow; Andrew Guzzetta; James C Powers; K Christopher Garcia; Aimee Shen; Matthew Bogyo

2009-01-01

395

New insights into the biological effects of anthrax toxins: linking cellular to organismal responses  

E-print Network

Review New insights into the biological effects of anthrax toxins: linking cellular to organismal responses Annabel Guichard a , Victor Nizet b,c , Ethan Bier a,* a Section of Cell and Developmental Biology The anthrax toxins lethal toxin (LT) and edema toxin (ET) are essential virulence factors produced by Bacillus

Nizet, Victor

396

Characterization of the Enzymatic Component of the ADP-Ribosyltransferase Toxin CDTa from Clostridium difficile  

Microsoft Academic Search

Certain strains of Clostridium difficile produce the ADP-ribosyltransferase CDT, which is a binary actin ADP-ribosylating toxin. The toxin consists of the binding component CDTb, which mediates receptor binding and cellular uptake, and the enzyme component CDTa. Here we studied the enzyme component (CDTa) of the toxin using the binding component of Clostridium perfringens iota toxin (Ib), which is interchangeable with

IRENE GULKE; GUNTHER PFEIFER; JAN LIESE; MICHAELA FRITZ; FRED HOFMANN; KLAUS AKTORIES; HOLGER BARTH

2001-01-01

397

Effects of composition of labile organic matter on biogenic production of methane in the coastal sediments of the Arabian Sea.  

PubMed

Coastal regions are potential zones for production of methane which could be governed by ecological/environmental differences or even sediment properties of a niche. In order to test the hypothesis that methanogenesis in most marine sediments could be driven more by proteins than by carbohydrates and lipid content of labile organic matter (LOM), incubation experiments were carried out with sediments from different environmental niches to measure methane production. The methane production rates were examined in relationship to the sediment biochemistry, i.e., carbohydrates, proteins, and lipids. The gas production measured by head space method ranged from 216 ng g(?-1) day(?-1) in the mangrove sediments to 3.1 ?g g(?-1) day(?-1) in the shallow Arabian Sea. LOM ranged from 1.56 to 2.85 mg g(?-1) in the shallow Arabian Sea, from 3.35 to 5.43 mg g(?-1) in the mangrove estuary, and from 0.66 to 0.70 mg g(?-1) in the sandy sediments with proteins contributing maximum to the LOM pool. Proteins influenced methane production in the clayey sediments of shallow depths of the Arabian Sea (r = 0.933, p < 0.001) and mangrove estuary (r = 0.981, p < 0.001) but in the sandy beach sediments, carbohydrates (r = 0.924, p < 0.001) governed the net methane production. The gas production was more pronounced in shallow and surface sediments and it decreased with depth apparently governed by the decrease in lability index. Thus, the lability index and protein content are important factors that determine methane production rates in these coastal ecosystems. PMID:21318266

Gonsalves, Maria-Judith; Fernandes, Christabelle E G; Fernandes, Sheryl Oliveira; Kirchman, David L; Bharathi, P A Loka

2011-11-01

398

Monitoring of (bio)available labile metal fraction in a drinking water treatment plant by diffusive gradients in thin films.  

PubMed

A performance study of diffusive gradients in thin films (DGT) and inductively coupled plasma optical emission spectrometry (ICP-OES) was applied for the monitoring of the labile fraction of metals Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn, in Sant Joan Despí Drinking Water Treatment Plant located in the South of Barcelona's Metropolitan Area (Spain). The DWTP monitoring protocol was optimized by working for 1 day of deployment (24 h) with the DGT device in contact with both treated and river water matrixes. Additionally, it was demonstrated that an increase in the deployment time of 1 week did not decrease the evaluated concentrations of the studied metals. The quality parameters of the DGT device and ICP-OES determination, such as limit of quantification, accuracy expressed as relative error (%) and reproducibility expressed as relative standard deviation, were evaluated. Good results were obtained for all the metals in ultrapure water; limits of quantification ranged from 1.5 ?g L(?-?1) for cadmium to 28 ?g L(?-?1) for zinc when deployment time of 24 h was used and from 0.2 ?g L(?-?1) for cadmium to 4 ?g L(?-?1) for zinc when this time was increased by 1 week. Accuracy and precisions lower than or equal to 10% were obtained at a parametric concentration value of the metals regulated in the European Drinking Water Guidelines (98/83/EC). DGT deployment was tested in river and treated water, and good results were obtained for Cd, Ni, Co and Zn, whereas for the other metals, a continuous control of their metallic labile fractions was monitored. Therefore, DGT device allows the continuous monitoring of the labile metal species in a drinking water treatment plant. PMID:21409356

Díaz, Alfredo; Arnedo, Rebeca; Céspedes-Sánchez, Raquel; Devesa, Ricard; Martin-Alonso, Jordi

2012-01-01

399

Impacts of Labile Organic Carbon Concentration on Organic and Inorganic Nitrogen Utilization by a Stream Biofilm Bacterial Community  

PubMed Central

In aquatic ecosystems, carbon (C) availability strongly influences nitrogen (N) dynamics. One manifestation of this linkage is the importance in the dissolved organic matter (DOM) pool of dissolved organic nitrogen (DON), which can serve as both a C and an N source, yet our knowledge of how specific properties of DOM influence N dynamics are limited. To empirically examine the impact of labile DOM on the responses of bacteria to DON and dissolved inorganic nitrogen (DIN), bacterial abundance and community composition were examined in controlled laboratory microcosms subjected to various combinations of dissolved organic carbon (DOC), DON, and DIN treatments. Bacterial communities that had colonized glass beads incubated in a stream were treated with various glucose concentrations and combinations of inorganic and organic N (derived from algal exudate, bacterial protein, and humic matter). The results revealed a strong influence of C availability on bacterial utilization of DON and DIN, with preferential uptake of DON under low C concentrations. Bacterial DON uptake was affected by the concentration and by its chemical nature (labile versus recalcitrant). Labile organic N sources (algal exudate and bacterial protein) were utilized equally well as DIN as an N source, but this was not the case for the recalcitrant humic matter DON treatment. Clear differences in bacterial community composition among treatments were observed based on terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes. C, DIN, and DON treatments likely drove changes in bacterial community composition that in turn affected the rates of DON and DIN utilization under various C concentrations. PMID:24038688

Leff, Laura G.

2013-01-01

400

Botulinum toxin A, brain and pain.  

PubMed

Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now. PMID:24915026

Matak, Ivica; Lackovi?, Zdravko

2014-01-01

401

Potentially Labile Soil Organic Matter in Erosional and Depositional Settings of an Undisturbed Zero-order Watershed  

NASA Astrophysics Data System (ADS)

In eroding slopes and depositional settings, the magnitude and significance of soil erosion induced terrestrial carbon dioxide sink is closely associated with how much of the soil organic matter is available in potentially labile form, as free or occluded light fraction (fLF and oLF, respectively) and its stability. Here we use (a) density fractionation to determine the amount of light fraction soil organic carbon (SOC), (b) solid state 13C-NMR of light fraction vs. bulk and mineral associated (dense) fraction SOC to determine chemical composition of the organic constituents, (c) incubation experiment to determine the labile fraction of bioavailable C, and (d) 14C content to determine the stability of SOC at two each eroding slope positions and depositional settings of an undisturbed eroding/depositional watershed. We found that the largest amount of light fraction was found at the top- and bottom-most topographic positions of the watershed while the midslope positions had lowest amount of fLF (profile average 4.5% of total C compared to 6% at the topmost summit site and 5.3% at the bottommost plain site) and oLF (profile average 12.7% of total C compared to 16% at the topmost summit site and 18% at the bottommost plain site). Our 13C-NMR and 14C results indicate that below the soil layer actively mixed by pocket gophers the oLF was older and more decomposed at the eroding slopes compared to the depositional settings. The oLF at the bottom of the eroding slope profiles appears to have undergone significant biochemical transformation or exists in a range of decompositional stages. In contrast, fLF buried at the depositional basins is more humified, but not necessarily older. We conclude that the effect of soil erosion and deposition on the magnitude and composition of the potentially labile SOC fraction is not straightforward and changes appreciably depending on the type of depositional basins considered. In general, our findings suggest that labile, physically-protected SOC was prevalent in the lowest lying, wet plain site, whereas SOM at the relatively sloping, and dry hollow appears to be old, and stabilized within aggregates and by chemical interactions with mineral surfaces.

Berhe, A. A.; Harden, J. W.; Torn, M. S.; Burton, S. D.; Kleber, M.; Harte, J.

2006-12-01

402

Biosecurity reference : CFR-listed agent and toxin summaries.  

SciTech Connect

This reference document provides summary information on the animal, plant, zoonotic, and human pathogens and toxins regulated and categorized by 9 CFR 331 and 7 CFR 121, 'Agricultural Bioterrorism Protection Act of 2002; Possession, Use and Transfer of Biological Agents and Toxins,' and 42 CFR 73, 'Possession, Use, and Transfer of Select Agents and Toxins.' Summary information includes, at a minimum, a description of the agent and its associated symptoms; often additional information is provided on the diagnosis, treatment, geographic distribution, transmission, control and eradication, and impacts on public health.

Barnett, Natalie Beth

2003-09-01

403

Botulinum toxin type A for the management of glabellar rhytids  

PubMed Central

There is an increasing demand for minimally-invasive cosmetic procedures to arrest the aging process. Botulinum toxin type A injections are the most commonly used nonsurgical cosmetic procedures in the United States. There has been research spanning over two decades dedicated to safety, efficacy, dosing, and complications of botulinum toxin type A. There are now two Food and Drug Administration (FDA) approved botulinum toxin type A options in the United States: Botox® and Dysport™, with new advances being made in the field. PMID:21437056

Tremaine, Anne Marie; McCullough, Jerry L

2010-01-01

404

Health Risk Assessment for Cyanobacterial Toxins in Seafood  

PubMed Central

Cyanobacteria (blue-green algae) are abundant in fresh, brackish and marine waters worldwide. When toxins produced by cyanobacteria are present in the aquatic environment, seafood harvested from these waters may present a health hazard to consumers. Toxicity hazards from seafood have been internationally recognised when the source is from marine algae (dinoflagellates and diatoms), but to date few risk assessments for cyanobacterial toxins in seafood have been presented. This paper estimates risk from seafood contaminated by cyanobacterial toxins, and provides guidelines for safe human consumption. PMID:22690165

Mulvenna, Vanora; Dale, Katie; Priestly, Brian; Mueller, Utz; Humpage, Andrew; Shaw, Glen; Allinson, Graeme; Falconer, Ian

2012-01-01

405

From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules  

PubMed Central

Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted. PMID:22069709

Nasiripourdori, Adak; Taly, Valerie; Grutter, Thomas; Taly, Antoine

2011-01-01

406

Effect of toxin A and B of Clostridium difficile on rabbit ileum and colon.  

PubMed Central

The effect of purified toxin A and partially purified toxin B on rabbit ileum and colon was investigated. Toxin A caused tissue damage which was followed by permeability changes and fluid accumulation in both tissues. Toxin A did not increase the permeability of the colon to the extent observed for ileum; secreted fluid contained less protein of plasma origin. Toxin B had no effect on either tissue. Secretory and tissue damaging properties of crude C difficile toxins were found to be due to toxin A. Images Fig. 4 Fig. 5 Fig. 6 PMID:3949240

Mitchell, T J; Ketley, J M; Haslam, S C; Stephen, J; Burdon, D W; Candy, D C; Daniel, R

1986-01-01

407

Isolation of Shiga toxin-resistant Vero cells and their use for easy identification of the toxin.  

PubMed Central

Shiga toxin-resistant Vero cells were isolated by treatment of the cells with nitrosoguanidine. These mutant cells were not affected by Shiga toxin at more than 1 microgram/ml, although the parent Vero cells were sensitive to 25 pg of the toxin per ml. Immunofluorescence studies showed that all the mutant cells had lost toxin-binding capacity. The cytotoxic activities of various bacterial cultures against the parent and mutant cells were compared. All samples from 10 strains of Shigella dysenteriae type 1 and all three strains of Escherichia coli O157:H7 tested showed cytotoxicity to the parent cells but not to the mutant cells. Samples from other organisms, such as Shigella flexneri, Shigella sonnei, Clostridium difficile, Aeromonas hydrophila, Aeromonas sobria, and other E. coli strains, either had no effect or were cytotoxic on both the parent and mutant cells. Thus, these mutant cells could be used to identify Shiga-like toxin and distinguish it from other cytotoxins. The results also suggest the presence of a receptor for Shiga-like toxin on Vero cells that is essential for expression of the cytotoxicity of Shiga toxin but is not essential for growth of Vero cells. PMID:3045003

Kongmuang, U; Honda, T; Miwatani, T

1988-01-01

408

Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved efficacy for targeting human CD25+ cells  

PubMed Central

Regulatory T cells (Treg) constitute a major inhibitory cell population which suppresses immune responses. Thus, Treg have proven to be key players in the induction of transplantation tolerance, protection from autoimmune disease and prevention of the development of effective anti-tumor immune reactions. Treg express high levels of the high affinity interleukin-2 receptor (IL-2R) consisting of IL-2R? (CD25) together with IL-2R? (CD122) and the common ?-chain (CD132). An effective reagent capable of depleting Treg in vivo would facilitate better cancer treatment and allow mechanistic studies of the role of Treg in transplantation tolerance and the development of autoimmune disease. In this study, we have developed a novel bivalent human IL-2 fusion toxin along with an Ontak®-like monovalent human IL-2 fusion toxin and compared the functional ability of these reagents in vitro. Here we show that genetically linking two human IL-2 domains in tandem, thereby generating a bivalent fusion toxin, results in significantly improved capacity in targeting human CD25+ cells in vitro. Binding analysis by flow cytometry showed that the bivalent human IL-2 fusion toxin has notably increased affinity for human CD25+ cells. In vitro functional analysis demonstrated that the bivalent isoform has an increased potency of approximately 2 logs in inhibiting cellular proliferation and protein synthesis in human CD25+ cells compared to the monovalent human IL-2 fusion toxin. Additionally, we performed two inhibition assays in order to verify that the fusion toxins target the cells specifically through binding of the human IL-2 domain of the fusion toxin to the human IL-2 receptor on the cell surface. These results demonstrated that 1) both monovalent and bivalent human IL-2 fusion toxins are capable of blocking the binding of biotinylated human IL-2 to human CD25 by flow cytometry; and 2) human IL-2 blocked the fusion toxins from inhibiting protein synthesis and cellular proliferation in vitro, thus confirming that the human IL-2 fusion toxins target the cells specifically through binding to the human IL-2 receptor. We believe that the bivalent human IL-2 fusion toxin will be a more potent, and therefore, more optimal agent than the current clinically-used monovalent fusion toxin (denileukin diftitox, Ontak®) for in vivo depletion of Treg. PMID:24462799

Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V.; Wei, Min; Madsen, Joren C.; Sachs, David H.; Huang, Christene A.; Wang, Zhirui

2014-01-01

409