Kid cleaves specific mRNAs at UUACU sites to rescue the copy number of plasmid R1

PubMed Central

Pimentel, Belén; Madine, Mark A; de la Cueva-Méndez, Guillermo

2005-01-01

Stability and copy number of extra-chromosomal elements are tightly regulated in prokaryotes and eukaryotes. Toxin Kid and antitoxin Kis are the components of the parD stability system of prokaryotic plasmid R1 and they can also function in eukaryotes. In bacteria, Kid was thought to become active only in cells that lose plasmid R1 and to cleave exclusively host mRNAs at UA(A/C/U) trinucleotide sites to eliminate plasmid-free cells. Instead, we demonstrate here that Kid becomes active in plasmid-containing cells when plasmid copy number decreases, cleaving not only host- but also a specific plasmid-encoded mRNA at the longer and more specific target sequence UUACU. This specific cleavage by Kid inhibits bacterial growth and, at the same time, helps to restore the plasmid copy number. Kid targets a plasmid RNA that encodes a repressor of the synthesis of an R1 replication protein, resulting in increased plasmid DNA replication. This mechanism resembles that employed by some human herpesviruses to regulate viral amplification during infection. PMID:16163387

Recent Developments in Antibody-Based Assays for the Detection of Bacterial Toxins

PubMed Central

Zhu, Kui; Dietrich, Richard; Didier, Andrea; Doyscher, Dominik; Märtlbauer, Erwin

2014-01-01

Considering the urgent demand for rapid and accurate determination of bacterial toxins and the recent promising developments in nanotechnology and microfluidics, this review summarizes new achievements of the past five years. Firstly, bacterial toxins will be categorized according to their antibody binding properties into low and high molecular weight compounds. Secondly, the types of antibodies and new techniques for producing antibodies are discussed, including poly- and mono-clonal antibodies, single-chain variable fragments (scFv), as well as heavy-chain and recombinant antibodies. Thirdly, the use of different nanomaterials, such as gold nanoparticles (AuNPs), magnetic nanoparticles (MNPs), quantum dots (QDs) and carbon nanomaterials (graphene and carbon nanotube), for labeling antibodies and toxins or for readout techniques will be summarized. Fourthly, microscale analysis or minimized devices, for example microfluidics or lab-on-a-chip (LOC), which have attracted increasing attention in combination with immunoassays for the robust detection or point-of-care testing (POCT), will be reviewed. Finally, some new materials and analytical strategies, which might be promising for analyzing toxins in the near future, will be shortly introduced. PMID:24732203

Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis

PubMed Central

de la Cueva-Méndez, Guillermo; Mills, Anthony D.; Clay-Farrace, Lorena; Díaz-Orejas, Ramón; Laskey, Ronald A.

2003-01-01

Plasmid R1 inhibits growth of bacteria by synthesizing an inhibitor of cell proliferation, Kid, and a neutralizing antidote, Kis, which binds tightly to the toxin. Here we report that this toxin and antidote, which have evolved to function in bacteria, also function efficiently in a wide range of eukaryotes. Kid inhibits cell proliferation in yeast, Xenopus laevis and human cells, whilst Kis protects. Moreover, we show that Kid triggers apoptosis in human cells. These effects can be regulated in vivo by modulating the relative amounts of antidote and toxin using inducible eukaryotic promoters for independent transcriptional control of their genes. These findings allow highly regulatable, selective killing of eukaryotic cells, and could be applied to eliminate cancer cells or specific cell lineages in development. PMID:12514130

A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter-kingdom effectors of Bartonella

PubMed Central

Liesch, Marius

2017-01-01

Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP) domain. Intriguingly, the FIC domain of the FicT toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal–the BID (Bep intracellular delivery) domain—similar to the Bartonella effector proteins (Beps) that are secreted into eukaryotic host cells via the host-targeting VirB T4SS. In this study, we show that the VbhT toxin is an interbacterial effector protein secreted via the conjugative Vbh T4SS that is closely related to the VirB T4SS and encoded by plasmid pVbh of B. schoenbuchensis. We therefore propose that the Vbh T4SS together with its effector VbhT represent an evolutionary missing link on a path that leads from a regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and BID domains has probably occurred independently in VbhT and the common ancestor of the Beps, suggesting parallel evolutionary paths. Moreover, several other examples of TA module toxins that are bona fide substrates of conjugative T4SS indicate that their recruitment as interbacterial effectors is prevalent and serves yet unknown biological functions in the context of bacterial conjugation. We propose that the adaptation for interbacterial transfer favors the exaptation of FicT and other TA module toxins as inter-kingdom effectors and may thus constitute an important stepping stone in the

A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter-kingdom effectors of Bartonella.

PubMed

Harms, Alexander; Liesch, Marius; Körner, Jonas; Québatte, Maxime; Engel, Philipp; Dehio, Christoph

2017-10-01

Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP) domain. Intriguingly, the FIC domain of the FicT toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal-the BID (Bep intracellular delivery) domain-similar to the Bartonella effector proteins (Beps) that are secreted into eukaryotic host cells via the host-targeting VirB T4SS. In this study, we show that the VbhT toxin is an interbacterial effector protein secreted via the conjugative Vbh T4SS that is closely related to the VirB T4SS and encoded by plasmid pVbh of B. schoenbuchensis. We therefore propose that the Vbh T4SS together with its effector VbhT represent an evolutionary missing link on a path that leads from a regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and BID domains has probably occurred independently in VbhT and the common ancestor of the Beps, suggesting parallel evolutionary paths. Moreover, several other examples of TA module toxins that are bona fide substrates of conjugative T4SS indicate that their recruitment as interbacterial effectors is prevalent and serves yet unknown biological functions in the context of bacterial conjugation. We propose that the adaptation for interbacterial transfer favors the exaptation of FicT and other TA module toxins as inter-kingdom effectors and may thus constitute an important stepping stone in the

Fragments of the bacterial toxin microcin B17 as gyrase poisons.

PubMed

Collin, Frédéric; Thompson, Robert E; Jolliffe, Katrina A; Payne, Richard J; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex.

Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

USDA-ARS?s Scientific Manuscript database

Disease pathways form overlapping networks, and hub proteins represent attractive targets for broad-spectrum drugs. Using bacterial toxins as a proof of concept, we describe a new approach of discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pa...

Fragments of the Bacterial Toxin Microcin B17 as Gyrase Poisons

PubMed Central

Collin, Frédéric; Thompson, Robert E.; Jolliffe, Katrina A.; Payne, Richard J.; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex. PMID:23593482

The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains.

PubMed

Beer, Lara-Antonia; Tatge, Helma; Schneider, Carmen; Ruschig, Maximilian; Hust, Michael; Barton, Jessica; Thiemann, Stefan; Fühner, Viola; Russo, Giulio; Gerhard, Ralf

2018-06-01

Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum , the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile . All these binary toxins have ADP-ribosyltransferases (ADPRT) as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin was intensively described as a tool for intracellular delivery of allogenic ADPRTs. Here, we firstly describe the binary toxin CDT from C. difficile as an effective tool for heterologous intracellular delivery. Even 60 kDa glucosyltransferase domains of large clostridial glucosyltransferases can be delivered into cells. The glucosyltransferase domains of five tested large clostridial glucosyltransferases were successfully introduced into cells as chimeric fusions to the CDTa adapter domain (CDTaN). Cell uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N -terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains.

Steady-state levels of G-protein beta-subunit expression are regulated by treatment of cells with bacterial toxins

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

Watkins, D.C.; Northup, J.K.; Malbon, C.C.

1987-05-01

Cultures of 3T3-L1 cells were incubated with either 10 ng/ml cholera toxin or 10 ng/ml pertussis toxin from 4 days prior to the initiation of differentiation and throughout the subsequent incubation. Toxin concentrations were sufficient to completely prevent the labelling of alpha-subunits with (/sup 32/P)NAD/sup +/ and pertussis toxin and to prevent by more than 90% the labelling with (/sup 32/P)NAD/sup +/ and cholera toxin in membranes prepared from these cells. Neither toxin prevented the differentiation to the adipocyte phenotype. Neither toxin prevented the increases in the relative amounts of G-proteins which occur upon differentiation. Both toxins dramatically decreased themore » amount of beta-subunits. As measured by quantitative immunoblotting with antisera specific for both the 35 kDa and 36 kDa beta-subunits, levels of beta-subunit were decreased by more than 50% of steady-state level of control cells. Thus, bacterial toxins which modifies G-protein alpha-subunits are capable of modulating the levels of beta-subunits in vivo. The basis for the regulation of G-protein subunit expression by bacterial toxins is under study.« less

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity.

PubMed

Kalb, Suzanne R; Boyer, Anne E; Barr, John R

2015-08-31

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A-G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin.

Antibody-based bacterial toxin detection

NASA Astrophysics Data System (ADS)

Menking, Darrell E.; Heitz, Jonathon M.; Anis, Nabil A.; Thompson, Roy G.

1994-03-01

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

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity

PubMed Central

Kalb, Suzanne R.; Boyer, Anne E.; Barr, John R.

2015-01-01

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A–G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin. PMID:26404376

Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes.

PubMed

LaRocca, Timothy J; Stivison, Elizabeth A; Hod, Eldad A; Spitalnik, Steven L; Cowan, Peter J; Randis, Tara M; Ratner, Adam J

2014-08-26

A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. In this work, we provide the first description of a new form of programmed cell death in erythrocytes (RBCs) that occurs as a consequence of cellular attack by human-specific bacterial toxins. By defining a new RBC

A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

PubMed

Tang, Cheng; Zhou, Xi; Nguyen, Phuong Tran; Zhang, Yunxiao; Hu, Zhaotun; Zhang, Changxin; Yarov-Yarovoy, Vladimir; DeCaen, Paul G; Liang, Songping; Liu, Zhonghua

2017-07-01

Voltage-gated sodium channels (Na V s) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na V s have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na V s. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic Na V s Ns V Ba (nonselective voltage-gated Bacillus alcalophilus ) and NaChBac (bacterial sodium channel from Bacillus halodurans ) (IC 50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns V Ba, whereas the local anesthetic drug lidocaine was shown to antagonize Ns V Ba without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns V Ba, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of Ns V Ba in one of the deactivated states. In mammalian Na V s, JZTx-27 preferably inhibited the inactivation of Na V 1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na V s. More important, we proposed that JZTx-27 stabilized the Ns V Ba VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na V s.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. © FASEB.

Bacterial Signaling to the Nervous System through Toxins and Metabolites.

PubMed

Yang, Nicole J; Chiu, Isaac M

2017-03-10

Mammalian hosts interface intimately with commensal and pathogenic bacteria. It is increasingly clear that molecular interactions between the nervous system and microbes contribute to health and disease. Both commensal and pathogenic bacteria are capable of producing molecules that act on neurons and affect essential aspects of host physiology. Here we highlight several classes of physiologically important molecular interactions that occur between bacteria and the nervous system. First, clostridial neurotoxins block neurotransmission to or from neurons by targeting the SNARE complex, causing the characteristic paralyses of botulism and tetanus during bacterial infection. Second, peripheral sensory neurons-olfactory chemosensory neurons and nociceptor sensory neurons-detect bacterial toxins, formyl peptides, and lipopolysaccharides through distinct molecular mechanisms to elicit smell and pain. Bacteria also damage the central nervous system through toxins that target the brain during infection. Finally, the gut microbiota produces molecules that act on enteric neurons to influence gastrointestinal motility, and metabolites that stimulate the "gut-brain axis" to alter neural circuits, autonomic function, and higher-order brain function and behavior. Furthering the mechanistic and molecular understanding of how bacteria affect the nervous system may uncover potential strategies for modulating neural function and treating neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

The DinJ/RelE Toxin-Antitoxin System Suppresses Bacterial Proliferation and Virulence of Xylella fastidiosa in Grapevine.

PubMed

Burbank, Lindsey P; Stenger, Drake C

2017-04-01

Xylella fastidiosa, the causal agent of Pierce's disease of grapes, is a slow-growing, xylem-limited, bacterial pathogen. Disease progression is characterized by systemic spread of the bacterium through xylem vessel networks, causing leaf-scorching symptoms, senescence, and vine decline. It appears to be advantageous to this pathogen to avoid excessive blockage of xylem vessels, because living bacterial cells are generally found in plant tissue with low bacterial cell density and minimal scorching symptoms. The DinJ/RelE toxin-antitoxin system is characterized here for a role in controlling bacterial proliferation and population size during plant colonization. The DinJ/RelE locus is transcribed from two separate promoters, allowing for coexpression of antitoxin DinJ with endoribonuclease toxin RelE, in addition to independent expression of RelE. The ratio of antitoxin/toxin expressed is dependent on bacterial growth conditions, with lower amounts of antitoxin present under conditions designed to mimic grapevine xylem sap. A knockout mutant of DinJ/RelE exhibits a hypervirulent phenotype, with higher bacterial populations and increased symptom development and plant decline. It is likely that DinJ/RelE acts to prevent excessive population growth, contributing to the ability of the pathogen to spread systemically without completely blocking the xylem vessels and increasing probability of acquisition by the insect vector.

Bacterial and fungal keratitis in Upper Egypt: In vitro screening of enzymes, toxins and antifungal activity

PubMed Central

Gharamah, Abdullah A; Moharram, Ahmed M; Ismail, Mady A; AL-Hussaini, Ashraf K

2014-01-01

Purpose: This work was conducted to study the ability of bacterial and fungal isolates from keratitis cases in Upper Egypt to produce enzymes, toxins, and to test the isolated fungal species sensitivity to some therapeutic agents. Materials and Methods: One hundred and fifteen patients clinically diagnosed to have microbial keratitis were investigated. From these cases, 37 bacterial isolates and 25 fungal isolates were screened for their ability to produce extra-cellular enzymes in solid media. In addition, the ability of fungal isolates to produce mycotoxins and their sensitivity to 4 antifungal agents were tested. Results: Protease, lipase, hemolysins, urease, phosphatase, and catalase were detected respectively in 48.65%, 37.84%, 59.46%, 43.24%, 67.57%, and 100% out of 37 bacterial isolates tested. Out of 25 fungal isolates tested during the present study, 80% were positive for protease, 84% for lipase and urease, 28% for blood hemolysis, and 100% for phosphatase and catalase enzymes. Thirteen fungal isolates were able to produce detectable amounts of 7 mycotoxins in culture medium (aflatoxins (B1, B2, G1, and G2), sterigmatocystin, fumagillin, diacetoxyscirpenol, zearalenone, T-2 toxin, and trichodermin). Among the antifungal agents tested in this study, terbinafine showed the highest effect against most isolates in vitro. Conclusion: In conclusion, the ability of bacterial and fungal isolates to produce extracellular enzymes and toxins may be aid in the invasion and destruction of eye tissues, which, in turn, lead to vision loss. PMID:24008795

The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily

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

Batot, Gaëlle; Michalska, Karolina; Ekberg, Greg

Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiI(Ykris) complex from Yersinia kris-tensenii ATCC 33638. CdiA-CTYkris adopts the same fold as angiogenin and other RNase A paralogs, but the toxin does not share sequence similarity with these nucleases and lacks the characteristic disulfide bonds of the superfamily. Consistentmore » with the structural homology, CdiA-CTYkris has potent RNase activity in vitro and in vivo. Structure-guided mutagenesis reveals that His175, Arg186, Thr276 and Tyr278 contribute to CdiA-CTYkris activity, suggesting that these residues participate in substrate binding and/or catalysis. CdiI(Ykris) binds directly over the putative active site and likely neutralizes toxicity by blocking access to RNA substrates. Significantly, CdiA-CTYkris is the first non-vertebrate protein found to possess the RNase A superfamily fold, and homologs of this toxin are associated with secretion systems in many Gram-negative and Gram-positive bacteria. These observations suggest that RNase Alike toxins are commonly deployed in inter-bacterial competition.« less

Quantitative analysis of fecal flora in goat kids with and without floppy kid syndrome.

PubMed

Bleul, U; Fassbind, N; Ghielmetti, G; Zoller, D; Liesegang, A; Hässig, M; Wittenbrink, M M; Prohaska, S

2013-01-01

Floppy kid syndrome (FKS) affects goat kids in the first month of life and is associated with high morbidity and mortality rates. The condition is characterized by neurological signs that can be ascribed to increased plasma D-lactate concentrations. The source of D-lactate has not been identified conclusively, but D-lactate-producing bacteria in the large intestine are thought to be involved. To determine the number of colony-forming unit (CFUs) of certain groups of bacteria in the feces of kids with and without FKS. Nineteen goat kids with clinical signs of FKS, acidemia (pH ≤ 7.2), and plasma D-lactate concentration >7 mM and 15 healthy goat kids without acidemia (pH >7.2) and D-lactate concentration <1 mM. In this case-control study, the goat kids were examined clinically and blood was collected to measure D-lactate concentration, blood gases, and acid-base parameters. Fecal samples were collected and the total aerobic bacterial count and CFU counts of coliforms, enterococci, staphylococci, streptococci, lactobacilli, and clostridia were determined using the surface plating method. Goat kids with FKS had a mean plasma D-lactate concentration of 10.9 ± 3.7 mM compared with 0.3 ± 0.9 mM in healthy kids, and significantly greater CFU counts for enterococci, streptococci, staphylococci, and lactobacilli than healthy kids. The groups of bacteria present in greater numbers in the feces of goat kids with FKS include several D-lactate-producing species, which makes dysbacteriosis a likely cause of the increased plasma D-lactate concentration in FKS. Copyright © 2013 by the American College of Veterinary Internal Medicine.

The ARTT motif and a unified structural understanding of substraterecognition in ADP ribosylating bacterial toxins and eukaryotic ADPribosyltransferases

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

Han, S.; Tainer, J.A.

2001-08-01

ADP-ribosylation is a widely occurring and biologically critical covalent chemical modification process in pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell division. The reaction is catalyzed by ADP-ribosyltransferases, which transfer the ADP-ribose moiety of NAD to a target protein with nicotinamide release. A family of bacterial toxins and eukaryotic enzymes has been termed the mono-ADP-ribosyltransferases, in distinction to the poly-ADP-ribosyltransferases, which catalyze the addition of multiple ADP-ribose groups to the carboxyl terminus of eukaryotic nucleoproteins. Despite the limited primary sequence homology among the different ADP-ribosyltransferases, a central cleft bearing NAD-binding pocket formed by the two perpendicular b-sheet core hasmore » been remarkably conserved between bacterial toxins and eukaryotic mono- and poly-ADP-ribosyltransferases. The majority of bacterial toxins and eukaryotic mono-ADP-ribosyltransferases are characterized by conserved His and catalytic Glu residues. In contrast, Diphtheria toxin, Pseudomonas exotoxin A, and eukaryotic poly-ADP-ribosyltransferases are characterized by conserved Arg and catalytic Glu residues. The NAD-binding core of a binary toxin and a C3-like toxin family identified an ARTT motif (ADP-ribosylating turn-turn motif) that is implicated in substrate specificity and recognition by structural and mutagenic studies. Here we apply structure-based sequence alignment and comparative structural analyses of all known structures of ADP-ribosyltransfeases to suggest that this ARTT motif is functionally important in many ADP-ribosylating enzymes that bear a NAD binding cleft as characterized by conserved Arg and catalytic Glu residues. Overall, structure-based sequence analysis reveals common core structures and conserved active sites of ADP-ribosyltransferases to support similar NAD binding mechanisms but differing mechanisms of target protein binding via sequence variations within

Cytotoxicity of bacterial-derived toxins to immortal lung epithelial and macrophage cells.

PubMed

Peterson, Dianne E; Collier, Jayne M; Katterman, Matthew E; Turner, Rachael A; Riley, Mark R

2010-03-01

Health risks associated with inhalation and deposition of biological materials have been a topic of great concern due to highly publicized cases of inhalation anthrax, of new regulations on the release of particulate matter, and to increased concerns on the hazards of indoor air pollution. Here, we present an evaluation of the sensitivity of two immortal cell lines (A549, human lung carcinoma epithelia) and NR8383 (rat alveolar macrophages) to a variety of bacterial-derived inhalation hazards and simulants including etoposide, gliotoxin, streptolysin O, and warfarin. The cell response is evaluated through quantification of changes in mitochondrial succinate dehydrogenase activity, release of lactate dehydrogenase, initiation of apoptosis, and through changes in morphology as determined by visible light microscopy and scanning electron microscopy. These cells display dose-response relations to each toxin, except for triton which has a step change response. The first observable responses of the epithelial cells to these compounds are changes in metabolism for one toxin (warfarin) and alterations in membrane permeability for another (gliotoxin). The other four toxins display a similar time course in response as gauged by changes in metabolism and loss of membrane integrity. Macrophages are more sensitive to most toxins; however, they display a lower level of stability. This information can be used in the design of cell-based sensors responding to these and similar hazards.

Transmammary transfer of toxicity to nursing kids from Isocoma pluriflora (rayless goldenrod) dosed to lactating goats.

PubMed

Pfister, James A; Stegelmeier, Bryan L; Lee, Stephen T; Davis, T Zane; Green, Ben T

2018-05-01

Rayless goldenrod (RG; Isocoma pluriflora) poisons livestock in the southwestern U.S., west Texas, and northern Mexico. The putative toxin(s) have historically been thought to be benzofuran ketones. Goats have been used successfully as a model of RG poisoning. The transmammary transfer of toxicity to offspring from lactating goats has not been studied, thus the objective of this study was to determine if nursing kids would become poisoned via mother's milk when the dams were dosed with RG. Twelve lactating goats (6 controls and 6 treated; all with twin kids) were dosed via oral gavage with alfalfa or rayless goldenrod at 2% of BW per day for 14 days. Two kids showed overt clinical signs near the end of the study; however, no dams showed clinical signs, and none developed exercise intolerance or muscle weakness. After day 11 of treatment, the RG kids showed increased (P < 0.05) serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine kinase (CK) activities until exposure to the plant via mothers' milk ended. Serum CK activity of kids declined rapidly over 7 days after transmammary exposure ended. Histopathology revealed that one kid had extensive myonecrosis that involved both myocardium and skeletal muscles. The other kids from RG-treated does had minimal myocyte degeneration and necrosis characterized by individual myofiber swelling, hypereosinophilia and loss of striation. Benzofuran ketones were not detected in the milk of lactating goats; further, dosing with RG did not alter milk composition. In summary, milk ingestion from does dosed with >300 mg/kg BW of benzofuran ketones from RG over 14 days increased mean CK concentrations in treated kids compared to controls; however kids rapidly recovered when exposure ended. Additional work is needed to better define benzofuran ketone metabolism, toxicity, and animal susceptibility. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-12-01

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

Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells.

PubMed

Ernst, Katharina; Schmid, Johannes; Beck, Matthias; Hägele, Marlen; Hohwieler, Meike; Hauff, Patricia; Ückert, Anna Katharina; Anastasia, Anna; Fauler, Michael; Jank, Thomas; Aktories, Klaus; Popoff, Michel R; Schiene-Fischer, Cordelia; Kleger, Alexander; Müller, Martin; Frick, Manfred; Barth, Holger

2017-06-02

Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C. difficile toxin CDT are composed of a transport (B) and a separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells and subsequently transport of the A-components from acidic endosomes into the cytosol, where the latter ADP-ribosylate G-actin resulting in cell rounding and cell death causing clinical symptoms. Protein folding enzymes, including Hsp90 and peptidyl-prolyl cis/trans isomerases facilitate transport of the A-components across endosomal membranes. Here, we identified Hsp70 as a novel host cell factor specifically interacting with A-components of C2, iota and CDT toxins to facilitate their transport into the cell cytosol. Pharmacological Hsp70-inhibition specifically prevented pH-dependent trans-membrane transport of A-components into the cytosol thereby protecting living cells and stem cell-derived human miniguts from intoxication. Thus, Hsp70-inhibition might lead to development of novel therapeutic strategies to treat diseases associated with bacterial ADP-ribosylating toxins.

The ng_ζ1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis.

PubMed

Rocker, Andrea; Peschke, Madeleine; Kittilä, Tiia; Sakson, Roman; Brieke, Clara; Meinhart, Anton

2018-04-27

Bacterial toxin-antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin-antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.

Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules.

PubMed

López-Villarejo, Juan; Diago-Navarro, Elizabeth; Hernández-Arriaga, Ana María; Díaz-Orejas, Ramón

2012-03-01

The coupling between the replication and parD (kis, kid) maintenance modules of R1 has been revisited here by the isolation of a significant collection of conditional replication mutants in the pKN1562 mini-R1 plasmid, and in its derivative, pJLV01, specifically affected in the RNase activity of the Kid toxin. This new analysis aims to identify key factors in this coupling. For this purpose we have quantified and characterized the restriction introduced by parD to isolate conditional replication mutants of this plasmid, a signature of the modular coupling. This restriction depends on the RNase activity of the Kid toxin and it is relieved by either over-expression of the Kis antitoxin or by preventing its degradation by Lon and ClpAP proteases. Based on these data and on the correlation between copy numbers and parD transcriptional levels obtained in the different mutants, it is proposed that a reduction of Kis antitoxin levels in response to inefficient plasmid replication is the key factor for coupling plasmid replication and parD modules. Copyright © 2012 Elsevier Inc. All rights reserved.

[Alteration of cholera toxin biosynthesis in Vibrio cholerae 01 as a result of temperate phage 139 integration into bacterial chromosome].

PubMed

Eroshenko, G A; Smirnova, N I

2002-01-01

Infection of V. cholerae 01 (classical and eltor biovars) cells with the temperate cholera phage 139 derived from V. cholerae serogroup 0139 followed by integration of the phage genome into the bacterial chromosome significantly increased the production of cholera toxin, the main virulence factor. The level of toxin biosynthesis in the lysogenic V. cholerae classical strain increased 3-fold and that in V. eltor thirty times in comparison with the parental strains. Increased production of cholera toxin was not associated with an increase in the number of copies of genes involved in its biosynthesis but seemed to be due to changes in toxinogenesis regulation.

Colibactin: More Than a New Bacterial Toxin.

PubMed

Faïs, Tiphanie; Delmas, Julien; Barnich, Nicolas; Bonnet, Richard; Dalmasso, Guillaume

2018-04-10

Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae ) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure.

Colibactin: More Than a New Bacterial Toxin

PubMed Central

Faïs, Tiphanie; Delmas, Julien; Barnich, Nicolas; Bonnet, Richard

2018-01-01

Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure. PMID:29642622

Nanoparticle-detained toxins for safe and effective vaccination

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Improved purification process for cholera toxin and its application to the quantification of residual toxin in cholera vaccines.

PubMed

Jang, Hyun; Kim, Hyo Seung; Kim, Jeong Ah; Seo, Jin Ho; Carbis, Rodney

2009-01-01

A simplified method for the purification of cholera toxin was developed. The 569B strain of Vibrio cholerae, a recognized hyper-producer of cholera toxin, was propagated in a bioreactor under conditions that promote the production of the toxin. The toxin was separated from the bacterial cells using 0.2-microm crossflow microfiltration, the clarified toxin was passed through the membrane into the permeate, and the bacterial cells were retained in the retentate. The 0.2-microm permeate was then concentrated 3-fold and diafiltered against 10 mM phosphate buffer, pH 7.6, using 30-kDa crossflow ultrafiltration. The concentrated toxin was loaded onto a cation exchange column, the toxin was bound to the column, and most of the impurities were passed unimpeded through the column. The toxin was eluted with a salt gradient of phosphate buffer, pH7.0, containing 1.0M NaCl. The peak containing the toxin was assayed for cholera toxin and protein and the purity was determined to be 92%. The toxin peak had a low endotoxin level of 3.1 EU/microg of toxin. The purified toxin was used to prepare antiserum against whole toxin, which was used in a G(M1) ganglioside-binding ELISA to determine residual levels of toxin in an oral inactivated whole-cell cholera vaccine. The G(M1) ganglioside-binding ELISA was shown to be very sensitive and capable of detecting as little as 1 ng/ml of cholera toxin.

Evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems

PubMed Central

Iyer, Lakshminarayan M.; Zhang, Dapeng; Rogozin, Igor B.; Aravind, L.

2011-01-01

The deaminase-like fold includes, in addition to nucleic acid/nucleotide deaminases, several catalytic domains such as the JAB domain, and others involved in nucleotide and ADP-ribose metabolism. Using sensitive sequence and structural comparison methods, we develop a comprehensive natural classification of the deaminase-like fold and show that its ancestral version was likely to operate on nucleotides or nucleic acids. Consequently, we present evidence that a specific group of JAB domains are likely to possess a DNA repair function, distinct from the previously known deubiquitinating peptidase activity. We also identified numerous previously unknown clades of nucleic acid deaminases. Using inference based on contextual information, we suggest that most of these clades are toxin domains of two distinct classes of bacterial toxin systems, namely polymorphic toxins implicated in bacterial interstrain competition and those that target distantly related cells. Genome context information suggests that these toxins might be delivered via diverse secretory systems, such as Type V, Type VI, PVC and a novel PrsW-like intramembrane peptidase-dependent mechanism. We propose that certain deaminase toxins might be deployed by diverse extracellular and intracellular pathogens as also endosymbionts as effectors targeting nucleic acids of host cells. Our analysis suggests that these toxin deaminases have been acquired by eukaryotes on several independent occasions and recruited as organellar or nucleo-cytoplasmic RNA modifiers, operating on tRNAs, mRNAs and short non-coding RNAs, and also as mutators of hyper-variable genes, viruses and selfish elements. This scenario potentially explains the origin of mutagenic AID/APOBEC-like deaminases, including novel versions from Caenorhabditis, Nematostella and diverse algae and a large class of fast-evolving fungal deaminases. These observations greatly expand the distribution of possible unidentified mutagenic processes catalyzed by

Coupling between the basic replicon and the Kis-Kid maintenance system of plasmid R1: modulation by Kis antitoxin levels and involvement in control of plasmid replication.

PubMed

López-Villarejo, Juan; Lobato-Márquez, Damián; Díaz-Orejas, Ramón

2015-02-05

kis-kid, the auxiliary maintenance system of plasmid R1 and copB, the auxiliary copy number control gene of this plasmid, contribute to increase plasmid replication efficiency in cells with lower than average copy number. It is thought that Kis antitoxin levels decrease in these cells and that this acts as the switch that activates the Kid toxin; activated Kid toxin reduces copB-mRNA levels and this increases RepA levels that increases plasmid copy number. In support of this model we now report that: (i) the Kis antitoxin levels do decrease in cells containing a mini-R1 plasmid carrying a repA mutation that reduces plasmid copy number; (ii) kid-dependent replication rescue is abolished in cells in which the Kis antitoxin levels or the CopB levels are increased. Unexpectedly we found that this coordination significantly increases both the copy number of the repA mutant and of the wt mini-R1 plasmid. This indicates that the coordination between plasmid replication functions and kis-kid system contributes significantly to control plasmid R1 replication.

Coupling between the Basic Replicon and the Kis-Kid Maintenance System of Plasmid R1: Modulation by Kis Antitoxin Levels and Involvement in Control of Plasmid Replication

PubMed Central

López-Villarejo, Juan; Lobato-Márquez, Damián; Díaz-Orejas, Ramón

2015-01-01

kis-kid, the auxiliary maintenance system of plasmid R1 and copB, the auxiliary copy number control gene of this plasmid, contribute to increase plasmid replication efficiency in cells with lower than average copy number. It is thought that Kis antitoxin levels decrease in these cells and that this acts as the switch that activates the Kid toxin; activated Kid toxin reduces copB-mRNA levels and this increases RepA levels that increases plasmid copy number. In support of this model we now report that: (i) the Kis antitoxin levels do decrease in cells containing a mini-R1 plasmid carrying a repA mutation that reduces plasmid copy number; (ii) kid-dependent replication rescue is abolished in cells in which the Kis antitoxin levels or the CopB levels are increased. Unexpectedly we found that this coordination significantly increases both the copy number of the repA mutant and of the wt mini-R1 plasmid. This indicates that the coordination between plasmid replication functions and kis-kid system contributes significantly to control plasmid R1 replication. PMID:25664511

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

PubMed

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

2018-06-07

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

The human chromokinesin Kid is a plus end-directed microtubule-based motor

PubMed Central

Yajima, Junichiro; Edamatsu, Masaki; Watai-Nishii, Junko; Tokai-Nishizumi, Noriko; Yamamoto, Tadashi; Toyoshima, Yoko Y.

2003-01-01

Kid is a kinesin-like DNA-binding protein known to be involved in chromosome movement during mitosis, although its actual motor function has not been demonstrated. Here, we describe the initial characterization of Kid as a microtubule-based motor using optical trapping microscopy. A bacterially expressed fusion protein consisting of a truncated Kid fragment (amino acids 1–388 or 1–439) is indeed an active microtubule motor with an average speed of ∼160 nm/s, and the polarity of movement is plus end directed. We could not detect processive movement of either monomeric Kid or dimerizing chimeric Kid; however, low levels of processivity (a few steps) cannot be detected with our method. These results are consistent with Kid having a role in chromosome congression in vivo, where it would be responsible for the polar ejection forces acting on the chromosome arms. PMID:12606572

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

PubMed

Popoff, M R; Boquet, P

1988-05-16

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

Naturally acquired antibodies against Clostridium perfringens epsilon toxin in goats.

PubMed

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

2008-09-15

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

Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors

PubMed Central

Mo, Irene Fung Ying; Yip, Kevin Hak Kong; Chan, Wing Keung; Law, Helen Ka Wai; Lau, Yu Lung; Chan, Godfrey Chi Fung

2008-01-01

Background Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings. Results We selected lipopolysaccharide (LPS) from Escherichia coli and lipoteichoic acid (LTA) from Streptococcus pyogenes as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria. Conclusion In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment. PMID:18799018

Toxin yet not toxic: Botulinum toxin in dentistry.

PubMed

Archana, M S

2016-04-01

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

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

PubMed

Ramisetty, Bhaskar Chandra Mohan; Santhosh, Ramachandran Sarojini

2017-07-01

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

Neutralization of Bacterial YoeBSpn Toxicity and Enhanced Plant Growth in Arabidopsis thaliana via Co-Expression of the Toxin-Antitoxin Genes

PubMed Central

Abu Bakar, Fauziah; Yeo, Chew Chieng; Harikrishna, Jennifer Ann

2016-01-01

Bacterial toxin-antitoxin (TA) systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeBSpn, which is one of four systems that had been demonstrated to be biologically functional. Overexpression of the yoeBSpn toxin gene resulted in cell stasis and eventually cell death in its native host, as well as in Escherichia coli. Our previous work showed that induced expression of a yoeBSpn toxin-Green Fluorescent Protein (GFP) fusion gene apparently triggered apoptosis and was lethal in the model plant, Arabidopsis thaliana. In this study, we investigated the effects of co-expression of the yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic A. thaliana. When co-expressed in Arabidopsis, the YefMSpn antitoxin was found to neutralize the toxicity of YoeBSpn-GFP. Interestingly, the inducible expression of both yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic hybrid Arabidopsis resulted in larger rosette leaves and taller plants with a higher number of inflorescence stems and increased silique production. To our knowledge, this is the first demonstration of a prokaryotic antitoxin neutralizing its cognate toxin in plant cells. PMID:27104531

AB toxins: a paradigm switch from deadly to desirable.

PubMed

Odumosu, Oludare; Nicholas, Dequina; Yano, Hiroshi; Langridge, William

2010-07-01

To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.

AB Toxins: A Paradigm Switch from Deadly to Desirable

PubMed Central

Odumosu, Oludare; Nicholas, Dequina; Yano, Hiroshi; Langridge, William

2010-01-01

To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity. PMID:22069653

Clostridium difficile binary toxin CDT

PubMed Central

Gerding, Dale N; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus

2014-01-01

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed. PMID:24253566

Anti-bacterial effect of essential oil from Xanthium strumarium against shiga toxin-producing Escherichia coli.

PubMed

Sharifi-Rad, J; Soufi, L; Ayatollahi, S A M; Iriti, M; Sharifi-Rad, M; Varoni, E M; Shahri, F; Esposito, S; Kuhestani, K; Sharifi-Rad, M

2016-09-19

Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 is one of the most important human pathogenic microorganisms, which can cause life-threatening infections. Xanthium strumarium L. is a plant with anti-bacterial activity against gram-negative and gram-positive bacteria. This study aims to demonstrate in vitro efficacy of the essential oil (EO) extracted from Xanthium strumarium L. against E. coli O157:H7. Using the agar test diffusion, the effect of Xanthium strumarium L. EO (5, 10, 15, 30, 60, and 120 mg/mL) was verified at each of the four different growth phases of E. coli O157:H7. Cell counts of viable cells and colony forming unit (CFU) were determined at regular time points using Breed's method and colony counting method, respectively. No viable cell was detectable after the 1 hour-exposure to X. strumarium EO at 30, 60, and 120 mg/mL concentrations. No bacterial colony was formed after 1 h until the end of the incubation period at 24 h. At lower concentrations, the number of bacteria cells decreased and colonies could be observed only after incubation. At the exponential phase, the EO at 15 mg/mL was only bacteriostatic, while from 30 mg/mL started to be bactericidal. X. strumarium EO antibacterial activity against Shiga toxin-producing E. coli O157:H7 is dependent on EO concentration and physiological state of the microorganisms tested. The best inhibitory activity was achieved during the late exponential and the stationary phases.

Bacterial Pore-Forming Toxins Promote the Activation of Caspases in Parallel to Necroptosis to Enhance Alarmin Release and Inflammation During Pneumonia.

PubMed

Gonzalez-Juarbe, Norberto; Bradley, Kelley M; Riegler, Ashleigh N; Reyes, Luis F; Brissac, Terry; Park, Sang-Sang; Restrepo, Marcos I; Orihuela, Carlos J

2018-04-11

Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining. Caspase activation was observed in lung samples from mice and non-human primates experiencing Gram-negative and Gram-positive bacterial pneumonia, respectively. During apoptosis, caspase activation normally leads to cell shrinkage, nuclear condensation, and immunoquiescent death. In contrast, caspase activity during PFT-induced necroptosis increased the release of alarmins to the extracellular milieu. Caspase-mediated alarmin release was found sufficient to activate resting macrophages, leading to Interleukin-6 production. In a mouse model of Gram-negative pneumonia, deletion of caspases -2 and -11, the mouse orthologue of caspase-4, reduced pulmonary inflammation, immune cell infiltration and lung damage. Thus, our study describes a previously unrecognized role for caspase activation in parallel to necroptosis, and indicates that their activity plays a critical pro-inflammatory role during bacterial pneumonia.

Raising Confident Kids

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Videos for Educators Search English Español Raising Confident Kids KidsHealth / For Parents / Raising Confident Kids What's in ...

Biodegradation of polyether algal toxins--isolation of potential marine bacteria.

PubMed

Shetty, Kateel G; Huntzicker, Jacqueline V; Rein, Kathleen S; Jayachandran, Krish

2010-12-01

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast. Bacterial growth on salinomycin was observed in most of the enrichment cultures from both regions with colony forming units ranging from 0 to 6×10(7) per mL. The salinomycin biodegradation efficiency of bacterial isolates determined using LC-MS ranged from 22% to 94%. Selected bacterial isolates were grown in media with brevetoxin as the sole carbon source to screen for brevetoxin biodegradation capability using ELISA. Out of the two efficient salinomycin biodegrading isolates MB-2 and MB-4, maximum brevetoxin biodegradation efficiency of 45% was observed with MB-4, while MB-2 was unable to biodegrade brevetoxin. Based on 16S rRNA sequence similarity MB-4 was found have a match with Chromohalobacter sp.

Kids Guide to Shots

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Safe Videos for Educators Search English Español A Kid's Guide to Shots KidsHealth / For Kids / A Kid's ...

Kid's Guide to Fever

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Safe Videos for Educators Search English Español A Kid's Guide to Fever KidsHealth / For Kids / A Kid's ...

Laryngitis (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Laryngitis KidsHealth / For Kids / Laryngitis What's in this article? How Your Voice ...

Tonsillitis (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Tonsillitis KidsHealth / For Kids / Tonsillitis Print Way in the back of your ...

Stroke (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Stroke KidsHealth / For Kids / Stroke What's in this article? What Happens During ...

Concussions (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Concussions KidsHealth / For Kids / Concussions What's in this article? Signs of a ...

Choking (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Choking KidsHealth / For Kids / Choking What's in this article? What Is Choking? ' ...

Nε-Fatty acylation of Rho GTPases by a MARTX toxin effector.

PubMed

Zhou, Yan; Huang, Chunfeng; Yin, Li; Wan, Muyang; Wang, Xiaofei; Li, Lin; Liu, Yanhua; Wang, Zhao; Fu, Panhan; Zhang, Ni; Chen, She; Liu, Xiaoyun; Shao, Feng; Zhu, Yongqun

2017-10-27

The multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are a family of large toxins that are extensively distributed in bacterial pathogens. MARTX toxins are autocatalytically cleaved to multiple effector domains, which are released into host cells to modulate the host signaling pathways. The Rho guanosine triphosphatase (GTPase) inactivation domain (RID), a conserved effector domain of MARTX toxins, is implicated in cell rounding by disrupting the host actin cytoskeleton. We found that the RID is an N ε -fatty acyltransferase that covalently modifies the lysine residues in the C-terminal polybasic region of Rho GTPases. The resulting fatty acylation inhibited Rho GTPases and disrupted Rho GTPase-mediated signaling in the host. Thus, RID can mediate the lysine N ε -fatty acylation of mammalian proteins and represents a family of toxins that harbor N-fatty acyltransferase activities in bacterial pathogens. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

PubMed

Wen, Jia; Fozo, Elizabeth M

2014-08-04

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

Respiratory disease, behavior, and survival of mountain goat kids

USGS Publications Warehouse

Blanchong, Julie A.; Anderson, Christopher A.; Clark, Nicholas J.; Klaver, Robert W.; Plummer, Paul J.; Cox, Mike; Mcadoo, Caleb; Wolff, Peregrine L.

2018-01-01

Bacterial pneumonia is a threat to bighorn sheep (Ovis canadensis) populations. Bighorn sheep in the East Humboldt Mountain Range (EHR), Nevada, USA, experienced a pneumonia epizootic in 2009–2010. Testing of mountain goats (Oreamnos americanus) that were captured or found dead on this range during and after the epizootic detected bacteria commonly associated with bighorn sheep pneumonia die‐offs. Additionally, in years subsequent to the bighorn sheep epizootic, the mountain goat population had low kid:adult ratios, a common outcome for bighorn sheep populations that have experienced a pneumonia epizootic. We hypothesized that pneumonia was present and negatively affecting mountain goat kids in the EHR. From June–August 2013–2015, we attempted to observe mountain goat kids with marked adult females in the EHR at least once per week to document signs of respiratory disease; identify associations between respiratory disease, activity levels, and subsequent disappearance (i.e., death); and estimate weekly survival. Each time we observed a kid with a marked adult female, we recorded any signs of respiratory disease and collected behavior data that we fit to a 3‐state discrete hidden Markov model (HMM) to predict a kid's state (active vs. sedentary) and its probability of disappearing. We first observed clinical signs of respiratory disease in kids in late July–early August each summer. We observed 8 of 31 kids with marked adult females with signs of respiratory disease on 13 occasions. On 11 of these occasions, the HMM predicted that kids were in the sedentary state, which was associated with increased probability of subsequent death. We estimated overall probability of kid survival from June–August to be 0.19 (95% CI = 0.08–0.38), which was lower than has been reported in other mountain goat populations. We concluded that respiratory disease was present in the mountain goat kids in the EHR and negatively affected their activity levels and survival

Artificial activation of toxin-antitoxin systems as an antibacterial strategy.

PubMed

Williams, Julia J; Hergenrother, Paul J

2012-06-01

Toxin-antitoxin (TA) systems are unique modules that effect plasmid stabilization via post-segregational killing of the bacterial host. The genes encoding TA systems also exist on bacterial chromosomes, and it has been speculated that these are involved in a variety of cellular processes. Interest in TA systems has increased dramatically over the past 5 years as the ubiquitous nature of TA genes on bacterial genomes has been revealed. The exploitation of TA systems as an antibacterial strategy via artificial activation of the toxin has been proposed and has considerable potential; however, efforts in this area remain in the early stages and several major questions remain. This review investigates the tractability of targeting TA systems to kill bacteria, including fundamental requirements for success, recent advances, and challenges associated with artificial toxin activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

KidsHealth

MedlinePlus

[Skip to Content] KidsHealth from Nemours for Parents - Knowledge, advice, and comfort for Kids - Homework help and how the body works for Teens - ... Para Niños Para Adolescentes for Educators Nemours About KidsHealth Partners Privacy Policy & Terms of Use

Xylella fastidiosa plasmid-encoded PemK toxin is an endoribonuclease.

USDA-ARS?s Scientific Manuscript database

Stable inheritance of pXF-RIV11 in Xylella fastidiosa is conferred by the pemI/pemK plasmid addiction system. PemK serves as a toxin inhibiting bacterial growth; PemI is the corresponding antitoxin that blocks activity of PemK toxin by direct binding. PemK toxin and PemI antitoxin were over-expre...

Cure4Kids for Kids: school-based cancer education outreach.

PubMed

Van Kirk Villalobos, Aubrey; Quintana, Yuri; Ribeiro, Raul C

2012-01-01

In 2006, St. Jude Children's Research Hospital created Cure4Kids for Kids, a school-based outreach program. The objectives of this community education program are to teach about cancer and healthy lifestyles and to inspire an interest in science and health-related careers. A multidisciplinary team of St. Jude and outside experts developed and pilot tested age-appropriate educational materials and activities with 4th grade students. Eight schools and more than 800 children have participated in the program since 2006. Teachers and students have demonstrated a very positive response to the program for it being both fun and educational. Cure4Kids for Kids resources have been collected into a teacher's kit and are now freely available online at www.cure4kids.org/kids.

Dissection of Host Susceptibility to Bacterial Infections and Its Toxins.

PubMed

Nashef, Aysar; Agbaria, Mahmoud; Shusterman, Ariel; Lorè, Nicola Ivan; Bragonzi, Alessandra; Wiess, Ervin; Houri-Haddad, Yael; Iraqi, Fuad A

2017-01-01

Infection is one of the leading causes of human mortality and morbidity. Exposure to microbial agents is obviously required. However, also non-microbial environmental and host factors play a key role in the onset, development and outcome of infectious disease, resulting in large of clinical variability between individuals in a population infected with the same microbe. Controlled and standardized investigations of the genetics of susceptibility to infectious disease are almost impossible to perform in humans whereas mouse models allow application of powerful genomic techniques to identify and validate causative genes underlying human diseases with complex etiologies. Most of current animal models used in complex traits diseases genetic mapping have limited genetic diversity. This limitation impedes the ability to create incorporated network using genetic interactions, epigenetics, environmental factors, microbiota, and other phenotypes. A novel mouse genetic reference population for high-resolution mapping and subsequently identifying genes underlying the QTL, namely the Collaborative Cross (CC) mouse genetic reference population (GRP) was recently developed. In this chapter, we discuss a variety of approaches using CC mice for mapping genes underlying quantitative trait loci (QTL) to dissect the host response to polygenic traits, including infectious disease caused by bacterial agents and its toxins.

Converting a Staphylococcus aureus toxin into effective cyclic pseudopeptide antibiotics.

PubMed

Solecki, Olivia; Mosbah, Amor; Baudy Floc'h, Michèle; Felden, Brice

2015-03-19

Staphylococcus aureus produces peptide toxins that it uses to respond to environmental cues. We previously characterized PepA1, a peptide toxin from S. aureus, that induces lytic cell death of both bacterial and host cells. That led us to suggest that PepA1 has an antibacterial activity. Here, we demonstrate that exogenously provided PepA1 has activity against both Gram-positive and Gram-negative bacteria. We also see that PepA1 is significantly hemolytic, thus limiting its use as an antibacterial agent. To overcome these limitations, we converted PepA1 into nonhemolytic derivatives. Our most promising derivative is a cyclic heptapseudopeptide with inconsequential toxicity to human cells, enhanced stability in human sera, and sharp antibacterial activity. Mechanistically, linear and helical PepA1 derivatives form pores at the bacterial and erythrocyte surfaces, while the cyclic peptide induces bacterial envelope reorganization, with insignificant action on the erythrocytes. Our work demonstrates that bacterial toxins might be an attractive starting point for antibacterial drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular mechanisms of action of bacterial exotoxins.

PubMed

Balfanz, J; Rautenberg, P; Ullmann, U

1996-07-01

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems.

PubMed

Goeders, Nathalie; Chai, Ray; Chen, Bihe; Day, Andrew; Salmond, George P C

2016-09-28

Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed.

Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia.

PubMed

González-Juarbe, Norberto; Gilley, Ryan Paul; Hinojosa, Cecilia Anahí; Bradley, Kelley Margaret; Kamei, Akinobu; Gao, Geli; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2015-12-01

Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention.

Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia

PubMed Central

González-Juarbe, Norberto; Gilley, Ryan Paul; Hinojosa, Cecilia Anahí; Bradley, Kelley Margaret; Kamei, Akinobu; Gao, Geli; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2015-01-01

Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention. PMID:26659062

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

PubMed

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

2016-03-07

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

Is Dieting OK for Kids?

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Educators Search English Español Is Dieting OK for Kids? KidsHealth / For Kids / Is Dieting OK for Kids? ...

Down Syndrome (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... people who have it. What's Life Like for Kids With Down Syndrome? Many kids with Down syndrome ...

The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis

PubMed Central

Park, Kyung-Duck; Pak, Sok Cheon; Park, Kwan-Kyu

2016-01-01

Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%–60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD. PMID:28025545

Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

PubMed Central

Goeders, Nathalie; Chai, Ray; Chen, Bihe; Day, Andrew; Salmond, George P. C.

2016-01-01

Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed. PMID:27690100

Cerebral Palsy (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Kids / Cerebral Palsy What's in this ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

Anthrax lethal and edema toxins in anthrax pathogenesis

PubMed Central

Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H.

2014-01-01

The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use CMG2 as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection. PMID:24684968

Belly Pain (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Belly Pain KidsHealth / For Kids / Belly Pain What's in this article? All About ...

Hodgkin Lymphoma (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

"Stomach Flu" (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español "Stomach Flu" KidsHealth / For Kids / "Stomach Flu" Print Many people talk about the " ...

Lactose Intolerance (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Lactose Intolerance KidsHealth / For Kids / Lactose Intolerance What's in this article? What Is ...

What's Puke? (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español What's Puke? KidsHealth / For Kids / What's Puke? What's in this article? How Does ...

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

USDA-ARS?s Scientific Manuscript database

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

Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin

PubMed Central

Byres, Emma; Paton, Adrienne W.; Paton, James C.; Löfling, Jonas C.; Smith, David F.; Wilce, Matthew C.J.; Talbot, Ursula M.; Chong, Damien C.; Yu, Hai; Huang, Shengshu; Chen, Xi; Varki, Nissi M.; Varki, Ajit; Rossjohn, Jamie; Beddoe, Travis

2009-01-01

AB5 toxins comprise an A subunit that corrupts essential eukaryotic cell functions, and pentameric B subunits that direct target cell uptake after binding surface glycans. Subtilase cytotoxin (SubAB) is an AB5 toxin secreted by Shiga toxigenic Escherichia coli (STEC)1, which causes serious gastrointestinal disease in humans2. SubAB causes haemolytic uraemic syndrome-like pathology in mice3 via SubA-mediated cleavage of BiP/GRP78, an essential endoplasmic reticulum chaperone4. Here we show that SubB has a strong preference for glycans terminating in the sialic acid N-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesised in humans. Structures of SubB-Neu5Gc complexes revealed the basis for this specificity, and mutagenesis of key SubB residues abrogated in vitro glycan recognition, cell binding and cytotoxicity. SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human-like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite human lack of Neu5Gc biosynthesis, assimilation of dietary Neu5Gc creates high-affinity receptors on human gut epithelia and kidney vasculature. This, together with the human lack of Neu5Gc-containing body fluid competitors, confers susceptibility to the gastrointestinal and systemic toxicities of SubAB. Ironically, foods rich in Neu5Gc are the most common source of STEC contamination. Thus a bacterial toxin’s receptor is generated by metabolic incorporation of an exogenous factor derived from food. PMID:18971931

Cardiac Catheterization (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cardiac Catheterization KidsHealth / For Kids / Cardiac Catheterization Print en español Cateterización cardíaca What ...

Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi

PubMed Central

Deng, Lingquan; Song, Jeongmin; Gao, Xiang; Wang, Jiawei; Yu, Hai; Chen, Xi; Varki, Nissi; Naito-Matsui, Yuko; Galán, Jorge E.; Varki, Ajit

2014-01-01

Salmonella Typhi is an exclusive human pathogen that causes typhoid fever. Typhoid toxin is a S. Typhi virulence factor that can reproduce most of the typhoid fever symptoms in experimental animals. Toxicity depends on toxin binding to terminally sialylated glycans on surface glycoproteins. Human glycans are unusual because of the lack of CMAH, which in other mammals converts N-acetylneuraminic acid (Neu5Ac) to N-glycolylneuraminic acid (Neu5Gc). Here we report that typhoid toxin binds to and is toxic towards cells expressing glycans terminated in Neu5Ac (expressed by humans) over glycans terminated in Neu5Gc (expressed by other mammals). Mice constitutively expressing CMAH thus displaying Neu5Gc in all tissues are resistant to typhoid toxin. The atomic structure of typhoid toxin bound to Neu5Ac reveals the structural bases for its binding specificity. These findings provide insight into the molecular bases for Salmonella Typhi’s host specificity and may help the development of therapies for typhoid fever. PMID:25480294

Antibody-mediated inhibition of ricin toxin retrograde transport.

PubMed

Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J

2014-04-08

Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin's binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. IMPORTANCE Ricin is the prototypic member of the AB family of medically important plant and bacterial toxins that includes cholera and Shiga toxins. Ricin is also a category B biothreat agent. Despite ongoing efforts to develop vaccines and antibody-based therapeutics against ricin, very little is known about the mechanisms by which antibodies neutralize this toxin. In general, it is thought that antibodies simply prevent toxins from attaching to cell surface receptors or promote their clearance through Fc receptor (FcR)-mediated uptake

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

PubMed

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

2017-12-12

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

Effects of inulin supplementation on selected faecal characteristics and health of neonatal Saanen kids sucking milk from their dams.

PubMed

Kara, C; Orman, A; Gencoglu, H; Kovanlıkaya, A; Meral, Y; Cetin, I; Yıbar, A; Kasap, S; Turkmen, I; Deniz, G

2012-12-01

Fifty newborn Saanen kids were used to study the effects of inulin supplementation on faecal score, faecal pH, selected faecal bacterial population, BW, body temperature, haematological traits, selected health parameters and the incidence of diarrhoea. Kids were sorted by parity of their dams and multiple birth (twin or triplet) and assigned to one of the two groups (control: CG, and experimental: EG) at birth. Each group consisted of 25 kids. The groups were similar with regard to sex and birth weight. All kids were fed colostrum for the first 3 days after birth, and then the kids in EG were adapted to inulin supplementation by an increased dosage from day 4 to 7. Each kid in EG was supplemented with 0.2 g, 0.3 g, 0.4 g, 0.5 g and 0.6 g inulin on day 4, 5, 6, 7 and from day 8 to 28, respectively, whereas the kids in CG did not receive inulin. Faecal score and faecal bacterial population were not affected by inulin supplementation (P > 0.05). There were differences in faecal pH on day 14 (P = 0.01) and 28 (P<0.05), whereas no difference in faecal pH on day 21 (P > 0.05) was detected between groups. No differences (P > 0.05) in BW and haematological traits were found between groups. Body temperature did not differ on day 14 and 21 (P > 0.05), whereas there was a difference in body temperature on day 28 (P = 0.01) between groups. The numbers of kids with pneumonia and kids treated for pneumonia and diarrhoea were similar for CG and EG. Kid losses during the study were the same for CG and EG. The incidence of diarrhoea was not affected by inulin supplementation (P > 0.05). Inulin supplemented to kids did not adversely affect faecal score. The effect of inulin on faecal pH was not consistent. The results of our study suggested that daily dose (0.6 g) of inulin might not be enough to observe effects of it. Our data will be useful to determine the dose and timing of inulin supplementation in future studies investigating the effects of inulin on the parameters associated

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

PubMed

Ramisetty, Bhaskar Chandra Mohan; Santhosh, Ramachandran Sarojini

2016-02-01

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

Toxin-Antitoxin Systems as Multilevel Interaction Systems

PubMed Central

Goeders, Nathalie; Van Melderen, Laurence

2014-01-01

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

Kid's Guide to Divorce

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... or mom. That's forever. That will never change. Kids Don't Cause Divorce! People divorce for lots ...

Carpal Tunnel Syndrome (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Search English Español Carpal Tunnel Syndrome KidsHealth / For Kids / Carpal Tunnel Syndrome What's in this article? Where ...

Defining the mRNA recognition signature of a bacterial toxin protein

DOE PAGES

Schureck, Marc A.; Dunkle, Jack A.; Maehigashi, Tatsuya; ...

2015-10-27

Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop tomore » recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.« less

Defining the mRNA recognition signature of a bacterial toxin protein

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

Schureck, Marc A.; Dunkle, Jack A.; Maehigashi, Tatsuya

Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop tomore » recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.« less

mRNA bound to the 30S subunit is a HigB toxin substrate

PubMed Central

Schureck, Marc A.; Maehigashi, Tatsuya; Miles, Stacey J.; Marquez, Jhomar; Dunham, Christine M.

2016-01-01

Activation of bacterial toxins during stress results in cleavage of mRNAs in the context of the ribosome. These toxins are thought to function as global translational inhibitors yet recent studies suggest each may have distinct mRNA specificities that result in selective translation for bacterial survival. Here we demonstrate that mRNA in the context of a bacterial 30S subunit is sufficient for ribosome-dependent toxin HigB endonucleolytic activity, suggesting that HigB interferes with the initiation step of translation. We determined the X-ray crystal structure of HigB bound to the 30S, revealing that two solvent-exposed clusters of HigB basic residues directly interact with 30S 16S rRNA helices 18, 30, and 31. We further show that these HigB residues are essential for ribosome recognition and function. Comparison with other ribosome-dependent toxins RelE and YoeB reveals that each interacts with similar features of the 30S aminoacyl (A) site yet does so through presentation of diverse structural motifs. PMID:27307497

Clostridial binary toxins: iota and C2 family portraits.

PubMed

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

2011-01-01

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

Clostridial Binary Toxins: Iota and C2 Family Portraits

PubMed Central

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

2011-01-01

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

HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.

PubMed

Chen, Huan-Da; Kao, Cheng-Yuan; Liu, Bang-Yu; Huang, Shin-Whei; Kuo, Cheng-Ju; Ruan, Jhen-Wei; Lin, Yen-Hung; Huang, Cheng-Rung; Chen, Yu-Hung; Wang, Horng-Dar; Aroian, Raffi V; Chen, Chang-Shi

2017-02-01

Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.

The action of the bacterial toxin microcin B17. Insight into the cleavage-religation reaction of DNA gyrase.

PubMed

Pierrat, Olivier A; Maxwell, Anthony

2003-09-12

We have examined the effects of the bacterial toxin microcin B17 (MccB17) on the reactions of Escherichia coli DNA gyrase. MccB17 slows down but does not completely inhibit the DNA supercoiling and relaxation reactions of gyrase. A kinetic analysis of the cleavage-religation equilibrium of gyrase was performed to determine the effect of the toxin on the forward (cleavage) and reverse (religation) reactions. A simple mechanism of two consecutive reversible reactions with a nicked DNA intermediate was used to simulate the kinetics of cleavage and religation. The action of MccB17 on the kinetics of cleavage and religation was compared with that of the quinolones ciprofloxacin and oxolinic acid. With relaxed DNA as substrate, only a small amount of gyrase cleavage complex is observed with MccB17 in the absence of ATP, whereas the presence of the nucleotide significantly enhances the effect of the toxin on both the cleavage and religation reactions. In contrast, ciprofloxacin, oxolinic acid, and Ca2+ show lesser dependence on ATP to stabilize the cleavage complex. MccB17 enhances the overall rate of DNA cleavage by increasing the forward rate constant (k2) of the second equilibrium. In contrast, ciprofloxacin increases the amount of cleaved DNA by a combined effect on the forward and reverse rate constants of both equilibria. Based on these results and on the observations that MccB17 only slowly inhibits the supercoiling and relaxation reactions, we suggest a model of the interaction of MccB17 with gyrase.

The role of toxins in Clostridium difficile infection.

PubMed

Chandrasekaran, Ramyavardhanee; Lacy, D Borden

2017-11-01

Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease. Published by Oxford University Press on behalf of FEMS 2017.

Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

PubMed Central

Van Melderen, Laurence; Saavedra De Bast, Manuel

2009-01-01

Bacterial toxin–antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes. PMID:19325885

Foodborne pathogens and their toxins.

PubMed

Martinović, Tamara; Andjelković, Uroš; Gajdošik, Martina Šrajer; Rešetar, Dina; Josić, Djuro

2016-09-16

Foodborne pathogens, mostly bacteria and fungi, but also some viruses, prions and protozoa, contaminate food during production and processing, but also during storage and transport before consuming. During their growth these microorganisms can secrete different components, including toxins, into the extracellular environment. Other harmful substances can be also liberated and can contaminate food after disintegration of food pathogens. Some bacterial and fungal toxins can be resistant to inactivation, and can survive harsh treatment during food processing. Many of these molecules are involved in cellular processes and can indicate different mechanisms of pathogenesis of foodborne organisms. More knowledge about food contaminants can also help understand their inactivation. In the present review the use of proteomics, peptidomics and metabolomics, in addition to other foodomic methods for the detection of foodborne pathogenic fungi and bacteria, is overviewed. Furthermore, it is discussed how these techniques can be used for discovering biomarkers for pathogenicity of foodborne pathogens, determining the mechanisms by which they act, and studying their resistance upon inactivation in food of animal and plant origin. Comprehensive and comparative view into the genome and proteome of foodborne pathogens of bacterial or fungal origin and foodomic, mostly proteomic, peptidomic and metabolomic investigation of their toxin production and their mechanism of action is necessary in order to get further information about their virulence, pathogenicity and survival under stress conditions. Furthermore, these data pave the way for identification of biomarkers to trace sources of contamination with food-borne microorganisms and their endo- and exotoxins in order to ensure food safety and prevent the outbreak of food-borne diseases. Therefore, detection of pathogens and their toxins during production, transport and before consume of food produce, as well as protection against

Kids and Concussions

MedlinePlus

... Features: Kids and Concussions Follow us Kids and Concussions What the experts think Every year, hundreds of ... this injury and its consequences. What is a concussion? A concussion is a type of brain injury ...

Comparative Genomics Evidence That Only Protein Toxins are Tagging Bad Bugs

PubMed Central

Georgiades, Kalliopi; Raoult, Didier

2011-01-01

The term toxin was introduced by Roux and Yersin and describes macromolecular substances that, when produced during infection or when introduced parenterally or orally, cause an impairment of physiological functions that lead to disease or to the death of the infected organism. Long after the discovery of toxins, early genetic studies on bacterial virulence demonstrated that removing a certain number of genes from pathogenic bacteria decreases their capacity to infect hosts. Each of the removed factors was therefore referred to as a “virulence factor,” and it was speculated that non-pathogenic bacteria lack such supplementary factors. However, many recent comparative studies demonstrate that the specialization of bacteria to eukaryotic hosts is associated with massive gene loss. We recently demonstrated that the only features that seem to characterize 12 epidemic bacteria are toxin–antitoxin (TA) modules, which are addiction molecules in host bacteria. In this study, we investigated if protein toxins are indeed the only molecules specific to pathogenic bacteria by comparing 14 epidemic bacterial killers (“bad bugs”) with their 14 closest non-epidemic relatives (“controls”). We found protein toxins in significantly more elevated numbers in all of the “bad bugs.” For the first time, statistical principal components analysis, including genome size, GC%, TA modules, restriction enzymes, and toxins, revealed that toxins are the only proteins other than TA modules that are correlated with the pathogenic character of bacteria. Moreover, intracellular toxins appear to be more correlated with the pathogenic character of bacteria than secreted toxins. In conclusion, we hypothesize that the only truly identifiable phenomena, witnessing the convergent evolution of the most pathogenic bacteria for humans are the loss of metabolic activities, i.e., the outcome of the loss of regulatory and transcription factors and the presence of protein toxins, alone, or

When Your Parents Fight (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... from a job or other worries. How Do Kids Feel When Their Parents Fight? Kids usually feel ...

Kids and Exercise

MedlinePlus

... a better outlook on life Besides enjoying the health benefits of regular exercise, fit kids sleep better. They' ... Can I Get My Kids to Be Active Outdoors? Strength Training What If I Don't Like ...

Disease-enhancing antibodies improve the efficacy of bacterial toxin-neutralizing antibodies

PubMed Central

Chow, Siu-Kei; Smith, Cameron; MacCarthy, Thomas; Pohl, Mary Ann; Bergman, Aviv; Casadevall, Arturo

2013-01-01

SUMMARY During infection, humoral immunity produces a polyclonal response with various immunoglobulins recognizing different epitopes within the microbe or toxin. Despite this diverse response, the biological activity of an antibody (Ab) is usually assessed by the action of a monoclonal population. We demonstrate that a combination of monoclonal antibodies (mAbs) that are individually disease-enhancing or neutralizing to Bacillus anthracis protective antigen (PA), a component of anthrax toxin, results in significantly augmented protection against the toxin. This boosted protection is Fc gamma receptor (FcγR)-dependent and involves the formation of stoichiometrically defined mAb-PA complexes that requires immunoglobulin bivalence and simultaneous interaction between PA and the two mAbs. The formation of these mAb-PA complexes inhibits PA oligomerization, resulting in protection. These data suggest that functional assessments of single Abs may inaccurately predict how the same Abs will operate in polyclonal preparations and imply that potentially therapeutic mAbs may be overlooked in single Ab screens. PMID:23601104

CPR: A Real Lifesaver (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... English Español CPR: A Real Lifesaver KidsHealth / For Kids / CPR: A Real Lifesaver What's in this article? ...

Scoop on Strep Throat (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Strep Throat KidsHealth / For Kids / Strep Throat What's in this article? What Is ...

Figuring Out Food Labels (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... English Español Figuring Out Food Labels KidsHealth / For Kids / Figuring Out Food Labels What's in this article? ...

Can Diabetes Be Prevented (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... English Español Can Diabetes Be Prevented? KidsHealth / For Kids / Can Diabetes Be Prevented? Print en español ¿Es ...

What a Pain! Kids and Growing Pains

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... for Educators Search English Español What a Pain! Kids and Growing Pains KidsHealth / For Kids / What a ...

The Kids Insight into Dementia Survey (KIDS): development and preliminary psychometric properties.

PubMed

Baker, Jess R; Low, Lee-Fay; Goodenough, Belinda; Jeon, Yun-Hee; Tsang, Ruby S M; Bryden, Christine; Hutchinson, Karen

2017-05-08

Children may have a foundational role in efforts to raise community awareness about dementia. There is some qualitative work with children with a relative with dementia, but little work into the insights of children as general citizens without affected family. One issue is an absence of measurement tools; thus the study aimed to design and pilot a psychometrically sound self-report measure of dementia attitudes for children. Using a multi-staged scale development process, stakeholder and expert input informed a 52-item Kids Insight into Dementia Survey (KIDS). After a pretest of KIDS with 21 Australian schoolchildren aged 10-12 years, exploratory factor analysis and reliability and validity testing were run on a revised KIDS with data from 203 similar-aged schoolchildren. The KIDS was reduced from 52 to 14 items, and a three-factor solution identified: 'Personhood,' 'Stigma,' and 'Dementia Understanding.' A strong positive correlation with an adult measure of dementia attitudes (r = .76) and a moderate positive correlation with a child measure of attitudes towards older adults (r = .47) indicated good concurrent validity. Internal consistency of .83 indicated good reliability. Results support the use of KIDS as a tool to measure children's insight into dementia, and to evaluate dementia education initiatives targeting the youth.

Talking to Your Kids about Virginity

MedlinePlus

... MusclesHuman Papillomavirus (HPV)Talking to Your Kids About Sex Home Family Health Kids and Teens Talking to Your Kids About Virginity ... by: familydoctor.org editorial staff Categories: Family Health, Kids and Teens, Sex and SexualityTags: child, teenager January 10, 2017 Copyright © ...

What "Being Overweight" Means (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... English Español What Being Overweight Means KidsHealth / For Kids / What Being Overweight Means Print en español ¿Qué ...

RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin.

PubMed

Los, Ferdinand C O; Kao, Cheng-Yuan; Smitham, Jane; McDonald, Kent L; Ha, Christine; Peixoto, Christina A; Aroian, Raffi V

2011-02-17

Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes, and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT and to restore integrity to the plasma membrane. One physical mechanism involved is the RAB-11-dependent expulsion of microvilli from the apical side of the intestinal epithelial cells. Specific vesicle-trafficking pathways thus protect cells against an attack by PFTs on plasma membrane integrity, via altered plasma membrane dynamics. Copyright © 2011 Elsevier Inc. All rights reserved.

Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish

PubMed Central

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

2014-01-01

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

Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia

PubMed Central

González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2017-01-01

We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling. PMID:28387756

Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia.

PubMed

González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2017-05-01

We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling.

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

PubMed

Kalb, Suzanne R; Barr, John R

2013-08-01

Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.

Influence of bacterial toxins on the GTPase activity of transducin from bovine retinal rod outer segments

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

Rybin, V.O.; Gureeva, A.A.

1986-05-10

The action of cholera toxin, capable of ADP-ribosylation of the activator N/sub s/ protein, and pertussis toxin, capable of ADP-ribosylation of the inhibitor N/sub i/ protein of the adenylate cyclase complex, on transducin, the GTP-binding protein of the rod outer segments of the retina, was investigated. It was shown that under the action of pertussis and cholera toxins, the GTPase activity of transducin is inhibited. Pertussin toxin inhibits the GTPase of native retinal rod outer segments by 30-40%, while GTPase of homogeneous transducin produces a 70-80% inhibition. The action of toxins on transducin depends on the presence and nature ofmore » the guanylic nucleotide with which incubation is performed. On the basis of the data obtained it is suggested that pertussis toxin interacts with pretransducin and with the transducin-GDP complex, while cholera toxin ADP-ribosylates the transducin-GTP complex and does not act on transducin lacking GTP.« less

Kids Speaking Up for Kids: Advocacy by Children, for Children

ERIC Educational Resources Information Center

Zygmunt-Fillwalk, Eva; Staley, Lynn; Kumar, Rashmi; Lin, Cecilia Lingfen; Moore, Catherine; Salakaya, Manana; Szecsi, Tunde

2007-01-01

This article describes a project called "Kids Speaking Up for Kids: Advocacy by Children, for Children". The project was simple in scope. The authors sought to collect stories of child advocacy--ways in which children were working on behalf of other children. They also sought to collect and profile children's voices and vision and so…

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

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

Cronin, M.J.; Evans, W.S.; Rogol, A.D.

1986-08-01

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

Botulinum toxin in pain treatment.

PubMed

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

2009-01-01

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

Kids in transition: the rehab experience.

PubMed

Bruce-Barrett, Cindy; Hodinott, Alastair; Manicat-Emo, Arbelle; Flaming, Tonya; Macgregor, Daune; Hogan, Iris; Carew, Chris; Cox, Sandi

2011-01-01

Holland Bloorview Kids Rehabilitation Hospital (formerly Bloorview Kids Rehab) is Canada's largest teaching hospital for pediatric rehabilitation and the only in-patient pediatric rehabilitation centre in Ontario. SickKids is a quaternary-level academic health sciences centre. The acute care neuroscience and trauma patient population at SickKids represents the largest volume of transitioning clients between the two organizations. For years, the number of medically unnecessary days associated with patients awaiting transfer from SickKids to Holland Bloorview for off-site rehabilitation was consistently driven by inefficient processes, multiple handovers, duplicitous efforts, fragmented communication and a lack of timely or complete referral information. Recognizing this situation as a threat to access, as well as a significant risk to patient health outcomes, SickKids and Holland Bloorview embarked on an exciting partnership (Kids in Transition: The Rehab Experience) as part of a larger Ministry of Health and Long-Term Care-funded initiative, the Flo Collaborative.

Excitable toxin-antitoxin modules coordinated through intracellular bottlenecks

NASA Astrophysics Data System (ADS)

Mather, William

Chronic infections and pathogenic biofilms present a serious threat to the health of humans by decreasing life expectancy and quality. The resilience of these microbial communities has been attributed to the spontaneous formation of persister cells, which constitute a small fraction of the population capable of surviving a wide range of environmental stressors. Gating of bacterial persistence has recently been linked to toxin-antitoxin (TA) modules, which are operons with an evolutionarily conserved motif that includes a toxin that halts cell growth and a corresponding antitoxin that neutralizes the toxin. While many such modules have been identified and studied in a wide range of organisms, little consideration of the interactions between multiple modules within a single host has been made. Moreover, the multitude of different antitoxin species are degraded by a relatively small number of proteolytic pathways, strongly suggesting competition between antitoxins for degradation machinery, i.e. queueing coupling. Here we present a theoretical understanding of the dynamics of multiple TA modules that are coupled through either proteolytic queueing, a toxic effect on cell growth rate, or both. We conclude that indirect queueing coordination between multiple TA modules may be central to controlling bacterial persistence. NSF Award Number MCB-1330180.

Kids With Two Moms or Two Dads

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Staying Safe Videos for Educators Search English Español Kids With Two Moms or Two Dads KidsHealth / For ...

Dietary Needs for Kids With Cerebral Palsy

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... for Educators Search English Español Dietary Needs for Kids With Cerebral Palsy KidsHealth / For Parents / Dietary Needs ...

Antibody-Mediated Inhibition of Ricin Toxin Retrograde Transport

PubMed Central

Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J.

2014-01-01

ABSTRACT Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin’s binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. PMID:24713323

Have You Heard of GERD? (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Español Have You Heard of GERD? KidsHealth / For Kids / Have You Heard of GERD? What's in this ...

Having Your Tonsils Taken Out (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Español Having Your Tonsils Taken Out KidsHealth / For Kids / Having Your Tonsils Taken Out What's in this ...

How Do Pain Relievers Work? (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Español How Do Pain Relievers Work? KidsHealth / For Kids / How Do Pain Relievers Work? Print en español ¿ ...

Cardiac troponin I in healthy newborn goat kids and in goat kids with cardiac nutritional muscular dystrophy.

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; El-Sayed, Mehana

2013-12-01

This study was designed to establish serum cardiac troponin I (cTnI) concentrations in healthy newborn goat kids and in those with cardiac nutritional muscular dystrophy (NMD). Thirty-five single full-term newborn goat kids (20 males and 15 females; age: 6.1 ± 3.5 h; weight 3.4 ± 0.68 kg), together with their respective mothers (Group 1; G1) were enrolled consecutively. Thirty-one goat kids (age: 9.5 ± 4.3 days) with NMD, together with 20 control goat kids (age: 7.8 ± 4.3 days) were also included in this study (Group 2; G2). Blood samples were collected from G1 within 12 h of birth and from G2 on admission. Serum samples were collected and analysed for cTnI. In G1, the mean serum concentration of cTnI in goat kids was 0.290 ± 0.37 ng/mL, with no statistically significant difference between male and female kids (P = 0.61). The mean cTnI concentration in the does was 0.017 ± 0.04, ng/mL. Serum values of cTnI in the goat kids and in their respective mothers differed significantly (P = 0.0001). In G2, the mean cTnI concentration was 0.02 ± 0.05 ng/mL in the control and 11.18 ± 20.07 ng/mL in the diseased goat kids, with a statistically significant difference between diseased and control goat kids (P = 0.017). Serum concentrations of cTnI are higher in goat kids than in their respective mothers. In conclusion, the cTnI assay appears to be a sensitive and specific marker for myocardial injury in goat kids.

Talking to Your Kids about Sex

MedlinePlus

... Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family Health Infants and ... Kids and Teens Talking to Your Kids About Sex Talking to Your Kids About Sex Share Print ...

Gun Safety (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Gun Safety KidsHealth / For Kids / Gun Safety What's in ... from guns outside the home. If You Have Guns in Your Home If your parents keep guns ...

About Anemia (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español About Anemia KidsHealth / For Kids / About Anemia What's in this ... to every cell in your body. What Is Anemia? Anemia happens when a person doesn't have ...

Breast Cancer (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Breast Cancer KidsHealth / For Kids / Breast Cancer What's in this ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

Kids Follow the Leader

Cancer.gov

Kids are like sponges—they seem to absorb everything around them. They notice what you’re wearing, what you say, and what you do. You might not even realize how much your kids pick up from you every day.

A cell-based fluorescent assay to detect the activity of AB toxins that inhibit protein synthesis

USDA-ARS?s Scientific Manuscript database

AB-type protein toxins, produced by numerous bacterial pathogens and some plants, elicit a cytotoxic effect involving the inhibition of protein synthesis. To develop an improved method to detect the inhibition of protein synthesis by AB-type toxins, the present study characterized a Vero cell line t...

[Consumption of psychoactive drugs and exposure to bacterial toxins carried by food: a dangerous association].

PubMed

Corma-Gómez, Anaïs; López-Sepúlveda, Rocío; Capitán-Del Río, Inés; Sánchez Mariscal, María Dolores; López-Hernández, Begoña

2017-11-01

To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. 18 cases with diarrhoea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focussed suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

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

PubMed

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

2017-04-01

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

An Overview of Helicobacter pylori VacA Toxin Biology

PubMed Central

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

2016-01-01

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

Cohort Profile: The Applied Research Group for Kids (TARGet Kids!)

PubMed Central

Carsley, Sarah; Borkhoff, Cornelia M; Maguire, Jonathon L; Birken, Catherine S; Khovratovich, Marina; McCrindle, Brian; Macarthur, Colin; Parkin, Patricia C

2015-01-01

The Applied Research Group for Kids (TARGet Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the TARGet Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. TARGet Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/. PMID:24982016

PemK toxin encoded by the Xylella fastidiosa IncP-1 plasmid pXF-RIV11 is a ribonuclease

USDA-ARS?s Scientific Manuscript database

Stable inheritance of the IncP-1 plasmid pXF-RIV11 in Xylella fastidiosa is conferred by the pemI/pemK plasmid addiction system. PemK serves as a toxin inhibiting bacterial growth; PemI is the corresponding antitoxin that blocks activity of PemK toxin by direct binding. Here, PemK toxin and PemI ant...

Geldanamycin Enhances Retrograde Transport of Shiga Toxin in HEp-2 Cells

PubMed Central

Simm, Roger; Torgersen, Maria Lyngaas; Sandvig, Kirsten

2015-01-01

The heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA) has been shown to alter endosomal sorting, diverting cargo destined for the recycling pathway into the lysosomal pathway. Here we investigated whether GA also affects the sorting of cargo into the retrograde pathway from endosomes to the Golgi apparatus. As a model cargo we used the bacterial toxin Shiga toxin, which exploits the retrograde pathway as an entry route to the cytosol. Indeed, GA treatment of HEp-2 cells strongly increased the Shiga toxin transport to the Golgi apparatus. The enhanced Golgi transport was not due to increased endocytic uptake of the toxin or perturbed recycling, suggesting that GA selectively enhances endosomal sorting into the retrograde pathway. Moreover, GA activated p38 and both inhibitors of p38 or its substrate MK2 partially counteracted the GA-induced increase in Shiga toxin transport. Thus, our data suggest that GA-induced p38 and MK2 activation participate in the increased Shiga toxin transport to the Golgi apparatus. PMID:26017782

Fitness for Kids Who Don't Like Sports

MedlinePlus

... Español Fitness for Kids Who Don't Like Sports KidsHealth / For Parents / Fitness for Kids Who Don' ... look for something new. Still Shopping for a Sport Some kids haven't found the right sport. ...

Taking the Bite out of Bruxism (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Taking the Bite Out of Bruxism KidsHealth / For Kids / Taking the Bite Out of Bruxism Print Do ...

When Will I Get My Period? (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... When Will I Get My Period? KidsHealth / For Kids / When Will I Get My Period? Print en ...

Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae

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

Jorgensen, Rene; Purdy, Alexandra E.; Fieldhouse, Robert J.

2008-07-15

The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC50 = 4.6 {+-} 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 {+-} 2 {mu}g/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity againstmore » ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-{angstrom} resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.« less

Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B ▿ †

PubMed Central

Permpoonpattana, Patima; Hong, Huynh A.; Phetcharaburanin, Jutarop; Huang, Jen-Min; Cook, Jenny; Fairweather, Neil F.; Cutting, Simon M.

2011-01-01

Clostridium difficile is a leading cause of nosocomial infection in the developed world. Two toxins, A and B, produced by most strains of C. difficile are implicated as virulence factors, yet only recently has the requirement of these for infection been investigated by genetic manipulation. Current vaccine strategies are focused mostly on parenteral delivery of toxoids. In this work, we have used bacterial spores (Bacillus subtilis) as a delivery vehicle to evaluate the carboxy-terminal repeat domains of toxins A and B as protective antigens. Our findings are important and show that oral immunization of the repeat domain of toxin A is sufficient to confer protection in a hamster model of infection designed to closely mimic the human course of infection. Importantly, neutralizing antibodies to the toxin A repeat domain were shown to be cross-reactive with the analogous domain of toxin B and, being of high avidity, provided protection against challenge with a C. difficile strain producing toxins A and B (A+B+). Thus, although many strains produce both toxins, antibodies to only toxin A can mediate protection. Animals vaccinated with recombinant spores were fully able to survive reinfection, a property that is particularly important for a disease with which patients are prone to relapse. We show that mucosal immunization, not parenteral delivery, is required to generate secretory IgA and that production of these neutralizing polymeric antibodies correlates with protection. This work demonstrates that an effective vaccine against C. difficile can be designed around two attributes, mucosal delivery and the repeat domain of toxin A. PMID:21482682

Possible mistranslation of Shiga toxin from pathogenic Escherichia coli as measured by MALDI-TOF and Orbitrap mass spectrometry

USDA-ARS?s Scientific Manuscript database

RATIONALE: Shiga toxin-producing Escherichia coli (STEC) are often subjected to DNA damaging antibiotics during culturing in order to elicit the bacterial SOS response and up-regulation of bacteriophage-encoded proteins including Shiga toxin (Stx). However, such antibiotic exposure and stress may al...

Observing the Confinement Potential of Bacterial Pore-Forming Toxin Receptors Inside Rafts with Nonblinking Eu3+-Doped Oxide Nanoparticles

PubMed Central

Türkcan, Silvan; Masson, Jean-Baptiste; Casanova, Didier; Mialon, Geneviève; Gacoin, Thierry; Boilot, Jean-Pierre; Popoff, Michel R.; Alexandrou, Antigoni

2012-01-01

We track single toxin receptors on the apical cell membrane of MDCK cells with Eu-doped oxide nanoparticles coupled to two toxins of the pore-forming toxin family: α-toxin of Clostridium septicum and ε-toxin of Clostridium perfringens. These nonblinking and photostable labels do not perturb the motion of the toxin receptors and yield long uninterrupted trajectories with mean localization precision of 30 nm for acquisition times of 51.3 ms. We were thus able to study the toxin-cell interaction at the single-molecule level. Toxins bind to receptors that are confined within zones of mean area 0.40 ± 0.05 μm2. Assuming that the receptors move according to the Langevin equation of motion and using Bayesian inference, we determined mean diffusion coefficients of 0.16 ± 0.01 μm2/s for both toxin receptors. Moreover, application of this approach revealed a force field within the domain generated by a springlike confining potential. Both toxin receptors were found to experience forces characterized by a mean spring constant of 0.30 ± 0.03 pN/μm at 37°C. Furthermore, both toxin receptors showed similar distributions of diffusion coefficient, domain area, and spring constant. Control experiments before and after incubation with cholesterol oxidase and sphingomyelinase show that these two enzymes disrupt the confinement domains and lead to quasi-free motion of the toxin receptors. Our control data showing cholesterol and sphingomyelin dependence as well as independence of actin depolymerization and microtubule disruption lead us to attribute the confinement of both receptors to lipid rafts. These toxins require oligomerization to develop their toxic activity. The confined nature of the toxin receptors leads to a local enhancement of the toxin monomer concentration and may thus explain the virulence of this toxin family. PMID:22677383

What's the Big Sweat about Dehydration? (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... for Educators Search English Español Dehydration KidsHealth / For Kids / Dehydration Print en español ¿Por qué es tan ...

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids.

PubMed

Nawito, M; Ahmed, Y F; Zayed, S M; Hecker, E

1998-01-01

Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats--as an important source of milk around the world--in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.

DC KIDS COUNT e-Databook Indicators

ERIC Educational Resources Information Center

DC Action for Children, 2012

2012-01-01

This report presents indicators that are included in DC Action for Children's 2012 KIDS COUNT e-databook, their definitions and sources and the rationale for their selection. The indicators for DC KIDS COUNT represent a mix of traditional KIDS COUNT indicators of child well-being, such as the number of children living in poverty, and indicators of…

Kids Do Well If They Can

ERIC Educational Resources Information Center

Greene, Ross

2008-01-01

Viewing challenging behavior as the result of lagging skills (kids do well if they can) rather than as poor motivation (kids do well if they want to) has significant ramifications for how adults interact with kids with behavioral challenges and try to help them. A wide range of lagging skills can set the stage for challenging behavior. Challenging…

Cohort Profile: The Applied Research Group for Kids (TARGet Kids!).

PubMed

Carsley, Sarah; Borkhoff, Cornelia M; Maguire, Jonathon L; Birken, Catherine S; Khovratovich, Marina; McCrindle, Brian; Macarthur, Colin; Parkin, Patricia C

2015-06-01

The Applied Research Group for Kids (TARGet Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the TARGet Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. TARGet Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

PubMed

Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

2017-03-01

The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

Teaching Kids Not to Bully

MedlinePlus

... and ability to form and sustain friendships. Understanding Bullying Behavior Kids bully for many reasons. Some bully ... children they perceive as weak. Helping Kids Stop Bullying Let your child know that bullying is unacceptable ...

Motivating Kids to Be Active

MedlinePlus

... genetics, and athletic ability combine to influence kids' attitudes toward participation in sports and other physical activities, ... kids can be physically fit. A parent's positive attitude will help a child who's reluctant to exercise. ...

Purification and characterization of chymosin and pepsin from kid.

PubMed

Moschopoulou, Ekaterini E; Kandarakis, Ioannis G; Alichanidis, Efstathios; Anifantakis, Emmanouil M

2006-02-01

The objective of this work was to study the characteristics of the gastric aspartic proteinases chymosin and pepsin which are constituents of the kid rennet. The two enzymes were extracted from abomasal tissue of one kid from a local indigenous breed, separated from each other by DEAE-cellulose chromatography and then were purified by gel filtration and anion-exchange chromatography. The molecular weights of the purified kid chymosin and pepsin as determined by gel filtration were 36 kDa and 40 kDa respectively. The isoelectric point of kid chymosin was as multiple forms of 3-6 zones at pH 4.6-5.1, while that of kid pepsin was at pH < or =3.0. Kid pepsin contained 0.37 molecules phosphorous per molecule and was totally inhibited by 5 muM pepstatin A, being more sensitive than kid chymosin. Both enzymes were almost equally as proteolytic as calf chymosin on total casein at pH 5.6. Kid pepsin activity was more pH and temperature dependent than kid chymosin activity. In comparison with the calf chymosin temperature sensitivity, the order of increased sensitivity was: calf chymosin <kid chymosin <kid pepsin.

The assembly dynamics of the cytolytic pore toxin ClyA

PubMed Central

Benke, Stephan; Roderer, Daniel; Wunderlich, Bengt; Nettels, Daniel; Glockshuber, Rudi; Schuler, Benjamin

2015-01-01

Pore-forming toxins are protein assemblies used by many organisms to disrupt the membranes of target cells. They are expressed as soluble monomers that assemble spontaneously into multimeric pores. However, owing to their complexity, the assembly processes have not been resolved in detail for any pore-forming toxin. To determine the assembly mechanism for the ring-shaped, homododecameric pore of the bacterial cytolytic toxin ClyA, we collected a diverse set of kinetic data using single-molecule spectroscopy and complementary techniques on timescales from milliseconds to hours, and from picomolar to micromolar ClyA concentrations. The entire range of experimental results can be explained quantitatively by a surprisingly simple mechanism. First, addition of the detergent n-dodecyl-β-D-maltopyranoside to the soluble monomers triggers the formation of assembly-competent toxin subunits, accompanied by the transient formation of a molten-globule-like intermediate. Then, all sterically compatible oligomers contribute to assembly, which greatly enhances the efficiency of pore formation compared with simple monomer addition. PMID:25652783

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

PubMed Central

LaRocca, Timothy J.; Stivison, Elizabeth A.; Hod, Eldad A.; Spitalnik, Steven L.; Cowan, Peter J.; Randis, Tara M.

2014-01-01

ABSTRACT A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. PMID:25161188

Molecular dynamics simulation of phosphorylated KID post-translational modification.

PubMed

Chen, Hai-Feng

2009-08-05

Kinase-inducible domain (KID) as transcriptional activator can stimulate target gene expression in signal transduction by associating with KID interacting domain (KIX). NMR spectra suggest that apo-KID is an unstructured protein. After post-translational modification by phosphorylation, KID undergoes a transition from disordered to well folded protein upon binding to KIX. However, the mechanism of folding coupled to binding is poorly understood. To get an insight into the mechanism, we have performed ten trajectories of explicit-solvent molecular dynamics (MD) for both bound and apo phosphorylated KID (pKID). Ten MD simulations are sufficient to capture the average properties in the protein folding and unfolding. Room-temperature MD simulations suggest that pKID becomes more rigid and stable upon the KIX-binding. Kinetic analysis of high-temperature MD simulations shows that bound pKID and apo-pKID unfold via a three-state and a two-state process, respectively. Both kinetics and free energy landscape analyses indicate that bound pKID folds in the order of KIX access, initiation of pKID tertiary folding, folding of helix alpha(B), folding of helix alpha(A), completion of pKID tertiary folding, and finalization of pKID-KIX binding. Our data show that the folding pathways of apo-pKID are different from the bound state: the foldings of helices alpha(A) and alpha(B) are swapped. Here we also show that Asn139, Asp140 and Leu141 with large Phi-values are key residues in the folding of bound pKID. Our results are in good agreement with NMR experimental observations and provide significant insight into the general mechanisms of binding induced protein folding and other conformational adjustment in post-translational modification.

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

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

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

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

Dealing with Bullies (For Kids)

MedlinePlus

... Videos for Educators Search English Español Dealing With Bullies KidsHealth / For Kids / Dealing With Bullies What's in ... do things they don't want to do. Bullying Is a Big Deal Bullying is a big ...

Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin

PubMed Central

Chakrabarti, Rima S; Ingham, Sally A; Kozlitina, Julia; Gay, Austin; Cohen, Jonathan C; Radhakrishnan, Arun; Hobbs, Helen H

2017-01-01

Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans. DOI: http://dx.doi.org/10.7554/eLife.23355.001 PMID:28169829

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

PubMed

Omernik, Andrzej; Płusa, Tadeusz

2015-09-01

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

Violent Kids: Can We Solve the Problem?

ERIC Educational Resources Information Center

Hinds, Michael deCourcy

2000-01-01

Offers three public policy perspectives on the issue of juvenile violence: (1) kids need a nonviolent popular culture; (2) kids at risk need more help; and (3) kids need more moral discipline. Presents a way to approach each of the perspectives. (Contains references.) (CMK)

Net Cetera: Chatting with Kids About Being Online

ERIC Educational Resources Information Center

Federal Trade Commission, 2009

2009-01-01

This booklet gives adults practical tips to help kids navigate the online world. Kids and parents have many ways of socializing and communicating online, but they come with certain risks. This guide encourages parents to reduce the risks by talking to kids about how they communicate--online and off--and helping kids engage in conduct they can be…

Regulating Toxin-Antitoxin Expression: Controlled Detonation of Intracellular Molecular Timebombs

PubMed Central

Hayes, Finbarr; Kędzierska, Barbara

2014-01-01

Genes for toxin-antitoxin (TA) complexes are widely disseminated in bacteria, including in pathogenic and antibiotic resistant species. The toxins are liberated from association with the cognate antitoxins by certain physiological triggers to impair vital cellular functions. TAs also are implicated in antibiotic persistence, biofilm formation, and bacteriophage resistance. Among the ever increasing number of TA modules that have been identified, the most numerous are complexes in which both toxin and antitoxin are proteins. Transcriptional autoregulation of the operons encoding these complexes is key to ensuring balanced TA production and to prevent inadvertent toxin release. Control typically is exerted by binding of the antitoxin to regulatory sequences upstream of the operons. The toxin protein commonly works as a transcriptional corepressor that remodels and stabilizes the antitoxin. However, there are notable exceptions to this paradigm. Moreover, it is becoming clear that TA complexes often form one strand in an interconnected web of stress responses suggesting that their transcriptional regulation may prove to be more intricate than currently understood. Furthermore, interference with TA gene transcriptional autoregulation holds considerable promise as a novel antibacterial strategy: artificial release of the toxin factor using designer drugs is a potential approach to induce bacterial suicide from within. PMID:24434949

Antibody to ricin a chain hinders intracellular routing of toxin and protects cells even after toxin has been internalized.

PubMed

Song, Kejing; Mize, R Ranney; Marrero, Luis; Corti, Miriam; Kirk, Jason M; Pincus, Seth H

2013-01-01

Mechanisms of antibody-mediated neutralization are of much interest. For plant and bacterial A-B toxins, A chain mediates toxicity and B chain binds target cells. It is generally accepted and taught that antibody (Ab) neutralizes by preventing toxin binding to cells. Yet for some toxins, ricin included, anti-A chain Abs afford greater protection than anti-B. The mechanism(s) whereby Abs to the A chain neutralize toxins are not understood. We use quantitative confocal imaging, neutralization assays, and other techniques to study how anti-A chain Abs function to protect cells. Without Ab, ricin enters cells and penetrates to the endoplasmic reticulum within 15 min. Within 45-60 min, ricin entering and being expelled from cells reaches equilibrium. These results are consistent with previous observations, and support the validity of our novel methodology. The addition of neutralizing Ab causes ricin accumulation at the cell surface, delays internalization, and postpones retrograde transport of ricin. Ab binds ricin for >6hr as they traffic together through the cell. Ab protects cells even when administered hours after exposure. CONCLUSIONS/KEY FINDINGS: We demonstrate the dynamic nature of the interaction between the host cell and toxin, and how Ab can alter the balance in favor of the cell. Ab blocks ricin's entry into cells, hinders its intracellular routing, and can protect even after ricin is present in the target organelle, providing evidence that the major site of neutralization is intracellular. These data add toxins to the list of pathogenic agents that can be neutralized intracellularly and explain the in vivo efficacy of delayed administration of anti-toxin Abs. The results encourage the use of post-exposure passive Ab therapy, and show the importance of the A chain as a target of Abs.

Antibody to Ricin A Chain Hinders Intracellular Routing of Toxin and Protects Cells Even after Toxin Has Been Internalized

PubMed Central

Song, Kejing; Mize, R. Ranney; Marrero, Luis; Corti, Miriam; Kirk, Jason M.; Pincus, Seth H.

2013-01-01

Background Mechanisms of antibody-mediated neutralization are of much interest. For plant and bacterial A-B toxins, A chain mediates toxicity and B chain binds target cells. It is generally accepted and taught that antibody (Ab) neutralizes by preventing toxin binding to cells. Yet for some toxins, ricin included, anti-A chain Abs afford greater protection than anti-B. The mechanism(s) whereby Abs to the A chain neutralize toxins are not understood. Methodology/Principal Findings We use quantitative confocal imaging, neutralization assays, and other techniques to study how anti-A chain Abs function to protect cells. Without Ab, ricin enters cells and penetrates to the endoplasmic reticulum within 15 min. Within 45–60 min, ricin entering and being expelled from cells reaches equilibrium. These results are consistent with previous observations, and support the validity of our novel methodology. The addition of neutralizing Ab causes ricin accumulation at the cell surface, delays internalization, and postpones retrograde transport of ricin. Ab binds ricin for >6hr as they traffic together through the cell. Ab protects cells even when administered hours after exposure. Conclusions/Key Findings We demonstrate the dynamic nature of the interaction between the host cell and toxin, and how Ab can alter the balance in favor of the cell. Ab blocks ricin’s entry into cells, hinders its intracellular routing, and can protect even after ricin is present in the target organelle, providing evidence that the major site of neutralization is intracellular. These data add toxins to the list of pathogenic agents that can be neutralized intracellularly and explain the in vivo efficacy of delayed administration of anti-toxin Abs. The results encourage the use of post-exposure passive Ab therapy, and show the importance of the A chain as a target of Abs. PMID:23638075

Treatment of keratitis-ichthyosis- deafness (KID) syndrome in children: a case report and review of the literature.

PubMed

Patel, Viraat; Sun, Grace; Dickman, Meghan; Khuu, Phuong; Teng, Joyce M C

2015-01-01

Keratitis-ichthyosis-deafness (KID) syndrome is a rare hereditary cornification disorder resulting from mutations in connexin 26, a protein important for intercellular communication. In addition to the characteristic clinical triad of congenital bilateral sensorineural hearing loss, keratitis, and erythrokeratoderma, affected individuals also suffer from chronic bacterial and fungal infections and have an increased risk of benign and malignant cutaneous tumors. Treatments with antibiotics, antifungals, and systemic retinoids have been reported with variable response. Ocular and skeletal toxicity from prolonged exposure to systemic retinoids is a major concern especially in children. We report a case of a 7-year-old boy with KID syndrome complicated by frequent infections who responded well to acitretin 0.5-1.0 mg/kg/day. The patient had significant improvement of the hyperkeratosis on the scalp, trunk, and extremities within 4 weeks after initiating treatment. The patient has been on treatment for over a year without notable ocular, skeletal, or laboratory side effects. A review of the literature focusing on therapeutic options for KID syndrome and concerns about safety and tolerability is presented. © 2014 Wiley Periodicals, Inc.

TerraKids: An Interactive Web Site where Kids Learn about Saving the Environment

ERIC Educational Resources Information Center

Twyman, Janet S.

2010-01-01

Whatever adults might accomplish on the green behavior change front, any sustained success in combating climate change will require the help of the world's more than 2.2 billion children. In "TerraKids," Janet Twyman describes a possible Web site where kids learn about their family's carbon footprint and what they can do to help reduce it.…

School Kids/Street Kids: Identity Development in Latino Students. Sociology of Education Series.

ERIC Educational Resources Information Center

Flores-Gonzalez, Nilda

Based on a year-long study and in-depth interviews with Latino high school students, this book focuses on why some develop a school kid identity that enables them to succeed in school, while others develop a street kid" identity and drop out. Interviews were conducted with approximately 10 stayers, 10 leavers, and 10 returners. The book…

Preparing Kids for Self-Care. Strong Families: Competent Kids. Family Workshop Leader's Guide.

ERIC Educational Resources Information Center

Prince William Cooperative Extension Service, Manassas, VA.

A program called Strong Families: Competent Kids was developed in response to the growing number of latchkey kids. The goals of the program are to help parents determine when their children are ready for self-care and to provide children with skills to manage self-care safely and confidently. It does not advocate that children should be left in…

Fungal toxins bind to the URF13 protein in maize mitochondria and Escherichia coli.

PubMed Central

Braun, C J; Siedow, J N; Levings, C S

1990-01-01

Expression of the maize mitochondrial T-urf13 gene results in a sensitivity to a family of fungal pathotoxins and to methomyl, a structurally unrelated systemic insecticide. Similar effects of pathotoxins and methomyl are observed when T-urf13 is cloned and expressed in Escherichia coli. An interaction between these compounds and the membrane-bound URF13 protein permeabilizes the inner mitochondrial and bacterial plasma membranes. To understand the toxin-URF13 effects, we have investigated whether toxin specifically binds to the URF13 protein. Our studies indicate that toxin binds to the URF13 protein in maize mitochondria and in E. coli expressing URF13. Binding analysis in E. coli reveals cooperative toxin binding. A low level of specific toxin binding is also demonstrated in cms-T and cms-T-restored mitochondria; however, binding does not appear to be cooperative in maize mitochondria. Competition and displacement studies in E. coli demonstrate that toxin binding is reversible and that the toxins and methomyl compete for the same, or for overlapping, binding sites. Two toxin-insensitive URF13 mutants display a diminished capability to bind toxin in E. coli, which identifies residues of URF13 important in toxin binding. A third toxin-insensitive URF13 mutant shows considerable toxin binding in E. coli, demonstrating that toxin binding can occur without causing membrane permeabilization. Our results indicate that toxin-mediated membrane permeabilization only occurs when toxin or methomyl is bound to URF13. PMID:2136632

Hey! A Mosquito Bit Me! (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Hey! A Mosquito Bit Me! KidsHealth / For Kids / Hey! A Mosquito Bit Me! Print en español ¡Ay! ¡ ... your skin. More on this topic for: Kids Hey! A Flea Bit Me! Hey! A Scorpion Stung ...

CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.

PubMed

Ho, Mengfei; Mettouchi, Amel; Wilson, Brenda A; Lemichez, Emmanuel

2018-05-03

Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer. In particular, through in silico analysis of the distribution of the CNF1-like deamidase active site Gly-Cys-(Xaa)n-His sequence motif in bacterial genomes, we unveil the wide distribution of the super-family of CNF-like toxins and CNF-like deamidase domains among members of the enterobacteriacae and in association with a large variety of toxin delivery systems. We extent our discussion with recent findings concerning cellular systems that control activated Rac1 GTPase stability and provide protection against cancer. These findings point to the urgency for developing holistic approaches toward personalized medicine that include monitoring for asymptomatic carriage of pathogenic toxin-producing bacteria and that ultimately might lead to improved public health and increased lifespans.

Cholera toxin subunit B-mediated intracellular trafficking of mesoporous silica nanoparticles toward the endoplasmic reticulum

NASA Astrophysics Data System (ADS)

Walker, William Andrew

In recent decades, pharmaceutical research has led to the development of numerous treatments for human disease. Nanoscale delivery systems have the potential to maximize therapeutic outcomes by enabling target specific delivery of these therapeutics. The intracellular localization of many of these materials however, is poorly controlled, leading to sequestration in degradative cellular pathways and limiting the efficacy of their payloads. Numerous proteins, particularly bacterial toxins, have evolved mechanisms to subvert the degradative mechanisms of the cell. Here, we have investigated a possible strategy for shunting intracellular delivery of encapsulated cargoes from these pathways by modifying mesoporous silica nanoparticles (MSNs) with the well-characterized bacterial toxin Cholera toxin subunit B (CTxB). Using established optical imaging methods we investigated the internalization, trafficking, and subcellular localization of our modified MSNs in an in vitro animal cell model. We then attempted to demonstrate the practical utility of this approach by using CTxB-modified mesoporous silica nanoparticles to deliver propidium iodide, a membrane-impermeant fluorophore.

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

PubMed

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

1997-01-01

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

For Kids | Volcano World | Oregon State University

Science.gov Websites

Volcanic Gases Volcanic Lightning Volcanic Sounds Volcanic Hazards Kids Only! Art Gallery Volcano Games Lightning Volcanic Sounds Volcanic Hazards Kids Only! Art Gallery Volcano Games Adventures and Fun Virtual volcano? Check out our games and fun section below! Kids' Volcano Art Gallery Games & Fun Stuff

KidSat: Image User's Manual

NASA Technical Reports Server (NTRS)

Way, JoBea; Andres, Paul; Baker, John; Goodson, Greg; Marshall, William; McGuire, John; Rackley, Kathleen; Stork, Elizabeth Jones; Yiu, Lisa

1999-01-01

The goal of KidSat was to provide young students with the opportunity to participate directly in the NASA space program and to enhance learning in the process. The KidSat pilot project was focused on using a color digital camera, mounted on the space shuttle, to take pictures of the Earth. These could be used to enhance middle school curricula. The project not only benefited middle school students, who were essentially the Science Team, responsible for deciding where to take pictures, but it also benefited high school students and undergraduates, who were essentially the Project Team, responsible for the development and implementation of the project. KidSat flew on three missions as part of the pilot project: STS-76, STS-81, and STS-86. This document describes the goals, project elements, results, and data for the three KidSat missions that made up the pilot program. It serves as a record for this pilot project and may be used as a reference for similar projects. It can also be a too] in using the data to its fullest extent. The KidSat Web page remains on-line at http://kidsat.jpl.nasa.gov/kidsat, and the images may be downloaded in their full resolution.

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

PubMed

Kitamura, Masaru

2002-02-15

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

Contact-dependent growth inhibition induces high levels of antibiotic-tolerant persister cells in clonal bacterial populations.

PubMed

Ghosh, Anirban; Baltekin, Özden; Wäneskog, Marcus; Elkhalifa, Dina; Hammarlöf, Disa L; Elf, Johan; Koskiniemi, Sanna

2018-05-02

Bacterial populations can use bet-hedging strategies to cope with rapidly changing environments. One example is non-growing cells in clonal bacterial populations that are able to persist antibiotic treatment. Previous studies suggest that persisters arise in bacterial populations either stochastically through variation in levels of global signalling molecules between individual cells, or in response to various stresses. Here, we show that toxins used in contact-dependent growth inhibition (CDI) create persisters upon direct contact with cells lacking sufficient levels of CdiI immunity protein, which would otherwise bind to and neutralize toxin activity. CDI-mediated persisters form through a feedforward cycle where the toxic activity of the CdiA toxin increases cellular (p)ppGpp levels, which results in Lon-mediated degradation of the immunity protein and more free toxin. Thus, CDI systems mediate a population density-dependent bet-hedging strategy, where the fraction of non-growing cells is increased only when there are many cells of the same genotype. This may be one of the mechanisms of how CDI systems increase the fitness of their hosts. © 2018 The Authors.

Atomistic details of the disordered states of KID and pKID. Implications in coupled binding and folding.

PubMed

Ganguly, Debabani; Chen, Jianhan

2009-04-15

Intrinsically disordered proteins (IDPs) are a newly recognized class of functional proteins for which a lack of stable tertiary fold is required for function. Because of the heterogeneous and dynamical nature, molecular modeling is necessary to provide the missing details of disordered states of IDP that are crucial for understanding their functions. In particular, generalized Born (GB) implicit solvent, combined with replica exchange (REX), might offer an optimal balance between accuracy and efficiency for modeling IDPs. We carried out extensive REX simulations in an optimized GB force field to characterize the disordered states of a regulatory IDP, KID domain of transcription factor CREB, and its phosphorylated form, pKID. The results revealed that both KID and pKID, though highly disordered on the tertiary level, are compact and mainly occupy a small number of helical substates. Interestingly, although phosphorylation of KID Ser133 leads only to marginal changes in average helicities on the ensemble level, underlying conformational substates differ significantly. In particular, pSer133 appears to restrict the accessible conformational space of the loop region and thus reduces the entropic cost of KID folding upon binding to the KIX domain of CREB-binding protein. Such an expanded role of phosphorylation in the KID:KIX recognition was not previously recognized because of a lack of substantial conformational changes on the ensemble level and inaccessibility of the structural details from experiments. The results also suggest that an implicit solvent-based modeling framework, despite various existing limitations, might be feasible for accurate atomistic simulation of small IDPs in general.

Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin

PubMed Central

Shapira, Assaf; Shapira, Shiran; Gal-Tanamy, Meital; Zemel, Romy; Tur-Kaspa, Ran; Benhar, Itai

2012-01-01

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express

Hybrid microarray based on double biomolecular markers of DNA and carbohydrate for simultaneous genotypic and phenotypic detection of cholera toxin-producing Vibrio cholerae.

PubMed

Shin, Hwa Hui; Seo, Jeong Hyun; Kim, Chang Sup; Hwang, Byeong Hee; Cha, Hyung Joon

2016-05-15

Life-threatening diarrheal cholera is usually caused by water or food contaminated with cholera toxin-producing Vibrio cholerae. For the prevention and surveillance of cholera, it is crucial to rapidly and precisely detect and identify the etiological causes, such as V. cholerae and/or its toxin. In the present work, we propose the use of a hybrid double biomolecular marker (DBM) microarray containing 16S rRNA-based DNA capture probe to genotypically identify V. cholerae and GM1 pentasaccharide capture probe to phenotypically detect cholera toxin. We employed a simple sample preparation method to directly obtain genomic DNA and secreted cholera toxin as target materials from bacterial cells. By utilizing the constructed DBM microarray and prepared samples, V. cholerae and cholera toxin were detected successfully, selectively, and simultaneously; the DBM microarray was able to analyze the pathogenicity of the identified V. cholerae regardless of whether the bacteria produces toxin. Therefore, our proposed DBM microarray is a new effective platform for identifying bacteria and analyzing bacterial pathogenicity simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins.

PubMed

Barth, Holger; Aktories, Klaus; Popoff, Michel R; Stiles, Bradley G

2004-09-01

Certain pathogenic species of Bacillus and Clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic "A-B" paradigm for protein toxins. The binary toxins produced by B. anthracis, B. cereus, C. botulinum, C. difficile, C. perfringens, and C. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. The "B" components are synthesized as precursors that are subsequently activated by serine-type proteases on the targeted cell surface and/or in solution. Following release of a 20-kDa N-terminal peptide, the activated "B" components form homoheptameric rings that subsequently dock with an "A" component(s) on the cell surface. By following an acidified endosomal route and translocation into the cytosol, "A" molecules disable a cell (and host organism) via disruption of the actin cytoskeleton, increasing intracellular levels of cyclic AMP, or inactivation of signaling pathways linked to mitogen-activated protein kinase kinases. Recently, B. anthracis has gleaned much notoriety as a biowarfare/bioterrorism agent, and of primary interest has been the edema and lethal toxins, their role in anthrax, as well as the development of efficacious vaccines and therapeutics targeting these virulence factors and ultimately B. anthracis. This review comprehensively surveys the literature and discusses the similarities, as well as distinct differences, between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine. The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria.

Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins

PubMed Central

Barth, Holger; Aktories, Klaus; Popoff, Michel R.; Stiles, Bradley G.

2004-01-01

Certain pathogenic species of Bacillus and Clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic “A-B” paradigm for protein toxins. The binary toxins produced by B. anthracis, B. cereus, C. botulinum, C. difficile, C. perfringens, and C. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. The “B” components are synthesized as precursors that are subsequently activated by serine-type proteases on the targeted cell surface and/or in solution. Following release of a 20-kDa N-terminal peptide, the activated “B” components form homoheptameric rings that subsequently dock with an “A” component(s) on the cell surface. By following an acidified endosomal route and translocation into the cytosol, “A” molecules disable a cell (and host organism) via disruption of the actin cytoskeleton, increasing intracellular levels of cyclic AMP, or inactivation of signaling pathways linked to mitogen-activated protein kinase kinases. Recently, B. anthracis has gleaned much notoriety as a biowarfare/bioterrorism agent, and of primary interest has been the edema and lethal toxins, their role in anthrax, as well as the development of efficacious vaccines and therapeutics targeting these virulence factors and ultimately B. anthracis. This review comprehensively surveys the literature and discusses the similarities, as well as distinct differences, between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine. The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria. PMID:15353562

Mixed biofilm formation by Shiga toxin-producing Escherichia coli and Salmonella enterica serovar Typhimurium enhanced bacterial resistance to sanitization due to extracellular polymeric substances.

PubMed

Wang, Rong; Kalchayanand, Norasak; Schmidt, John W; Harhay, Dayna M

2013-09-01

Shiga toxin-producing Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium are important foodborne pathogens capable of forming single-species biofilms or coexisting in multispecies biofilm communities. Bacterial biofilm cells are usually more resistant to sanitization than their planktonic counterparts, so these foodborne pathogens in biofilms pose a serious food safety concern. We investigated how the coexistence of E. coli O157:H7 and Salmonella Typhimurium strains would affect bacterial planktonic growth competition and mixed biofilm composition. Furthermore, we also investigated how mixed biofilm formation would affect bacterial resistance to common sanitizers. Salmonella Typhimurium strains were able to outcompete E. coli strains in the planktonic growth phase; however, mixed biofilm development was highly dependent upon companion strain properties in terms of the expression of bacterial extracellular polymeric substances (EPS), including curli fimbriae and exopolysaccharide cellulose. The EPS-producing strains with higher biofilm-forming abilities were able to establish themselves in mixed biofilms more efficiently. In comparison to single-strain biofilms, Salmonella or E. coli strains with negative EPS expression obtained significantly enhanced resistance to sanitization by forming mixed biofilms with an EPS-producing companion strain of the other species. These observations indicate that the bacterial EPS components not only enhance the sanitizer resistance of the EPS-producing strains but also render protections to their companion strains, regardless of species, in mixed biofilms. Our study highlights the potential risk of cross-contamination by multispecies biofilms in food safety and the need for increased attention to proper sanitization practices in food processing facilities.

A bioanalytical platform for simultaneous detection and quantification of biological toxins.

PubMed

Weingart, Oliver G; Gao, Hui; Crevoisier, François; Heitger, Friedrich; Avondet, Marc-André; Sigrist, Hans

2012-01-01

Prevalent incidents support the notion that toxins, produced by bacteria, fungi, plants or animals are increasingly responsible for food poisoning or intoxication. Owing to their high toxicity some toxins are also regarded as potential biological warfare agents. Accordingly, control, detection and neutralization of toxic substances are a considerable economic burden to food safety, health care and military biodefense. The present contribution describes a new versatile instrument and related procedures for array-based simultaneous detection of bacterial and plant toxins using a bioanalytical platform which combines the specificity of covalently immobilized capture probes with a dedicated instrumentation and immuno-based microarray analytics. The bioanalytical platform consists of a microstructured polymer slide serving both as support of printed arrays and as incubation chamber. The platform further includes an easy-to-operate instrument for simultaneous slide processing at selectable assay temperature. Cy5 coupled streptavidin is used as unifying fluorescent tracer. Fluorescence image analysis and signal quantitation allow determination of the toxin's identity and concentration. The system's performance has been investigated by immunological detection of Botulinum Neurotoxin type A (BoNT/A), Staphylococcal enterotoxin B (SEB), and the plant toxin ricin. Toxins were detectable at levels as low as 0.5-1 ng · mL(-1) in buffer or in raw milk.

Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

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

Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.

2010-09-27

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less

Structural constraints-based evaluation of immunogenic avirulent toxins from Clostridium botulinum C2 and C3 toxins as subunit vaccines.

PubMed

Prisilla, A; Prathiviraj, R; Sasikala, R; Chellapandi, P

2016-10-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 and C3 toxins in addition to botulinum neurotoxins in avian and mammalian cells. C2 and C3 toxins are members of bacterial ADP-ribosyltransferase superfamily, which modify the eukaryotic cell surface proteins by ADP-ribosylation reaction. Herein, the mutant proteins with lack of catalytic and pore forming function derived from C2 (C2I and C2II) and C3 toxins were computationally evaluated to understand their structure-function integrity. We have chosen many structural constraints including local structural environment, folding process, backbone conformation, conformational dynamic sub-space, NAD-binding specificity and antigenic determinants for screening of suitable avirulent toxins. A total of 20 avirulent mutants were identified out of 23 mutants, which were experimentally produced by site-directed mutagenesis. No changes in secondary structural elements in particular to α-helices and β-sheets and also in fold rate of all-β classes. Structural stability was maintained by reordered hydrophobic and hydrogen bonding patterns. Molecular dynamic studies suggested that coupled mutations may restrain the binding affinity to NAD(+) or protein substrate upon structural destabilization. Avirulent toxins of this study have stable energetic backbone conformation with a common blue print of folding process. Molecular docking studies revealed that avirulent mutants formed more favorable hydrogen bonding with the side-chain of amino acids near to conserved NAD-binding core, despite of restraining NAD-binding specificity. Thus, structural constraints in the avirulent toxins would determine their immunogenic nature for the prioritization of protein-based subunit vaccine/immunogens to avian and veterinary animals infected with C. botulinum. Copyright © 2016 Elsevier B.V. All rights reserved.

Mycobacterium tuberculosis toxin Rv2872 is an RNase involved in vancomycin stress response and biofilm development.

PubMed

Wang, Xiaoyu; Zhao, Xiaokang; Wang, Hao; Huang, Xue; Duan, Xiangke; Gu, Yinzhong; Lambert, Nzungize; Zhang, Ke; Kou, Zhenhao; Xie, Jianping

2018-06-11

Bacterial toxin-antitoxin (TA) systems are emerging important regulators of multiple cellular physiological events and candidates for novel antibiotic targets. To explore the role of Mycobacterium tuberculosis function, unknown toxin gene Rv2872 was heterologously expressed in Mycobacterium smegmatis (MS_Rv2872). Upon induction, MS_Rv2872 phenotype differed significantly from the control, such as increased vancomycin resistance, retarded growth, cell wall, and biofilm structure. This phenotype change might result from the RNase activity of Rv2872 as purified Rv2872 toxin protein can cleave the products of several key genes involved in abovementioned phenotypes. In summary, toxin Rv2872 was firstly reported to be a endonuclease involved in antibiotic stress responses, cell wall structure, and biofilm development.

2008 KidsCount in Colorado!

ERIC Educational Resources Information Center

Colorado Children's Campaign, 2008

2008-01-01

"KidsCount in Colorado!" is an annual publication of the Colorado Children's Campaign, which provides the best available state- and county-level data to measure and track the education, health and general well-being of the state's children. KidsCount in Colorado! informs policy debates and community discussions, serving as a valuable…

Kid Whispering and the inside Kid

ERIC Educational Resources Information Center

Chambers, J. C.; Freado, Mark

2009-01-01

The most challenging youth have learned to be experts at outwitting helping professionals. Often with hurt kids, if interactions move beyond the stuff plainly spoken and capture the emotional nuance, the student will respond with an amplification of his emotional tone. Hurt, abandonment and rejection make this student adult wary and impact his…

Sickle Cell Anemia Disease (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Kids / Sickle Cell Disease What's ... to stay in the hospital. What Causes Sickle Cell Disease? Sickle cell disease is an inherited (say: ...

[Malaria in the Republic of Djibouti. Strategy for control using a biological antilarval campaign: indigenous larvivorous fishes (Aphanius dispar) and bacterial toxins].

PubMed

Louis, J P; Albert, J P

1988-01-01

The authors take stock of the present situation of malaria in the Republic of Djibouti which, after several decades of silence, seems to have been reintroduced at the beginning of the seventies. Actually it is hypo-endemic malaria with Plasmodium falciparum of which the only vector seems to be Anopheles arabiensis, gambiae complex. The specificity of the larvae nests allows a control strategy based on the only treatment of larvae sites by biological control: larvivorous fishes (Aphanius Dispar) and in addition the pin-point use of bacterial toxins as a complementary measure. The first results obtained in the rural zones around the capital are encouraging and permit to envisage the extensions of such a strategy to the whole of the territory of the Republic.

Yersinia enterocolitica YopT and Clostridium difficile Toxin B Induce Expression of GILZ in Epithelial Cells

PubMed Central

Köberle, Martin; Göppel, David; Grandl, Tanja; Gaentzsch, Peer; Manncke, Birgit; Berchtold, Susanne; Müller, Steffen; Lüscher, Bernhard; Asselin-Labat, Marie-Liesse; Pallardy, Marc; Sorg, Isabel; Langer, Simon; Barth, Holger; Zumbihl, Robert; Autenrieth, Ingo B.; Bohn, Erwin

2012-01-01

Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype Yersinia enterocolitica which carry the pYV plasmid upregulated GILZ mRNA levels and protein expression in epithelial cells. Infection of HeLa cells with different Yersinia mutant strains revealed that the protease activity of YopT, which cleaves the membrane-bound form of Rho GTPases was sufficient to induce GILZ expression. Similarly, Clostridium difficile toxin B, another bacterial inhibitor of Rho GTPases induced GILZ expression. YopT and toxin B both increased transcriptional activity of the GILZ promoter in HeLa cells. GILZ expression could not be linked to the inactivation of an individual Rho GTPase by these toxins. However, forced expression of RhoA and RhoB decreased basal GILZ promoter activity. Furthermore, MAPK activation proved necessary for profound GILZ induction by toxin B. Promoter studies and gel shift analyses defined binding of upstream stimulatory factor (USF) 1 and 2 to a canonical c-Myc binding site (E-box) in the GILZ promoter as a crucial step of its trans-activation. In addition we could show that USF-1 and USF-2 are essential for basal as well as toxin B induced GILZ expression. These findings define a novel way of GILZ promoter trans-activation mediated by bacterial toxins and differentiate it from those mediated by dexamethasone or deprivation of IL-2. PMID:22792400

Shhh! No Opinions in the Library: "IndyKids" and Kids' Right to an Independent Press

ERIC Educational Resources Information Center

Vender, Amanda

2011-01-01

"Nintendo Power," "Sports Illustrated for Kids," and a biography of President Obama were on prominent display as the author entered the branch library in Forest Hills, Queens. The librarian looked skeptical when the author asked the librarian if she could leave copies of "IndyKids" newspapers on the free literature table. The branch manager…

A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis.

PubMed

Mutschler, Hannes; Gebhardt, Maike; Shoeman, Robert L; Meinhart, Anton

2011-03-01

Most genomes of bacteria contain toxin-antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress response. Members of the epsilon/zeta TA family are found throughout the genomes of pathogenic bacteria and were shown not only to stabilize resistance plasmids but also to promote virulence. The broad distribution of epsilon/zeta systems implies that zeta toxins utilize a ubiquitous bacteriotoxic mechanism. However, whereas all other TA families known to date poison macromolecules involved in translation or replication, the target of zeta toxins remained inscrutable. We used in vivo techniques such as microscropy and permeability assays to show that pneumococcal zeta toxin PezT impairs cell wall synthesis and triggers autolysis in Escherichia coli. Subsequently, we demonstrated in vitro that zeta toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) and that this activity is counteracted by binding of antitoxin. After identification of the product we verified the kinase activity in vivo by analyzing metabolite extracts of cells poisoned by PezT using high pressure liquid chromatograpy (HPLC). We further show that phosphorylated UNAG inhibitis MurA, the enzyme catalyzing the initial step in bacterial peptidoglycan biosynthesis. Additionally, we provide what is to our knowledge the first crystal structure of a zeta toxin bound to its substrate. We show that zeta toxins are novel kinases that poison bacteria through global inhibition of peptidoglycan synthesis. This provides a fundamental understanding of how epsilon/zeta TA systems stabilize mobile genetic elements. Additionally, our results imply a mechanism that connects activity of zeta toxin PezT to virulence of pneumococcal infections

Evaluation of the Farmers' Markets for Kids programme.

PubMed

Dannefer, Rachel; Bryan, Erica; Osborne, Alyce; Sacks, Rachel

2016-12-01

To assess the impact of Farmers' Markets for Kids, a farmers' market-based, child-oriented nutrition education programme, on attitudes and behaviours related to preparing and consuming produce among child participants and their caregivers in New York City (NYC). Retrospective pre-test/post-test cross-sectional survey with caregivers of children participating in Farmers' Markets for Kids classes. Four NYC farmers' markets where Farmers' Markets for Kids classes are implemented; these markets serve low-income communities. Two hundred and twelve adult caregivers of children who participated in Farmers' Markets for Kids classes. Caregivers reported that children's consumption of fruits and vegetables had increased since participating in Farmers' Markets for Kids and that their children more frequently assisted with food preparation; both of these improvements were statistically significant. Caregivers also reported significant improvements in attitudes: since participating in Farmers' Markets for Kids, their children were more willing to try new fruits and vegetables and caregivers found it easier to prepare fruits and vegetables for their children. Almost all respondents (99 %) reported purchasing more fruits and vegetables since participating in Farmers' Markets for Kids and 95 % had prepared the programme's recipes at home. Findings suggest that Farmers' Markets for Kids may be an effective approach for increasing produce consumption among participating children and improving related attitudes among children and caregivers. This evaluation provides support for future efforts to undertake more rigorous evaluations of such programmes.

A novel Hsp70 inhibitor prevents cell intoxication with the actin ADP-ribosylating Clostridium perfringens iota toxin

PubMed Central

Ernst, Katharina; Liebscher, Markus; Mathea, Sebastian; Granzhan, Anton; Schmid, Johannes; Popoff, Michel R.; Ihmels, Heiko; Barth, Holger; Schiene-Fischer, Cordelia

2016-01-01

Hsp70 family proteins are folding helper proteins involved in a wide variety of cellular pathways. Members of this family interact with key factors in signal transduction, transcription, cell-cycle control, and stress response. Here, we developed the first Hsp70 low molecular weight inhibitor specifically targeting the peptide binding site of human Hsp70. After demonstrating that the inhibitor modulates the Hsp70 function in the cell, we used the inhibitor to show for the first time that the stress-inducible chaperone Hsp70 functions as molecular component for entry of a bacterial protein toxin into mammalian cells. Pharmacological inhibition of Hsp70 protected cells from intoxication with the binary actin ADP-ribosylating iota toxin from Clostridium perfringens, the prototype of a family of enterotoxins from pathogenic Clostridia and inhibited translocation of its enzyme component across cell membranes into the cytosol. This finding offers a starting point for novel therapeutic strategies against certain bacterial toxins. PMID:26839186

Weighty Issues for Kids: Taking Aim at Childhood Obesity

MedlinePlus

... Weighty Issues for Kids Taking Aim at Childhood Obesity Send us your comments Kids face a lot ... of lifelong medical conditions. That problem is childhood obesity. Kids won’t be able to tackle this ...

Mother goats do not forget their kids' calls.

PubMed

Briefer, Elodie F; Padilla de la Torre, Monica; McElligott, Alan G

2012-09-22

Parent-offspring recognition is crucial for offspring survival. At long distances, this recognition is mainly based on vocalizations. Because of maturation-related changes to the structure of vocalizations, parents have to learn successive call versions produced by their offspring throughout ontogeny in order to maintain recognition. However, because of the difficulties involved in following the same individuals over years, it is not clear how long this vocal memory persists. Here, we investigated long-term vocal recognition in goats. We tested responses of mothers to their kids' calls 7-13 months after weaning. We then compared mothers' responses to calls of their previous kids with their responses to the same calls at five weeks postpartum. Subjects tended to respond more to their own kids at five weeks postpartum than 11-17 months later, but displayed stronger responses to their previous kids than to familiar kids from other females. Acoustic analyses showed that it is unlikely that mothers were responding to their previous kids simply because they confounded them with the new kids they were currently nursing. Therefore, our results provide evidence for strong, long-term vocal memory capacity in goats. The persistence of offspring vocal recognition beyond weaning could have important roles in kin social relationships and inbreeding avoidance.

Apraxia-Kids

MedlinePlus

... About Apraxia Apraxia-KIDS Library Family Start Guide SLP Start Guide Apraxia Information Downloads Research Symposium Videos ... to Help How to Get Listed In Our SLP Directory Events CASANA Sponsored Events Educational Events Conferences ...

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

PubMed Central

Byrne, Barry; Stack, Edwina; Gilmartin, Niamh; O'Kennedy, Richard

2009-01-01

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided. PMID:22408533

Ultrasensitive detection of protein translocated through toxin pores in droplet-interface bilayers

PubMed Central

Fischer, Audrey; Holden, Matthew A.; Pentelute, Brad L.; Collier, R. John

2011-01-01

Many bacterial toxins form proteinaceous pores that facilitate the translocation of soluble effector proteins across cellular membranes. With anthrax toxin this process may be monitored in real time by electrophysiology, where fluctuations in ionic current through these pores inserted in model membranes are used to infer the translocation of individual protein molecules. However, detecting the minute quantities of translocated proteins has been a challenge. Here, we describe use of the droplet-interface bilayer system to follow the movement of proteins across a model membrane separating two submicroliter aqueous droplets. We report the capture and subsequent direct detection of as few as 100 protein molecules that have translocated through anthrax toxin pores. The droplet-interface bilayer system offers new avenues of approach to the study of protein translocation. PMID:21949363

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

PubMed Central

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

2011-01-01

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

ASA24-Kids (no longer available)

Cancer.gov

ASA24-Kids-2014 was released in February 2014 and until March 2017, researchers can register new studies in this version of the ASA24® system. Funding is not currently available for a mobile accessible version for kids, such as ASA24-2016.

Messing with Bacterial Quorum Sensing

PubMed Central

González, Juan E.; Keshavan, Neela D.

2006-01-01

Quorum sensing is widely recognized as an efficient mechanism to regulate expression of specific genes responsible for communal behavior in bacteria. Several bacterial phenotypes essential for the successful establishment of symbiotic, pathogenic, or commensal relationships with eukaryotic hosts, including motility, exopolysaccharide production, biofilm formation, and toxin production, are often regulated by quorum sensing. Interestingly, eukaryotes produce quorum-sensing-interfering (QSI) compounds that have a positive or negative influence on the bacterial signaling network. This eukaryotic interference could result in further fine-tuning of bacterial quorum sensing. Furthermore, recent work involving the synthesis of structural homologs to the various quorum-sensing signal molecules has resulted in the development of additional QSI compounds that could be used to control pathogenic bacteria. The creation of transgenic plants that express bacterial quorum-sensing genes is yet another strategy to interfere with bacterial behavior. Further investigation on the manipulation of quorum-sensing systems could provide us with powerful tools against harmful bacteria. PMID:17158701

The Trojan Horse of the microbiological arms race: phage-encoded toxins as a defence against eukaryotic predators.

PubMed

Arnold, Jason W; Koudelka, Gerald B

2014-02-01

Phage-encoded Shiga toxin (Stx) acts as a bacterial defence against the eukaryotic predator Tetrahymena. To function as an effective bacterial anti-predator defence, Stx must kill a broad spectrum of predators. Consistent with that assertion, we show here that bacterially encoded Stx efficiently kills the bacteriovore Acanthamoeba castellanii in co-culture. We also show that, in addition to Stx, the phage-encoded exotoxin, diphtheria toxin (Dtx) expressed by Corynebacterium diphtheriae also can function as part of an anti-predator strategy; it kills Acanthamoeba in co-culture. Interestingly, only exotoxins produced by bacteria internalized by the Acanthamoeba predator are cytolethal; the presence of purified Dtx or Stx in culture medium has no effect on predator viability. This finding is consistent with our results indicating that intoxication of Acanthamoeba by these exotoxins does not require a receptor. Thus bacteria, in the disguise of a food source, function as a 'Trojan Horse', carrying genes encoding an exotoxin into target organisms. This 'Trojan Horse' mechanism of exotoxin delivery into predator cells allows intoxication of predators that lack a cell surface receptor for the particular toxin, allowing bacteria-bearing exotoxins to kill a broader spectrum of predators, increasing the fitness of the otherwise 'defenceless' prey bacteria. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Leucoencephalomyelitis of goat kids.

PubMed

O'Sullivan, B M; Eaves, F W; Baxendell, S A; Rowan, K J

1978-10-01

A leucoencephalomyelitis in 6 goat kids 2 to 5 months old is described. The disease was characterised by fever, ataxia, posterior paresis, circling and hyperaesthesia progressing to prostration. The neural lesion was confined to the white matter of the cerebellum and posterior brain stem in 4 kids, but in 2 others the cervical spinal cord was the main site affected. The lesion was characterised microscopically by dense perivascular cuffing with mononuclear cells, infiltration of the parenchyma with macrophages and a proliferation of glial cells and by a marked primary demyelination. In more advanced lesions, areas of the neurophil were replaced by a loose glial scar. There were associated pulmonary lesions of interstitial pneumonitis and hyperplasia of the peribronchiolar lymphoid tissue. Attempts to isolate an aetiological agent and to transmit the disease to young goat kids and lambs were unsuccessful. The disease has not been reported before in Australia but has distinct similarities to an infectious leucoencephalomyelitis of young goats which has been described in North America.

Antimicrobial Nanoparticle for the Treatment of Bacterial Infection

NASA Astrophysics Data System (ADS)

Pornpattananangkul, Dissaya

Liposomes are spherical lipid vesicles with bilayered membrane structure, which have been recognized as one of the most widely used carriers for delivering a myriad of pharmaceuticals. Liposomes can carry both hydrophilic and hydrophobic agents with high efficiency and protect them from undesired effects of external conditions. However, the applications of liposomes are usually limited by their instability during storage. They are inclined to fuse with one another immediately after preparation, resulting in undesired mixing, increase in size, and payload loss. To overcome this limitation, this dissertation will focus on the technology to stabilize liposomes during storage and destabilize at specific conditions in order to allow controllable therapeutic release, as well as demonstrate their application to treat one of the bacterial infection diseases, acne vulgaris. The first area of this research is stimuli-responsive liposomes development, where the liposomes are stabilized by introducing gold nanoparticles to adsorb to their surface. As a result, the liposomes are prevented from fusing with one another and undesirable payload release during storage or physiological environments. Moreover, therapeutic is controllably released depending on environment conditions, such as acidic pH and bacterial virulence factor. In case of acid-responsive liposomes, the bound gold nanoparticles can effectively prevent liposomes from fusing with one another at neutral pH value, while at acidic environment (e.g. pH<5), the gold particle stabilizers will fall off from the liposomes, thereby reinstalling the fusion activity of liposomes. The fusion activity of the stabilized liposomes is found to be 25% at pH=7, in contrast to 80% at pH=4. Another stimulus that can activate drug release from liposomes is virulence factor released from bacteria themselves, such as bacterial toxin. When nanoparticle-stabilized liposomes encounter with bacteria that secrete toxin, the toxin will insert

Experimental giardiasis in goat kids.

PubMed

Koudela, B; Vítovec, J

1998-01-15

The clinical, pathological and parasitological features of giardiasis resulting from experimental inoculation with 3 x 10(6) Giardia cysts were studied in goat kids. All experimentally inoculated goat kids given Giardia cysts became infected. Three of the eight inoculated kids had decreased appetite, formless feces and become slightly depressed beginning 7 or 8 days post inoculation. The mean duration of the appearance of abnormal feces was 6 days. Irregular and intermitted cysts shedding started after prepatent periods of 6-10 days and lasted throughout this study (10 weeks). The evidence of high infectivity and fast transmission of Giardia were observed under standard zoohygienic conditions. The characteristics of intestinal lesions were similar to those found in other hosts infected with Giardia. The most severe lesions were seen in the duodenum and proximal jejunum, and consisted of moderate villus atrophy, villus blunting, crypt hyperplasia and inflammatory infiltration in the lamina propria. Scanning electron microscopy revealed ultrastructural alterations in the microvillus border of enterocytes. Mucosal smears and histological sections of the gall bladder displayed Giardia trophozoites and gall bladder epithelium hyperplasia together with bile ductular proliferation in the liver tissue in two kids.

New monoclonal antibodies against a novel subtype of Shiga toxin 1 produced by Enterobacter cloacae and their use in analysis of human serum

USDA-ARS?s Scientific Manuscript database

Shiga toxin (Stx) is a major virulence factor for several bacterial pathogens that cause potentially fatal illness, including Escherichia coli and Shigella spp. The continual emergence of new subtypes of Stxs presents challenges in clinical diagnosis of infections caused by Shiga toxin-producing org...

An interbacterial NAD(P) + glycohydrolase toxin requires elongation factor Tu for delivery to target cells

DOE PAGES

Whitney, John C.; Quentin, Dennis; Sawai, Shin; ...

2015-10-08

Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD + and NADP +. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tumore » (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Lastly, visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.« less

An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

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

Whitney, John C.; Quentin, Dennis; Sawai, Shin

2015-10-08

Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD + and NADP +. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tumore » (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.« less

Alpha-Toxin Promotes Staphylococcus aureus Mucosal Biofilm Formation

PubMed Central

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

2012-01-01

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

A Bioanalytical Platform for Simultaneous Detection and Quantification of Biological Toxins

PubMed Central

Weingart, Oliver G.; Gao, Hui; Crevoisier, François; Heitger, Friedrich; Avondet, Marc-André; Sigrist, Hans

2012-01-01

Prevalent incidents support the notion that toxins, produced by bacteria, fungi, plants or animals are increasingly responsible for food poisoning or intoxication. Owing to their high toxicity some toxins are also regarded as potential biological warfare agents. Accordingly, control, detection and neutralization of toxic substances are a considerable economic burden to food safety, health care and military biodefense. The present contribution describes a new versatile instrument and related procedures for array-based simultaneous detection of bacterial and plant toxins using a bioanalytical platform which combines the specificity of covalently immobilized capture probes with a dedicated instrumentation and immuno-based microarray analytics. The bioanalytical platform consists of a microstructured polymer slide serving both as support of printed arrays and as incubation chamber. The platform further includes an easy-to-operate instrument for simultaneous slide processing at selectable assay temperature. Cy5 coupled streptavidin is used as unifying fluorescent tracer. Fluorescence image analysis and signal quantitation allow determination of the toxin’s identity and concentration. The system’s performance has been investigated by immunological detection of Botulinum Neurotoxin type A (BoNT/A), Staphylococcal enterotoxin B (SEB), and the plant toxin ricin. Toxins were detectable at levels as low as 0.5–1 ng·mL−1 in buffer or in raw milk. PMID:22438766

Kid-Short Marfan Score (Kid-SMS) Is a Useful Diagnostic Tool for Stratifying the Pre-Test Probability of Marfan Syndrome in Childhood

PubMed Central

Stark, Veronika C.; Arndt, Florian; Harring, Gesa; von Kodolitsch, Yskert; Kozlik-Feldmann, Rainer; Mueller, Goetz C.; Steiner, Kristoffer J.; Mir, Thomas S.

2015-01-01

Due to age dependent organ manifestation, diagnosis of Marfan syndrome (MFS) is a challenge, especially in childhood. It is important to identify children at risk of MFS as soon as possible to direct those to appropriate treatment but also to avoid stigmatization due to false diagnosis. We published the Kid-Short Marfan Score (Kid-SMS) in 2012 to stratify the pre-test probability of MFS in childhood. Hence we now evaluate the predictive performance of Kid-SMS in a new cohort of children. We prospectively investigated 106 patients who were suspected of having MFS. At baseline, children were examined according to Kid-SMS. At baseline and follow-up visit, diagnosis of MFS was established or rejected using standard current diagnostic criteria according to the revised Ghent Criteria (Ghent-2). At baseline 43 patients were identified with a risk of MFS according to Kid-SMS whereas 21 patients had Ghent-2 diagnosis of MFS. Sensitivity was 100%, specificity 77%, negative predictive value 100% and Likelihood ratio of Kid-SMS 4.3. During follow-up period, three other patients with a stratified risk for MFS were diagnosed according to Ghent-2. We confirm very good predictive performance of Kid-SMS with excellent sensitivity and negative predictive value but restricted specificity. Kid-SMS avoids stigmatization due to diagnosis of MFS and thus restriction to quality of life. Especially outpatient pediatricians and pediatric cardiologists can use it for primary assessment. PMID:28943606

Kid-Short Marfan Score (Kid-SMS) Is a Useful Diagnostic Tool for Stratifying the Pre-Test Probability of Marfan Syndrome in Childhood.

PubMed

Stark, Veronika C; Arndt, Florian; Harring, Gesa; von Kodolitsch, Yskert; Kozlik-Feldmann, Rainer; Mueller, Goetz C; Steiner, Kristoffer J; Mir, Thomas S

2015-03-12

Due to age dependent organ manifestation, diagnosis of Marfan syndrome (MFS) is a challenge, especially in childhood. It is important to identify children at risk of MFS as soon as possible to direct those to appropriate treatment but also to avoid stigmatization due to false diagnosis. We published the Kid-Short Marfan Score (Kid-SMS) in 2012 to stratify the pre-test probability of MFS in childhood. Hence we now evaluate the predictive performance of Kid-SMS in a new cohort of children. We prospectively investigated 106 patients who were suspected of having MFS. At baseline, children were examined according to Kid-SMS. At baseline and follow-up visit, diagnosis of MFS was established or rejected using standard current diagnostic criteria according to the revised Ghent Criteria (Ghent-2). At baseline 43 patients were identified with a risk of MFS according to Kid-SMS whereas 21 patients had Ghent-2 diagnosis of MFS. Sensitivity was 100%, specificity 77%, negative predictive value 100% and Likelihood ratio of Kid-SMS 4.3. During follow-up period, three other patients with a stratified risk for MFS were diagnosed according to Ghent-2. We confirm very good predictive performance of Kid-SMS with excellent sensitivity and negative predictive value but restricted specificity. Kid-SMS avoids stigmatization due to diagnosis of MFS and thus restriction to quality of life. Especially outpatient pediatricians and pediatric cardiologists can use it for primary assessment.

Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins*

PubMed Central

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

2014-01-01

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

Hello! Kids Network around the World.

ERIC Educational Resources Information Center

Lynes, Kristine

1996-01-01

Describes Kids Network, an educational network available from the National Geographic Society that allows students in grades four through six to become part of research teams that include students from around the world. Computer hardware requirements and a list of Kids Network research questions are listed in a sidebar. (JMV)

Diagnostic multiplex PCR for toxin genotyping of Clostridium perfringens isolates.

PubMed

Baums, Christoph G; Schotte, Ulrich; Amtsberg, Gunter; Goethe, Ralph

2004-05-20

In this study we provide a protocol for genotyping Clostridium perfringens with a new multiplex PCR. This PCR enables reliable and specific detection of the toxin genes cpa, cpb, etx, iap, cpe and cpb2 from heat lysed bacterial suspensions. The efficiency of the protocol was demonstrated by typing C. perfringens reference strains and isolates from veterinary bacteriological routine diagnostic specimens.

Identification of a lambda toxin-negative Clostridium perfringens strain that processes and activates epsilon prototoxin intracellularly.

PubMed

Harkness, Justine M; Li, Jihong; McClane, Bruce A

2012-10-01

Clostridium perfringens type B and D strains produce epsilon toxin (ETX), which is one of the most potent clostridial toxins and is involved in enteritis and enterotoxemias of domestic animals. ETX is produced initially as an inactive prototoxin that is typically then secreted and processed by intestinal proteases or possibly, for some strains, lambda toxin. During the current work a unique C. perfringens strain was identified that intracellularly processes epsilon prototoxin to an active form capable of killing MDCK cells. This activated toxin is not secreted but instead is apparently released upon lysis of bacterial cells entering stationary phase. These findings broaden understanding of the pathogenesis of type B and D infections by identifying a new mechanism of ETX activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diabetes Control: Why It's Important (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español Diabetes Control: Why It's Important KidsHealth / For Kids / Diabetes Control: ... Can Make Blood Sugar Levels Be Out of Control? Managing diabetes is like a three-way balancing ...

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Parental Characteristics and Reasons Associated With Purchasing Kids' Meals for Their Children.

PubMed

Lee-Kwan, Seung Hee; Park, Sohyun; Maynard, Leah M; Blanck, Heidi M; McGuire, Lisa C; Collins, Janet L

2018-02-01

Characteristics of parents who purchased kids' meals, reasons for the purchase, and desire for healthy options were examined. Quantitative, cross-sectional study. National. The SummerStyles survey data of 1147 parents (≥18 years). Self-reported outcome variables were purchase of kids' meals (yes/no), reasons for the purchase (13 choices), and desire for healthy options (yes/no). We used multivariable logistic regression to estimate odds ratios (ORs) for purchasing kids' meals based on parental sociodemographic and behavioral characteristics. Over half (51%) of parents reported purchasing kids' meals in the past month. The adjusted OR of purchasing kids' meals were significantly higher among younger parents (OR = 3.44 vs ≥50 years) and among parents who consumed sugar-sweetened beverages (SSBs) daily (OR = 2.70 vs none). No differences were found for race/ethnicity, income, and education. Parents who purchased kids' meals reported that the top 3 reasons for purchase were (1) because their children asked for kids' meals, (2) habit, and (3) offering of healthier sides such as fruits or fruit cups. Thirty-seven percent of parents who did not purchase kids' meals expressed willingness to purchase kids' meals if healthy options were available; this willingness was highest among younger parents (47%; P < .05). Kids' meal purchases were somewhat common. Our findings on characteristics of parents who frequently bought kids' meals (ie, younger parents and SSB consumers), common reasons for purchasing kids' meals, and willingness to buy healthier kids' meal can be used to inform intervention efforts to improve quality of kids' meals.

Awakening interest in the natural sciences - BASF's Kids' Labs.

PubMed

Lang, Cinthia

2012-01-01

At BASF's Ludwigshafen headquarters, kids and young adults in grades 1-13 can learn about chemistry in the Kids' Labs. Different programs exist for different levels of knowledge. In the two 'Hands-on Lab H(2)O & Co.' Kids' Labs, students from grades 1-6 explore the secrets of chemistry. BASF Kids' Labs have now been set up in over 30 countries. In Switzerland alone, almost 2,000 students have taken part in the 'Water Loves Chemistry' Kids' Lab since it was started in 2011. In Alsace, 600 students have participated to date. In the Teens' Lab 'Xplore Middle School', middle school students explore five different programs with the themes 'substance labyrinth', 'nutrition', 'coffee, caffeine & co.', 'cosmetics' and 'energy'. Biotechnological methods are the focus of the Teens' Lab 'Xplore Biotech' for students taking basic and advanced biology courses. In the 'Xplore High School' Teens' Lab, chemistry teachers present their own experimental lab instruction for students in basic and advanced chemistry courses. The Virtual Lab has been expanding the offerings of the BASF Kids' Labs since 2011. The online lab was developed by the company for the International Year Of Chemistry and gives kids and young adults the opportunity to do interactive experiments outside of the lab.

Virulence and the Environment: a Novel Role for Vibrio cholerae Toxin-Coregulated Pili in Biofilm Formation on Chitin

PubMed Central

Reguera, Gemma; Kolter, Roberto

2005-01-01

The toxin-coregulated pilus (TCP) of Vibrio cholerae is required for intestinal colonization and cholera toxin acquisition. Here we report that TCP mediates bacterial interactions required for biofilm differentiation on chitinaceous surfaces. We also show that undifferentiated TCP− biofilms have reduced ecological fitness and, thus, that chitin colonization may represent an ecological setting outside the host in which selection for a host colonization factor may take place. PMID:15866944

Epsilon toxin: a fascinating pore-forming toxin.

PubMed

Popoff, Michel R

2011-12-01

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

Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

PubMed

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

2011-06-01

Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Simultaneous Microcystis Algicidal and Microcystin Degrading Capability by a Single Acinetobacter Bacterial Strain.

PubMed

Li, Hong; Ai, Hainan; Kang, Li; Sun, Xingfu; He, Qiang

2016-11-01

Measures for removal of toxic harmful algal blooms often cause lysis of algal cells and release of microcystins (MCs). In this study, Acinetobacter sp. CMDB-2 that exhibits distinct algal lysing activity and MCs degradation capability was isolated. The physiological response and morphological characteristics of toxin-producing Microcystis aeruginosa, the dynamics of intra- and extracellular MC-LR concentration were studied in an algal/bacterial cocultured system. The results demonstrated that Acinetobacter sp. CMDB-2 caused thorough decomposition of algal cells and impairment of photosynthesis within 24 h. Enhanced algal lysis and MC-LR release appeared with increasing bacterial density from 1 × 10 3 to 1 × 10 7 cells/mL; however, the MC-LR was reduced by nearly 94% within 14 h irrespective of bacterial density. Measurement of extracellular and intracellular MC-LR revealed that the toxin was decreased by 92% in bacterial cell incubated systems relative to control and bacterial cell-free filtrate systems. The results confirmed that the bacterial metabolite caused 92% lysis of Microcystis aeruginosa cells, whereas the bacterial cells were responsible for approximately 91% reduction of MC-LR. The joint efforts of the bacterium and its metabolite accomplished the sustainable removal of algae and MC-LR. This is the first report of a single bacterial strain that achieves these dual actions.

Stool C difficile toxin

MedlinePlus

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

Enhanced detection and identification of Shiga toxin 1 and 2 from pathogenic bacteria by MALDI-TOF-TOF-MS/MS-PSD and top-down proteomic analysis

USDA-ARS?s Scientific Manuscript database

Shiga toxin producing Escherichia coli (STEC) represent a continuing threat to the Nation’s food supply and public health. Shiga toxin genes (stx) are encoded in lambda-like bacteriophages whose genome is inserted into the bacterial DNA. Environmental stress can trigger bacteriophage replication a...

Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.

PubMed

Alam, Shahabuddin; Javor, Sacha; Degardin, Melissa; Ajami, Dariush; Rebek, Mitra; Kissner, Teri L; Waag, David M; Rebek, Julius; Saikh, Kamal U

2015-08-01

Both Gram-positive and Gram-negative pathogens or pathogen-derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88-mediated pro-inflammatory cellular immunity for host defense. However, dysregulated MyD88-mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro-inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non-polar cyclohexane linker which strongly inhibited the production of pro-inflammatory cytokines in human primary cells to SEB (IC50 1-50 μm) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200 μm). Consistent with cytokine inhibition, in a ligand-induced cell-based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88-mediated NF-kB-dependent expression of reporter activity (IC50 10-30 μm). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro-inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. © 2014 John Wiley & Sons A/S.

An Acoustic Plate Mode Sensor for Biowarfare Toxins, Phase II

DTIC Science & Technology

1997-10-01

Biological agents -- such as bacteria , bacterial toxins and viruses -- must be detected rapidly to allow their neutralization or the quick treatment of...Results were comparable. 16 * r Cyclic voltammetry (CV) studies indicate that the monolayers made with the thiodialkyne, D1, which have been photolyzed...Microprocessor system development is ahead of schedule. Preliminary biosensor data is offered using Y. Pestis. The data indi- cates marginal detection

National CPS Certification | A Program of Safe Kids Worldwide

Science.gov Websites

the Tech! ABOUT THE PROGRAM National CPS Certification Training is a program of Safe Kids Worldwide ; E-Vouchers FAQS/HELP FAQs Fees Forms Policies & Procedures Who We Are NHTSA Safe Kids CPS-board State Farm Follow us on Facebook Copyright © 2017 by Safe Kids Worldwide - Child Passenger Safety

Bringing Kids into the Scientific Review Process.

PubMed

Kastner, Sabine; Knight, Robert T

2017-01-04

Frontiers for Young Minds puts kids in charge of scientific publications by having them control the review process. This provides kids the ability to shape the way science is taught and to better understand the scientific method. Copyright © 2017 Elsevier Inc. All rights reserved.

Review of the inhibition of biological activities of food-related selected toxins by natural compounds.

PubMed

Friedman, Mendel; Rasooly, Reuven

2013-04-23

There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term 'chemical genetics' has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet.

Review of the Inhibition of Biological Activities of Food-Related Selected Toxins by Natural Compounds

PubMed Central

Friedman, Mendel; Rasooly, Reuven

2013-01-01

There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet. PMID:23612750

KIDS COUNT in Virginia 1996: Kids and Communities.

ERIC Educational Resources Information Center

Nezlek, John B.; Galano, Joseph; Gholston, Susan E.

This KIDS COUNT report examines statewide trends in the well-being of Virginia's children. The statistical portrait is organized into six general areas of children's well-being: (1) healthy births; (2) children's health; (3) school success; (4) risky behavior; (5) families; and (6) community well-being. Key indicators in these six areas include…

Characterizing RecA-Independent Induction of Shiga toxin2-Encoding Phages by EDTA Treatment

PubMed Central

Imamovic, Lejla; Muniesa, Maite

2012-01-01

Background The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. Methodology/Principal Findings The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage λ induction (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. Conclusions/Significance Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon of induction and release of Stx phages as an important factor in the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) and in the emergence of new pathogenic strains. PMID:22393404

Toxin-Antitoxin Systems Are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli

PubMed Central

Norton, J. Paul; Mulvey, Matthew A.

2012-01-01

Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a subset is associated with strains of extraintestinal pathogenic E. coli (ExPEC). These pathogens colonize diverse niches and are a major cause of sepsis, meningitis, and urinary tract infections. Using a murine infection model, we show that two TA systems (YefM-YoeB and YbaJ-Hha) independently promote colonization of the bladder by the reference uropathogenic ExPEC isolate CFT073, while a third TA system comprised of the toxin PasT and the antitoxin PasI is critical to ExPEC survival within the kidneys. The PasTI TA system also enhances ExPEC persister cell formation in the presence of antibiotics and markedly increases pathogen resistance to nutrient limitation as well as oxidative and nitrosative stresses. On its own, low-level expression of PasT protects ExPEC from these stresses, whereas overexpression of PasT is toxic and causes bacterial stasis. PasT-induced stasis can be rescued by overexpression of PasI, indicating that PasTI is a bona fide TA system. By mutagenesis, we find that the stress resistance and toxic effects of PasT can be uncoupled and mapped to distinct domains. Toxicity was specifically linked to sequences within the N-terminus of PasT, a region that also promotes the development of persister cells. These results indicate discrete, multipurpose functions for a TA-associated toxin and demonstrate that individual TA systems can provide bacteria with pronounced fitness advantages dependent on toxin expression levels and the specific environmental niche occupied. PMID:23055930

Kids' Quest: Autism

MedlinePlus

... I Have Information For… Parents / Educators What is autism and how do I recognize a kid who might be diagnosed as having an autism spectrum disorder? Recommend on Facebook Tweet Share Compartir ...

Intimin, tir, and shiga toxin 1 do not influence enteropathogenic responses to shiga toxin-producing Escherichia coli in bovine ligated intestinal loops.

PubMed

Stevens, Mark P; Marchès, Olivier; Campbell, June; Huter, Veronika; Frankel, Gad; Phillips, Alan D; Oswald, Eric; Wallis, Timothy S

2002-02-01

Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype- and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle.

Intimin, Tir, and Shiga Toxin 1 Do Not Influence Enteropathogenic Responses to Shiga Toxin-Producing Escherichia coli in Bovine Ligated Intestinal Loops

PubMed Central

Stevens, Mark P.; Marchès, Olivier; Campbell, June; Huter, Veronika; Frankel, Gad; Phillips, Alan D.; Oswald, Eric; Wallis, Timothy S.

2002-01-01

Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype- and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle. PMID:11796630

Interactions of Kid–Kis toxin–antitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid–Kis oligomers

PubMed Central

Monti, Maria C.; Hernández-Arriaga, Ana M.; Kamphuis, Monique B.; López-Villarejo, Juan; Heck, Albert J. R.; Boelens, Rolf; Díaz-Orejas, Ramón; van den Heuvel, Robert H. H.

2007-01-01

The parD operon of Escherichia coli plasmid R1 encodes a toxin–antitoxin system, which is involved in plasmid stabilization. The toxin Kid inhibits cell growth by RNA degradation and its action is neutralized by the formation of a tight complex with the antitoxin Kis. A fascinating but poorly understood aspect of the kid–kis system is its autoregulation at the transcriptional level. Using macromolecular (tandem) mass spectrometry and DNA binding assays, we here demonstrate that Kis pilots the interaction of the Kid–Kis complex in the parD regulatory region and that two discrete Kis-binding regions are present on parD. The data clearly show that only when the Kis concentration equals or exceeds the Kid concentration a strong cooperative effect exists between strong DNA binding and Kid2–Kis2–Kid2–Kis2 complex formation. We propose a model in which transcriptional repression of the parD operon is tuned by the relative molar ratio of the antitoxin and toxin proteins in solution. When the concentration of the toxin exceeds that of the antitoxin tight Kid2–Kis2–Kid2 complexes are formed, which only neutralize the lethal activity of Kid. Upon increasing the Kis concentration, (Kid2–Kis2)n complexes repress the kid–kis operon. PMID:17317682

New insights into the biological effects of anthrax toxins: linking cellular to organismal responses

PubMed Central

Guichard, Annabel; Nizet, Victor; Bier, Ethan

2013-01-01

The anthrax toxins lethal toxin (LT) and edema toxin (ET), are essential virulence factors produced by B. anthracis. These toxins act during two distinct phases of anthrax infection. During the first, prodromal phase, which is often asymptomatic, anthrax toxins act on cells of the immune system to help the pathogen establish infection. Then, during the rapidly progressing (or fulminant) stage of the disease bacteria disseminate via a hematological route to various target tissues and organs, which are typically highly vascularized. As bacteria proliferate in the bloodstream LT and ET begin to accumulate rapidly reaching a critical threshold level that will cause death even when the bacterial proliferation is curtailed by antibiotics. During this final phase of infection the toxins cause an increase in vascular permeability and a decrease in function of target organs including the heart, spleen, kidney, adrenal gland, and brain. In this review, we examine the various biological effects of anthrax toxins, focusing on the fulminant stage of the disease and on mechanisms by which the two toxins may collaborate to cause cardiovascular collapse. We discuss normal mechanisms involved in maintaining vascular integrity and based on recent studies indicating that LT and ET cooperatively inhibit membrane trafficking to cell-cell junctions we explore several potential mechanisms by which the toxins may achieve their lethal effects. We also summarize the effects of other potential virulence factors secreted by B. anthracis and consider the role of toxic factors in the evolutionarily recent emergence of this devastating disease. PMID:21930233

Phages and the Evolution of Bacterial Pathogens: from Genomic Rearrangements to Lysogenic Conversion

PubMed Central

Brüssow, Harald; Canchaya, Carlos; Hardt, Wolf-Dietrich

2004-01-01

Comparative genomics demonstrated that the chromosomes from bacteria and their viruses (bacteriophages) are coevolving. This process is most evident for bacterial pathogens where the majority contain prophages or phage remnants integrated into the bacterial DNA. Many prophages from bacterial pathogens encode virulence factors. Two situations can be distinguished: Vibrio cholerae, Shiga toxin-producing Escherichia coli, Corynebacterium diphtheriae, and Clostridium botulinum depend on a specific prophage-encoded toxin for causing a specific disease, whereas Staphylococcus aureus, Streptococcus pyogenes, and Salmonella enterica serovar Typhimurium harbor a multitude of prophages and each phage-encoded virulence or fitness factor makes an incremental contribution to the fitness of the lysogen. These prophages behave like “swarms” of related prophages. Prophage diversification seems to be fueled by the frequent transfer of phage material by recombination with superinfecting phages, resident prophages, or occasional acquisition of other mobile DNA elements or bacterial chromosomal genes. Prophages also contribute to the diversification of the bacterial genome architecture. In many cases, they actually represent a large fraction of the strain-specific DNA sequences. In addition, they can serve as anchoring points for genome inversions. The current review presents the available genomics and biological data on prophages from bacterial pathogens in an evolutionary framework. PMID:15353570

The Kid-Short Marfan Score (Kid-SMS) - an easy executable risk score for suspected paediatric patients with Marfan syndrome.

PubMed

Mueller, Goetz C; Stark, Veronika; Steiner, Kristoffer; Weil, Jochen; von Kodolitsch, Yskert; Mir, Thomas S

2013-02-01

Due to age-dependent manifestations, diagnosis of Marfan syndrome (MFS) in children and adolescents is sophisticated. Although revised Ghent criteria is a major step forward, its utility in children is still restricted due to expensive and technically advanced diagnostics. As early diagnosis submits long-term benefits concerning prognosis, the need of an appropriate diagnostic tool for risk stratification of suspected paediatric patients with Marfan is justified. Sixty paediatric patients with Marfan were subject to a standardized diagnostic programme. All clinical symptoms of the revised Ghent nosology were analysed concerning age at first clinical manifestation, prevalence and likelihood ratio for MFS. Symptoms with early onset, high prevalence and high positive likelihood ratio were identified and combined for a risk score called Kid-Short Marfan Score (Kid-SMS). Three risk categories for suspicion of Marfan syndrome were developed. Finally, the Kid-SMS was operated in 130 paediatric patients with suspected MFS. Kid-SMS identified significantly more suspected patients with Marfan compared with Ghent nosology, revised Ghent and genetics alone without oversensitivity. Whereas diagnosis of MFS in childhood is sophisticated, Kid-SMS is a useful tool for risk stratification of suspected paediatric patients with Marfan by easy executable diagnostics, especially for paediatricians and paediatric cardiologists. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

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

PubMed Central

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

2016-01-01

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

Thermal stability and structural changes in bacterial toxins responsible for food poisoning

PubMed Central

Regenthal, Paulina; Hansen, Jesper S.; André, Ingemar

2017-01-01

The staphylococcal enterotoxins (SEs) are secreted by the bacteria Staphylococcus aureus and are the most common causative agent in staphylococcal food poisoning. The staphylococcal enterotoxin A (SEA) has been associated with large staphylococcal food poisoning outbreaks, but newer identified SEs, like staphylococcal enterotoxin H (SEH) has recently been shown to be present at similar levels as SEA in food poisoning outbreaks. Thus, we set out to investigate the thermo-stability of the three-dimensional structures of SEA, SEH and staphylococcal enterotoxin E (SEE), since heat inactivation is a common method to inactivate toxins during food processing. Interestingly, the investigated toxins behaved distinctly different upon heating. SEA and SEE were more stable at slightly acidic pH values, while SEH adopted an extremely stable structure at neutral pH, with almost no effects on secondary structural elements upon heating to 95°C, and with reversible formation of tertiary structure upon subsequent cooling to room temperature. Taken together, the data suggests that the family of staphylococcal enterotoxins have different ability to withstand heat, and thus the exact profile of heat inactivation for all SEs causing food poisoning needs to be considered to improve food safety. PMID:28207867

Teaching Kids to Be Smart About Social Media

MedlinePlus

... media can be a hub for things like cyberbullying and questionable activities. Without meaning to, kids can ... to websites Concerns and Consequences Besides problems like cyberbullying and online predators, kids also can face the ...

Healthy Family 2009: 6 "Bests" About Kids' Exercise

MedlinePlus

... Past Issues Healthy Family 2009 6 "Bests" About Kids' Exercise Past Issues / Winter 2009 Table of Contents ... one hour of physical activity a day helps kids to: Feel less stressed Feel better about themselves ...

Cdc2-mediated phosphorylation of Kid controls its distribution to spindle and chromosomes

PubMed Central

Ohsugi, Miho; Tokai-Nishizumi, Noriko; Shiroguchi, Katsuyuki; Toyoshima, Yoko Y.; Inoue, Jun-ichiro; Yamamoto, Tadashi

2003-01-01

The chromokinesin Kid is important in chromosome alignment at the metaphase plate. Here, we report that Kid function is regulated by phosphorylation. We identify Ser427 and Thr463 as M phase-specific phosphorylation sites and Cdc2–cyclin B as a Thr463 kinase. Kid with a Thr463 to alanine mutation fails to be localized on chromosomes and is only detected along spindles, although it retains the ability to bind DNA or chromosomes. Localization of rigor-type mutant Kid, which shows nucleotide-independent microtubule association, is also confined to the spindle, implying that strong association of Kid with the spindle can sequester it from chromosomes. T463A substitution in DNA-binding domain-truncated Kid consistently enhances its spindle localization. At physiological ionic strength, unphosphorylated Kid shows ATP-independent microtubule association, whereas Thr463-phosphorylated Kid shows ATP dependency. Moreover, the stalk region of unphosphorylated Kid interacts with microtubules and the interaction is weakened when Thr463 is phosphorylated. Our data suggest that phosphorylation on Thr463 of Kid downregulates its affinity for microtubules to ensure reversible association with spindles, allowing Kid to bind chromosomes and exhibit its function. PMID:12727876

The Cool Kids Coalition.

PubMed

Corrarino, J E; Walsh, P J; Boyle, M L; Anselmo, D

2000-01-01

The Cool Kids Coalition was initiated as a community response to more than 214 hospitalizations of children under the age of five for burns over a 6-year period in one township in Long Island, NY. The coalition was started by public health nurses in partnership with the local chapter of the National Safe Kids Campaign. Goals included: 1. parent education regarding scald burn prevention; 2. development of innovative interventions for those at risk; and 3, development of innovative community approaches to scald prevention. Coalition members had diverse backgrounds and the coalition integrated non-traditional partners in injury control. The coalition doubled in size due to overwhelming community interest, growing within a few months from an initial group of 15 to a well-represented group of 30. Innovative programs were implemented that reached more than 3,000 parents, both in the community and home. Teaching was conducted with parents in the target population in Head Start centers, homeless shelters, the home, libraries, child care centers, a shelter for teen parents, etc. Member agencies incorporated the booklet and materials into their individual programs. The development of the Cool Kids Coalition illustrates the power of nursing in community health.

Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers.

PubMed

Fuchs, Hendrik; Weng, Alexander; Gilabert-Oriol, Roger

2016-07-01

The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

PubMed Central

Fuchs, Hendrik; Weng, Alexander; Gilabert-Oriol, Roger

2016-01-01

The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments. PMID:27376327

Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins

PubMed Central

Grinberg, Yehudit; Benhar, Itai

2017-01-01

Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called “human cytotoxic fusion proteins”, in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies. PMID:28574434

Kid-mediated chromosome compaction ensures proper nuclear envelope formation.

PubMed

Ohsugi, Miho; Adachi, Kenjiro; Horai, Reiko; Kakuta, Shigeru; Sudo, Katsuko; Kotaki, Hayato; Tokai-Nishizumi, Noriko; Sagara, Hiroshi; Iwakura, Yoichiro; Yamamoto, Tadashi

2008-03-07

Toward the end of mitosis, neighboring chromosomes gather closely to form a compact cluster. This is important for reassembling the nuclear envelope around the entire chromosome mass but not individual chromosomes. By analyzing mice and cultured cells lacking the expression of chromokinesin Kid/kinesin-10, we show that Kid localizes to the boundaries of anaphase and telophase chromosomes and contributes to the shortening of the anaphase chromosome mass along the spindle axis. Loss of Kid-mediated anaphase chromosome compaction often causes the formation of multinucleated cells, specifically at oocyte meiosis II and the first couple of mitoses leading to embryonic death. In contrast, neither male meiosis nor somatic mitosis after the morula-stage is affected by Kid deficiency. These data suggest that Kid-mediated anaphase/telophase chromosome compaction prevents formation of multinucleated cells. This protection is especially important during the very early stages of development, when the embryonic cells are rich in ooplasm.

Inhibition of cholera toxin and other AB toxins by polyphenolic compounds

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

Lee, Ki-Young; Lee, Bong-Jin

2016-10-22

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

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

PubMed

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

2016-10-26

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

2013 Kids Count in Colorado! Community Matters

ERIC Educational Resources Information Center

Colorado Children's Campaign, 2013

2013-01-01

"Kids Count in Colorado!" is an annual publication of the Children's Campaign, providing state and county level data on child well-being factors including child health, education, and economic status. Since its first release 20 years ago, "Kids Count in Colorado!" has become the most trusted source for data and information on…

Added sugars in kids' meals from chain restaurants.

PubMed

Scourboutakos, Mary J; Semnani-Azad, Zhila; L'Abbé, Mary R

2016-06-01

To analyze the added sugars in kids' meals from Canadian chain restaurants in relation to the World Health Organization's proposed sugar recommendation (less than 5% of total daily calories should come from added sugars) and current recommendation (less than 10% of total daily calories should come from added sugars). Total sugar levels were retrieved from the websites of 10 fast-food and 7 sit-down restaurants in 2010. The added sugar levels in 3178 kids' meals from Canadian chain restaurants were calculated in 2014 (in Toronto, Canada) by subtracting all naturally occurring sugars from the total sugar level. The average amount of added sugars in restaurant kids' meals (25 ± 0.36 g) exceeded the WHO's proposed daily recommendation for sugar intake. There was a wide range of added sugar levels in kids' meals ranging from 0 g to 114 g. 50% of meals exceeded the WHO's proposed daily sugar recommendation, and 19% exceeded the WHO's current daily sugar recommendation. There is a wide range of sugar levels in kids' meals from restaurants, and many contain more than a day's worth of sugar.

Poisons, ruffles and rockets: bacterial pathogens and the host cell cytoskeleton.

PubMed

Steele-Mortimer, O; Knodler, L A; Finlay, B B

2000-02-01

The cytoskeleton of eukaryotic cells is affected by a number of bacterial and viral pathogens. In this review we consider three recurring themes of cytoskeletal involvement in bacterial pathogenesis: 1) the effect of bacterial toxins on actin-regulating small GTP-binding proteins; 2) the invasion of non-phagocytic cells by the bacterial induction of ruffles at the plasma membrane; 3) the formation of actin tails and pedestals by intracellular and extracellular bacteria, respectively. Considerable progress has been made recently in the characterization of these processes. It is becoming clear that bacterial pathogens have developed a variety of sophisticated mechanisms for utilizing the complex cytoskeletal system of host cells. These bacterially-induced processes are now providing unique insights into the regulation of fundamental eukaryotic mechanisms.

Approaches to treatment of emerging Shiga toxin-producing Escherichia coli infections highlighting the O104:H4 serotype

PubMed Central

Rahal, Elias A.; Fadlallah, Sukayna M.; Nassar, Farah J.; Kazzi, Natalie; Matar, Ghassan M.

2015-01-01

Shiga toxin-producing Escherichia coli (STEC) are a group of diarrheagenic bacteria associated with foodborne outbreaks. Infection with these agents may result in grave sequelae that include fatality. A large number of STEC serotypes has been identified to date. E. coli serotype O104:H4 is an emerging pathogen responsible for a 2011 outbreak in Europe that resulted in over 4000 infections and 50 deaths. STEC pathogenicity is highly reliant on the production of one or more Shiga toxins that can inhibit protein synthesis in host cells resulting in a cytotoxicity that may affect various organ systems. Antimicrobials are usually avoided in the treatment of STEC infections since they are believed to induce bacterial cell lysis and the release of stored toxins. Some antimicrobials have also been reported to enhance toxin synthesis and production from these organisms. Various groups have attempted alternative treatment approaches including the administration of toxin-directed antibodies, toxin-adsorbing polymers, probiotic agents and natural remedies. The utility of antibiotics in treating STEC infections has also been reconsidered in recent years with certain modalities showing promise. PMID:25853096

Effect of environmental conditions on production of toxic shock syndrome toxin 1 by Staphylococcus aureus.

PubMed Central

Wong, A C; Bergdoll, M S

1990-01-01

The kinetics of toxic shock syndrome toxin 1 (TSST-1) production by Staphylococcus aureus was studied in a fermentor in which aeration rate, atmospheric composition, pH, and temperature were controlled. The toxin was synthesized at a maximal rate during the exponential phase. High bacterial populations were not necessarily accompanied by high TSST-1 yields. Aerobiosis increased TSST-1 production, but excessive aeration had an adverse effect. Addition of CO2 enhanced TSST-1 yield by increasing toxin production rate and efficiency. Cultures with no pH control made more TSST-1 than those maintained at pH 5.5 to 7.5. Maximum TSST-1 yields were obtained when cultures were supplied with air (20 cm3/min) and CO2 (5 cm3/min) via a sintered glass sparger. PMID:2108084

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

PubMed

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

2017-07-03

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

Dietary protein level and performance of growing Baladi kids.

PubMed

Abdelrahman, M M; Aljumaah, R S

2014-01-01

A study was conducted to evaluate the effect of feeding different levels of protein to black Baladi breed kids. Weanling Baladi kids (n=18; 75 to 90 days old) were selected and individually housed at our experimental farm. Kids were divided randomly to one of the three treatments for 12 weeks. The three dietary treatments were: T1: control ration, formulated according to NRC to cover the protein (level 1) and other nutrients requirements. T2: ration formulated to cover only 75% of protein (level 2) recommended by NRC. T3: control diet + 2.4 g undegradable methionine (Smartamine®)/day/kid (level 3). Feed intake, initial and monthly body weights were recorded. Blood samples were collected monthly and analyzed for metabolites and Co, Zn and Cu levels. Decreasing the dietary level of protein (T2) negatively affected (P<0.05) the total live weight gain, average daily gain and feed conversion ratio when compared with the control and T3 groups. Moreover, treatment, time and time × treatment caused a significant change on Co concentration in blood serum with higher value at the end of the experiment. Treatments had a significant effect (P<0.05) on blood serum cholesterol and protein levels. Undegradable methionine supplementation (T3) significantly increased longissimus dorsi weight, fat thickness and omental fat%. In conclusion, feeding Baladi kids below the NRC requirements of protein negatively affect the growth performance and feed efficiency. The recommended protein level by NRC for growing kids cover the requirements of growing black Baladi kids for maximum growth and productivity.

Dietary protein level and performance of growing Baladi kids

PubMed Central

Abdelrahman, M. M.; Aljumaah, R. S.

2014-01-01

A study was conducted to evaluate the effect of feeding different levels of protein to black Baladi breed kids. Weanling Baladi kids (n=18; 75 to 90 days old) were selected and individually housed at our experimental farm. Kids were divided randomly to one of the three treatments for 12 weeks. The three dietary treatments were: T1: control ration, formulated according to NRC to cover the protein (level 1) and other nutrients requirements. T2: ration formulated to cover only 75% of protein (level 2) recommended by NRC. T3: control diet + 2.4 g undegradable methionine (Smartamine®)/day/kid (level 3). Feed intake, initial and monthly body weights were recorded. Blood samples were collected monthly and analyzed for metabolites and Co, Zn and Cu levels. Decreasing the dietary level of protein (T2) negatively affected (P<0.05) the total live weight gain, average daily gain and feed conversion ratio when compared with the control and T3 groups. Moreover, treatment, time and time × treatment caused a significant change on Co concentration in blood serum with higher value at the end of the experiment. Treatments had a significant effect (P<0.05) on blood serum cholesterol and protein levels. Undegradable methionine supplementation (T3) significantly increased longissimus dorsi weight, fat thickness and omental fat%. In conclusion, feeding Baladi kids below the NRC requirements of protein negatively affect the growth performance and feed efficiency. The recommended protein level by NRC for growing kids cover the requirements of growing black Baladi kids for maximum growth and productivity. PMID:27175130

Binding of ATP by pertussis toxin and isolated toxin subunits

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

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

1990-07-03

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

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

Chronic copper poisoning in Angora kids.

PubMed

Belford, C J; Raven, C R; Black, H

1989-12-01

The investigation of five field cases of chronic copper poisoning in a group of 100 Angora kids is reported. Toxicity was confirmed by the demonstration of Heinz body anaemias, necrotizing liver disease, haemoglobinuric nephrosis and excessive levels of copper in blood, livers and kidneys. The dietary history of the kids is described. Tissue levels of copper and reported interactions between selenium, zinc and copper are discussed. Therapeutic and preventative measures are suggested.

Kids Count in Indiana: 1996 Data Book.

ERIC Educational Resources Information Center

Erickson, Judith B.

This Kids Count report is the third in a series examining statewide trends in the well-being of Indiana's children. The report combines statistics of special concern in Indiana with 10 national Kids Count well-being indicators: (1) percent low birthweight; (2) infant mortality rate; (3) child death rate; (4) birth rate to unmarried teens ages 15…

Humour and Connecting with Kids in Pain

ERIC Educational Resources Information Center

Digney, John

2009-01-01

Emotional pain which manifests itself in problem behaviours is, for many children and youth, a part of their everyday struggle through life. Kids growing up in residential care or in a dysfunctional family or setting suffer this pain. Connecting with kids in pain, the primary task for youth workers, is made all the more difficult, the greater the…

Serogroup-Specific Bacterial Engineered Glycoproteins as Novel Antigenic Targets for Diagnosis of Shiga Toxin-Producing-Escherichia coli-Associated Hemolytic-Uremic Syndrome

PubMed Central

Melli, Luciano J.; Ciocchini, Andrés E.; Caillava, Ana J.; Vozza, Nicolás; Chinen, Isabel; Rivas, Marta; Feldman, Mario F.

2014-01-01

Human infection with Shiga toxin-producing Escherichia coli (STEC) is a major cause of postdiarrheal hemolytic-uremic syndrome (HUS), a life-threatening condition characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. E. coli O157:H7 is the dominant STEC serotype associated with HUS worldwide, although non-O157 STEC serogroups can cause a similar disease. The detection of anti-O157 E. coli lipopolysaccharide (LPS) antibodies in combination with stool culture and detection of free fecal Shiga toxin considerably improves the diagnosis of STEC infections. In the present study, we exploited a bacterial glycoengineering technology to develop recombinant glycoproteins consisting of the O157, O145, or O121 polysaccharide attached to a carrier protein as serogroup-specific antigens for the serological diagnosis of STEC-associated HUS. Our results demonstrate that using these antigens in indirect ELISAs (glyco-iELISAs), it is possible to clearly discriminate between STEC O157-, O145-, and O121-infected patients and healthy children, as well as to confirm the diagnosis in HUS patients for whom the classical diagnostic procedures failed. Interestingly, a specific IgM response was detected in almost all the analyzed samples, indicating that it is possible to detect the infection in the early stages of the disease. Additionally, in all the culture-positive HUS patients, the serotype identified by glyco-iELISAs was in accordance with the serotype of the isolated strain, indicating that these antigens are valuable not only for diagnosing HUS caused by the O157, O145, and O121 serogroups but also for serotyping and guiding the subsequent steps to confirm diagnosis. PMID:25472487

Validation of Gujarati Version of ABILOCO-Kids Questionnaire

PubMed Central

Diwan, Jasmin; Patel, Pankaj; Bansal, Ankita B.

2015-01-01

Background ABILOCO-Kids is a measure of locomotion ability for children with cerebral palsy (CP) aged 6 to 15 years & is available in English & French. Aim To validate the Gujarati version of ABILOCO-Kids questionnaire to be used in clinical research on Gujarati population. Materials and Methods ABILOCO-Kids questionnaire was translated into Gujarati from English using forward-backward-forward method. To ensure face & content validity of Gujarati version using group consensus method, each item was examined by group of experts having mean experience of 24.62 years in field of paediatric and paediatric physiotherapy. Each item was analysed for content, meaning, wording, format, ease of administration & scoring. Each item was scored by expert group as either accepted, rejected or accepted with modification. Procedure was continued until 80% of consensus for all items. Concurrent validity was examined on 55 children with Cerebral Palsy (6-15 years) of all Gross Motor Functional Classification System (GMFCS) level & all clinical types by correlating score of ABILOCO-Kids with Gross Motor Functional Measure & GMFCS. Result In phase 1 of validation, 16 items were accepted as it is; 22 items accepted with modification & 3 items went for phase 2 validation. For concurrent validity, highly significant positive correlation was found between score of ABILOCO-Kids & total GMFM (r=0.713, p<0.005) & highly significant negative correlation with GMFCS (r= -0.778, p<0.005). Conclusion Gujarati translated version of ABILOCO-Kids questionnaire has good face & content validity as well as concurrent validity which can be used to measure caregiver reported locomotion ability in children with CP. PMID:26557603

Validation of Gujarati Version of ABILOCO-Kids Questionnaire.

PubMed

Diwan, Shraddha; Diwan, Jasmin; Patel, Pankaj; Bansal, Ankita B

2015-10-01

ABILOCO-Kids is a measure of locomotion ability for children with cerebral palsy (CP) aged 6 to 15 years & is available in English & French. To validate the Gujarati version of ABILOCO-Kids questionnaire to be used in clinical research on Gujarati population. ABILOCO-Kids questionnaire was translated into Gujarati from English using forward-backward-forward method. To ensure face & content validity of Gujarati version using group consensus method, each item was examined by group of experts having mean experience of 24.62 years in field of paediatric and paediatric physiotherapy. Each item was analysed for content, meaning, wording, format, ease of administration & scoring. Each item was scored by expert group as either accepted, rejected or accepted with modification. Procedure was continued until 80% of consensus for all items. Concurrent validity was examined on 55 children with Cerebral Palsy (6-15 years) of all Gross Motor Functional Classification System (GMFCS) level & all clinical types by correlating score of ABILOCO-Kids with Gross Motor Functional Measure & GMFCS. In phase 1 of validation, 16 items were accepted as it is; 22 items accepted with modification & 3 items went for phase 2 validation. For concurrent validity, highly significant positive correlation was found between score of ABILOCO-Kids & total GMFM (r=0.713, p<0.005) & highly significant negative correlation with GMFCS (r= -0.778, p<0.005). Gujarati translated version of ABILOCO-Kids questionnaire has good face & content validity as well as concurrent validity which can be used to measure caregiver reported locomotion ability in children with CP.

Decline of maternal antibodies to small ruminant lentivirus in goat kids.

PubMed

Czopowicz, Michał; Szaluś-Jordanow, Olga; Mickiewicz, Marcin; Moroz, Agata; Witkowski, Lucjan; Markowska-Daniel, Iwona; Reczyńska, Daria; Bagnicka, Emilia; Kaba, Jarosław

2018-06-06

We carried out this study to determine for how long small ruminant lentivirus (SRLV)-specific antibodies can be detected by three commercial ELISA kits in goat kids after suckling infected does in field conditions. Forty-one kids born to SRLV-seropositive asymptomatic does were blood sampled prior to colostrum consumption, and then weekly for 6 months in total. The sera were screened with three commercial ELISA kits: whole-virus ELISA (wELISA), recombinant transmembrane and capsid antigen ELISA (TM/CA-ELISA), and surface antigen ELISA (SU-ELISA). All but one kid were seronegative in all three ELISAs right after birth. At the age of 1 week all kids turned seropositive in wELISA, 39 kids (95%) in TM/CA-ELISA, and 35 kids (85%) in SU-ELISA. All seropositive kids turned seronegative in wELISA by the 15th week, and in SU-ELISA by the 19th week (median of 8 weeks in both ELISA), whereas in TM/CA-ELISA five kids (13% of 39 initially seropositive) were still seropositive at the age of 6 months (median of 11 weeks). Antibody levels at the age of 1 week proved significantly linked to the duration of maternal antibodies in all three ELISAs and could be employed to predict for how long maternal antibodies would remain detectable. © 2018 Japanese Society of Animal Science.

Feeding soywaste or pellet on performance and carcass characteristics of post-weaning kids.

PubMed

Rahman, Mohammad Mijanur; Khadijah, Wan Embong Wan; Abdullah, Ramli Bin

2016-08-01

Twelve Jermasia kids were individually housed in pens to study the effects of soywaste on growth performance and carcass characteristics and to compare such effects with commercial pellet. Kids were divided into a pellet group and a soywaste group, including six kids (3 males and 3 females) in each group. Pellet or soywaste was offered to kids at a rate of 2.0 % dry matter (DM) of body weight/day in addition to Napier grass ad libitum. In last 10 days of experiment, kids were housed in metabolism crates for faeces collection. At the end of the experiment, three males from each group were slaughtered. Kids fed soywaste diet consumed more grass and neutral detergent fibre (NDF) than those fed pellet. The same trend was found for the digestibilities of DM, organic matter (OM) and NDF. Conversely, kids fed soywaste diet consumed less soywaste supplement than kids fed pellet. No treatment effects were observed on total intakes of DM, OM and crude protein (CP) including CP digestibility. Similarly, no effects were found on carcass and non-carcass components, except for lean, lean to fat ratio and kidney weight which were higher for kids fed soywaste diet. Results indicate that soywaste is effective as a feed for growing kids.

Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates.

PubMed

Sursal, Tolga; Stearns-Kurosawa, Deborah J; Itagaki, Kiyoshi; Oh, Sun-Young; Sun, Shiqin; Kurosawa, Shinichiro; Hauser, Carl J

2013-01-01

Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. Systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS, and postinfective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern reflecting cellular injury. Circulating bacterial 16S DNA (bDNA) is a pathogen-associated pattern (PAMP) reflecting ongoing infection. We developed quantitative polymerase chain reaction assays to quantify these markers, and predicting their plasma levels might help distinguish sterile injury from infection. To study these events in primates, we assayed banked serum from Papio baboons that had undergone a brief challenge of intravenous Bacillus anthracis delta Sterne (modified to remove toxins) followed by antibiotics (anthrax) that causes organ failure and death. To investigate the progression of sepsis to "severe" sepsis and death, we studied animals where anthrax was pretreated with drotrecogin alfa (activated protein C), which attenuates sepsis in baboons. We also contrasted lethal anthrax bacteremia against nonlethal E. coli bacteremia and against sterile tissue injury from Shiga-like toxin 1. Bacterial DNA and mtDNA levels in timed samples were correlated with blood culture results and assays of organ function. Sterile injury by Shiga-like toxin 1 increased mtDNA, but bDNA was undetectable: consistent with the absence of infection. The bacterial challenges caused parallel early bDNA and mtDNA increases, but bDNA detected pathogens even after bacteria were undetectable by culture. Sublethal E. coli challenge only caused transient rises in mtDNA consistent with a self-limited injury. In lethal

Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways

PubMed Central

Willett, Julia L. E.; Gucinski, Grant C.; Fatherree, Jackson P.; Low, David A.; Hayes, Christopher S.

2015-01-01

Contact-dependent growth inhibition (CDI) systems function to deliver toxins into neighboring bacterial cells. CDI+ bacteria export filamentous CdiA effector proteins, which extend from the inhibitor-cell surface to interact with receptors on neighboring target bacteria. Upon binding its receptor, CdiA delivers a toxin derived from its C-terminal region. CdiA C-terminal (CdiA-CT) sequences are highly variable between bacteria, reflecting the multitude of CDI toxin activities. Here, we show that several CdiA-CT regions are composed of two domains, each with a distinct function during CDI. The C-terminal domain typically possesses toxic nuclease activity, whereas the N-terminal domain appears to control toxin transport into target bacteria. Using genetic approaches, we identified ptsG, metI, rbsC, gltK/gltJ, yciB, and ftsH mutations that confer resistance to specific CdiA-CTs. The resistance mutations all disrupt expression of inner-membrane proteins, suggesting that these proteins are exploited for toxin entry into target cells. Moreover, each mutation only protects against inhibition by a subset of CdiA-CTs that share similar N-terminal domains. We propose that, following delivery of CdiA-CTs into the periplasm, the N-terminal domains bind specific inner-membrane receptors for subsequent translocation into the cytoplasm. In accord with this model, we find that CDI nuclease domains are modular payloads that can be redirected through different import pathways when fused to heterologous N-terminal “translocation domains.” These results highlight the plasticity of CDI toxin delivery and suggest that the underlying translocation mechanisms could be harnessed to deliver other antimicrobial agents into Gram-negative bacteria. PMID:26305955

Surface-enhanced Raman for monitoring toxins in water

NASA Astrophysics Data System (ADS)

Spencer, Kevin M.; Sylvia, James M.; Clauson, Susan L.; Bertone, Jane F.; Christesen, Steven D.

2004-02-01

Protection of the drinking water supply from a terrorist attack is of critical importance. Since the water supply is vast, contamination prevention is difficult. Therefore, rapid detection of contaminants, whether a military chemical/biological threat, a hazardous chemical spill, naturally occurring toxins, or bacterial build-up is a priority. The development of rapid environmentally portable and stable monitors that allow continuous monitoring of the water supply is ideal. EIC Laboratories has been developing Surface-Enhanced Raman Spectroscopy (SERS) to detect chemical agents, toxic industrial chemicals (TICs), viruses, cyanotoxins and bacterial agents. SERS is an ideal technique for the Joint Service Agent Water Monitor (JSAWM). SERS uses the enhanced Raman signals observed when an analyte adsorbs to a roughened metal substrate to enable trace detection. Proper development of the metal substrate will optimize the sensitivity and selectivity towards the analytes of interest.

Isolation, purification and spectrometric analysis of PSP toxins from moraxella sp., a bacterium associated with a toxic dinoflagellate

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

Boyce, S.D.; Doucette, G.J.

1994-12-31

Paralytic shellfish poisoning (PSP) is a seafood intoxication syndrome caused by the injestion of shellfish contaminated with toxins produced by algae known as dinoflagellates. The PSP toxins, saxitoxin and its derivatives, act to block voltage-dependent sodium channels and can cause paralysis and even death at higher doses. It is well documented that bacteria coexist with many harmful or toxic algal species, though the exact nature of the association in relation to toxin production is unknown. Recently, the bacterium Moraxella sp. was isolated from the PSP toxin producing dinoflagellate Alexandrium tamarense. Through HPLC analysis and saxitoxin receptor binding assays performed onmore » crude bacterial extracts, it appears that Moraxella sp. is capable of producing saxitoxin and several of its derivatives. However, physical confirmation (e.g. mass spectrometry) of these results is still needed.« less

78 FR 19799 - United States Mint Kids' Baseball Coin Design Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF THE TREASURY United States Mint United States Mint Kids' Baseball Coin Design Challenge ACTION: Notification of the Opening of the United States Mint Kids' Baseball Coin Design Challenge on April 11, 2013. SUMMARY: The United States Mint announces the opening of a national kids' baseball...

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

PubMed

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

2015-12-01

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

How to Protect Kids from Child Molesters

ERIC Educational Resources Information Center

Ayers, Lauren

2007-01-01

When one mother was asked how often she worried about her child's safety, she replied, "Every time she goes out the door." Many parents rely on school abuse prevention programs to teach kids how to stay safe. But what if these programs actually increase the risk of sex crimes that target kids? What happens if parental efforts to safeguard kids…

What Happens in the Operating Room? (For Kids)

MedlinePlus

... to stay a while after your surgery. Other times, a kid can have minor surgery and go home the ... be able to stay with you until it's time for surgery. Sometimes, parents can even be there while their kid gets the anesthesia. But parents can't stay ...

Epidemiological Observations on Cryptosporidiosis in Diarrheic Goat Kids in Greece.

PubMed

Giadinis, Nektarios D; Papadopoulos, Elias; Lafi, Shawkat Q; Papanikolopoulou, Vasiliki; Karanikola, Sofia; Diakou, Anastasia; Vergidis, Vergos; Xiao, Lihua; Ioannidou, Evi; Karatzias, Harilaos

2015-01-01

This study aimed at investigating the occurrence of Cryptosporidium spp. in diarrheic goat kids in Greece and the risk factors associated with cryptosporidiosis. Altogether, 292 diarrheic 4-15-day-old goat kids from 54 dairy goat herds of Northern Greece were examined. Oocysts of Cryptosporidium spp. were detected in 223 of 292 (76.4%) goat kids and the intensity of infection was scored as "high" in 142 samples, "moderate" in 45 samples, and "low" in 36 samples. Larger herds (>200 animals) had higher infection rates than smaller ones, although this difference was not statistically significant. Significantly higher infection rates were observed in herds during late kidding season (1 January to 30 April) compared to the early one (1 September to 31 December). These results suggest that cryptosporidiosis is very common in diarrheic goat kids in Greece, especially in large herds during the late parturition season.

Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

PubMed

von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

2016-07-01

Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action. © 2016 The Author(s). published by Portland Press Limited on behalf

Partial facial duplication (diprosopus) in a goat kid.

PubMed

Mukaratirwa, S; Sayi, S T

2006-03-01

The anatomical and clinical features of a live-born diprosopic goat kid are described. The kid had two faces with two eyes each, two complete oral cavities and nostrils and two ears. Caudal to the neck, the kid grossly appeared normal. Both mouths of the kid showed synchronous suckling motions. Elevated respiratory and heart rates were recorded and the temperature was subnormal. Radiological examination showed a single trunk and vertebral column, normal limbs, two sets of jaws, three orbits, and contrast radiography revealed a single patent oesophagus. There was maxillary and mandibular duplication resulting in two faces. There was a cleft palate. The oropharyngeal regions of each face merged to form a single laryngopharynx and oesophagus. There was a single brain with hypoplasia of the cerebellum. The left and right cerebral hemispheres were fused rostrally, and there was duplication of the optic chiasma and the pituitary gland. The olfactory tract was absent and the superficial origins of most of the cranial nerves were not discernible.

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

PubMed

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

2015-12-01

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

Food Safety and Nutrition Information for Kids and Teens

MedlinePlus

... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Resources for You Consumers Kids & Teens ... More sharing options Linkedin Pin it Email Print Food Safety & Nutrition Information for Kids and Teens Fun & ...

Three Dimensional Structure of the MqsR:MqsA Complex: A Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties

PubMed Central

Kim, Younghoon; Arruda, Jennifer M.; Davenport, Andrew; Wood, Thomas K.; Peti, Wolfgang; Page, Rebecca

2009-01-01

One mechanism by which bacteria survive environmental stress is through the formation of bacterial persisters, a sub-population of genetically identical quiescent cells that exhibit multidrug tolerance and are highly enriched in bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified as the gene most highly upregulated in persisters. Here, we report multiple individual and complex three-dimensional structures of MqsR and its antitoxin MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair. MqsR adopts an α/β fold that is homologous with the RelE/YoeB family of bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly, it also binds the promoters of genes important for E. coli physiology (e.g., mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal domain. These studies reveal that TA systems, especially the antitoxins, are significantly more diverse than previously recognized and provide new insights into the role of toxins in maintaining the persister state. PMID:20041169

Superantigens Modulate Bacterial Density during Staphylococcus aureus Nasal Colonization

PubMed Central

Xu, Stacey X.; Kasper, Katherine J.; Zeppa, Joseph J.; McCormick, John K.

2015-01-01

Superantigens (SAgs) are potent microbial toxins that function to activate large numbers of T cells in a T cell receptor (TCR) Vβ-specific manner, resulting in excessive immune system activation. Staphylococcus aureus possesses a large repertoire of distinct SAgs, and in the context of host-pathogen interactions, staphylococcal SAg research has focused primarily on the role of these toxins in severe and invasive diseases. However, the contribution of SAgs to colonization by S. aureus remains unclear. We developed a two-week nasal colonization model using SAg-sensitive transgenic mice expressing HLA-DR4, and evaluated the role of SAgs using two well-studied stains of S. aureus. S. aureus Newman produces relatively low levels of staphylococcal enterotoxin A (SEA), and although we did not detect significant TCR-Vβ specific changes during wild-type S. aureus Newman colonization, S. aureus Newman Δsea established transiently higher bacterial loads in the nose. S. aureus COL produces relatively high levels of staphylococcal enterotoxin B (SEB), and colonization with wild-type S. aureus COL resulted in clear Vβ8-specific T cell skewing responses. S. aureus COL Δseb established consistently higher bacterial loads in the nose. These data suggest that staphylococcal SAgs may be involved in regulating bacterial densities during nasal colonization. PMID:26008236

Development without germ cells: the role of the germ line in zebrafish sex differentiation.

PubMed

Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

2005-03-15

The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin-antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males.

Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

PubMed

Prisilla, A; Prathiviraj, R; Chellapandi, P

2017-04-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

In silico analysis of protein toxin and bacteriocins from Lactobacillus paracasei SD1 genome and available online databases

PubMed Central

Surachat, Komwit; Sangket, Unitsa; Deachamag, Panchalika; Chotigeat, Wilaiwan

2017-01-01

Lactobacillus paracasei SD1 is a potential probiotic strain due to its ability to survive several conditions in human dental cavities. To ascertain its safety for human use, we therefore performed a comprehensive bioinformatics analysis and characterization of the bacterial protein toxins produced by this strain. We report the complete genome of Lactobacillus paracasei SD1 and its comparison to other Lactobacillus genomes. Additionally, we identify and analyze its protein toxins and antimicrobial proteins using reliable online database resources and establish its phylogenetic relationship with other bacterial genomes. Our investigation suggests that this strain is safe for human use and contains several bacteriocins that confer health benefits to the host. An in silico analysis of protein-protein interactions between the target bacteriocins and the microbial proteins gtfB and luxS of Streptococcus mutans was performed and is discussed here. PMID:28837656

Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cells.

PubMed

Barth, Holger; Stiles, Bradley G

2008-01-01

Binary bacterial toxins are unique AB-type toxins, composed of two non-linked proteins that act as a binding/translocation component and an enzyme component. All known actin-ADP-ribosylating toxins from clostridia possess this binary structure. This toxin family is comprised of the prototypical Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin, Clostridium difficile CDT, and Clostridium spiroforme toxin. Once in the cytosol of host cells, these toxins transfer an ADP-ribose moiety from nicotinamide-adenosine-dinucleotide onto G-actin that then leads to depolymerization of actin filaments. In recent years much progress has been made towards understanding the cellular uptake mechanism of binary actin-ADP-ribosylating toxins, and in particular that of C2 toxin. Both components act in a precisely concerted manner to intoxicate eukaryotic cells. The binding/translocation (B-) component forms a complex with the enzyme (A-) component and mediates toxin binding to a cell-surface receptor. Following receptor-mediated endocytosis, the enzyme component escapes from acidic endosomes into the cytosol. Acidification of endosomes triggers pore formation by the binding/translocation component in endosomal membranes and the enzyme component subsequently translocates through the pore. This step requires a host cell chaperone, Hsp90. Due to their unique structure, binary toxins are naturally "tailor made" for transporting foreign proteins into the cytosol of host cells. Several highly specific and cell-permeable recombinant fusion proteins have been designed and successfully used in experimental cell research. This review will focus on the recent progress in studying binary actin ADP-ribosylating toxins as highly effective virulence factors and innovative tools for cell physiology as well as pharmacology.

Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis.

PubMed

Slayden, Richard A; Dawson, Clinton C; Cummings, Jason E

2018-06-01

There has been a significant reduction in annual tuberculosis incidence since the World Health Organization declared tuberculosis a global health threat. However, treatment of M. tuberculosis infections requires lengthy multidrug therapeutic regimens to achieve a durable cure. The development of new drugs that are active against resistant strains and phenotypically diverse organisms continues to present the greatest challenge in the future. Numerous phylogenomic analyses have revealed that the Mtb genome encodes a significantly expanded repertoire of toxin-antitoxin (TA) loci that makes up the Mtb TA system. A TA loci is a two-gene operon encoding a 'toxin' protein that inhibits bacterial growth and an interacting 'antitoxin' partner that neutralizes the inhibitory activity of the toxin. The presence of multiple chromosomally encoded TA loci in Mtb raises important questions in regard to expansion, regulation and function. Thus, the functional roles of TA loci in Mtb pathogenesis have received considerable attention over the last decade. The cumulative results indicate that they are involved in regulating adaptive responses to stresses associated with the host environment and drug treatment. Here we review the TA families encoded in Mtb, discuss the duplication of TA loci in Mtb, regulatory mechanism of TA loci, and phenotypic heterogeneity and pathogenesis.

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

PubMed

Lazarovici, P; Yavin, E

1985-01-25

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

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone

PubMed Central

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-01-01

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822

Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses

PubMed Central

Gillespie, Eugene J.; Ho, Chi-Lee C.; Balaji, Kavitha; Clemens, Daniel L.; Deng, Gang; Wang, Yao E.; Elsaesser, Heidi J.; Tamilselvam, Batcha; Gargi, Amandeep; Dixon, Shandee D.; France, Bryan; Chamberlain, Brian T.; Blanke, Steven R.; Cheng, Genhong; de la Torre, Juan Carlos; Brooks, David G.; Jung, Michael E.; Colicelli, John; Damoiseaux, Robert; Bradley, Kenneth A.

2013-01-01

Pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. One common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. To identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. Here we report that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone, the most active compound identified in the screen, inhibits intoxication by lethal toxin and blocks the entry of multiple other acid-dependent bacterial toxins and viruses into mammalian cells. This compound, which we named EGA, also delays lysosomal targeting and degradation of the EGF receptor, indicating that it targets host-membrane trafficking. In contrast, EGA does not block endosomal recycling of transferrin, retrograde trafficking of ricin, phagolysosomal trafficking, or phagosome permeabilization by Franciscella tularensis. Furthermore, EGA does not neutralize acidic organelles, demonstrating that its mechanism of action is distinct from pH-raising agents such as ammonium chloride and bafilomycin A1. EGA is a powerful tool for the study of membrane trafficking and represents a class of host-targeted compounds for therapeutic development to treat infectious disease. PMID:24191014

What Medicines Are and What They Do (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español What Medicines Are and What They Do KidsHealth / For Kids / ... of others? Let's find out. A Rainbow of Medicine One medicine might be a pink liquid, another ...

Campus Kids Mentoring Program: Fifteen Years of Success

ERIC Educational Resources Information Center

Shepard, Jerri

2009-01-01

This article features Campus Kids, a mentoring program located at Gonzaga University in Spokane, Washington. Gonzaga is a Jesuit University with a strong commitment to social justice and humanistic education. Campus Kids began, in the true sense of a community partnership, as an attempt to connect community resources (potential university…

Inhibitory effects of anthocyanins on secretion of Helicobacter pylori CagA and VacA toxins.

PubMed

Kim, Sa-Hyun; Park, Min; Woo, Hyunjun; Tharmalingam, Nagendran; Lee, Gyusang; Rhee, Ki-Jong; Eom, Yong Bin; Han, Sang Ik; Seo, Woo Duck; Kim, Jong Bae

2012-01-01

Anthocyanins have been studied as potential antimicrobial agents against Helicobacter pylori. We investigated whether the biosynthesis and secretion of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190 (CagA(+)/VacA(+)) was used in this study to investigate the inhibitory effects of anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G), pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on expression and secretion of H. pylori toxins. Anthocyanins were added to bacterial cultures and Western blotting was used to determine secretion of CagA and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA resulting in intracellular accumulation of CagA and VacA. C3G had no effect on cagA and vacA expression but suppressed secA transcription. As SecA is involved in translocation of bacterial proteins, the down-regulation of secA expression by C3G offers a mechanistic explanation for the inhibition of toxin secretion. To our knowledge, this is the first report suggesting that C3G inhibits secretion of the H. pylori toxins CagA and VacA via suppression of secA transcription.

Inhibitory Effects of Anthocyanins on Secretion of Helicobacter pylori CagA and VacA Toxins

PubMed Central

Kim, Sa-Hyun; Park, Min; Woo, Hyunjun; Tharmalingam, Nagendran; Lee, Gyusang; Rhee, Ki-Jong; Eom, Yong Bin; Han, Sang Ik; Seo, Woo Duck; Kim, Jong Bae

2012-01-01

Anthocyanins have been studied as potential antimicrobial agents against Helicobacter pylori. We investigated whether the biosynthesis and secretion of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190 (CagA+/VacA+) was used in this study to investigate the inhibitory effects of anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G), pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on expression and secretion of H. pylori toxins. Anthocyanins were added to bacterial cultures and Western blotting was used to determine secretion of CagA and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA resulting in intracellular accumulation of CagA and VacA. C3G had no effect on cagA and vacA expression but suppressed secA transcription. As SecA is involved in translocation of bacterial proteins, the down-regulation of secA expression by C3G offers a mechanistic explanation for the inhibition of toxin secretion. To our knowledge, this is the first report suggesting that C3G inhibits secretion of the H. pylori toxins CagA and VacA via suppression of secA transcription. PMID:23155357

Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies.

PubMed

Rudolph, Michael J; Vance, David J; Cheung, Jonah; Franklin, Matthew C; Burshteyn, Fiana; Cassidy, Michael S; Gary, Ebony N; Herrera, Cristina; Shoemaker, Charles B; Mantis, Nicholas J

2014-08-26

Ricin is a select agent toxin and a member of the RNA N-glycosidase family of medically important plant and bacterial ribosome-inactivating proteins. In this study, we determined X-ray crystal structures of the enzymatic subunit of ricin (RTA) in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies that differ in their respective toxin-neutralizing activities. None of the VHHs made direct contact with residues involved in RTA's RNA N-glycosidase activity or induced notable allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping structural epitopes on the surface of the toxin and differed in the degree to which they made contact with prominent structural elements in two folding domains of the RTA. In general, RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) elements, with the most potent neutralizing antibody having the shortest and most conformationally constrained CDR3. These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clostridial Binary Toxins: Basic Understandings that Include Cell Surface Binding and an Internal "Coup de Grâce".

PubMed

Stiles, Bradley G

2017-01-01

Clostridium species can make a remarkable number of different protein toxins, causing many diverse diseases in humans and animals. The binary toxins of Clostridium botulinum, C. difficile, C. perfringens, and C. spiroforme are one group of enteric-acting toxins that attack the actin cytoskeleton of various cell types. These enterotoxins consist of A (enzymatic) and B (cell binding/membrane translocation) components that assemble on the targeted cell surface or in solution, forming a multimeric complex. Once translocated into the cytosol via endosomal trafficking and acidification, the A component dismantles the filamentous actin-based cytoskeleton via mono-ADP-ribosylation of globular actin. Knowledge of cell surface receptors and how these usurped, host-derived molecules facilitate intoxication can lead to novel ways of defending against these clostridial binary toxins. A molecular-based understanding of the various steps involved in toxin internalization can also unveil therapeutic intervention points that stop the intoxication process. Furthermore, using these bacterial proteins as medicinal shuttle systems into cells provides intriguing possibilities in the future. The pertinent past and state-of-the-art present, regarding clostridial binary toxins, will be evident in this chapter.

The Protective Antigen Component of Anthrax Toxin Forms Functional Octameric Complexes

PubMed Central

Kintzer, Alexander F.; Thoren, Katie L.; Sterling, Harry J.; Dong, Ken C.; Feld, Geoffrey K.; Tang, Iok I.; Zhang, Teri T.; Williams, Evan R.; Berger, James M.; Krantz, Bryan A.

2009-01-01

The assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. We begin to address this question using anthrax toxin as a model. The protective antigen (PA) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (LF) and edema factor (EF), to form toxic complexes. To disrupt the host, these toxic complexes are endocytosed, such that the PA oligomer forms a membrane-spanning channel that LF and EF translocate through to enter the cytosol. We show using single-channel electrophysiology that PA channels contain two populations of conductance states, which correspond with two different PA pre-channel oligomers observed by electron microscopy—the well-described heptamer and a novel octamer. Mass spectrometry demonstrates that the PA octamer binds four LFs, and assembly routes leading to the octamer are populated with even-numbered, dimeric and tetrameric, PA intermediates. Both heptameric and octameric PA complexes can translocate LF and EF with similar rates and efficiencies. Here we also report a 3.2-Å crystal structure of the PA octamer. The octamer comprises ∼20−30% of the oligomers on cells, but outside of the cell, the octamer is more stable than the heptamer under physiological pH. Thus the PA octamer is a physiological, stable, and active assembly state capable of forming lethal toxins that may withstand the hostile conditions encountered in the bloodstream. This assembly mechanism may provide a novel means to control cytotoxicity. PMID:19627991

Connecting Kids to Technology: Challenges and Opportunities. KIDS COUNT Snapshot.

ERIC Educational Resources Information Center

Wilhelm, Tony; Carmen, Delia; Reynolds, Megan

The 2000 KIDS COUNT Data Book examined the isolation that plagues many low-income families. The lack of home Internet access will only deepen the isolation as opportunities and meaningful connections to support services become primarily available online. This snapshot examines the demographics of the digital divide between those who have and those…

Alternative Fuels Data Center: Camp Discovery Helps Kids Build an Electric

Science.gov Websites

Dune Buggy Camp Discovery Helps Kids Build an Electric Dune Buggy to someone by E-mail Share Alternative Fuels Data Center: Camp Discovery Helps Kids Build an Electric Dune Buggy on Facebook Tweet about Alternative Fuels Data Center: Camp Discovery Helps Kids Build an Electric Dune Buggy on Twitter Bookmark

Anthrax Toxin

DTIC Science & Technology

1984-10-26

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

Thyroid Disorders (For Kids)

MedlinePlus

... of thyroid disorder or thyroid disease. Hyperthyroidism (say: hi-per-THYE-roy-diz-em) happens when the ... Kids with the opposite problem have hypothyroidism (say: hi-po-THYE-roy-diz-em). In this case, ...

Kids' Quest: Vision Impairment

MedlinePlus

... most important job. Return to Steps World-Wide Web Search Kids Health: What is Vision Impairment What ... for the Blind (AFB) created the Braille Bug web site to teach sighted children about braille, and ...

Larvicidal Activities of Indigenous Bacillus thuringiensis Isolates and Nematode Symbiotic Bacterial Toxins against the Mosquito Vector, Culex pipiens (Diptera: Culicidae).

PubMed

Ahmed, Ashraf M; Hussein, Hamdy I; El-Kersh, Talat A; Al-Sheikh, Yazeed A; Ayaad, Tahany H; El-Sadawy, Hanan A; Al-Mekhlafi, Fahd A; Ibrahim, Mohamed S; Al-Tamimi, Jameel; Nasr, Fahd A

2017-06-01

The incidence of mosquito-borne diseases and the resistance of mosquitoes to conventional pesticides have recently caused a panic to the authorities in the endemic countries. This study was conducted to identify native larvicidal biopesticides against Culex pipiens for utilization in the battle against mosquito-borne diseases. Larvicidal activities of new indigenous Bacillus thuringiensis isolates and crude toxin complexes (TCs) of two nematode bacterial-symbionts, Photorhabdus luminescens akhurstii (HRM1) and Ph. luminescens akhurstii (HS1) that tested against Cx. pipiens . B. thuringiensis isolates were recovered from different environmental samples in Saudi Arabia, and the entomopathogenic nematodes, Heterorhabditis indica (HRM1) and He. sp (HS1) were isolated from Egypt. Larvicidal activities (LC 50 and LC 95 ) of the potentially active B. thuringiensis strains or TCs were then evaluated at 24 and 48h post-treatment. Three B. thuringiensis isolates were almost as active as the reference B. thuringiensis israelensis (Bti-H14), and seven isolates were 1.6-5.4 times more toxic than Bti-H14. On the other hand, the TCs of the bacterial symbionts, HRM1 and HS1, showed promising larvicidal activities. HS1 showed LC 50 of 2.54 folds that of HRM1 at 24h post-treatment. Moreover, histopathological examinations of the HS1-treated larvae showed deformations in midgut epithelial cells at 24h post-treatment. Synergistic activity and molecular characterization of these potentially active biocontrol agents are currently being investigated. These results may lead to the identification of eco-friend mosquito larvicidal product(s) that could contribute to the battle against mosquito-borne diseases.

Larvicidal Activities of Indigenous Bacillus thuringiensis Isolates and Nematode Symbiotic Bacterial Toxins against the Mosquito Vector, Culex pipiens (Diptera: Culicidae)

PubMed Central

Ahmed, Ashraf M; Hussein, Hamdy I; El-Kersh, Talat A; Al-Sheikh, Yazeed A; Ayaad, Tahany H; El-Sadawy, Hanan A; Al-Mekhlafi, Fahd A; Ibrahim, Mohamed S; Al-Tamimi, Jameel; Nasr, Fahd A

2017-01-01

Background: The incidence of mosquito-borne diseases and the resistance of mosquitoes to conventional pesticides have recently caused a panic to the authorities in the endemic countries. This study was conducted to identify native larvicidal biopesticides against Culex pipiens for utilization in the battle against mosquito-borne diseases. Methods: Larvicidal activities of new indigenous Bacillus thuringiensis isolates and crude toxin complexes (TCs) of two nematode bacterial-symbionts, Photorhabdus luminescens akhurstii (HRM1) and Ph. luminescens akhurstii (HS1) that tested against Cx. pipiens. B. thuringiensis isolates were recovered from different environmental samples in Saudi Arabia, and the entomopathogenic nematodes, Heterorhabditis indica (HRM1) and He. sp (HS1) were isolated from Egypt. Larvicidal activities (LC50 and LC95) of the potentially active B. thuringiensis strains or TCs were then evaluated at 24 and 48h post-treatment. Results: Three B. thuringiensis isolates were almost as active as the reference B. thuringiensis israelensis (Bti-H14), and seven isolates were 1.6–5.4 times more toxic than Bti-H14. On the other hand, the TCs of the bacterial symbionts, HRM1 and HS1, showed promising larvicidal activities. HS1 showed LC50 of 2.54 folds that of HRM1 at 24h post-treatment. Moreover, histopathological examinations of the HS1-treated larvae showed deformations in midgut epithelial cells at 24h post-treatment. Conclusion: Synergistic activity and molecular characterization of these potentially active biocontrol agents are currently being investigated. These results may lead to the identification of eco-friend mosquito larvicidal product(s) that could contribute to the battle against mosquito-borne diseases. PMID:29062851

Pediatric burns: Kids' Inpatient Database vs the National Burn Repository.

PubMed

Soleimani, Tahereh; Evans, Tyler A; Sood, Rajiv; Hartman, Brett C; Hadad, Ivan; Tholpady, Sunil S

2016-04-01

Burn injuries are one of the leading causes of morbidity and mortality in young children. The Kids' Inpatient Database (KID) and National Burn Repository (NBR) are two large national databases that can be used to evaluate outcomes and help quality improvement in burn care. Differences in the design of the KID and NBR could lead to differing results affecting resultant conclusions and quality improvement programs. This study was designed to validate the use of KID for burn epidemiologic studies, as an adjunct to the NBR. Using the KID (2003, 2006, and 2009), a total of 17,300 nonelective burn patients younger than 20 y old were identified. Data from 13,828 similar patients were collected from the NBR. Outcome variables were compared between the two databases. Comparisons revealed similar patient distribution by gender, race, and burn size. Inhalation injury was more common among the NBR patients and was associated with increased mortality. The rates of respiratory failure, wound infection, cellulitis, sepsis, and urinary tract infection were higher in the KID. Multiple regression analysis adjusting for potential confounders demonstrated similar mortality rate but significantly longer length of stay for patients in the NBR. Despite differences in the design and sampling of the KID and NBR, the overall demographic and mortality results are similar. The differences in complication rate and length of stay should be explored by further studies to clarify underlying causes. Investigations into these differences should also better inform strategies to improve burn prevention and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Carcass composition and meat quality of equally mature kids and lambs.

PubMed

Santos, V A C; Silva, S R; Azevedo, J M T

2008-08-01

Carcass composition and meat quality attributes of 55 suckling kids (27 males and 28 females) and 57 suckling lambs (28 males and 29 females) of Portuguese native breeds were investigated. These suckling kid and lamb meats are European meat quality labels produced according to "Cabrito de Barroso- PGI" and "Borrego Terrincho-PDO" specifications, respectively. Female kids were slaughtered at 9.1 +/- 0.36 kg of BW, and male kids were slaughtered at 10.4 +/- 0.37 kg of BW, corresponding to 20.1 and 17.7% of maturity, respectively. Female lambs were slaughtered at 8.6 +/- 0.53 kg of BW, and male lambs were slaughtered at 9.9 +/- 0.23 kg of BW, corresponding to 19.9 and 17.1% of maturity, respectively. At 24 h postmortem, various yield and quality measurements were collected. The left sides of the carcasses were dissected into muscle, subcutaneous fat, intermuscular fat, and bone. Final pH, instrumental color (L*, a*, b*), carcass measurements, and kidney knob and pelvic fat were also determined. Samples of LM were taken from the lumbar and thoracic cuts for intramuscular and meat quality determinations. At 72 h postmortem, a sample of LM was used for cooking losses and Warner-Bratzler shear force determination. Suckling lambs had greater dressing proportion than suckling kids (P < 0.01). Carcass fatness was not affected by species (P > 0.05), but females had greater kidney knob and pelvic fat proportion than males (P < 0.01). Lambs had greater proportions of the highly valued leg cut and lower proportions of shoulder, anterior rib, and neck cuts than kids. Dissection results indicated that kid carcasses had greater muscle content and lower dissected fat and bone than lambs. Kids had greater (P < 0.001) muscle ultimate pH value than lambs (5.8 +/- 0.02 vs. 5.6 +/- 0.02). Males had greater (P < 0.05) muscle ultimate pH value than females (5.7 +/- 0.02 vs. 5.6 +/- 0.02). The kid meat was significantly lighter (P < 0.05) and less yellow (P < 0.001) than the lamb meat. Kids

Macromineral requirements for the maintenance and growth of Boer crossbred kids.

PubMed

Fernandes, M H M R; Resende, K T; Tedeschi, L O; Teixeira, I A M A; Fernandes, J S

2012-12-01

Advances in mineral nutrition of goats have been made during the last decade, especially in our understanding of Ca and P requirements. However, few studies have focused on the mineral requirements of crossbred Boer goats in their growth phase. Our objective for this study was to determine the macromineral (Ca, P, Mg, K, and Na) requirements for the maintenance and growth of intact, male three-fourths Boer × one-fourth Saanen kids (n = 34; 20.5 ± 0.24 kg of initial BW). Two trials were conducted: 1 for maintenance and 1 for growth requirements. In the maintenance trial, 28 kids were used. The baseline (BL) group consisted of 7 randomly selected kids averaging 21.2 ± 0.36 kg BW and 122 d old. The remaining kids (n = 21; age 168 ± 5 d) were randomly allocated into 7 slaughter groups (blocks) including 3 animals distributed among 3 amounts of DMI (treatments: ad libitum and restricted to 70 or 40% of ad libitum intake). Animals in a group were slaughtered when the ad libitum-treatment kid in the block reached 35 kg BW. The BL and ad libitum-fed groups in the maintenance trial were also part of the growth trial. Therefore, in the growth trial, 20 kids fed for ad libitum intake were used as follows: 7 kids slaughtered at 21.2 ± 0.36 kg BW (BL), 6 kids slaughtered at 28.2 ± 0.39 kg BW (intermediate slaughter), and 7 kids slaughtered at 35.6 ± 0.36 kg BW. Empty whole bodies of the kids (head + feet, hide, internal organs + blood, and carcass) were weighed, ground, mixed, and subsampled for chemical analyses. Daily maintenance requirements, calculated using the comparative slaughter technique (P < 0.001), were estimated as 32.3 ± 1.1 mg Ca, 30.8 ± 1.2 mg P, 1.31 ± 0.5 mg Mg, 8.41 ± 3.0 mg K, and 5.14 ± 1.0 mg Na/kg of empty BW (EBW). Net requirements for growth increased from 6.2 to 6.6 g Ca, 5.3 to 5.4 g P, and 0.29 to 0.30 g Mg and decreased from 1.20 to 1.07 g K and 0.65 to 0.59 g Na/kg of EBW gain for kids from 20 to 35 kg BW. This study indicated that the

Focus Group Outcomes of the Happy Kids Program

ERIC Educational Resources Information Center

Anderson, Karen; Ferguson, Neil; Partington, Gary; Byrne, Matt

2015-01-01

In this article, the outcomes of The Happy Kids project, a strategy to improve the social and emotional well-being of primary school students, were examined. Results indicated that the Happy Kids program had demonstrated positive social and emotional outcomes for students in all schools, in particular, a positive impact upon students' confidence,…

Bioterrorism: toxins as weapons.

PubMed

Anderson, Peter D

2012-04-01

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

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

PubMed Central

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

2016-01-01

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

The chromokinesin Kid is required for maintenance of proper metaphase spindle size.

PubMed

Tokai-Nishizumi, Noriko; Ohsugi, Miho; Suzuki, Emiko; Yamamoto, Tadashi

2005-11-01

The human chromokinesin Kid/kinesin-10, a plus end-directed microtubule (MT)-based motor with both microtubule- and DNA-binding domains, is required for proper chromosome alignment at the metaphase plate. Here, we performed RNA interference experiments to deplete endogenous Kid from HeLa cells and confirmed defects in metaphase chromosome arm alignment in Kid-depleted cells. In addition, we noted a shortening of the spindle length, resulting in a pole-to-pole distance only 80% of wild type. The spindle microtubule-bundles with which Kid normally colocalize became less robust. Rescue of the two Kid deficiency phenotypes-imprecise chromosome alignment at metaphase and shortened spindles- exhibited distinct requirements. Mutants lacking either the DNA-binding domain or the MT motor ATPase failed to rescue the former defect, whereas rescue of the shortened spindle phenotype required neither activity. Kid also exhibits microtubule bundling activity in vitro, and rescue of the shortened spindle phenotype and the bundling activity displayed similar domain requirements, except that rescue required a coiled-coil domain not needed for bundling. These results suggest that distinct from its role in chromosome movement, Kid contributes to spindle morphogenesis by mediating spindle microtubules stabilization.

Biotinylation of environmentally isolated Shiga toxin-producing Escherichia coli (STEC) – specific bacteriophages for biosensor and biocontrol applications

USDA-ARS?s Scientific Manuscript database

Like common bacteriophages, Shiga toxin-producing Escherichia coli (STEC) bacteriophages are viruses that recognize and bind to specific bacterial host (STEC) for propagation. They co-exist with STEC hosts, which cause epidemic food and waterborne illnesses, but may act as host populations limiting ...

KIDS COUNT Data Book, 2007: State Profiles of Child Well-Being

ERIC Educational Resources Information Center

Annie E. Casey Foundation, 2007

2007-01-01

KIDS COUNT is a national and state-by-state effort to track the status of children in the U.S. By providing policymakers and citizens with benchmarks of child well-being, KIDS COUNT seeks to enrich local, state, and national discussions concerning ways to secure better futures for all children. This 18th annual 2007 KIDS COUNT Data Book examines…

Healthy Drinks for Kids

MedlinePlus

... for: Parents Kids Teens Caffeine Calcium Sports and Energy Drinks: Should Your Child Drink Them? What Should Preschoolers ... Caffeine Confusion What's a Healthy Alternative to Water? Energy Drinks and Food Bars: Power or Hype? A Guide ...

Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

PubMed

Chellapandi, Paulchamy; Prisilla, Arokiyasamy

2017-01-01

Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced by this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships with them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems in eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Carcass measurements and meat quality characteristics of dairy suckling kids compared to an indigenous genotype.

PubMed

Ekiz, Bulent; Ozcan, Mustafa; Yilmaz, Alper; Tölü, Cemil; Savaş, Türker

2010-06-01

Effects of genotype on carcass measurements and meat quality were investigated by using 24 suckling kids from Turkish Saanen, Gokceada and Maltese breeds. Carcass quality characteristics of indigenous kids (Gokceada) were lower than those of dairy type (Turkish Saanen and Maltese) kids. Breed effect on ultimate meat pH, cooking loss, drip loss and Warner Bratzler shear force values were not significant. Meat samples from Turkish Saanen kids had higher redness (at 0, 1 and 24h) and yellowness (at 24h) values than Gokceada kids (P<0.05). Breed had no significant effect on sensory characteristics except flavour intensity. Flavour intensity scores given to meat samples of Maltese kids were higher than those of Turkish Saanen and Gokceada kids (P<0.01). In conclusion, dairy type breeds should be considered for meat production as well, with meat from Maltese kids potentially offering better colour and flavour intensity than that of Turkish Saanen kids. Copyright 2010 Elsevier Ltd. All rights reserved.

Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

PubMed

Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

2016-08-01

Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Captive Kids: A Report on Commercial Pressures on Kids at School.

ERIC Educational Resources Information Center

Consumers Union of the United States, Yonkers, NY. Education Services.

This report identifies some of the different forms that in-school commercialism takes, from outright advertising in school hallways to sponsored educational materials that often contain brand-name plugs and biased messages. It examines the reasons why corporations and other commercial organizations are interested in marketing to kids in the…

Statistical inconsistencies in the KiDS-450 data set

NASA Astrophysics Data System (ADS)

Efstathiou, George; Lemos, Pablo

2018-05-01

The Kilo-Degree Survey (KiDS) has been used in several recent papers to infer constraints on the amplitude of the matter power spectrum and matter density at low redshift. Some of these analyses have claimed tension with the Planck Λ cold dark matter cosmology at the ˜2σ-3σ level, perhaps indicative of new physics. However, Planck is consistent with other low-redshift probes of the matter power spectrum such as redshift-space distortions and the combined galaxy-mass and galaxy-galaxy power spectra. Here, we perform consistency tests of the KiDS data, finding internal tensions for various cuts of the data at ˜2.2σ-3.5σ significance. Until these internal tensions are understood, we argue that it is premature to claim evidence for new physics from KiDS. We review the consistency between KiDS and other weak lensing measurements of S8, highlighting the importance of intrinsic alignments for precision cosmology.

Bright Not Broken: Gifted Kids, ADHD, and Autism

ERIC Educational Resources Information Center

Kennedy, Diane M.; Banks, Rebecca S.; Grandin, Temple

2011-01-01

The future of our society depends on our gifted children--the population in which we'll find our next Isaac Newton, Albert Einstein, or Virginia Woolf. Yet the gifts and talents of some of our most brilliant kids may never be recognized because these children fall into a group known as twice exceptional, or "2e." Twice exceptional kids are both…

Middle Grade Tell-Alls: Wimpy Kid Read-Alikes

ERIC Educational Resources Information Center

Giffard, Sue

2011-01-01

On the "New York Times" Children's Best Sellers list for more than two years, Jeff Kinney's "Diary of a Wimpy Kid" still causes groups of children to enthusiastically exclaim that it's the "best book ever." What is it that kids love about Greg Heffley and his escapades? Why are they overcome with laughter while simply trying to explain his humor?…

Carcass characteristics of Neuquén Criollo kids in Patagonia region, Argentina.

PubMed

Zimerman, M; Domingo, E; Lanari, M R

2008-07-01

Carcass characteristics of 336 kids from the Neuquén Criollo breed were evaluated. Two categories were taken into account: three months and 5 to 7 months kids. Live weight, carcass weights, measurement and indexes of 304 kids were calculated in a study done in a commercial slaughterhouse located in Chos Malal town. Thirty two carcass left sides were dissected into the major components: muscle, bone, fat and remaining tissues. Three months kids were compared with 5 to 7 months kids. The slaughter live weight of the former was 16.3kg and the latter was 22.4kg. Cold carcass weight and dressing percentage differed significantly (p<0.001) between age categories. Three months kids had a higher percentage of bones (26.8 vs. 21.7%; p<0.001) and a lower percentage of fat (10.8 vs. 15%; p<0.01) than those at 5-7 months, but both had similar percentages of muscle (56.4 vs. 57%; p=NS). There were significant differences in the percentages of primal carcass cuts: hind leg (32 vs. 34%; p<0.001), shoulder (22 vs. 20%; p<0.001) and neck, (10 vs. 8%; p<0.01) for three months vs. 5-7 months old kids, respectively.

Millipede toxin

MedlinePlus

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

Dizziness and Balance Problems in Kids: Spinning Sensations and Unsteadiness

MedlinePlus

... Print this issue Dizziness and Balance Problems in Kids Spinning Sensations and Unsteadiness En español Send us ... comments Most people feel dizzy now and then. Kids, like adults, may occasionally feel lightheaded or unsteady. ...

"Kiwi Kids Are Weet-Bix[TM] Kids"--Body Matters in Childhood

ERIC Educational Resources Information Center

Burrows, Lisette

2010-01-01

A wide array of health policies and initiatives have emerged in New Zealand recently in an attempt to resurrect a presumed "lost", adventure-loving, physically capable and non-obese Kiwi kid. Chief among these is "Mission-On"--a 67 million dollar package of 10 initiatives designed to explicitly target the eating and exercise…

Keeping Kids Healthy.

ERIC Educational Resources Information Center

Mays, Sharon; And Others

This pamphlet offers a collection of items relating to child health in the day care setting. Included is an overview of a collaborative project to develop a comprehensive set of national standards for health, nutrition, safety, and sanitation in child care programs. Contents of the project's resource kit, "Keeping Kids Healthy and Parents at…

Mass spectrometry-based method of detecting and distinguishing type 1 and type 2 Shiga-like toxins in human serum

USDA-ARS?s Scientific Manuscript database

Shiga-like toxins (verotoxins) are a class of AB5 holotoxins that are responsible for the virulence associated with bacterial pathogens such as Shigella dysenteriae, shigatoxigenic and enterohemorrhagic strains of Escherichia coli (STEC and EHEC), and some Enterobacter strains. The actual expression...

Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen and Thymus Tissues and Mortality in Mice

USDA-ARS?s Scientific Manuscript database

The Shiga toxin (Stxs) producing bacterial strain, Escherichia coli O157:H7, colonizes the distal small intestine and the colon, initiating a very broad spectrum of illnesses such as hemolytic-uremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal ...

[Cloning of Clostridium perfringens alpha-toxin gene and extracellular expression in Escherichia coli].

PubMed

Inoue, Masaharu; Kikuchi, Maho; Komoriya, Tomoe; Watanabe, Kunitomo; Kouno, Hideki

2007-01-01

Clostridium perfringens (C. perfringens) is a Gram-positive bacterial pathogen that widely propagets in the soil and the gastrointestinal tract of human and animals. This bacteria causes food poisoning, gas gangrene and other various range of infectious diseases. But there is no standard diagnosis method of C. perfringens. In order to develop a new type of immunoassay for clinical purpose, we studied expression and extracellular secretion of recombinant alpha-toxin having enzyme activity in E. coli expression system. Cloning was carried out after PCR amplification from C. perfringens GAI 94074 which was clinical isolate. Three kinds of fragment were cloned using pET100/D-TOPO vector. These fragments coded for ribosome binding site, signal peptide, and alpha-toxin gene respectively. Recombinant pET100 plasmid transformed into TOP 10 cells and the obtained plasmids were transformed into BL21 (DE3) cells. Then, the transformants were induced expression with IPTG. In conclusion, we successfully cloned, expressed and exteracellular secreted C. perfringens alpha-toxin containing signal peptide. Biologically, the obtained recombinant protein was positive for phospholipase C activity.

Effects of dietary pomegranate seed pulp on oxidative stability of kid meat.

PubMed

Emami, A; Nasri, M H Fathi; Ganjkhanlou, M; Zali, A; Rashidi, L

2015-06-01

This study was conducted to evaluate the effects of dietary pomegranate seed pulp (PSP) on meat color and lipid stability of kids. Thirty-two Mahabadi male kids were randomly assigned to one of four diets with different levels of PSP: 1 - diet without PSP (Control), 2 - diet containing 5% PSP (PSP5), 3 - diet containing 10% PSP (PSP10), and 4 - diet containing 15% PSP (PSP15). The kids were slaughtered at the end of the study and m. longissimus lumborum (LL) was sampled. The TBARS values of both raw and cooked meat were decreased (P<0.0001) by increasing levels of PSP in the diet. The meat of kids fed PSP15 showed higher a* and C* values (P<0.01) and lower H* and b* values (P<0.001), than kids fed with Control diet. The results of this experiment indicated that replacing barley and corn grains with PSP in the diet may improve the color and lipid stability of kid meat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cytolethal Distending Toxin From Campylobacter jejuni Requires the Cytoskeleton for Toxic Activity.

PubMed

Méndez-Olvera, Estela T; Bustos-Martínez, Jaime A; López-Vidal, Yolanda; Verdugo-Rodríguez, Antonio; Martínez-Gómez, Daniel

2016-10-01

Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus. Campylobacter jejuni ATCC 33291 and seven isolates donated from Instituto de Biotecnologia were used in this study. The presence of CDT genes in C. jejuni strains was determined by PCR. To evaluate the effect of CDT, HeLa cells were treated with bacterial lysate, and the damage and morphological changes were analyzed by microscopy, immunofluorescence staining, and flow cytometry. To evaluate the role of the cytoskeleton, HeLa cells were treated with either latrunculin A or by nocodazole and analyzed by microscopy, flow cytometry, and immunoquantification (ELISA). The results obtained showed that the eight strains of C. jejuni , including the reference strain, had the ability to produce the toxin. Usage of latrunculin A and nocodazole, two cytoskeletal inhibitors, blocked the toxic effect in cells treated with the toxin. This phenomenon was evident in flow cytometry analysis and immunoquantification of Cdc2-phosphorylated. This work showed that the cytotoxic activity of the C. jejuni CDT is dependent on its endocytosis. The alteration in the microtubules and actin filaments caused a blockage transit of the toxin, preventing it from reaching the nucleus of the cell, as well as preventing DNA fragmentation and alteration of the cell cycle. The CDT toxin appears to be an important element for the pathogenesis of campylobacteriosis, since all clinical isolates showed the presence of cdtA , cdtB and cdtC genes.

Cytolethal Distending Toxin From Campylobacter jejuni Requires the Cytoskeleton for Toxic Activity

PubMed Central

Méndez-Olvera, Estela T.; Bustos-Martínez, Jaime A.; López-Vidal, Yolanda; Verdugo-Rodríguez, Antonio; Martínez-Gómez, Daniel

2016-01-01

Background Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. Objectives The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus. Methods Campylobacter jejuni ATCC 33291 and seven isolates donated from Instituto de Biotecnologia were used in this study. The presence of CDT genes in C. jejuni strains was determined by PCR. To evaluate the effect of CDT, HeLa cells were treated with bacterial lysate, and the damage and morphological changes were analyzed by microscopy, immunofluorescence staining, and flow cytometry. To evaluate the role of the cytoskeleton, HeLa cells were treated with either latrunculin A or by nocodazole and analyzed by microscopy, flow cytometry, and immunoquantification (ELISA). Results The results obtained showed that the eight strains of C. jejuni, including the reference strain, had the ability to produce the toxin. Usage of latrunculin A and nocodazole, two cytoskeletal inhibitors, blocked the toxic effect in cells treated with the toxin. This phenomenon was evident in flow cytometry analysis and immunoquantification of Cdc2-phosphorylated. Conclusions This work showed that the cytotoxic activity of the C. jejuni CDT is dependent on its endocytosis. The alteration in the microtubules and actin filaments caused a blockage transit of the toxin, preventing it from reaching the nucleus of the cell, as well as preventing DNA fragmentation and alteration of the cell cycle. The CDT toxin appears to be an important element for the pathogenesis of campylobacteriosis, since all clinical isolates showed the presence of cdtA, cdtB and cdtC genes. PMID:27942359

Contribution of pertussis toxin to the pathogenesis of pertussis disease

PubMed Central

Carbonetti, Nicholas H.

2015-01-01

Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

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

PubMed

Cardoso, Francisco

2018-06-01

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

Particle size fractionation of paralytic shellfish toxins (PSTs): seasonal distribution and bacterial production in the St Lawrence estuary, Canada.

PubMed

Michaud, S; Levasseur, M; Doucette, G; Cantin, G

2002-10-01

We determined the seasonal distribution of paralytic shellfish toxins (PSTs) and PST producing bacteria in > 15, 5-15, and 0.22-5 microm size fractions in the St Lawrence. We also measured PSTs in a local population of Mytilus edulis. PST concentrations were determined in each size fraction and in laboratory incubations of sub-samples by high performance liquid chromatography (HPLC), including the rigorous elimination of suspected toxin 'imposter' peaks. Mussel toxin levels were determined by mouse bioassay and HPLC. PSTs were detected in all size fractions during the summer sampling season, with 47% of the water column toxin levels associated with particles smaller than Alexandrium tamarense (< 15 microm). Even in the > 15 microm size fraction, we estimated that as much as 92% of PSTs could be associated with particles other than A. tamarense. Our results stress the importance of taking into account the potential presence of PSTs in size fractions other than that containing the known algal producer when attempting to model shellfish intoxication, especially during years of low cell abundance. Finally, our HPLC results confirmed the presence of bacteria capable of autonomous PST production in the St Lawrence as well as demonstrating their regular presence and apparent diversity in the plankton. Copyright 2002 Elsevier Science Ltd.

A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

PubMed

Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

2015-12-02

Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. Copyright © 2015, American Association for the Advancement of Science.

A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

PubMed Central

Nguyen, Annalee W.; Wagner, Ellen K.; Laber, Joshua R.; Goodfield, Laura L.; Smallridge, William E.; Harvill, Eric T.; Papin, James F.; Wolf, Roman F.; Padlan, Eduardo A.; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A.

2016-01-01

In spite of wide-spread vaccination, pertussis rates are rising in industrialized countries and remain high world-wide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. Here, we humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human IgG1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the B. pertussis-induced rise in white blood cell count and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated but not control animals experienced a blunted rise in white blood cell count and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

Mathematical modeling of growth of non-O157 Shiga Toxin-producing Escherichia coli in raw ground beef

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate the growth of Shiga toxin-producing Escherichia coli (STEC, including serogroups O45, O103, O111, O121, and O145) in raw ground beef and to develop mathematical models to describe the bacterial growth under different temperature conditions. Three prima...

Carcass and meat quality of Gokceada Goat kids reared under extensive and semi-intensive production systems.

PubMed

Ozcan, Mustafa; Yalcintan, Hulya; Tölü, Cemil; Ekiz, Bulent; Yilmaz, Alper; Savaş, Türker

2014-01-01

The aim was to compare the carcass and meat quality characteristics of male and female Gokceada Goat kids produced in extensive (n=20) and semi-intensive (n=20) systems. In extensive and semi-intensive produced kids pre-slaughter weights were 17.44 and 12.51 kg; cold carcass weights were 8.66 and 5.35 kg and cold dressing percentages were 54.9 and 49.28%, respectively. The effect of kid sex was not significant on hot and cold dressing percentages, back fat thickness, M. longissimus dorsi section area, carcass fatness and conformation scores, and carcass measurements, while female kids had higher omental and mesenteric fat and kidney knob and channel fat percentages than male kids. Extensive produced kids had lower meat lightness. Panellists evaluated extensive system kids with higher scores of kid odour intensity, flavour intensity and overall acceptability. It was concluded that it would be more appropriate to use an extensive system in Gokceada Goat breeding for kid meat production. © 2013.

Antibacterial activity of plant extracts on foodborne bacterial pathogens and food spoilage bacteria

USDA-ARS?s Scientific Manuscript database

Bacterial foodborne diseases are caused by consumption of foods contaminated with bacteria and/or their toxins. In this study, we evaluated antibacterial properties of twelve different extracts including turmeric, lemon and different kinds of teas against four major pathogenic foodborne bacteria inc...

Kids Club: A School-Age Program Guide for Directors.

ERIC Educational Resources Information Center

Sisson, Linda G.

This handbook for administrators of school-age day care programs offers guidelines on implementing Kids Club programs. Kids Clubs coordinate family and public school resources to meet elementary children's needs for adult supervision and guidance when the children are not in school and their parents are at work. The handbook consists of seven…

The Chromokinesin Kid Is Required for Maintenance of Proper Metaphase Spindle SizeD⃞

PubMed Central

Tokai-Nishizumi, Noriko; Ohsugi, Miho; Suzuki, Emiko; Yamamoto, Tadashi

2005-01-01

The human chromokinesin Kid/kinesin-10, a plus end-directed microtubule (MT)-based motor with both microtubule- and DNA-binding domains, is required for proper chromosome alignment at the metaphase plate. Here, we performed RNA interference experiments to deplete endogenous Kid from HeLa cells and confirmed defects in metaphase chromosome arm alignment in Kid-depleted cells. In addition, we noted a shortening of the spindle length, resulting in a pole-to-pole distance only 80% of wild type. The spindle microtubule-bundles with which Kid normally colocalize became less robust. Rescue of the two Kid deficiency phenotypes—imprecise chromosome alignment at metaphase and shortened spindles— exhibited distinct requirements. Mutants lacking either the DNA-binding domain or the MT motor ATPase failed to rescue the former defect, whereas rescue of the shortened spindle phenotype required neither activity. Kid also exhibits microtubule bundling activity in vitro, and rescue of the shortened spindle phenotype and the bundling activity displayed similar domain requirements, except that rescue required a coiled-coil domain not needed for bundling. These results suggest that distinct from its role in chromosome movement, Kid contributes to spindle morphogenesis by mediating spindle microtubules stabilization. PMID:16176979

Comparing clinical effects of marbofloxacin and gamithromycin in goat kids with pneumonia.

PubMed

Kacar, Yigit; Batmaz, Hasan; Yilmaz, Ozge E; Mecitoglu, Zafer

2018-06-20

The aim of this study was to compare the clinical efficacy of a single-dose of gamithromycin (GM) or marbofloxacin (MR) in kids with naturally occurring pneumonia. Thirty-six kids, aged 2-2.5 months, with body weight ranging from 12 kg to 18 kg were presented with clinical signs of pneumonia. The most prominent clinical findings were an increase in the respiratory rate, crackling lung sounds on auscultation, coughing, nasal discharge and an increased rectal temperature. Mannheimia haemolytica and Mycoplasma spp. colonies were isolated from microbiological examination of six transtracheal washes and lung tissues of one necropsied kid. The severity of pneumonia was evaluated by using cumulative clinical score (CCS). The CCS of the 36 kids used in the study were four and above. Kids were randomly divided into two equal groups; the GM group received a single subcutaneous dose of GM at a dosage of 6 mg/kg and the MR group received MR intramuscularly at a dosage of 8 mg/kg as a single-dose. No side effects related to the drugs were detected in either group. All 36 kids were clinically examined 3 weeks after the initiation of the treatment. Clinical signs in both groups were almost completely absent at the end of the study. A single administration of GM or MR was successfully used in the treatment of kids with pneumonia.

Pertussis toxin

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

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

1985-01-01

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

The investigation of epsilon toxin effects on different cancerous cell lines and its synergism effect with methotrexate.

PubMed

Shekarsaraei, Azin Gholami; Hasannia, Sadegh; Pirooznia, Nazanin; Ataiee, Fariba

2014-01-01

The overall goal of this study is to use a bacterial toxin as drug delivery agents for chemotherapy drugs and overcome the development of resistance to these medicines. COR-L105 and MDA-MB 231 which are epithelial-like were used in this study. Cytotoxicity assays were performed by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) as metabolic indicator. The toxin was essential to kill 50% (CT50) and IC 50 value (inhibition growth value) for methotrexate were determined as optical density at 540 nm. Epsilon toxin-loaded PLGA nanoparticles were prepared using non-aqueous technique. Surface morphology, in vitro drug release, and encapsulation efficiency of the nanoparticles was determined. Results confirmed that using non-toxic concentration of epsilon toxin, resistance to cancerous cell decreased significantly, which could be an important result in cancer therapy. The synergistic effect of MTX and epsilon toxin showed that bio toxins can be used as supplement with chemical drugs and increase the effect of chemotherapy. The results illustrated that application of PLGA as drug delivery system due to its controlled release properties was beneficial. These finding proposed that due to the ease of local accessibility of lung tumors with aerosol drug delivery, biotoxins can directly be used with chemotherapy drugs in aerosol form.

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

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

Won, JaeSeon; Nam, PilWon; Lee, YongChan

2009-04-24

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

Climate Literacy for Kids: Finding Medium, Message, and Stance

NASA Astrophysics Data System (ADS)

Fisher, D. K.; Leon, N.; Jackson, R.; Greene, M. P.

2011-12-01

As part of NASA's Global Climate Change (climate.nasa.gov) website (winner of the 2011Webby Award for Best Science Site), Climate Kids (climate.nasa.gov/kids) presents positive role models for green careers and encourages kids to be good climate citizens. But before they will care, they must understand. Climate Kids helps kids understand climate science by communicating at their own science awareness and maturity level, and by giving them concrete ways to start helping Earth now. Climate Kids, as informal education, speaks to upper-elementary-school-age kids in their own language and using some of their favorite media. In addition to simple, liberally illustrated text explanations of the basic science concepts, cartoons and games reinforce the concepts in a fun way. A growing section on green careers interviews enthusiastic individuals currently practicing their professions. In explaining what they do, these individuals reinforce the climate science concepts and "how to help" suggestions elsewhere on the site. The games also reinforce the green career choices. "Green Careers" currently features a "green" general contractor, a home energy auditor, a water-wise landscaper, a recycling program educator, and a renewable energy scientist. The message of the scientist, who designs wind energy farms and "architectural wind" arrays, is reinforced by the "Power-up" game. In this game, players move a wind turbine up or down to capture the wind and move a solar array back and forth to stay out of cloud shadows. Depending on how many "windows" of the game's "city" light up using these alternative energy sources, the player earns a bronze, silver, gold, or platinum "medal." A recycling game reinforces the messages of the recycling program educator about the importance of recycling in saving energy, what can and cannot be recycled, and how long trash items remain in a landfill before decomposing. In the game, a variety of throw-away objects rains down from the top of the screen

Inhibition of Shiga toxin 2 (Stx2) in apple juices and its resistance to pasteurization.

PubMed

Rasooly, Reuven; Do, Paula M; Levin, Carol E; Friedman, Mendel

2010-06-01

In the present study, we evaluated Shiga toxin (Stx2) activity in apple juices by measuring a decrease in dehydrogenase activity of Vero cells with the microculture tetrazolium (MTT) assay. Freshly prepared juice from Red Delicious apples and Golden Delicious apples inhibited the biological activity of the bacterial toxin Stx2 produced by E. coli O157:H7 strains. Studies with immunomagnetic beads bearing specific antibodies against the toxin revealed that Stx2 activity was restored when removed from the apple juice. SDS gel electrophoresis revealed no difference (P < 0.05) in the densities or molecular weights between Stx2 in either PBS or apple juices. These results suggest that Stx2 may be reversibly bound to small molecular weight constituents in the juice. The Stx2 toxin was not inactivated on exposure to heat programs (63 degrees C for 30 min, 72 degrees C for 15 s, 89 degrees C for 1 s) commonly used to pasteurize apple juice, but lost all activity when exposed to 100 degrees C for 5 min. The results suggest that pasteurization of apple juice used to inactivate E. coli O157:H7 has no effect on Stx2, and that food-compatible and safe antitoxin compounds can be used to inhibit the biological activity of the Shiga toxin.

Third Culture Kids and College Support: A Case Study

ERIC Educational Resources Information Center

Holdren, Sarah Jennifer

2013-01-01

This single site case study applies the "Transition Cycle" framework (Pollock & Van Reken, 2009) to an institutionally-based, student-run support program for Third Culture Kids. The purpose of this study was to examine how Lewis and Clark College responded to the presence of Third Culture Kid, or Global Nomad, students on campus by…

Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

PubMed Central

Ruan, Xiaosai; Sack, David A.; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

PubMed

Ruan, Xiaosai; Sack, David A; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent

Get Your Kids Moving and Check Some Chores off Your List

MedlinePlus

... a Healthy Heart Healthy Kids Our Kids Programs Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's ...

Make the Most of Play - Tips for Kids to Get Active

MedlinePlus

... a Healthy Heart Healthy Kids Our Kids Programs Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's ...

Toxin Plasmids of Clostridium perfringens

PubMed Central

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

2013-01-01

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

Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1.

PubMed

Ivie, Susan E; McClain, Mark S

2012-09-25

Clostridium perfringens epsilon toxin belongs to the aerolysin-like family of pore-forming toxins and is one of the most potent bacterial toxins known. The epsilon toxin causes fatal enterotoxemia in sheep, goats, and possibly humans. Evidence indicates that the toxin binds to protein receptors including hepatitis A virus cellular receptor 1 (HAVCR1), but the region of the toxin responsible for cell binding has not been identified. In the present study, we identify amino acids within the epsilon toxin important for this cell interaction. Site-specific mutagenesis was used to investigate the role of a surface-accessible cluster of aromatic amino acids, and purified mutant proteins were tested in a series of cell-culture assays to assess cytotoxic activity and cell binding. When added to cells, four mutant proteins (Etx-Y29E, Etx-Y30E, Etx-Y36E and Etx-Y196E) were severely impaired in their ability to not only kill host cells, but also in their ability to permeabilize the plasma membrane. Circular dichroism spectroscopy and thermal stability studies revealed that the wild-type and mutant proteins were similarly folded. Additional experiments revealed that these mutant proteins were defective in binding to host cells and to HAVCR1. These data indicate that an amino acid motif including Y29, Y30, Y36, and Y196 is important for the ability of epsilon toxin to interact with cells and HAVCR1.

Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1

PubMed Central

Ivie, Susan E.; McClain, Mark S.

2012-01-01

Clostridium perfringens epsilon toxin belongs to the aerolysin-like family of pore-forming toxins and is one of the most potent bacterial toxins known. The epsilon toxin causes fatal enterotoxemia in sheep, goats, and possibly humans. Evidence indicates that the toxin binds to protein receptors including hepatitis A virus cellular receptor 1 (HAVCR1), but the region of the toxin responsible for cell binding has not been identified. In the present study, we identify amino acids within the epsilon toxin important for this cell interaction. Site-specific mutagenesis was used to investigate the role of a surface-accessible cluster of aromatic amino acids, and purified mutant proteins were tested in a series of cell-culture assays to assess cytotoxic activity and cell binding. When added to cells, four mutant proteins (Etx-Y29E, Etx-Y30E, Etx-Y36E and Etx-Y196E) were severely impaired in their ability to not only kill host cells, but also in their ability to permeabilize the plasma membrane. Circular dichroism spectroscopy and thermal stability studies revealed that the wild-type and mutant proteins were similarly folded. Additional experiments revealed that these mutant proteins were defective in binding to host cells and to HAVCR1. These data indicate that an amino acid motif including Y29, Y30, Y36, and Y196 is important for the ability of epsilon toxin to interact with cells and HAVCR1. PMID:22938730

Clinical acceptability of the sense_assess© kids: Children and youth perspectives.

PubMed

Taylor, Susan; McLean, Belinda; Blair, Eve; Carey, Leeanne Mary; Valentine, Jane; Girdler, Sonya; Elliott, Catherine

2018-04-01

The sense_assess© kids is a standardised, norm-referenced assessment designed to measure the functional somatosensation capacity of the upper limb of children with cerebral palsy. The objective of the current study was to determine if the sense_assess© kids was clinically acceptable to children and youth. A questionnaire was completed by participants following administration of the sense_assess© kids by a trained occupational therapist. Twenty-six children with spastic hemiplegic cerebral palsy (aged 6-15 years six months; mean 10 years eight months; 16 boys) were recruited. Participants responded to questions regarding the administration and level of difficulty of the sense_assess© kids using a Q-Sort of 'like' and 'dislike', Likert scales and short answers. Content analysis was applied. Twenty-one of twenty-six children, indicated that they were 'very happy' or 'happy' with the administration process of the sense_assess© kids. Most participants indicated that they liked the sensation they felt in the hand when tested. This study has demonstrated the acceptability of sense_assess© kids for the population for whom it is intended. © 2017 Occupational Therapy Australia.

Complications after craniosynostosis surgery: comparison of the 2012 Kids' Inpatient Database and Pediatric NSQIP Database.

PubMed

Lin, Yimo; Pan, I-Wen; Mayer, Rory R; Lam, Sandi

2015-12-01

OBJECT Research conducted using large administrative data sets has increased in recent decades, but reports on the fidelity and reliability of such data have been mixed. The goal of this project was to compare data from a large, administrative claims data set with a quality improvement registry in order to ascertain similarities and differences in content. METHODS Data on children younger than 12 months with nonsyndromic craniosynostosis who underwent surgery in 2012 were queried in both the Kids' Inpatient Database (KID) and the American College of Surgeons Pediatric National Surgical Quality Improvement Program (Peds NSQIP). Data from published clinical craniosynostosis surgery series are reported for comparison. RESULTS Among patients younger than 12 months of age, a total of 1765 admissions were identified in KID and 391 in Peds NSQIP in 2012. Only nonsyndromic patients were included. The mean length of stay was 3.2 days in KID and 4 days in Peds NSQIP. The rates of cardiac events (0.5% in KID, 0.3% in Peds NSQIP, and 0.4%-2.2% in the literature), stroke/intracranial bleeds (0.4% in KID, 0.5% in Peds NSQIP, and 0.3%-1.2% in the literature), infection (0.2% in KID, 0.8% in Peds NSQIP, and 0%-8% in the literature), wound disruption (0.2% in KID, 0.5% in Peds NSQIP, 0%-4% in the literature), and seizures (0.7% in KID, 0.8% in Peds NSQIP, 0%-0.8% in the literature) were low and similar between the 2 data sets. The reported rates of blood transfusion (36% in KID, 64% in Peds NSQIP, and 1.7%-100% in the literature) varied between the 2 data sets. CONCLUSIONS Both the KID and Peds NSQIP databases provide large samples of surgical patients, with more cases reported in KID. The rates of complications studied were similar between the 2 data sets, with the exception of blood transfusion events where the retrospective chart review process of Peds NSQIP captured almost double the rate reported in KID.

Caught in the Crossfire: Kids, Politics, and America's Future

ERIC Educational Resources Information Center

Grossberg, Lawrence

2005-01-01

"Caught in the Crossfire" reveals how the United States has been gradually changing from a society that celebrates childhood into one that is hostile to and afraid of its own children. Today kids are often seen as a threat to our social and moral values. In schools, some behavior is criminalized, and growing numbers of kids find…

Kid depletion in mouse oocytes associated with multinucleated blastomere formation and inferior embryo development.

PubMed

Egashira, Akiyoshi; Yamauchi, Nobuhiko; Islam, Md Rashedul; Yamagami, Kazuki; Tanaka, Asami; Suyama, Hikaru; El-Sayed, El-Sharawy Mohamed; Tabata, Shoji; Kuramoto, Takashi

2016-08-01

This study investigated the knockdown (KD) of Kid on maturation developmental competence and multinucleation of mouse germinal vesicle (GV) oocytes after parthenogenetic activation. Data revealed that Kid messenger RNA (mRNA) was expressed in GV and MII stage oocyte and 1- and 2-cell embryos. Additionally, Kid mRNA expression in the Kid KD group decreased by nearly 46% compared to the control small interfering RNA (siRNA) groups. The rate of multinucleated embryos in the Kid KD group (52.4%) was significantly higher (P < 0.05) than the control siRNA group (4.7%). Finally, the developmental rates were significantly lower in the Kid siRNA group at > 4-cell stage (28.6% vs. 53.5%) and the blastocyst stage (2.4% vs. 23.3%) compared to the control siRNA groups. Suppression of Kid using siRNA caused multinucleation in early embryos with high frequency and it may increase 2- to 4-cell arrested embryos and reduce the developmental competence to blastocyst. © 2016 Japanese Society of Animal Science.

Report: Prevalence and antibiotic trials against Salmonella enterica isolated from diarrheic lambs and kids.

PubMed

Iqbal, Muhammad Kashif; Ijaz, Muhammad; Aslam, Hassaan Bin; Farooqi, Shahid Hussain; Ahmad, Syed Saleem; Akhtar, Raheela

2017-11-01

Salmonella enterica (S. enterica) is the major zoonotic threat for small ruminants and humans responsible for huge economic losses and high mortality in Pakistan. Lambs and kids of Lahore district were examined to determine the prevalence, hematology and chemotherapy of S. enterica. A total of 200 diarrheic samples (n=100 lambs; n=100 kids) were collected and examined; 59 (29.50%) were found positive for S. enterica. Lambs had lightly greater prevalence (31%) than kids (29%). The frequency analysis (OR=1.16 [reciprocal =0.87]) showed non-significant difference in both the lambs and kids. The significant decrease (Pℜ0.001) in hemoglobin, pack cell volume and total erythrocyte count was observed in infected lambs and kids. Results of in-vitro antibiotic susceptibility test revealed that S. enteric isolated from both lambs and kids were susceptible to levofloxacin, ciprofloxacin, ofloxacin, gentamicin, azithromycin, tobramycin, amoxicillin, ampicillin and nalidixic acid. Where as the results of in vivo antibiotic trials showed that isolates from both lambs and the kids with diarrhea were susceptible to levofloxacin and ciprofloxacin.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

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

Peters, Diane E.; Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA; Hoover, Benjamin

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6more » syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

PubMed

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

PubMed Central

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; Mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA- activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32%–87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. PMID:24971906

The Adenylate Cyclase Toxins of Bacillus anthracis and Bordetella pertussis Promote Th2 Cell Development by Shaping T Cell Antigen Receptor Signaling

PubMed Central

Rossi Paccani, Silvia; Benagiano, Marisa; Capitani, Nagaja; Zornetta, Irene; Ladant, Daniel; Montecucco, Cesare; D'Elios, Mario M.; Baldari, Cosima T.

2009-01-01

The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, to modulate APC activation, resulting in the expression of Th2–driving cytokines. On the other hand, cAMP has been demonstrated to induce a Th2 bias when present during T cell priming, suggesting that bacterial cAMP elevating toxins may directly affect the Th1/Th2 balance. Here we have investigated the effects on human CD4+ T cell differentiation of two adenylate cyclase toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which differ in structure, mode of cell entry, and subcellular localization. We show that low concentrations of ET and CyaA, but not of their genetically detoxified adenylate cyclase defective counterparts, potently promote Th2 cell differentiation by inducing expression of the master Th2 transcription factors, c-maf and GATA-3. We also present evidence that the Th2–polarizing concentrations of ET and CyaA selectively inhibit TCR–dependent activation of Akt1, which is required for Th1 cell differentiation, while enhancing the activation of two TCR–signaling mediators, Vav1 and p38, implicated in Th2 cell differentiation. This is at variance from the immunosuppressive toxin concentrations, which interfere with the earliest step in TCR signaling, activation of the tyrosine kinase Lck, resulting in impaired CD3ζ phosphorylation and inhibition of TCR coupling to ZAP-70 and Erk activation. These results demonstrate that, notwithstanding their differences in their intracellular localization, which result in focalized cAMP production, both toxins directly affect the Th1/Th2 balance by interfering with the same steps in TCR signaling, and suggest that their adjuvanticity is likely to result from their combined effects on APC and CD4+ T cells. Furthermore, our results strongly support the key role of cAMP in the adjuvanticity of these toxins. PMID:19266022

T3SS-Independent Uptake of the Short-Trip Toxin-Related Recombinant NleC Effector of Enteropathogenic Escherichia coli Leads to NF-κB p65 Cleavage.

PubMed

Stolle, Anne-Sophie; Norkowski, Stefanie; Körner, Britta; Schmitz, Jürgen; Lüken, Lena; Frankenberg, Maj; Rüter, Christian; Schmidt, M Alexander

2017-01-01

Effector proteins secreted by the type 3 secretion system (T3SS) of pathogenic bacteria have been shown to precisely modulate important signaling cascades of the host for the benefit of the pathogens. Among others, the non-LEE encoded T3SS effector protein NleC of enteropathogenic Escherichia coli (EPEC) is a Zn-dependent metalloprotease and suppresses innate immune responses by directly targeting the NF-κB signaling pathway. Many pathogenic bacteria release potent bacterial toxins of the A-B type, which-in contrast to the direct cytoplasmic injection of T3SS effector proteins-are released first into the environment. In this study, we found that NleC displays characteristics of bacterial A-B toxins, when applied to eukaryotic cells as a recombinant protein. Although lacking a B subunit, that typically mediates the uptake of toxins, recombinant NleC (rNleC) induces endocytosis via lipid rafts and follows the endosomal-lysosomal pathway. The conformation of rNleC is altered by low pH to facilitate its escape from acidified endosomes. This is reminiscent of the homologous A-B toxin AIP56 of the fish pathogen Photobacterium damselae piscicida ( Phdp ). The recombinant protease NleC is functional inside eukaryotic cells and cleaves p65 of the NF-κB pathway. Here, we describe the endocytic uptake mechanism of rNleC, characterize its intracellular trafficking and demonstrate that its specific activity of cleaving p65 requires activation of host cells e.g., by IL1β. Further, we propose an evolutionary link between some T3SS effector proteins and bacterial toxins from apparently unrelated bacteria. In summary, these properties might suggest rNleC as an interesting candidate for future applications as a potential therapeutic against immune disorders.

Saturated or unsaturated fat supplemented maternal diets influence omental adipose tissue proteome of suckling goat-kids.

PubMed

Restelli, Laura; Marques, Andreia T; Savoini, Giovanni; Invernizzi, Guido; Carisetti, Michela; Lecchi, Cristina; Bendixen, Emoke; Ceciliani, Fabrizio

2017-11-03

The aim of the present study was to investigate how maternal diet can influence the adipose tissue of goat kids. Omental adipose tissue proteomes of goat-kids from mothers fed with diet enriched with stearic acid (ST-kids), fish oil (FO-kids) and standard diets (CTRL) were determined by quantitative iTRAQ 2D-LC-MS/MS analysis. Twenty proteins were found to be differentially expressed in suckling kids' omental adipose tissue. Stearic acid induces changes in a higher number of proteins when compared to fish oil. Eleven proteins, namely AARS, ECl1, PMSC2, CP, HSPA8, GPD1, RPL7, OGDH, RPL24, FGA and RPL5 were decreased in ST-kids only. Four proteins, namely DLST, EEF1G, BCAP31 and RALA were decreased in FO-kids only, and one, NUCKS1, was increased. Four proteins, namely PMSC1, PPIB, TUB5×2 and EIF5A1, were be less abundant in both ST- and FO- kids. Most of the protein whose abundance was decreased in ST kids (10 out of 15) are involved in protein metabolism and catabolism pathways. Qualitative gene expression analysis confirmed that all the proteins identified by mass spectrometry, with the exception of FGA, were produced by adipose tissue. Quantitative gene expression analysis demonstrated that two proteins, namely CP, a minor acute phase protein, and ECl1, involved in fatty acid beta oxidation, were downregulated at mRNA level as well. ECl1 gene expression was downregulated in ST-kids AT as compared to Ctrl-kids and CP was downregulated in both ST- and FO-kids. The present results demonstrate that it is possible to influence adipose goat-kid proteome by modifying the maternal diet. Copyright © 2017. Published by Elsevier Ltd.

Behaviour of crossbred does and their kids at parturition under extensive and intensive conditions.

PubMed

Mellado, Miguel; Véliz, Francisco G; García, José E; De Santiago, Ángeles

2012-03-01

Data from 82 kiddings from mixed-breed (native x dairy goats) goats reared on rangeland (n = 47) or confinement (n = 35) were used to determine the influence of various factors on length of labour, standing of newborn kids and time to first suckling in pluriparous goats. Both groups were mated at the same time to bucks of the same genotype in February. During the kidding time in July, the goats were monitored for 24 h in order to register parturition traits and kid birth weight and body measurements. For all goats, blood samples were collected at parturition in order to establish the nutritional state of goats. Grazing goats had lower body weight and body condition score (P < 0.01) than pen-fed goats, as well as lower values for some blood metabolites indicative of low body energy reserves. For both grazing and pen-fed goats, the majority of kiddings (>93%) occurred during daylight hours. No kiddings were registered from 2300 to 0500 hours. No effects of height at withers, thoracic circumference and sex of kids at birth were found to influence length of labour. Labour was shorter (P < 0.01) for pen-fed does than grazing goats (10.6 ± 1.18 min vs. 15.4 ± 1.2 min; mean ± SD). The length of parturition was considerably longer (P < 0.05) for twin-bearing does than for single-bearing does (16.6 ± 1.76 min vs. 11.2 ± 0.81 min, respectively). The interval between parturition and standing of kids was shorter (P < 0.05) for kids from litters weighing >3.3 kg (entire litter) than kids from litters with <3.3 kg (22.7 ± 1.82 min vs. 31.1 ± 2.76 min). Time to first suckling was longer (P < 0.05) for kids delivered from pen-fed does than kids from grazing does (57.8 ± 7.57 min vs. 42.9 ± 3.05 min). These results confirm that, independently of type of production system (intensive or extensive), kiddings of does are concentrated during daylight hours. These results also indicate that conformation

Delivery of CdiA Nuclease Toxins into Target Cells during Contact-Dependent Growth Inhibition

PubMed Central

Webb, Julia S.; Nikolakakis, Kiel C.; Willett, Julia L. E.; Aoki, Stephanie K.

2013-01-01

Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiAUPEC536 were used to visualize transfer of CdiA from CDIUPEC536+ inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiAUPEC536 protein is deposited onto the surface of target bacteria. CdiAUPEC536 transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiAUPEC536 is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiAUPEC536 prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI+ inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes. PMID:23469034

9 CFR 311.28 - Carcasses of young calves, pigs, kids, lambs, and foals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Carcasses of young calves, pigs, kids... PARTS § 311.28 Carcasses of young calves, pigs, kids, lambs, and foals. Carcasses of young calves, pigs, kids, lambs, and foals are unwholesome and shall be condemned if (a) the meat has the appearance of...

9 CFR 311.28 - Carcasses of young calves, pigs, kids, lambs, and foals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Carcasses of young calves, pigs, kids... PARTS § 311.28 Carcasses of young calves, pigs, kids, lambs, and foals. Carcasses of young calves, pigs, kids, lambs, and foals are unwholesome and shall be condemned if (a) the meat has the appearance of...

9 CFR 311.28 - Carcasses of young calves, pigs, kids, lambs, and foals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Carcasses of young calves, pigs, kids... PARTS § 311.28 Carcasses of young calves, pigs, kids, lambs, and foals. Carcasses of young calves, pigs, kids, lambs, and foals are unwholesome and shall be condemned if (a) the meat has the appearance of...

9 CFR 311.28 - Carcasses of young calves, pigs, kids, lambs, and foals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Carcasses of young calves, pigs, kids... PARTS § 311.28 Carcasses of young calves, pigs, kids, lambs, and foals. Carcasses of young calves, pigs, kids, lambs, and foals are unwholesome and shall be condemned if (a) the meat has the appearance of...

9 CFR 311.28 - Carcasses of young calves, pigs, kids, lambs, and foals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Carcasses of young calves, pigs, kids... PARTS § 311.28 Carcasses of young calves, pigs, kids, lambs, and foals. Carcasses of young calves, pigs, kids, lambs, and foals are unwholesome and shall be condemned if (a) the meat has the appearance of...

Toxin-Based Therapeutic Approaches

PubMed Central

Shapira, Assaf; Benhar, Itai

2010-01-01

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

Lamb and kid mortality in village flocks in the coastal savanna zone of Ghana.

PubMed

Turkson, P K

2003-12-01

A cohort study was designed to observe and follow up mortality in lambs and kids in 88 flocks of sheep and goats under the traditional production system in five villages within the coastal savanna zone of Ghana over a 2-year period. The overall mortality rates for kids and lambs were 30.8% and 33.5%, respectively. Significantly higher proportions of kids (80.2%) and lambs (75.6%) up to 3 months of age died compared to kids and lambs from 4 to 12 months of age. The differences in mortality rates, either between male and female kids and lambs or between single-born and multiple-birth kids and lambs, were not significant. The odds ratio (OR) and relative risks (RR) for lambs and kids, on the basis of sex and birth types, were not significant; neither were the values obtained for attributable risk, attributable fraction, population attributable risk and population attributable fraction. The overall mortality rate on the basis of species of animal was not significant. At the village level, significant differences in the proportions of mortality on the basis of sex were seen in two villages. At Akotokyir, more male lambs (54.2%) died compared to females (27.6%), while at Apewosika more female lambs (42.2%) died compared to males (16.7%). The only significant difference in mortality proportions on the basis of birth type at the village level was seen at Apewosika, where more single-born kids died (52.8%) compared to kids born with sibling(s) (28.4%). The significant ORs for mortalities were 3.10 for male lambs at Akotokyir, 3.35 for female lambs at Apewosika and 2.82 for single-born kids at Apewosika. The corresponding RRs were equally significant. On the basis of species, significantly more lambs died at Akotokyir (44.2%) and Kwesimprah (44.7%) compared to kids. The implications of these findings are discussed.

Caught in the Crossfire: Kids, Politics, and America's Future

ERIC Educational Resources Information Center

Grossberg, Lawrence

2005-01-01

Caught in the Crossfire reveals how the United States has been gradually changing from a society that celebrates childhood into one that is hostile to and afraid of its own children. Today kids are often seen as a threat to our social and moral values. In schools, some behavior is criminalized, and growing numbers of kids find themselves in penal…

The development of the pupillary light reflex and menace response in neonatal lambs and kids.

PubMed

Raoofi, Afshin; Mirfakhraie, Pejman; Yourdkhani, Sorush

2011-03-01

The aim of this study was to investigate the development of the pupillary light reflex and menace response in neonatal lambs and goat kids. Thirty lambs and 33 kids were assessed daily from birth until the pupillary light reflex and menace response had become established. All animals had a controlled pupillary light reflex within 20 h of birth. Lambs and kids had developed menace responses by 8 ± 3 and 14 ± 2 days, respectively. The Mann-Whitney test revealed a significant difference (P < 0.001) in the ages at which lambs and kids developed a menace response. Male kids developed this response significantly (P = 0.006) later than females. There was no sex difference in the menace response in the lambs. Overall, the findings indicated that lambs develop a menace response earlier than kids, and female kids develop this response more rapidly than their male counterparts. Copyright © 2010 Elsevier Ltd. All rights reserved.

Counseling Third Culture Kids.

ERIC Educational Resources Information Center

Barringer, Carolyn Fox

Third Culture Kids (TCKs) represent a group of youth who have lived overseas with their families for business, service, or missionary work. The implications of living in multiple cultures, especially during the developmental and formative years of youth, warrant investigation. This study informs the US counseling community about the…

New Jersey Kids Count 2011: The State of Our Children

ERIC Educational Resources Information Center

Advocates for Children of New Jersey, 2011

2011-01-01

"New Jersey Kids Count 2011" again documents both advances and setbacks in key areas that affect child well-being--poverty, health, child protection, education, including early learning, and adolescent well-being. To better gauge New Jersey's progress in essential areas, a "New Jersey Kids Count Report Card" that identifies…

Raising Kids Who Read: What Parents and Teachers Can Do

ERIC Educational Resources Information Center

Willingham, Daniel T.

2015-01-01

Everyone agrees that reading is important, but kids today tend to lose interest in reading before adolescence. In "Raising Kids Who Read", bestselling author and psychology professor Daniel T. Willingham explains this phenomenon and provides practical solutions for engendering a love of reading that lasts into adulthood. Like…

A Leader's Guide to What Do You Stand for? For Kids CD-ROM

ERIC Educational Resources Information Center

Lewis, Barbara A.

2010-01-01

Kids of any age can learn the basics of good character and figure out what they stand for. This leader's guide is a companion to the children's book, "What Do You Stand For? For Kids". The 11 lessons on the CD-ROM provide a complete course for kids on caring, citizenship, cooperation, fairness, forgiveness, honesty, relationships, respect,…

Evaluation of oral tilmicosin efficacy against severe cryptosporidiosis in neonatal kids under field conditions.

PubMed

Paraud, C; Pors, I; Chartier, C

2010-05-28

Many compounds have been screened for their potential anti-cryptosporidial activity in ruminants but none of them has been totally efficient in controlling the disease. Macrolide antibiotics have demonstrated some activity against Cryptosporidium spp. in humans. Tilmicosin is a macrolide antibiotic, available in France in an oral form (Pulmotil AC, Lilly France). The preventive efficacy of tilmicosin was evaluated in a goat farm experiencing severe clinical cryptosporidiosis in kids. Twenty-two kids were separated from their dams just after birth and placed in a separated pen. They were divided into 3 groups: an untreated group (10 kids), group 1 (6 kids) receiving tilmicosin at 25mg/kg BW/day and group 2 (6 kids) receiving tilmicosin at 50mg/kg BW/day. Tilmicosin was individually given by oral route from day 2 of age for 10 days. Three times a week, individual faecal samples were performed to assess the oocyst output. Clinical data, i.e. diarrhea and mortality, were recorded. In control kids, the highest prevalence and intensity of excretion were observed between day 6 and day 16 of age and mortality reached 90%. Excretion dynamic and clinical consequences were similar in both treated kid groups. Finally, tilmicosin did not demonstrate any activity against severe kid cryptosporidiosis in field conditions. (c) 2010 Elsevier B.V. All rights reserved.

Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer.

PubMed

Fagan-Solis, Katerina D; Reaves, Denise K; Rangel, M Cristina; Popoff, Michel R; Stiles, Bradley G; Fleming, Jodie M

2014-07-02

Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy. In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines. Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity. Collectively, these data are the first to show that iota toxin has the potential to be an

Birthdate, mass and survival in mountain goat kids: effects of maternal characteristics and forage quality.

PubMed

Côté, Steeve D; Festa-Bianchet, Marco

2001-04-01

In temperate environments, early-born ungulates may enjoy a longer growth period before winter, and so attain a higher body mass and an increased probability of survival compared to late-born ones. We assessed the effects of maternal characteristics, forage quality and population density on kid birthdate, mass and survival in a population of marked mountain goats (Oreamnos americanus) in Alberta. The duration and timing of the birth season were similar in all years. Births were highly synchronised: 80% of kids were born within 2 weeks of the first birth. Maternal age, maternal social rank and density did not affect kid birthdate or mass. Previous breeding experience was not related to kid birthdate, but kids born to pluriparous mothers were heavier during summer than kids born to primiparous mothers. Male and female kids had similar mass and accumulated mass linearly during summer. Early-born kids were heavier than late-born kids. Faecal crude protein (FCP) in late spring and maternal mass were positively related to kid mass. Survival to weaning appeared higher for males (90%) than for females (78%), but survival to 1 year was 65% for both sexes. FCP in late spring, density, birthdate and mass did not affect kid survival to weaning in either sex. Survival to 1 year increased with FCP in late spring for females, but not for males. Survival to 1 year was independent of birthdate for both sexes, but heavy females survived better than light ones. Multiple logistic regression revealed a positive effect of mass on survival to 1 year when the sexes were pooled. Our results suggest that mountain goats are constrained to give birth in a short birth season synchronised with forage productivity.

Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity

PubMed Central

Masuda, Hisako; Inouye, Masayori

2017-01-01

Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes. Despite the prevalence of recognition sequences in many mRNA, preferential digestion seems to occur at specific positions within mRNA and also in certain reading frames. In this review, a variety of tools utilized to study the nuclease activities of toxins over the past 15 years will be reviewed. A recent adaptation of an RNA-seq-based technique to analyze entire sets of cellular RNA will be introduced with an emphasis on its strength in identifying novel targets and redefining recognition sequences. The differences in biochemical properties and postulated physiological roles will also be discussed. PMID:28420090

Kids and Smoking (For Parents)

MedlinePlus

... young smokers are more likely to experiment with marijuana, cocaine, heroin, or other drugs. The Attraction for ... KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- ...

Kids' Share 2008: How Children Fare in the Federal Budget

ERIC Educational Resources Information Center

Carasso, Adam; Steuerle, C. Eugene; Reynolds, Gillian; Vericker, Tracy; Macomber, Jennifer

2008-01-01

"Kids' Share 2008," a second annual report, looks comprehensively at trends in federal spending and tax expenditures on children. This report updates the previous year's report, "Kids' Share 2007," adding in actual (rather than projected) budget numbers for 2007 and projections of spending within the children's budget against other federal…

The App Squad: SLJ's Advisors Weigh in on Kids' Book Apps

ERIC Educational Resources Information Center

Ishizuka, Kathy

2011-01-01

In this article, "School Library Journal's" ("SLJ") advisors talk about book apps for kids. They discuss what they like, what one should look for in discerning the best for kids and teens, and where this all might be headed.

A single-step purification and molecular characterization of functional Shiga toxin 2 variants from pathogenic Escherichia coli

USDA-ARS?s Scientific Manuscript database

Shiga toxin (Stx) 2 variants, Stx2a, Stx2c, Stx2d and Stx2g were purified to homogeneity from bacterial culture supernatants by a one-step monoclonal anti-Stx affinity chromatography method. The method was based on the binding affinity of these Stxs for a monoclonal antibody against the Stx2 A-subun...

Identification and characterization of two novel toxins expressed by the lethal honey bee pathogen Paenibacillus larvae, the causative agent of American foulbrood.

PubMed

Fünfhaus, Anne; Poppinga, Lena; Genersch, Elke

2013-11-01

Paenibacillus larvae is a Gram-positive bacterial pathogen causing the epizootic American foulbrood in honey bee larvae. Four so-called enterobacterial repetitive intergenic consensus (ERIC) genotypes of P. larvae exist with P. larvae genotypes ERIC I and ERIC II being responsible for disease outbreaks all over the world. Very few molecular data on the pathogen, on pathogenesis or on virulence factors exist. We now identified two genomic loci in P. larvae ERIC I coding for two binary AB toxins, Plx1 and Plx2. In silico analyses revealed that Plx1 is the third member of an enigmatic family of AB toxins so far only comprising MTX1 of Lysinibacillus sphaericus and pierisin-like toxins expressed by several butterflies. Plx2 is also remarkable because the A-domain is highly similar to C3 exoenzymes, which normally are single domain proteins, while the B-domain is homologous to B-domains of C2-toxins. We constructed P. larvae mutants lacking expression of Plx1, Plx2 or both toxins and demonstrated that these toxins are important virulence factors for P. larvae ERIC I. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

S+T+R+O+N+G Kids Life Skills Program: Levels K-5.

ERIC Educational Resources Information Center

Silbert, Linda Bress; Silbert, Alvin J.

Strong kids have the fortitude to resist drug/alcohol abuse and other tendencies towards anti-social behavior. Research has shown that strong kids have attained a high level of development in six crucial areas. The S+T+R+O+N+G Kids Program builds upon each of these areas: (1) Self-Esteem; (2) Trust; (3) Responsibility; (4) Options; (5) Needs; (6)…

The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin complex.

PubMed

Yang, Guowei; Waterfield, Nicholas R

2013-01-01

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5∶1∶1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man.

Vigour in West African Dwarf kids within the first 24 h post-partum.

PubMed

Abdul-Rahman, I I; Bernard, A

2017-03-01

One hundred and fifty West African Dwarf (WAD) kids were tested at the National Goats Breeding Station to determine the effects of some neonatal factors on their vigour levels within the first 24 h post-partum. The kids were also tested to establish the relationship between maternal weight, rectal temperature, times of first standing and sucking, sucking period and vigour. The distance covered (in meters) by a kid towards its mother during a 5-min test period was considered as vigour trait. Vigour levels increased significantly (p < 0.05) with increasing age within the first 24 h post-partum. Kids born to second parity mothers had higher (p < 0.05) vigour than those born to first parity mothers. Similarly, high birth weight kids had higher (p < 0.05) vigour levels than low birth weight kids. Weak positive and negative correlations (p < 0.05), respectively, were found between vigour and rectal temperature, and vigour and the time of first successfully standing. However, there was moderate positive correlation (p < 0.01) between vigour and sucking period. The time it took for the newborn kid to stand up for the first time also correlated weakly and negatively (p < 0.01) with the duration of sucking by the newborn within the first 5 min of accessing the teat. Vigour within the first 24 h post-partum in WAD kids increased with increasing age, parity and birth weight and might be responsible for the earlier and longer sucking time and periods, respectively, in high birth weight kids and those dropped by multiparous does.

[Use of bevacizumab (Avastin) in KID syndrome: case report].

PubMed

Caye, Luiza; Scheid, Karin; Pizzol, Melissa Manfroi Dal; Freda, Roberto

2010-01-01

KID syndrome is a congenital ectodermal dysplasia characterized by the association of keratitis, hyperkeratotic skin lesions and neurosensorial hearing loss. Ocular involvement occurs in 95% of patients. Although KID syndrome cutaneous manifestations have been studied in-depth, the treatment and prognosis of ophthalmic impairment have not been described in detail. At present, the treatment of the ocular damage caused by the syndrome is symptomatic and there are no studies defining a treatment that could change the disease course. In this case, ophthalmologic findings of a patient with KID syndrome and the use of subconjunctival bevacizumab to treat corneal neovascularization are described. In spite of the absence of improvement in this patient and the few reports of this disease, additional studies with bevacizumab to treat corneal deep neovascularization are suggested.

Farmers' perceptions of goat kid mortality under communal farming in Eastern Cape, South Africa.

PubMed

Slayi, Mhlangabezi; Maphosa, Viola; Fayemi, Olutope Peter; Mapfumo, Lizwell

2014-10-01

Rearing of goats under communal farming conditions is characterised by high kid mortality and low weaning percentages. A survey was conducted to determine farmers' perceptions on the causes of kid mortality during summer under the communal farming system in Nkonkobe Local Municipality in the Eastern Cape, South Africa. This was done by administering questionnaires to a total of 162 respondents in 14 villages around Nkonkobe Local Municipality. The study showed that majority of farmers (75 %) keep flock sizes of less than 10 goats and kids, and this indicates that goat production in Nkonkobe Local Municipality is suppressed. According to the farmers, diseases (89 %), endo-parasites (72 %) and ecto-parasites (68 %) were perceived as the major causes of kid mortality. Other causes reported include starvation (15 %), extreme weather conditions (28 %), abortion (7 %), theft (35 %), diarrhoea (43 %), accidents (10 %) and wounds (9 %). The low number of goats could be attributed to high mortalities. It was also found that all causes reported by farmers played a role in high kid mortality in Nkonkobe Local Municipality. However, the causes which require more emphasis to formulate extension support were tick-borne diseases and parasites. This study provided baseline information on possible causes of kid mortalities in Nkonkobe Local Municipality. There is, however, a need to conduct further studies to determine actual causes of high kid mortalities so as to develop preventive strategies that would minimize kid mortality for good economic returns.

A portable cell-based optical detection device for rapid detection of Listeria and Bacillus toxins

NASA Astrophysics Data System (ADS)

Banerjee, Pratik; Banada, Padmapriya P.; Rickus, Jenna L.; Morgan, Mark T.; Bhunia, Arun K.

2005-11-01

A mammalian cell-based optical biosensor was built to detect pathogenic Listeria and Bacillus species. This sensor measures the ability of the pathogens to infect and induce cytotoxicity on hybrid lymphocyte cell line (Ped-2E9) resulting in the release of alkaline phosphatase (ALP) that can be detected optically using a portable spectrophotometer. The Ped-2E9 cells were encapsulated in collagen gel matrices and grown in 48-well plates or in specially designed filtration tube units. Toxin preparations or bacterial cells were introduced and ALP release was assayed after 3-5 h. Pathogenic L. monocytogenes strains or the listeriolysin toxins preparation showed cytotoxicity ranging from 55% - 92%. Toxin preparations (~20 μg/ml) from B. cereus strains showed 24 - 98% cytotoxicity. In contrast, a non-pathogenic L. innocua (F4247) and a B. substilis induced only 2% and 8% cytotoxicity, respectively. This cell-based detection device demonstrates its ability to detect the presence of pathogenic Listeria and Bacillus species and can potentially be used onsite for food safety or in biosecurity application.

Youth Count: Exploring How KIDS COUNT Grantees Address Youth Issues

ERIC Educational Resources Information Center

Wilson-Ahlstrom, Alicia; Gaines, Elizabeth; Ferber, Thaddeus; Yohalem, Nicole

2005-01-01

Inspired by the 2004 Kids Count Databook essay, "Moving Youth From Risk to Opportunity," this new report highlights the history of data collection, challenges and innovative strategies of 12 Annie E. Casey Foundation KIDS COUNT grantees in their work to serve the needs of older youth. (Contains 3 figures, 2 tables, and 9 notes.)

Connect! How To Get Your Kids To Talk to You.

ERIC Educational Resources Information Center

Smith, Carl B.; And Others

Describing the benefits parents and kids have gained from sharing reading and talking about books, this book shows parents how to bring their family closer together and support their child's academic and emotional development. The book suggests that not only does shared reading promote communication and mutual respect, it helps kids do better in…

Evaluation of in vitro properties of di-tri-octahedral smectite on clostridial toxins and growth.

PubMed

Weese, J S; Cote, N M; deGannes, R V G

2003-11-01

Clostridial colitis and endotoxaemia of intestinal origin are significant causes of morbidity and mortality in horses. Intestinal adsorbents are available for treatment of these conditions; however, little information exists supporting their use. To evaluate the ability of di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C. perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions of metronidazole in vitro. Clostridium difficile toxins, C. perfringens enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octahedral smectite, then tested for the presence of clostridial toxins or endotoxin using commercial tests. Serial dilutions of smectite were tested for the ability to inhibit growth of C. perfringens in culture broth, and to interfere with the effect of metronidazole on growth of C. perfringens in culture broth. Clostridium difficile toxins A and B, and C. perfringens enterotoxin were completely bound at dilutions of 1:2 to 1:16. Partial binding of C. difficile toxins occurred at dilutions up to 1:256 while partial binding of C. perfringens enterotoxin occurred up to a dilution of 1:128. Greater than 99% binding of endotoxin occurred with dilutions 1:2 to 1:32. No inhibition of growth of C. difficile or C. perfringens was present at any dilution, and there was no effect on the action of metronidazole. Di-tri-octahedral smectite possesses the ability to bind C. difficile toxins A and B, C. perfringens enterotoxin and endotoxin in vivo while having no effect on bacterial growth or the action of metronidazole. In vivo studies are required to determine whether di-tri-octahedral smectite might be a useful adjunctive treatment of clostridial colitis and endotoxaemia in horses.

A Nanocoaxial-Based Electrochemical Sensor for the Detection of Cholera Toxin

NASA Astrophysics Data System (ADS)

Archibald, Michelle M.; Rizal, Binod; Connolly, Timothy; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

2015-03-01

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml - 1 μg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, the nanocoaxial array provides a simple electrochemical readout and a miniaturized platform with multiplexing capabilities for the simultaneous detection of multiple biomarkers, giving the nanocoax a desirable advantage over the standard method towards POC applications. Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml - 1 μg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical

Effects of newborn characteristics and length of colostrum feeding period on passive immune transfer in goat kids.

PubMed

Castro, N; Capote, J; Morales-Delanuez, A; Rodríguez, C; Argüello, A

2009-04-01