Publications

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the control of anthrax. 194818867321
anthrax of the eyelid. 194818866203
the effect of inflammation on the development of immunity to anthrax in guinea pigs. 194818863439
the effect of inflammation on the survival of guinea pigs infected with anthrax. 194818863438
anthrax in american bison bos bison l. 194818863405
[not available]. 194718856997
discovery of new therapeutic targets by the informational spectrum method.the field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. here we review the application of the informational spectrum method (ism), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (hiv)-1, anthrax, highly pathogenic ...200818855700
identification of a surrogate marker for infection in the african green monkey model of inhalation anthrax.in 2001, a bioterrorism attack involving bacillus anthracis spore-laced letters resulted in 22 cases of inhalation anthrax, with five fatalities. this incident identified gaps in our health care system and precipitated a renewed interest in identifying both therapeutics and rapid diagnostic assays. to address those gaps, well-characterized animal models that resemble the human disease are needed. in addition, a rapid assay for a reliable diagnostic marker is key to the success of these efforts. ...200818852240
new classes of gram-positive selective antibacterials: inhibitors of mrsa and surrogates of the causative agents of anthrax and tuberculosis.an antimicrobial phenolic stilbene, (e)-3-hydroxy-5-methoxystilbene, 1 was recently isolated from the leaves of comptonia peregrina (l.) coulter and shown to possess inhibitory activity against several gram-positive bacteria, including isolates of methicillin-resistant staphylococcus aureus (mrsa), mycobacterium bovis bcg, and avirulent bacillusanthracis (sterne strain), among others. these results prompted the design and synthesis of two new classes of compounds, phenoxystyrenes and phenothiost ...200818849164
in vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins.there is a lot of interest towards creating therapies and vaccines for bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. systemic injection of lethal factor (lf), edema factor (ef) and protective antigen (pa) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. availability of toxins labeled with imageable radioisotopes w ...200818848660
personalized vaccines: the emerging field of vaccinomics.the next 'golden age' in vaccinology will be ushered in by the new science of vaccinomics. in turn, this will inform and allow the development of personalized vaccines, based on our increasing understanding of immune response phenotype: genotype information. rapid advances in developing such data are already occurring for hepatitis b, influenza, measles, mumps, rubella, anthrax and smallpox vaccines. in addition, newly available data suggest that some vaccine-related adverse events may also be g ...200818847302
the bacillus anthracis slel (yaah) protein is an n-acetylglucosaminidase involved in spore cortex depolymerization.bacillus anthracis spores, the infectious agents of anthrax, are notoriously difficult to remove from contaminated areas because they are resistant to many eradication methods. these resistance properties are due to the spore's dehydration and dormancy and to the multiple protective layers surrounding the spore core, one of which is the cortex. in order for b. anthracis spores to germinate and resume growth, the cortex peptidoglycan must be depolymerized. this study reports on analyses of slel ( ...200818835992
amoxicillin for postexposure inhalational anthrax in pediatrics: rationale for dosing recommendations.we reviewed information about the safety and plasma pharmacokinetic data for amoxicillin, specifically related to its potential use for postexposure inhalational anthrax. amoxicillin (45 mg/kg/d) given orally in 3 divided doses to pediatric patients <40 kg should yield an adequate time above the mic for susceptible bacillus anthracis (< or =0.5 microg/ml) over most of the dosing interval (75-100%). doses <45 mg/kg/d and dosing intervals longer than 8 hours should not be used for postexposure inh ...200818833025
effect of cpg oligonucleotides on vaccine-induced b cell memory.adding synthetic oligodeoxynucleotides containing unmethylated cpg motifs to anthrax vaccine adsorbed (ava, the licensed human vaccine) increases the speed and magnitude of the resultant ab response. ab titers persist in the protective range for >1 year, significantly longer than in animals vaccinated with ava alone. unexpectedly, a majority of mice immunized with cpg-adjuvanted ava maintained resistance to anthrax infection even after their ab titers had declined into the subprotective range. t ...200818832738
anthrax investigation. nas study may fail to settle anthrax case. 200818832614
circular dichroism and magnetic circular dichroism studies of the biferrous site of the class ib ribonucleotide reductase from bacillus cereus: comparison to the class ia enzymes.the rate limiting step in dna biosynthesis is the reduction of ribonucleotides to form the corresponding deoxyribonucleotides. this reaction is catalyzed by ribonucleotide reductases (rnrs) and is an attractive target against rapidly proliferating pathogens. class i rnrs are binuclear non-heme iron enzymes and can be further divided into subclasses. class ia is found in many organisms, including humans, while class ib has only been found in bacteria, notably some pathogens. both bacillus anthrac ...200818831534
bioterrorism and the anaesthesiologist's perspective.the use of non-conventional agents aimed at causing panic and terror among civilians has a long history. there have been uninterrupted threats and the use of biological and chemical weaponry from the time of early tribal conflicts to the iran-iraq war. the sole practical experience has come from the release of the nerve gas sarin in a tokyo subway (1994) and the inhalational anthrax discovered in florida (2001). drills that simulate scenarios of biological/chemical mass infestation have yielded ...200818831299
producing, controlling, and stabilizing pasteur's anthrax vaccine: creating a new industry and a health market.when pasteur and chamberland hastily set up their small biological industry to meet the agricultural demand for the anthrax vaccine, their methods for preparation and production had not yet been stabilized. the process of learning how to standardize biological products was accelerated in 1882 when vaccination accidents required the revision of production norms as the first hypotheses on fixity, inalterability, and transportability of vaccines were invalidated and replaced by procedures for conti ...200818831139
computational insights into the interaction of the anthrax lethal factor with the n-terminal region of its substrates.the anthrax lethal factor is a zinc metalloprotease toxin secreted by bacillus anthracis which cleaves at the n-terminal region of six mitogen activated protein kinase kinases (meks) in the cell. additionally, it is known to cleave a nine residue peptide "lf10," 50-fold more efficiently than nine residues of mek1. there is very little sequence similarity between the mek n-termini, thus, it is unclear how the lethal factor can accommodate and cleave the diverse n-termini of the meks and whether t ...200918831046
effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.in 1999, the us congress directed the centers for disease control and prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (ava).200818827210
characterization of bacillus anthracis iron-regulated surface determinant (isd) proteins containing neat domains.three iron-regulated surface determinant (isd) proteins, containing near transporter (neat) domains (gbaa4789-7), constitute part of an eight-member bacillus anthracis operon. gbaa4789 (isdc), previously characterized by others as a haem-binding protein, and two novel isd proteins characterized in this study, gbaa4788 (isdj) and gbaa4787 (isdk) proteins, can be translated from two alternative overlapping transcriptional units. the three neat-containing isd proteins are shown to be expressed in v ...200818826411
evaluation of five commercial nucleic acid extraction kits for their ability to inactivate bacillus anthracis spores and comparison of dna yields from spores and spiked environmental samples.this study evaluated five commercial extraction kits for their ability to recover dna from bacillus anthracis spores and spiked environmental samples. the kits evaluated represent the major types of methodologies which are commercially available for dna or total nucleic acid extraction, and included the chargeswitch gdna mini bacteria kit, nuclisens isolation kit, puregene genomic dna purification kit, qiaamp dna blood mini kit, and the ultraclean microbial dna isolation kit. extraction methods ...200918824041
electrically active polyaniline coated magnetic (eapm) nanoparticle as novel transducer in biosensor for detection of bacillus anthracis spores in food samples.electrically active polyaniline coated magnetic (eapm) nanoparticle-based biosensor has been developed for the detection of bacillus anthracis endospores in contaminated food samples. the 100 nm-diameter eapm nanoparticles are synthesized from aniline monomer (made electrically active by acid doping) coating the surface of gamma iron oxide cores. the magnetic, electrical, and structural characteristics of the synthesized eapm nanoparticles have been studied using superconducting quantum interfer ...200918823768
[phenotypic and genetic features of cultural-morphologic variants of bacillus anthracis].comparative analysis of mvla-genotypes of 6 bacillus anthracis strains and 40 their variants differing on capsule- and toxin synthesis, hemolytic, proteolytic and lecitinase activity, nutritional requirements, susceptibility to anthrax bacteriophages, virulence, immunogenicity, and presence of genes for capsule and toxin synthesis was performed. results of phylogenetic analysis of 5 chromosome locuses and plasmid locus pxo1aat which are variable for this sample of b. anthracis cultures showed th ...200818822496
suppression of dendritic cell activation by anthrax lethal toxin and edema toxin depends on multiple factors including cell source, stimulus used, and function tested.bacillus anthracis produces lethal toxin (lt) and edema toxin (et), and they suppress the function of lps-stimulated dendritic cells (dcs). because dcs respond differently to various microbial stimuli, we compared toxin effects in bone marrow dcs stimulated with either lps or legionella pneumophila (lp). lt, not et, was more toxic for cells from balb/c than from c57bl/6 (b6) as measured by 7-aad uptake; however, et suppressed cd11c expression. lt suppressed il-12, il-6, and tnf-alpha in cells fr ...200818821847
antibacterial activity of the fruits of iranian torilis leptophylla against some clinical pathogens.the aim of this study was to examine the antimicrobial activity of the methanolic extract of torilis leptophylla was tested on eleven bacteria (bacillus anthracis, bacillus subtilis, bacillus pumilus, staphylococcus aureus, bacillus licheniformis, brucella melitensis, escherichia coli, salmonella typhi, proteus mirabilis, bordetella bronshiseptica and pseudomonas aeruginosa). tested extract was effective against all bacteria but not b. subtilis. consequently, the ethanolic extract had antibacter ...200818819541
nir spectroscopic investigation of two fluoroquinolones, levofloxacin and ofloxacin, and their tablets for qualitative identification of commercial products on the market.a rapid and nondestructive identification method for ofloxacin (oflx) and levofloxacin (lvfx) utilizing diffusion reflectance near-infrared (nir) spectroscopy was developed. an obvious difference in spectral patterns between lvfx that is used for commercial tablets and lvfx hcl that can be purchased as a reagent at a low price was also observed. these quinolones are especially important for use as drugs against bio-terrorism because of their effectiveness against anthrax infection. therefore, th ...200818819512
using molecular docking, 3d-qsar, and cluster analysis for screening structurally diverse data sets of pharmacological interest.in this study, we propose a drug design approach which includes docking, molecular fingerprints based cluster analysis, and 'induced' descriptors based receptor-dependent 3d-qsar. the method was shown to be very useful for screening and modeling structurally diverse data sets of pharmacological interest. different from other receptor-dependent 3d-qsar, no ambiguous alignments are required for the construction of the models, and the computational cost is relatively lower. moreover, 'induced' desc ...200818816024
immunological dynamics in response to two anthrax vaccines in mice.in order to understand the variation of humoral and cellular immune responses to a16r live spore and ava vaccine and to identify efficient immunological parameters for the early evaluation of post immunization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of balb/c mice with the anthrax vaccines. the results show that both anti-ava and anti-spore antibodies were detectable in the a16r live spore vaccinated group while high titers of anti-a ...200818815750
role of the n-terminal amino acid of bacillus anthracis lethal factor in lethal toxin cytotoxicity and its effect on the lethal toxin neutralization assay.the cytotoxic activity of lethal factor (lf), a critical reagent used in the cell-based lethal toxin neutralization assay to assess anthrax vaccines, was shown to depend on the identity of its n-terminal amino acid, which plays a role in the targeting of lf to the proteasome for degradation. these results demonstrate that care must be taken to ensure that lf preparations used in standardized cell-based assays are not altered at their n-terminal ends.200818815235
ratio of lethal and edema factors in rabbit systemic anthrax.bacillus anthracis secretes two binary toxins: lethal toxin (pa + lf) and edema toxin (pa + ef) that play a major role in the pathogenesis of anthrax. their activities can synergize or interfere among each other, depending on the cell type. it is therefore fundamental to know their concentration ratio in vivo. here, we report the first determination of the concentration ratio of anthrax toxin components lf/ef in the serum of rabbits infected with b. anthracis spores.200818812184
passive administration of monoclonal antibodies to anthrolysin o prolong survival in mice lethally infected with bacillus anthracis.bacillus anthracis has two major virulence factors: a tripartite toxin that produces lethal and edema toxins and a polyglutamic acid capsule. a recent report suggested that a toxin belonging to the cholesterol dependent cytolysin (cdc) family, anthrolysin o (alo) was a new virulence factor for b. anthracis but subsequent studies have questioned its relevance in pathogenesis. in this study, we examined the immunogenicity of recombinant anthrolysin o (ralo) in mice.200818811967
bioterrorism update--information for the dentist.the united states was awakened to the perils of bioterrorism in october 2001 with the news that letters laced with anthrax had been mailed to the media and select politicians. at that time, it became evident that a widescale attack using a bioweapon of mass destruction could rapidly overwhelm the health care system. dentists could make a tremendous contribution to the response of such an attack by gaining an understanding of the bioweapons that could be used, as well as the symptoms of their dis ...200818810910
inhibition of bacillus anthracis spore outgrowth by nisin.the lantibiotic nisin has previously been reported to inhibit the outgrowth of spores from several bacillus species. however, the mode of action of nisin responsible for outgrowth inhibition is poorly understood. by using b. anthracis sterne 7702 as a model, nisin acted against spores with a 50% inhibitory concentration (ic(50)) and an ic(90) of 0.57 microm and 0.90 microm, respectively. viable b. anthracis organisms were not recoverable from cultures containing concentrations of nisin greater t ...200818809941
cytoplasmic delivery of antigens, by bacillus subtilis enhances th1 responses.endospores of the gram-positive bacterium, bacillus subtilis, have been used successfully for delivery of antigens where the immunogen is expressed on the spore surface. in this work the spore has been engineered to deliver antigens to the cytoplasm of macrophages by expressing listeriolysin o (llo) or a derivative, llo(l461t), that is stable at neutral ph, from the b. subtilis vegetative cell. following phagocytosis spores were shown to germinate in the phagosome enabling secretion of llo/llo(l ...200818809450
activity of the bacillus anthracis 20 kda protective antigen component.anthrax is caused by bacillus anthracis that produce two exotoxins, lethal toxin and edema toxin. the lethal toxin is composed of the lethal factor (lf) complexed with the cell binding protective antigen (pa83, 83 kda). likewise, the edema factor (ef) binds to the pa83 to form the edema toxin. once pa83 is bound to the host cell surface, a furin-like protease cleaves the full-length, inactive protein into 63 kda and 20 kda antigens (pa63 and pa20). pa63 forms a heptamer and is internalized via r ...200818808698
towards a human oral vaccine for anthrax: the utility of a salmonella typhi ty21a-based prime-boost immunization strategy.we previously demonstrated the ability of an orally administered attenuated salmonella enterica serovar typhimurium strain expressing the protective antigen (pa) of bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [stokes mg, titball rw, neeson bn, et al. oral administration of a salmonella enterica-based vaccine expressing bacillus anthracis protective antigen confers protection against aerosolized b. anthracis. infect immun 2007;75(april (4)):1827-34]. to ...200818805452
rapid detection of bacillus anthracis using monoclonal antibody functionalized qcm sensor.since the anthrax spore bioterrorism attacks in america in 2001, the early detection of bacillus anthracis spores and vegetative cells has gained significant interest. at present, many polyclonal antibody-based quartz crystal microbalance (qcm) sensors have been developed to detect b. anthracis simulates. to achieve a simultaneous rapid detection of b. anthracis spores and vegetative cells, this paper presents a biosensor that utilizes an anti-b. anthracis monoclonal antibody designated to 8g3 ( ...200918804365
cathelicidin administration protects mice from bacillus anthracis spore challenge.cathelicidins are a family of cationic peptides expressed in mammals that possess numerous bactericidal and immunomodulatory properties. in vitro analyses showed that human, mouse, and pig cathelicidins inhibited bacillus anthracis bacterial growth at micromolar concentrations in the presence or absence of capsule. combined in vitro analyses of the effects of each peptide on spore germination and vegetative outgrowth by time lapse phase contrast microscopy, transmission electron microscopy, and ...200818802102
antibody-mediated targeting of the urokinase-type plasminogen activator proteolytic function neutralizes fibrinolysis in vivo.urokinase-type plasminogen activator (upa) plays a central role in tissue remodeling processes. most of our understanding of the role of upa in vivo is derived from studies using gene-targeted upa-deficient mice. to enable in vivo studies on the specific interference with upa functionality in mouse models, we have now developed murine monoclonal antibodies (mabs) directed against murine upa by immunization of upa-deficient mice with the recombinant protein. guided by enzyme-linked immunosorbent ...200818799467
the symmetry rule: a seven-year study of symptoms and explanatory labels among gulf war veterans.noticing medical symptoms can cause one to search for explanatory labels such as "ate bad food" or even "exposed to anthrax," and perhaps these labels may cause new symptom reports. the present study examined whether there is empirical support for this symptom-label "symmetry rule." we interviewed veterans (n= 362) from the gulf war registry in 1995 and 2002 about their medical symptoms and about their exposure to war-related hazards and stressors. health symptom reports were strongly correlated ...200818795995
complete nucleotide sequencing and analysis of the 65-kb highly conjugative enterococcus faecium plasmid pmg1: identification of the transfer-related region and the minimum region required for replication.pmg1 (65.1 kb) is a highly conjugative, pheromone-independent enterococcus faecium plasmid that carries a tn4001-like transposon encoding gentamicin resistance. the complete nucleotide sequence (65 029 bp) of the pmg1 plasmid was determined and 73 orfs lying in the same transcription orientation were identified. sixty-one of the 73 orfs showed a high degree of similarity (90-100% identity at the amino acid level) to the orfs of the phtbeta plasmids. like the phtbeta plasmid, 22 of the pmg1 plasm ...200818795955
why do uk military personnel refuse the anthrax vaccination?the purpose of this study was to understand the reasons why some uk military personnel refused the anthrax vaccination. data were collected from 5,302 members of the uk armed forces who had been deployed to iraq since 2003 and had been offered the anthrax vaccination. as part of a larger questionnaire, information was collected on acceptance or refusal of the vaccination. twenty-eight percent of participants refused the anthrax vaccination; of these 51% indicated that they refused vaccination be ...200818795833
camp imaging of cells treated with pertussis toxin, cholera toxin, and anthrax edema toxin.the enzymatic activity of the three most studied bacterial toxins that increase the cytosolic camp level: pertussis toxin (pt), cholera toxin (ct), and anthrax edema toxin (et), was imaged by fluorescence videomicroscopy. three different cell lines were transfected with a fluorescence resonance energy transfer biosensor based on the pka regulatory and catalytic subunits fused to cfp and yfp, respectively. real-time imaging of cells expressing this camp biosensor provided time and space resolved ...200818793614
molecular characterization of a variant of bacillus anthracis-specific phage ap50 with improved bacteriolytic activity.the genome sequence of a bacillus anthracis-specific clear plaque mutant phage, ap50c, contains 31 open reading frames spanning 14,398 bp, has two mutations compared to wild-type ap50t, and has a colinear genome architecture highly similar to that of gram-positive tectiviridae phages. spontaneous ap50c-resistant b. anthracis mutants exhibit a mucoid colony phenotype.200818791014
naturally acquired antibodies to bacillus anthracis protective antigen in vultures of southern africa.sera from 19 wild caught vultures in northern namibia and 15 (12 wild caught and three captive bred but with minimal histories) in north west province, south africa, were examined by an enzyme-linked immunosorbent assay (elisa) for antibodies to the bacillus anthracis toxin protective antigen (pa). as assessed from the baseline established with a control group of ten captive reared vultures with well-documented histories, elevated titres were found in 12 of the 19 (63%) wild caught namibian bird ...200818788202
chimeric hepatitis b virus core particles carrying an epitope of anthrax protective antigen induce protective immunity against bacillus anthracis.the major aim of present study is to develop and evaluate chimeric virus-like particles (vlps) displaying a neutralizing epitope of anthrax protective antigen (pa) as a potential vaccine against anthrax. the truncated hepatitis b virus core (hbc) protein (aa 1-144) was used as a carrier, and the 2beta2-2beta3 loop of the pa domain 2 (aa 302-325) which has been shown contains a dominant neutralizing epitope was inserted into the major immunodominant region (mir) of the hbc. the recombinant protei ...200818786589
private and public economic incentives for the control of animal diseases: the case of anthrax in livestock.this study examined the roles of the public and private sectors as economic components of anthrax control with direct reference to the 2005 anthrax outbreak in livestock in north dakota. anthrax is an endemic disease in north dakota, which often causes disease outbreaks in livestock, leading to economic losses to the livestock industry. the economic incentives and interests behind public and private control of an anthrax outbreak are investigated. anthrax management is most effective with the pa ...200818786071
probing the ph-dependent prepore to pore transition of bacillus anthracis protective antigen with differential oxidative protein footprinting.the protective antigen (pa) component of the anthrax toxin (atx) plays an essential role in the pathogenesis of the bioterrorism bacterium bacillus anthracis. after oligomerization on the cell surface and docking of lethal factor and/or edema factor, pa is internalized and undergoes a conformational change when exposed to the low ph of the endosome to form a membrane-penetrating pore. while the structure of the pa prepore has been determined, precise structural information regarding the pore sta ...200818785752
cross-contamination of clinical specimens with bacillus anthracis during a laboratory proficiency test--idaho, 2006.on july 18, 2006, the utah department of health notified epidemiologists at the idaho department of health and welfare that bacillus anthracis, the causative agent for anthrax, had been isolated from a patient. on the same day, the idaho epidemiologists were notified by the idaho bureau of laboratories of a specimen from a second patient received for anthrax testing. the two reports resulted briefly in alerts to the federal bureau of investigation (fbi) and precautionary treatment of one of the ...200818784641
evaluation of body mass index, pre-vaccination serum progesterone levels and anti-anthrax protective antigen immunoglobulin g on injection site adverse events following anthrax vaccination in women.in 2002, cdc initiated the anthrax vaccination program (avp) to provide voluntary pre-exposure anthrax vaccination for individuals at high risk for exposure to bacillus anthracis spores. the avp offered an opportunity to investigate hypothesized reasons for a reported gender difference in injection site adverse events (aes) following anthrax vaccine adsorbed (ava).200818781705
recombinant bacillus subtilis expressing the clostridium perfringens alpha toxoid is a candidate orally delivered vaccine against necrotic enteritis.recombinant bacillus subtilis endospores have been used to vaccinate against tetanus and anthrax. in this work, we have developed spores that could be used to vaccinate against clostridium perfringens alpha toxin and that could be used to protect against gas gangrene in humans and necrotic enteritis in poultry. the primary active agent in both cases is alpha toxin. a carboxy-terminal segment of the alpha toxin gene (cpa) fused to the glutathione-s-transferase (gst) gene was cloned in b. subtilis ...200818779344
interferon protects mice against inhalation anthrax.interferons (ifns) play a role in innate immunity during many viral, bacterial, and protozoal infections. with the increasing threat of bioterrorist attacks with bacillus anthracis, its high lethality, and the limited effectiveness of antibiotics, alternative treatments are being studied. antibodies to protective antigen (pa) are promising, as is ifn. during many bacterial infections, production of and protection by ifns has been reported, including b. anthracis in vitro. in vivo, we find that ( ...200818778201
protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.in this study, the efficacy of two experimental vaccines against bacillus anthracis toxinaemia was evaluated in the rabbit model. a recombinant protective antigen (rpa) mutant and a trivalent vaccine (tv) composed by the rpa, a inactive mutant of lethal factor (mlf-y728a; e735a) and a inactive mutant of edema factor (mef-k346r), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in new zealand white rabbits. rabbits vaccinated subcutaneously with r ...200818775462
effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen.peptide nucleic acid (pna) is highly stable and binds to complementary rna and dna with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. we investigated whether protectiveantigen (pa, a non-toxic component of anthrax toxin) could transport antisense pna oligomers into reporter cells that contain luciferase transgenes with mutant beta-globin ivs2 intronic inserts, which permit aberrant pre-mrna splicing and impair luciferase expression. pna oligomers antisense ...200818774771
construction of bacillus thuringiensis wild-type s76 and cry- derivatives expressing a green fluorescent protein: two potential marker organisms to study bacteria-plant interactions.collectively, the species bacillus thuringiensis, bacillus cereus, and bacillus anthracis represent microorganisms of high economic, medical, and biodefense importance. although the genetic correlation and pathogenic characteristics have been extensively dissected, the ecological properties of these three species in their natural environments remain poorly understood. thus, a tractable marker for detecting these bacteria under specific environmental and physiological conditions is a valuable too ...200818772942
biodefense versus bioterrorism. 200818771576
role of n-terminal amino acids in the potency of anthrax lethal factor.anthrax lethal factor (lf) is a zn(+2)-dependent metalloprotease that cleaves several mapk kinases and is responsible for the lethality of anthrax lethal toxin (lt). we observed that a recombinant lf (lf-hma) which differs from wild type lf (lf-a) by the addition of two residues (his-met) to the native ala (a) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. we hypothesized that the "n-end rule", which relates the half-life of ...200818769623
an alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock.abstract:200818768085
expression, purification, crystallization and preliminary x-ray studies of a prolyl-4-hydroxylase protein from bacillus anthracis.collagen prolyl-4-hydroxylase (c-p4h) catalyzes the hydroxylation of specific proline residues in procollagen, which is an essential step in collagen biosynthesis. a new form of p4h from bacillus anthracis (anthrax-p4h) that shares many characteristics with the type i c-p4h from human has recently been characterized. the structure of anthrax-p4h could provide important insight into the chemistry of c-p4hs and into the function of this unique homodimeric p4h. x-ray diffraction data of selenomethi ...200818765905
bacillus anthracis edema toxin activates nuclear glycogen synthase kinase 3beta.bacillus anthracis edema toxin (et) generates high levels of cyclic amp and impacts a complex network of signaling pathways in targeted cells. in the current study, we sought to identify kinase signaling pathways modulated by et to better understand how this toxin alters cell physiology. using a panel of small-molecule inhibitors of mammalian kinases, we found that inhibitors of glycogen synthase kinase 3 beta (gsk-3beta) protected cells from et-induced changes in the cell cycle. gsk-3beta inhib ...200818765729
environmental monitoring for biological threat agents using the autonomous pathogen detection system with multiplexed polymerase chain reaction.we have developed and field-tested a now operational civilian biodefense capability that continuously monitors the air in high-risk locations for biological threat agents. this stand-alone instrument, called the autonomous pathogen detection system (apds), collects and selectively concentrates particles from the air into liquid samples and analyzes the samples using multiplexed pcr amplification coupled with microsphere array detection. during laboratory testing, we evaluated the apds instrument ...200818763806
inhaled non-capsulated bacillus anthracis in a/j mice: nasopharynx and alveolar space as dual portals of entry, delayed dissemination, and specific organ targeting.bacillus anthracis virulence is dependent on toxins and capsule. encapsulation is associated with dissemination. we hypothesized that eliminating capsule would modify the portal of entry and the spread of bacteria. using a bioluminescent model of inhalational anthrax, we demonstrated that aerosolized spores of a capsule-deficient strain administered at moderate doses initiated infection in the nasopharynx. dissemination beyond the nasopharynx was delayed for at least 24h and then targeted the ki ...200818762267
targeting of the bcla and bclb proteins to the bacillus anthracis spore surface.the exosporium is the outermost layer of the bacillus anthracis spore. the predominant protein on the exosporium surface is bcla, a collagen-like glycoprotein. bcla is incorporated on the spore surface late in the b. anthracis sporulation pathway. a second collagen-like protein, bclb, has been shown to be surface-exposed on b. anthracis spores. we have identified sequences near the n-terminus of the bcla and bclb glycoproteins responsible for the incorporation of these proteins into the exospori ...200818761690
transcriptional analysis of the conjugative plasmid paw63 from bacillus thuringiensis.the broad-host range plasmid paw63 is a model for the study of molecular mechanisms associated with conjugation in the gram-positive bacillus cereus group. its main features are a conjugative apparatus that includes type iv secretion system-like components and two group ii introns, b.th.i1 and b.th.i2, located within conjugation genes, as well as a putative regulatory control circuit. furthermore, paw63 shares a common backbone with pxo2, the second virulence plasmid of bacillus anthracis, and w ...200818761035
texas isolates closely related to bacillus anthracis ames. 200818760033
forensic microbiology and the reinterpretation of history. 200818759677
petrobactin biosynthesis: asbb catalyzes condensation of spermidine with n8-citryl-spermidine and its n1-(3,4-dihydroxybenzoyl) derivative.the asbb enzyme, which is involved in the biosynthesis of the virulence-conferring siderophore petrobactin in bacillus anthracis, is shown to catalyze efficient atp-dependent condensation of spermidine, but not n1-(3,4-dihydroxbenzoyl)-spermidine, with n8-citryl-spermidine or n1-(3,4-dihydroxbenzoyl)-n8-citryl-spermidine, suggesting that n1-(3,4-dihydroxbenzoyl)-spermidine is very unlikely to be a significant intermediate in petrobactin biosynthesis, contrary to previous suggestions.200818758617
structural elucidation of the nonclassical secondary cell wall polysaccharide from bacillus cereus atcc 10987. comparison with the polysaccharides from bacillus anthracis and b. cereus type strain atcc 14579 reveals both unique and common structural features.nonclassical secondary cell wall polysaccharides constitute a major cell wall structure in the bacillus cereus group of bacteria. the structure of the secondary cell wall polysaccharide from bacillus cereus atcc 10987, a strain that is closely related to bacillus anthracis, was determined. this polysaccharide was released from the cell wall with aqueous hydrogen fluoride (hf) and purified by gel filtration chromatography. the purified polysaccharide, hf-ps, was characterized by glycosyl composit ...200818757856
the anthrax files. 200818756706
preparing for disaster: response matrices in the usa and uk.disasters, whether man-made or naturally occurring, require complex responses across multiple government agencies and private sector elements, including the media. these factors mandate that, for effective disaster management and because of the unpredictability of such events, response structures must be in place in advance, ready to be activated on short notice, with lines of responsibility clearly delineated and mechanisms for coordination of efforts already established. disaster response expe ...200818756376
too close for comfort. nancy haigwood is interviewed by rex dalton. 200818756221
pilot-scale experimental and theoretical investigations into the thermal destruction of a bacillus anthracis surrogate embedded in building decontamination residue bundles.bacillus anthracis (b. anthracis) spores were released through the u.s. mail system in 2001, highlighting the need to develop efficacious methods of decontaminating and disposing of materials contaminated with biological agents. incineration of building decontamination residue is a disposal option for such material, although the complete inactivation of bacterial spores via this technique is not a certainty. tests revealed that under some circumstances, geobacillus stearothermophilus (g. stearot ...200818754498
fbi to reveal anthrax data. 200818754132
non-canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development.anthrax receptor (atr) shares similarities with molecules relevant to haematopoiesis. this suggests that anthrax proteins might bind to these mimicking molecules and exert non-specific haematopoietic effects. the haematopoietic system is the site of immune cell development in the adult. as such, atr ligand, protective antigen (pa) and the other anthrax proteins, lethal factor, edema factor, could be significant to haematopoietic responses against bacillus anthracis infection. because haematopoie ...200918752638
louis pasteur-his contribution to anthrax, vaccination and the evolution of a principle of active immunization. 192318738937
a case of anthrax. 191518736527
determining the efficacy of liquid sporicides against spores of bacillus subtilis on a hard nonporous surface using the quantitative three step method: collaborative study.a collaborative study was conducted to validate the quantitative three step method (tsm), a method designed to measure the performance of liquid sporicides on a hard nonporous surface. ten laboratories agreed to participate in the collaborative study; data from 8 of 10 participating laboratories were used in the final statistical analysis. the tsm uses 5 x 5 x 1 mm glass coupons (carriers) upon which spores have been inoculated and which are introduced into liquid sporicidal agent contained in a ...200818727544
polyvalency: a promising strategy for drug design.the simultaneous binding of multiple ligands on one entity to multiple receptors on another can result in an affinity that is significantly greater than that for the binding of a single ligand to a single receptor. this concept of "polyvalency" can be used to design molecules that are potent inhibitors of toxins and pathogens. we describe the design of potent polyvalent inhibitors that neutralize anthrax toxin in vivo as well as our attempts to elucidate the relationship between inhibitor struct ...200818727104
bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin.acquisition of iron is necessary for the replication of nearly all bacterial pathogens; however, iron of vertebrate hosts is mostly sequestered by heme and bound to hemoglobin within red blood cells. in bacillus anthracis, the spore-forming agent of anthrax, the mechanisms of iron scavenging from hemoglobin are unknown. we report here that b. anthracis secretes isdx1 and isdx2, two neat domain proteins, to remove heme from hemoglobin, thereby retrieving iron for bacterial growth. unlike other gr ...200818725935
preventing voltage-dependent gating of anthrax toxin channels using engineered disulfides.the channel-forming component of anthrax toxin, (pa(63))(7), is a heptameric water-soluble protein at neutral ph, but under acidic conditions it spontaneously inserts into lipid bilayers to form a 14-stranded beta-barrel ion-conducting channel. this channel plays a vital role in anthrax pathogenesis because it serves as a conduit for the membrane translocation of the two enzymatic components of anthrax toxin, lethal factor and edema factor. anthrax channels open and close in response to changes ...200818725530
is 60 days of ciprofloxacin administration necessary for postexposure prophylaxis for bacillus anthracis?sixty days of ciprofloxacin administration at 500 mg every 12 h is currently recommended for the prophylaxis of inhalational exposure to bacillus anthracis. we examined bacillus anthracis (delta-sterne strain) in our hollow-fiber infection model. we measured the ciprofloxacin concentrations achieved and the number of organisms present before heat shock (total population) and after heat shock (spore population). we fit a mathematical model to these data. monte carlo simulation with differing init ...200818725437
assessing bioterrorism preparedness and response of rural veterinarians: experiences and training needs.veterinarians play a unique role in emergency preparedness and response, and federal agencies and academic institutions therefore allocate considerable resources to provide training to enhance their readiness. however, the level of preparedness of veterinarians in many rural regions is yet to be improved. this article reports an assessment of the bioterrorism preparedness, specifically the experience and training needs, of rural veterinarians in north texas. the study employed a cross-sectional ...200818723813
esat-6-like protein secretion in bacillus anthracis.proteins of the wxg100 family represent the prototypical substrates of bacterial type vii secretion systems that typically encompass 100 residues, lack canonical signal peptides, and form helix-turn-helix hairpin structures with wxg positioned in the turn element. bacillus anthracis encodes six wxg100 proteins, herein referred to as esxb, esxl, esxp, esxq, esxv, and esxw. with the exception of esxb, b. anthracis proteins harbor c-terminal extensions that are appended to canonical wxg domains. wh ...200818723613
fact sheet: anthrax. 200818720582
case not closed. 200818719537
anthrax investigation. six anthrax science questions the fbi has yet to answer. 200818719255
anthrax investigation. fbi discusses microbial forensics--but key questions remain unanswered. 200818719254
functional interactions between anthrax toxin receptors and the wnt signalling protein lrp6.to exert its activity, anthrax toxin must be endocytosed and its enzymatic toxic subunits delivered to the cytoplasm. it has been proposed that, in addition to the anthrax toxin receptors (atrs), lipoprotein-receptor-related protein 6 (lrp6), known for its role in wnt signalling, is also required for toxin endocytosis. these findings have however been challenged. we show that lrp6 can indeed form a complex with atrs, and that this interaction plays a role both in wnt signalling and in anthrax to ...200818717822
atomic resolution structures of escherichia coli and bacillus anthracis malate synthase a: comparison with isoform g and implications for structure-based drug discovery.enzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as mycobacterium tuberculosis and candida albicans. two isoforms have been identified for malate synthase, the second enzyme in the pathway. isoform a, found in fungi and plants, comprises approximately 530 residues, whereas isoform g, found only in bacteria, is larger by approximately 200 residues. crystal structures of malate synthase isoform g from escherichia coli and mycobacterium tuberculosis were ...200818714089
single-walled carbon nanotube as a unique scaffold for the multivalent display of sugars.single-walled carbon nanotube (swnt) is a pseudo-one-dimensional nanostructure capable of carrying/displaying a large number of bioactive molecules and species in aqueous solution. in this work, a series of dendritic beta-d-galactopyranosides and alpha-d-mannopyranosides with a terminal amino group were synthesized and used for the functionalization of swnts, which targeted the defect-derived carboxylic acid moieties on the nanotube surface. the higher-order sugar dendrons were more effective in ...200818712920
crystal structure of a family gt4 glycosyltransferase from bacillus anthracis orf ba1558. 200818712829
a novel approach to development of monoclonal antibodies using native antigen for immunization and recombinant antigen for screening.the production of monoclonal antibodies (mab) specific to microbes is rapidly growing. finding an appropriate antigen to screen hybridoma clones has become increasingly important. however, the conventional method, in which the purified antigen from the microbe is routinely used for screening, cannot avoid selection of false positive hybridoma clones, since even highly purified antigen is found to be contaminated with some other proteins from the microbe. in this study, mabs against anthrax prote ...200818707549
plant-produced hepatitis b core protein chimera carrying anthrax protective antigen domain-4.the hepatitis b core antigen (hbcag) can generate a strong immune response and is recognized as an effective carrier for foreign epitopes. the domain-4 epitope of the anthrax protective antigen (pa-d4) plays an essential role in generating protective immunity against virulent bacillus anthracis. here we report the successful production of a recombinant protein comprised of the antigenic pa-d4 integrated into the c/e1 loop of hbcag in transgenic low-alkaloid nicotiana tabacum. sera of mice inject ...200818707542
molecular modeling and dynamics studies of shikimate kinase from bacillus anthracis.bacillus anthracis has been used as weapon in bioterrorist activities, with high mortality, despite anti-microbial treatment, which strongly indicates a need of new drugs to treat anthrax. shikimate pathway is a seven-step biosynthetic route which generates chorismic acid. the shikimate pathway is essential for many pathological organisms, whereas it is absent in mammals. therefore, these enzymes are potential targets for the development of non-toxic anti-microbial agents and herbicides and have ...200818706819
anthrax case ignites new forensics field. 200818704053
anthrax investigation. full-genome sequencing paved the way from spores to a suspect. 200818703714
a single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.here we confirm that intranasal (in) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. the optimum dose of rpa in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all subsequent experiments. rabbits received a single dose of either 150microg rpa, 150microg rpa+150microg of a conjugated 10-mer peptide representing the b ...200818703110
anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis.anthrax meningitis is the main neurological complication of systemic infection with bacillus anthracis approaching 100% mortality. the presence of bacilli in brain autopsies indicates that vegetative bacteria are able to breach the blood-brain barrier (bbb). the bbb represents not only a physical barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. currently, the basic pathogenic mechanisms by which ...200818698416
responding to a bioterrorism attack--one scenario: part 1.this article continues the discussions introduced in an earlier article submitted to the health care manager entitled "epidemic simulation for syndromic surveillance," wherein a format for analysis of the incidence of a bioterrorist attack was presented. this article outlines a simulation conducted as part of a federal grant award administered through the center for biological defense at the university of south florida. the disease entity simulated was an attack of anthrax introduced into the ce ...200818695399
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