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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
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
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
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
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
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
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
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
heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin.anthrax lethal toxin (lt) rapidly kills macrophages from certain mouse strains in a mechanism dependent on the breakdown of unknown protein(s) by the proteasome, formation of the nalp1b (nlrp1b) inflammasome and subsequent activation of caspase-1. we report that heat-shocking lt-sensitive macrophages rapidly protects them against cytolysis by inhibiting caspase-1 activation without upstream effects on lt endocytosis or cleavage of the toxin's known cytosolic substrates (mitogen-activated protein ...200818671821
studies on the antifungal properties of n-thiolated beta-lactams.n-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including staphylococcus aureus and bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. we now have found that these lactams also possess antifungal activity against candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. the mode of action and str ...200818672374
towards on-site pathogen detection using antibody-based sensors.in this paper, the recent progress within biosensors for plant pathogen detection will be reviewed. bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. focus will be put on antibody surface-immobilisation strategies as well as the use of antibodies in the widely used sensors, quartz crystal microbalance, surface plasmon resonance and cantilevers. we will describe the available data on a ...200818675543
dual promoters control expression of the bacillus anthracis virulence factor atxa.the atxa virulence regulator of bacillus anthracis is required for toxin and capsule gene expression. atxa is a phosphotransferase system regulatory domain-containing protein whose activity is regulated by phosphorylation/dephosphorylation of conserved histidine residues. here we report that transcription of the atxa gene occurs from two independent promoters, p1 (previously described by dai et al. [z. dai, j. c. sirard, m. mock, and t. m. koehler, mol. microbiol. 16:1171-1181, 1995]) and p2, wh ...200818676674
the anthrax vaccine adsorbed vaccine generates protective antigen (pa)-specific cd4+ t cells with a phenotype distinct from that of naive pa t cells.cellular immune responses against protective antigen (pa) of bacillus anthracis in subjects that received the anthrax vaccine adsorbed (ava) vaccine were examined. multiple cd4(+) t-cell epitopes within pa were identified by using tetramer-guided epitope mapping. pa-reactive cd4(+) t cells with a cd45ra(-) phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (pbmc) with pa-specific tetramers. surprisingly, pa-specific t cells were also detected in pbmc of ...200818678674
solubility improvement of an anthrax toxin peptide inhibitor by rational amino acid randomization.we previously described a potent anthrax toxin inhibitor, based on a phage-library-selected peptide sequence, synthesized as a tetra-branched molecule on a lysine core and further modified for improvement of activity [pini et al., biochem. j., 2006, 395, 157]. this branched peptide had very low solubility because of several hydrophobic residues in the peptide sequence. this complicated molecule purification and manufacturing. here we report a rational modification of the peptide sequence, obtain ...200818680450
death renews biosecurity debate. 200818685659
bioterrorism. scientists seek answers, ponder future after anthrax case suicide. 200818687926
naturally acquired anthrax antibodies in a cheetah (acinonyx jubatus) in botswana.an outbreak of anthrax in the jwana game reserve in jwaneng, botswana, was first observed when three cheetahs (acinonyx jubatus) died of the disease in november 2004. in the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (elisa), for antibodies to the protective antigen (pa) of bacillus anthracis. of the 23 cheetahs, 16 regularly accessed the reserve. antibodies to pa were detected in one cheetah col ...200818689661
treatment of experimental anthrax with recombinant capsule depolymerase.bacillus anthracis produces an antiphagocytic gamma-linked poly-d-glutamic acid capsule that is required for virulence. capsule depolymerase (capd) is a membrane-associated poly-gamma-glutamate-specific depolymerase encoded on the b. anthracis capsule plasmid, px02, that is reported to contribute to virulence by anchoring the capsule to the peptidoglycan and partially degrading high-molecular-weight capsule from the bacterial surface. we previously demonstrated that treatment with capd effective ...200818160516
function, structure and regulation of the vacuolar (h+)-atpases.the vacuolar atpases (or v-atpases) are atp-driven proton pumps that function to both acidify intracellular compartments and to transport protons across the plasma membrane. intracellular v-atpases function in such normal cellular processes as receptor-mediated endocytosis, intracellular membrane traffic, prohormone processing, protein degradation and neurotransmitter uptake, as well as in disease processes, including infection by influenza and other viruses and killing of cells by anthrax and d ...200818406336
infectious agents of bioterrorism: a review for emergency physicians.the terrorist attacks on the united states in 2001 and the anthrax release soon after brought the issue of bioterrorism to the forefront in the medical community. bioterrorism is the use of a biologic weapon to create terror and panic. biologic weapons, or bioweapons, can be bacteria, fungi, viruses, or biologic toxins. because the emergency department represents the front line of defense for the recognition of agents of bioterrorism, it is essential that emergency physicians have the ability to ...200818406986
biological and biochemical characterization of anthrax lethal factor, a proteolytic inhibitor of mek signaling pathways.the secretion of factors that block critical intracellular signaling pathways is a common strategy used by pathogenic bacteria for disabling host defenses and causing disease. anthrax lethal toxin (letx) has been shown to cleave and inactivate mitogen-activated protein kinase (mapk) kinases (mkks or meks) and to inhibit mkk signaling. cleavage of mkks by letx prevents activation of their downstream substrates, the mapks. because mapk pathways regulate a variety of crucial cellular functions incl ...200818413261
[the strategic plan for preparedness and response to bioterrorism in korea].following the anthrax bioterrorism attacks in the us in 2001, the korean government established comprehensive countermeasures against bioterrorism. these measures included the government assuming management of all infectious agents that cause diseases, including smallpox, anthrax, plaque, botulism, and the causative agents of viral hemorrhagic fevers (ebola fever, marburg fever, and lassa fever) for national security. in addition, the korean government is reinforcing the ability to prepare and r ...200818664725
stable and potent polyvalent anthrax toxin inhibitors: raft-inspired domain formation in liposomes that contain pegylated lipids. 200818666271
early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.effective prophylaxis and treatment for infections caused by biological threat agents (bta) rely upon early diagnosis and rapid initiation of therapy. most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most bta are indistinguishable flu-like signs.200818667072
intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters.the current model for virulence gene regulation in bacillus anthracis involves several trans-acting factors, the most important of which appears to be the anthrax toxin activator encoded by the atxa gene. atxa is a positive regulator of the toxin genes paga, cya and lef, and of a number of other plasmid- and chromosome-encoded genes. the atxa protein (56 kda) possesses a predicted winged-helix dna-binding domain and phosphotransferase system-regulated domains, but the mechanism for positive regu ...200818667583
the response to a specific germinant by bacillus anthracis spores in primary mouse macrophages is modulated by a protein encoded on the pxo1 plasmid.a bacillus anthracis sterne pxo1 plasmid-encoded protein designated cot43 was found in coat extracts of purified spores. cot43 is a tetratricopeptide repeat domain protein related to those which function as phosphatases in the sporulation phosphorelay and as regulators of competence and pathogenic factors. the synthesis of cot43 began in the late exponential phase downstream from a sigmaa promoter (as mapped by race) and it was present at least until the formation of phase white endospores. ther ...200818654763
recombinant bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen.inactivated bacillus anthracis spores given with protective antigen (pa) contribute to immunity against anthrax in several animal models. antiserum raised against whole irradiated b. anthracis spores has been shown to have anti-germination and opsonic activities in vitro. based on these observations, we hypothesized that surface-exposed spore proteins might serve as supplemental components of a pa-based anthrax vaccine. the protective anti-spore serum was tested for reactivity with recombinant f ...200818657585
protein expression pattern of murine macrophages treated with anthrax lethal toxin.anthrax lethal toxin (letx; a combination of protective antigen and lethal factor) secreted by the vegetative cells of bacillus anthracis is cytotoxic for certain macrophage cell lines. the role of letx in mediating these effects is complicated largely due to the difficulty in identifying and assigning functions to the affected proteins. to analyze the protein profile of murine macrophages treated with letx, we employed two-dimensional polyacrylamide gel electrophoresis and maldi-tof ms, and int ...200818657635
characterization of the catalytic activity of the gamma-phage lysin, plyg, specific for bacillus anthracis.bacillus anthracis causes anthrax, a lethal disease affecting humans that has attracted attention due to its bioterrorism potential. plyg is a lysin of gamma-phage, which specifically infects b. anthracis and lyses its cell wall. plyg contains a t7 lysozyme-like amidase domain, which appears to be the catalytic domain, in the n-terminal region and has a high degree of sequence similarity with plyl, which is an n-acetylmuramoyl-l-alanine amidase encoded by the b. anthracis genome. here, we demons ...200818662316
effect of bacillus anthracis virulence factors on human dendritic cell activation.bacillus anthracis possesses three primary virulence factors: capsule, lethal toxin (lt), and edema toxin (et). dendritic cells (dcs) are critical to innate and acquired immunity and represent potential targets for these factors. we examined the ability of b. anthracis spores and bacilli to stimulate human monocyte-derived dc (mddc), primary myeloid dc (mdc), and plasmacytoid dc (pdc) cytokine secretion. exposure of mddcs and mdcs to spores or vegetative bacilli of the genetically complete strai ...200818662733
design and synthesis of aryl ether inhibitors of the bacillus anthracis enoyl-acp reductase.the problem of increasing bacterial resistance to the current generation of antibiotics is well documented. known resistant pathogens such as methicillin-resistant staphylococcus aureus are becoming more prevalent, while the potential exists for developing drug-resistant pathogens for use as bioweapons, such as bacillus anthracis. the biphenyl ether antibacterial agent, triclosan, exhibits broad-spectrum activity by targeting the fatty acid biosynthetic pathway through inhibition of enoyl-acyl c ...200818663709
chemical synthesis and immunological properties of oligosaccharides derived from the vegetative cell wall of bacillus anthracis. 200818563773
the effect of salt and phage concentrations on the binding sensitivity of magnetoelastic biosensors for bacillus anthracis detection.this article presents an investigation of the effect of salt and phage concentrations on the binding affinity of magnetoelastic (me) biosensors. the sensors were fabricated by immobilizing filamentous phage on the me platform surface for the detection of bacillus anthracis spores. in response to the binding of spores to the phage on the me biosensor, a corresponding decrease occurs in resonance frequency. transmission electron microscopy (tem) was used to verify the structure of phage under diff ...200818563848
de novo asymmetric synthesis of anthrax tetrasaccharide and related tetrasaccharide.a de novo asymmetric approach to the natural product anthrax tetrasaccharide 1 and an analogue 2 with an anomeric hexyl azide group has been developed from acetylfuran. the construction of the tetrasaccharide was achieved by a traditional [3 + 1] glycosylation strategy. an iterative diastereoselective palladium-catalyzed glycosylation, luche reduction, diastereoselective dihydroxylation, and regioselective acylation were employed for the assembly of the l-rhamno-trisaccharide building block. the ...200818563936
domain specificity of the human antibody response to bacillus anthracis protective antigen.protective antigen (pa) is the cell surface recognition moiety of the bacillus anthracis a-b toxin system, and the active immunogenic component in the currently licensed human anthrax vaccine (biothrax, or ava). the serum antibody response to the pa protein is polyclonal and complex both in terms of the antibody combining sites utilized to bind pa and the pa-associated epitopes recognized. we have cloned, sequenced, and expressed a large panel of pa-specific human monoclonal antibodies from seve ...200818565627
multiplex pathogen detection based on spatially addressable microarrays of barcoded resins.suspension microsphere immunoassays are rapidly gaining recognition in antigen identification and infectious disease biodetection due to their simplicity, versatility and high-throughput multiplex screening. we demonstrate a multiplex assay based on antibody-functionalized barcoded resins (bcrs) to identify pathogen antigens in complex biological fluids. the binding event of a particular antibody on given bead (fluorescence) and the identification of the specific pathogen agent (vibrational fing ...200818566958
groel as a molecular scaffold for structural analysis of the anthrax toxin pore.we analyzed the 440-kda transmembrane pore formed by the protective antigen (pa) moiety of anthrax toxin in the presence of groel by negative-stain electron microscopy. groel binds both the heptameric pa prepore and the pa pore. the latter interaction retards aggregation of the pore, prolonging its insertion-competent state. two populations of unaggregated pores were visible: groel-bound pores and unbound pores. this allowed two virtually identical structures to be reconstructed, at 25-a and 28- ...200818568038
properties and applications of antimicrobial peptides in biodefense against biological warfare threat agents.recent advances in knowledge of the properties of antimicrobial peptides (amps) are reviewed. amps are typically small, positively charged, amphipathic peptides that interact electrostatically and non-stereospecifically with the bacterial cell membrane, resulting in its permeabilization and cell death. classes of amps, their mechanisms of action, hemolytic activity, and cytotoxicity towards host cells are discussed. a particular focus is amps with potential for use in defense against biological ...200818568863
analysis of suspicious powders following the post 9/11 anthrax scare.following the 9/11 terrorist attacks, set environmental, inc., a chicago-based environmental and hazardous materials management company received a large number of suspicious powders for analysis.200818570168
investigations and control measures following a case of inhalation anthrax in east london in a drum maker and drummer, october 2008.the patient is believed to have acquired the infection from making animal hide drums. environmental investigations identified one drum and two pieces of animal skins contaminated with anthrax spores.200819094916
an essential role for the antiviral endoribonuclease, rnase-l, in antibacterial immunity.type i ifns were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. accordingly, established mediators of ifn antiviral activity may mediate previously unrecognized antibacterial functions. rnase-l is the terminal component of an rna decay pathway that is an important mediator of ifn-induced antiviral activity. here, we identify a role for rnase-l in the host antibacterial response. rnase-l(-/-) mice exhibited ...200819075243
[characteristics of the immune response to the lethal toxin of bacillus anthracis].we and other authors have recently shown that the pattern of the immune response to components of anthrax, the bacillus anthracis lethal toxin, is complex. in addition to neutralizing antibodies, the antitoxin antibody pool contains antibodies enhancing the toxin lethal action. we mapped the epitopes in the protective antigen that are responsible for the induction of both antibody types. in this study, we obtained new data on the cytotoxicity of the b. anthracis lethal toxin toward the j774 a.1 ...200819060938
characterization of a bacillus anthracis spore coat-surface protein that influences coat-surface morphology.bacterial spores are encased in a multilayered proteinaceous shell, called the coat. in many bacillus spp., the coat protects against environmental assault and facilitates germination. in bacillus anthracis, the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. here, we characterize a b. anthracis spore protein, called cotbeta, which is encoded only in the genomes of the bacillus cereus group. we found that cotbeta is synthesized specificall ...200819054101
knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in tanzania.many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-sahara african region. these include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. the current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-d ...200819046464
neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax.bacillus anthracis infection is associated with severe hemostatic disturbances but their roles and contribution to fatality remain incompletely characterized. we undertook analyses of circulating antithrombin levels during the course of infection using a comparison of lethal and nonlethal murine anthrax models. plasma samples were obtained from dba/2 mice challenged intraperitoneally with the spores of either toxigenic b. anthracis sterne strain or nontoxigenic, avirulent delta sterne strain. we ...200819049643
discrimination between biothreat agents and 'near neighbor' species using a resequencing array.timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. this study aims to evaluate the potential of resequencing arrays for this purpose. albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify bacillus anthracis, francisella tularensis, yersinia pestis and distinguish them from benign 'near neighbor' species in ...200819049648
medical toxicology and public health-update on research and activities at the centers for disease control and prevention and the agency for toxic substances and disease registry.an extensive review of cdc epidemiological responses to human outbreaks of anthrax from occupational settings between the years of 1950 and 2001 documented a variety of approaches to mitigation and decontamination [2]. these approaches included taking no action, burning contaminated materials, chlorinating water supplies, instituting administrative and engineering controls and ppe, vaccinating potentially exposed individuals, and in 2 instances, fumigating with formaldehyde vapor (now considered ...200819031383
spatial localization of bacteria controls coagulation of human blood by 'quorum acting'.blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. bacil ...200819031531
mastitis caused by bacillus anthracis in a beef cow.a mixed-breed beef cow was presented with swelling of the front and hind left quarters of the mammary gland and mild depression. direct examination and culture of the serosanguinous-like milk samples collected from these quarters were consistent with bacillus anthracis infection.200819043486
the bicarbonate transporter is essential for bacillus anthracis lethality.in the pathogenic bacterium bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. elevated co2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. we identified a previously uncharacterized abc transporter (bas2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essen ...200819023421
enhancement of the immune responses of mice to bacillus anthracis protective antigen by cia07 combined with alum.anthrax is an acute zoonotic disease caused by infection with bacillus anthracis. b. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. in this study, we investigated the adjuvant activity of cia07 to anthrax protective antigen (pa). a/j mice were immunized intraperitoneally once, or twice with a 4-week interval, with recombinant pa alone or combined with alum, cpg1826, or cia07 as adjuvant, and serum anti-pa igg antibody responses were measur ...200819023533
novel acyl phosphate mimics that target plsy, an essential acyltransferase in gram-positive bacteria.plsy is a recently discovered acyltransferase that executes an essential step in membrane phospholipid biosynthesis in gram- positive bacteria. by using a bioisosteric replacement approach to generate substrate-based inhibitors of plsy as potential novel antibacterial agents, a series of stabilized acyl phosphate mimetics, including acyl phosphonates, acyl alpha,alpha-difluoromethyl phosphonates, acyl phosphoramides, reverse amide phosphonates, acyl sulfamates, and acyl sulfamides were designed ...200819016283
identification, characterization and activation mechanism of a tyrosine kinase of bacillus anthracis.bacillus subtilis has three active tyrosine kinases, ptka, ptkb and mcsb, which play an important role in the physiology of the bacterium. genome sequence analysis and biochemical experiments indicated that the ortholog of mcsb, bas0080, is the only active tyrosine kinase present in bacillus anthracis. the autophosphorylation of mcsb of b. anthracis was enhanced in the presence of an activator protein mcsa (bas0079), a property similar to that reported for b. subtilis. however, the process of en ...200819016839
after the anthrax. 200818998336
a multi-level spatial clustering algorithm for detection of disease outbreaks.in this paper, we proposed a multi-level spatial clustering (msc) algorithm for rapid detection of emerging disease outbreaks prospectively. we used the semi-synthetic data for algorithm evaluation. we applied bard algorithm [1] to generate outbreak counts for simulation of aerosol release of anthrax. we compared msc with two spatial clustering algorithms: kulldorff's spatial scan statistic [2] and bayesian spatial scan statistic [3]. the evaluation results showed that the areas under roc had no ...200818999304
bacillus anthracis peptidoglycan stimulates an inflammatory response in monocytes through the p38 mitogen-activated protein kinase pathway.we hypothesized that the peptidoglycan component of b. anthracis may play a critical role in morbidity and mortality associated with inhalation anthrax. to explore this issue, we purified the peptidoglycan component of the bacterial cell wall and studied the response of human peripheral blood cells. the purified b. anthracis peptidoglycan was free of non-covalently bound protein but contained a complex set of amino acids probably arising from the stem peptide. the peptidoglycan contained a polys ...200819002259
[the anthrax researcher took his life--was he a bioterrorist?]. 200819006871
risk factors associated with anthrax outbreak in animals in north dakota, 2005: a retrospective case-control study.we identified the risk factors associated with the anthrax outbreak of 2005 in animals in north dakota.200819006977
synthetic and crystallographic studies of a new inhibitor series targeting bacillus anthracis dihydrofolate reductase.bacillus anthracis, the causative agent of anthrax, poses a significant biodefense danger. serious limitations in approved therapeutics and the generation of resistance have produced a compelling need for new therapeutic agents against this organism. bacillus anthracis is known to be insensitive to the clinically used antifolate, trimethoprim, because of a lack of potency against the dihydrofolate reductase enzyme. herein, we describe a novel lead series of b. anthracis dihydrofolate reductase i ...200819007108
development of isothermal taqman assays for detection of biothreat organisms.taqman probe (dual-labeled dna probe)-based real-time detection, one of the most sensitive and specific fluorescent detection methods, has been widely utilized in conjunction with polymerase chain reaction (pcr). helicase-dependent amplification (hda) is an isothermal amplification technology that has a similar reaction scheme to pcr, but replaces thermocycling with a helicase capable of unwinding a dna duplex. here we describe a novel isothermal real-time detection method (hda-taqman) that comb ...200819007339
responding to a bioterrorism attack-one scenario: part 2.this article continues the discussions introduced in the earlier article submitted to the health care manager that is titled epidemic simulation for syndromic surveillance, where a format for analysis of the incidence of a bioterrorist attack was presented. part 2 of this series provides a discussion of the observed outcomes from the simulation techniques. this simulation was conducted as part of a federal grant award administered through the center for biological defense at the university of so ...200819011411
transcriptional and apoptotic responses of thp-1 cells to challenge with toxigenic, and non-toxigenic bacillus anthracis.bacillus anthracis secretes several virulence factors targeting different host organs and cell types during inhalational anthrax infection. the bacterial expression of a key virulence factor, lethal toxin (letx) is closely tied to another factor, edema toxin (edtx). both are transcribed on the same virulence plasmid (pxo1) and both have been the subject of much individual study. their combined effect during virulent anthrax likely modulates both the global transcriptional and the phenotypic resp ...200819014542
evidence-based spectrum of antimicrobial activity for disinfection of bronchoscopes.processing of bronchoscopes after a physical examination has to eliminate all micro-organisms that could have contaminated the endoscope and that may harm the following patient. the aim of this analysis is to define those micro-organisms that may contaminate the bronchoscope during the examination and that may cause disease in other patients.200818994685
bacillus anthracis o-succinylbenzoyl-coa synthetase: reaction kinetics and a novel inhibitor mimicking its reaction intermediate.o-succinylbenzoyl-coa (osb-coa) synthetase (ec 6.2.1.26) catalyzes the atp-dependent condensation of o-succinylbenzoate (osb) and coa to form osb-coa, the fourth step of the menaquinone biosynthetic pathway in bacillus anthracis. gene knockout studies have highlighted this enzyme as a potential target for the discovery of new antibiotics. here we report the first studies on the kinetic mechanism of b. anthracis osb-coa synthetase, classifying it as an ordered bi uni uni bi ping-pong mechanism. t ...200818973344
germline humanization of a non-human primate antibody that neutralizes the anthrax toxin, by in vitro and in silico engineering.fab 35pa83 is an antibody fragment of non-human primate origin that neutralizes the anthrax lethal toxin. human antibodies are usually preferred when clinical use is envisioned, even though their framework regions (fr) may carry mutations introduced during affinity maturation. these hypermutations can be immunogenic and therefore fr that are encoded by human germline genes, encountered in igms and thus part of the "self" proteins, are preferable. accordingly, the proportion of fr residues in 35p ...200818976662
using mahalanobis distance to compare genomic signatures between bacterial plasmids and chromosomes.plasmids are ubiquitous mobile elements that serve as a pool of many host beneficial traits such as antibiotic resistance in bacterial communities. to understand the importance of plasmids in horizontal gene transfer, we need to gain insight into the 'evolutionary history' of these plasmids, i.e. the range of hosts in which they have evolved. since extensive data support the proposal that foreign dna acquires the host's nucleotide composition during long-term residence, comparison of nucleotide ...200818953039
anthrax edema toxin modulates pka- and creb-dependent signaling in two phases.anthrax edema toxin (edtx) is an adenylate cyclase which operates in the perinuclear region of host cells. however, the action of edtx is poorly understood, especially at molecular level. the ability of edtx to modulate camp-dependent signaling was studied in jurkat t cells and was compared with that of other camp-rising agents: bordetella pertussis adenylate cyclase toxin, cholera toxin and forskolin.200818958164
anthrax in transit; practical experience and intellectual exchange.focusing on three anglo-american outbreaks of industrial anthrax, this essay engages the question of how local circumstances influenced the transmission of scientific knowledge in the late nineteenth century. walpole (massachusetts), glasgow, and bradford (yorkshire) served as important nodes of transnational investigation into anthrax. knowledge about the morphology and behavior of bacillus anthracis changed little while in transit between these nodes, even during complex debates about the natu ...200818959192
structural and functional analysis of asbf: origin of the stealth 3,4-dihydroxybenzoic acid subunit for petrobactin biosynthesis.petrobactin, a virulence-associated siderophore produced by bacillus anthracis, chelates ferric iron through the rare 3,4-isomer of dihydroxybenzoic acid (3,4-dhba). most catechol siderophores, including bacillibactin and enterobactin, use 2,3-dhba as a biosynthetic subunit. significantly, siderocalin, a factor involved in human innate immunity, sequesters ferric siderophores bearing the more typical 2,3-dhba moiety, thereby impeding uptake of iron by the pathogenic bacterial cell. in contrast, ...200818955706
association and decontamination of bacillus spores in a simulated drinking water system.the objective of this work was to elucidate the disinfectant susceptibility of bacillus anthracis sterne (ba) and a commercial preparation of bacillus thuringiensis (bt) spores associated with a simulated drinking water system. biofilms composed of indigenous water system bacteria were accumulated on copper and polyvinyl chloride (pvc) pipe material surfaces in a low-flow pipe loop and uniformly mixed tank reactor (cdc biofilm reactor). application of a distributed shear during spore contact res ...200818947853
aryl acid adenylating enzymes involved in siderophore biosynthesis: fluorescence polarization assay, ligand specificity, and discovery of non-nucleoside inhibitors via high-throughput screening.the design and synthesis of a fluorescent probe fl-sal-ams 6 based on the tight-binding inhibitor 5'- o-[ n-(salicyl)sulfamoyl]adenosine (sal-ams) is described for the aryl acid adenylating enzymes (aaaes) known as mbta, ybte, ente, vibe, dhbe, and base involved in siderophore biosynthesis from mycobacterium tuberculosis, yersinia pestis, escherichia coli, vibrio cholerae, bacillus subtilis, and acinetobacter baumannii, respectively. the probe was successfully used to develop a fluorescence pola ...200818928302
the danger of lime use in agricultural anthrax disinfection procedures: the potential role of calcium in the preservation of anthrax spores.previously, lime (calcium oxide) was recommended by the canadian food inspection agency (cfia) as an anthrax disinfectant. however, a recent scientific review of the subject has found evidence to suggest that exposure of anthrax spores to calcium may aid in their survival and viability. for this reason, the cfia no longer recommends the use of lime for agricultural anthrax disinfection.200819252713
protective antigen composite nanofibers as a transdermal anthrax vaccine.anthrax, a disease caused by the gram positive bacteria bacillus anthracis, has become an increasing threat to public health in the last several years, due to its use as an agent of biological warfare. the currently utilized human anthrax vaccine, which confers immunity through the host antibody recognition of protective antigen (pa), requires a three dose regimen and annual booster shots after the initial vaccination to maintain its efficacy. the long term goal of this project is to produce an ...200819162840
the anthrax vaccine and research: reactions from postal workers and public health professionals.during the 2001 anthrax attacks, public health agencies faced operational and communication decisions about the use of antibiotic prophylaxis and the anthrax vaccine with affected groups, including postal workers. this communication occurred within an evolving situation with incomplete and uncertain data. guidelines for prophylactic antibiotics changed several times, contributing to confusion and mistrust. at the end of 60 days of taking antibiotics, people were offered an additional 40 days' su ...200819117431
molecular modeling as a tool for drug discovery.with the progression of structural genomics projects, comparative modeling remains an increasingly important method of choice to obtain 3d structure of proteins. it helps to bridge the gap between the available sequence and structure information by providing reliable and accurate protein models. comparative modeling based on more than 30% sequence identity is now approaching its natural template-based limits and further improvements require the development of effective refinement techniques capa ...200819128219
effects of anthrax lethal toxin on human primary keratinocytes.to investigate the effects of anthrax lethal toxin (letx) on human primary keratinocytes.200819120626
aptamer selection express: a novel method for rapid single-step selection and sensing of aptamers.here we describe a new dna capture element (dce) sensing system, based on the quenching and dequenching of a double-stranded aptamer. this system shows very good sensitivity and thermal stability. while quenching, dequenching, and separating the dce systems made from different aptamers (all selected by selex), an alternative method to rapidly select aptamers was developed-the aptamer selection express (asexp). this process has been used to select aptamers against different types of targets (baci ...200819183794
dispensing medical countermeasures for public health emergencies: workshop summarywith the threat of an anthrax attack as the case study, on march 3–4, 2008, the institute of medicine (iom) forum on medical and public health preparedness for catastrophic events hosted a workshop titled “medical countermeasures dispensing.” the workshop was organized by an independent planning committee. the following is a summary of the presentations and discussion that transpired during the workshop. any opinions, conclusions, or recommendation ...200820669413
induction of natural competence in bacillus cereus atcc14579.natural competence is the ability of certain microbes to take up exogenous dna from the environment and integrate it in their genome. competence development has been described for a variety of bacteria, but has so far not been shown to occur in bacillus cereus. however, orthologues of most proteins involved in natural dna uptake in bacillus subtilis could be identified in b. cereus. here, we report that b. cereus atcc14579 can become naturally competent. when expressing the b. subtilis comk prot ...200821261842
rat survival to anthrax lethal toxin is likely controlled by a single gene.we examined whether survival of different rat strains administered anthrax lethal toxin is genetically determined. a reproducible test population of first filial generation hybrid rats was bred based on the susceptibility of progenitors to anthrax lethal toxin and to maximize genetic diversity across the strains. these rats were then tested with varying doses of anthrax lethal toxin. we found that all 'sensitive' strains died within 2 h following systemic administration of 240 mug/kg lethal toxi ...200817440430
extending the bacillus cereus group genomics to putative food-borne pathogens of different toxicity.the bacillus cereus group represents sporulating soil bacteria containing pathogenic strains which may cause diarrheic or emetic food poisoning outbreaks. multiple locus sequence typing revealed a presence in natural samples of these bacteria of about 30 clonal complexes. application of genomic methods to this group was however biased due to the major interest for representatives closely related to bacillus anthracis. albeit the most important food-borne pathogens were not yet defined, existing ...200817434157
bactericidal activity of chlorine-loaded carbide-derived carbon against escherichia coli and bacillus anthracis.the authors investigated the bactericidal activity of high-chlorine-content nanoporous carbide-derived carbon (cdc) against the gram-positive, spore-forming bacterium bacillus anthracis and the common gram-negative enteric bacterium escherichia coli. chlorine-loaded nanoporous cdc produced by thermochemical etching of metals and metalloids by chlorination of carbides can retain up to 40 wt % of chlorine. etching temperature and the structure and composition of carbides allow tuning the porosity ...200817635016
modeling the structure of mab 14b7 bound to the anthrax protective antigen.the anthrax protective antigen (pa) is a key component of the tripartite anthrax toxin. monoclonal antibody (mab) 14b7 and its engineered, affinity-matured variants have been shown to be effective in blocking pa binding to cellular receptors and mitigating anthrax toxicity. here, we perform computational structural modeling of the mab 14b7-pa interaction. our objectives are to determine the structure of the 14b7-pa complex, to deduce a structural explanation for the affinity maturation from the ...200817671962
properties of bacillus anthracis spores prepared under various environmental conditions.bacillus anthracis makes highly stable, heat-resistant spores which remain viable for decades. effect of various stress conditions on sporulation in b. anthracis was studied in nutrient-deprived and sporulation medium adjusted to various ph and temperatures. the results revealed that sporulation efficiency was dependent on conditions prevailing during sporulation. sporulation occurred earlier in culture sporulating at alkaline ph or in pbs than control. spores formed in pbs were highly sensitive ...200817713759
paratope diversity in the human antibody response to bacillus anthracis protective antigen.the active component of the licensed human anthrax vaccine (biothrax, or ava) is a bacillus anthracis toxin known as protective antigen (pa). second generation anthrax vaccines currently under development are also based on a recombinant form of pa. since the current and future anthrax vaccines are based on this toxin, it is important that the immunobiology of this protein in vaccinated humans be understood in detail. we have isolated and analyzed the pa-specific antibody repertoire from an ava-v ...200817707509
anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome.anthrax lethal toxin (lt) is cytotoxic to macrophages from certain inbred mouse strains. the gene controlling macrophage susceptibility to lt is nalp1b. nalp1b forms part of the inflammasome, a multiprotein complex involved in caspase-1 activation and release of interleukin (il)-1beta and il-18. we confirm the role of caspase-1 in lt-mediated death by showing that caspase inhibitors differentially protected cells against lt, with the degree of protection corresponding to each compound's ability ...200817850338
construction, crystal structure and application of a recombinant protein that lacks the collagen-like region of bcla from bacillus anthracis spores.spores of bacillus anthracis, the causative agent of anthrax, are enclosed by an exosporium, which consists of a basal layer surrounded by a nap of hair-like filaments. the major structural component of the filaments is called bcla, which comprises a central collagen-like region (clr) and a globular c-terminal domain. here, the entire clr coding sequence of bcla was removed, and the resulting protein (tbcla) produced in escherichia coli. the crystallographic structure of tbcla was determined to ...200817879302
crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (ba3989) from bacillus anthracis at 2.4-a resolution. 200817894349
nlr proteins: integral members of innate immunity and mediators of inflammatory diseases.the innate immune system is the first line of defense against microorganisms and is conserved in plants and animals. the nucleotide-binding domain, leucine rich containing (nlr) protein family is a recent addition to the members of innate immunity effector molecules. these proteins are characterized by a central oligomerization domain, termed nucleotide-binding domain (nbd) and a protein interaction domain, leucine-rich repeats (lrrs) at the c terminus. it has been shown that nlr proteins are lo ...200817875812
discrimination of bacillus anthracis and closely related microorganisms by analysis of 16s and 23s rrna with oligonucleotide microarray.analysis of 16s rrna sequences is a commonly used method for the identification and discrimination of microorganisms. however, the high similarity of 16s and 23s rrna sequences of bacillus cereus group organisms (up to 99-100%) and repeatedly failed attempts to develop molecular typing systems that would use dna sequences to discriminate between species within this group have resulted in several suggestions to consider b. cereus and b. thuringiensis, or these two species together with b. anthrac ...200817950718
carbohydrate-based experimental therapeutics for cancer, hiv/aids and other diseases.this review, primarily for general readers, briefly presents experimental approaches to therapeutics of cancer, hiv/aids and various other diseases based on advances in glycobiology and glycochemistry. experimental cancer and hiv/aids vaccines are being developed in attempts to overcome weak immunological responses to carbohydrate-rich surface antigens using carriers, adjuvants and novel carbohydrate antigen constructs. current carbohydrate-based vaccines are used for typhus, pneumonia, meningit ...200817963823
development and implementation of a single-chain fv antibody for specific detection of bacillus anthracis spores.a single-chain fv (scfv) antibody was developed and applied for efficient and specific detection of bacillus anthracis spores. the antibody was isolated from a phage display library prepared from spleens of mice immunized with a water-soluble extract of the outer membrane of the b. anthracis spore (exosporium). the library (7 x 10(6) pfu) was biopanned against live, native b. anthracis atcc delta14185 spores suspended in solution, resulting in the isolation of a unique soluble scfv antibody. the ...200817965209
coplot: a tool for visualizing multivariate data in medicine.many critical questions in medicine require the analysis of complex multivariate data, often from large data sets describing numerous variables for numerous subjects. in this paper, we describe coplot, a tool for visualizing multivariate data in medicine. coplot is an adaptation of multidimensional scaling (mds) that addresses several key limitations of mds, namely that mds maps do not allow for visualization of both observations and variables simultaneously and that the axes on an mds map have ...200817972340
matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature.anthrax lethal toxin (lt), a virulence factor secreted by bacillus anthracis, is selectively toxic to human melanomas with the braf v600e activating mutation because of its proteolytic activities toward the mitogen-activated protein kinase kinases (meks). to develop lt variants with lower in vivo toxicity and high tumor specificity, and therefore greater potential for clinical use, we generated a mutated lt that requires activation by matrix metalloproteinases (mmps). this engineered toxin was l ...200817974567
emilins interact with anthrax protective antigen and inhibit toxin action in vitro.the informational spectrum method (ism) is a virtual spectroscopy method for the fast analysis of potential protein-protein relationships. by applying the ism approach to the genebank protein database the vascular proteins emilin1 (elastin microfibril interface located protein), emilin2, mmn1, and mmn2 were identified as additional anthrax pa antigen interacting molecules. this virtual molecular interaction was formally proven by solid phase assays using recombinant proteins. the interaction is ...200817988845
bacterial pore-forming toxins: the (w)hole story?pore-forming toxins (pfts) are the most common class of bacterial protein toxins and constitute important bacterial virulence factors. the mode of action of pft is starting to be better understood. in contrast, little is known about the cellular response to this threat. recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation, mount a defense, even repair the damaged membrane and thus survive. these responses involve a variety of signal-trans ...200817989920
cell wall carbohydrate compositions of strains from the bacillus cereus group of species correlate with phylogenetic relatedness.members of the bacillus cereus group contain cell wall carbohydrates that vary in their glycosyl compositions. recent multilocus sequence typing (mlst) refined the relatedness of b. cereus group members by separating them into clades and lineages. based on mlst, we selected several b. anthracis, b. cereus, and b. thuringiensis strains and compared their cell wall carbohydrates. the cell walls of different b. anthracis strains (clade 1/anthracis) were composed of glucose (glc), galactose (gal), n ...200817981984
supercat: a supertree database for combined and integrative multilocus sequence typing analysis of the bacillus cereus group of bacteria (including b. cereus, b. anthracis and b. thuringiensis).the bacillus cereus group of bacteria is an important group including mammalian and insect pathogens, such as b. anthracis, the anthrax bacterium, b. thuringiensis, used as a biological pesticide and b. cereus, often involved in food poisoning incidents. to characterize the population structure and epidemiology of these bacteria, five separate multilocus sequence typing (mlst) schemes have been developed, which makes results difficult to compare. therefore, we have developed a database that comp ...200817982177
where and how do anthrax toxins exit endosomes to intoxicate host cells?the role of bacillus anthracis virulence factors in its pathogenesis has been subjected to intense investigation with the aim of finding novel preventive and therapeutic protocols. toxins that are endocytosed and act in the cytosol of host cells have a central role in b. anthracis infection. understanding of anthrax toxin cell entry has increased during the past few years and a composite picture is emerging. nevertheless, unanswered and controversial questions remain, particularly concerning the ...200717983750
cutaneous anthrax in the artibonite valley of haiti: 1992-2002.more cutaneous anthrax cases were noted at hospital albert schweitzer (has) in the artibonite valley of haiti. we examine the incidence of anthrax in the artibonite between 1992 and 2002, describe the clinical presentation of cutaneous anthrax, and determine risk factors for anthrax. in 1992 has reported 1 case of anthrax for an incidence of 4 cases per million persons/year. in 2002, there were 20 cases of anthrax for an incidence of 72 cases per million persons/year. this is a 17-fold increase ...200717984330
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