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chemical genetics reveals a kinase-independent role for protein kinase r in pyroptosis.formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. pyroptotic cell death induced by anthrax lethal toxin (lt) is a model for inflammasome-mediated caspase-1 activation. we discovered 7-desacetoxy-6,7-dehydrogedunin (7dg) in a phenotypic screen as a small molecule that protects macrophages from lt-induced death. using chemical proteomics, we identified protein kinase r (pkr) as the target of 7dg and show that rnai knockdown of pkr phe ...201323603659
exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (pa) with one of three reported cell surface toxin receptors (antxr). receptor binding has been shown to influence host susceptibility to the toxins. despite this crucial role for antxr in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about antxr expression on human leucocytes. we characterized the expr ...201323607659
anthrax lethal toxin downregulates claudin-5 expression in human endothelial tight junctions.vascular leakage pathologies such as pleural effusion and hemorrhage are hallmarks of anthrax pathogenesis. we previously reported that anthrax lethal toxin (lt), the major virulence factor of anthrax, reduces barrier function in cultured primary human microvascular endothelial cells. here, we show that lt-induced barrier dysfunction is accompanied by the reduced expression of the endothelial tight junction (tj) protein claudin-5 but no change in the expression of other tj components occludin, z ...201323626836
interactions of antimicrobial peptide chrysophsin-3 with bacillus anthracis in sporulated, germinated, and vegetative states.bacillus anthracis spores contain on their surface multilayered protein coats that provide barrier properties, mechanical strength, and elasticity that aid in protecting the sporulated state and preventing germination, outgrowth, and transition into the virulent vegetative bacterial state. in this work, the antimicrobial peptide (amp) chrysophsin-3 was tested against b. anthracis in each of the three distinct metabolic states (sporulated, germinated, and vegetative) for its bacteria-killing acti ...201323631815
anthrax toxin-mediated delivery of the pseudomonas exotoxin a enzymatic domain to the cytosol of tumor cells via cleavable ubiquitin fusions.anthrax toxin proteins from bacillus anthracis constitute a highly efficient system for delivering cytotoxic enzymes to the cytosol of tumor cells. however, exogenous proteins delivered to the cytosol of cells are subject to ubiquitination on lysines and proteasomal degradation, which limit their potency. we created fusion proteins containing modified ubiquitins with their c-terminal regions fused to the pseudomonas exotoxin a catalytic domain (peiii) in order to achieve delivery and release of ...201323631917
characterization of the native form of anthrax lethal factor for use in the toxin neutralization assay.the cell-based anthrax toxin neutralization assay (tna) is used to determine functional antibody titers of sera from animals and humans immunized with anthrax vaccines. the anthrax lethal toxin is a critical reagent of the tna composed of protective antigen (pa) and lethal factor (lf), which are neutralization targets of serum antibodies. cytotoxic potency of recombinant lf (rlf) lots can vary substantially, causing a challenge in producing a renewable supply of this reagent for validated tnas. ...201323637044
igg subclass and heavy chain domains contribute to binding and protection by mabs to the poly γ-d-glutamic acid capsular antigen of bacillus anthracis.bacterial capsules are common targets for antibody-mediated immunity. the capsule of bacillus anthracis is unusual among capsules because it is composed of a polymer of poly-γ-d-glutamic acid (γdpga). we previously generated murine igg3 monoclonal antibodies (mabs) to γdpga that were protective in a murine model of pulmonary anthrax. igg3 antibodies are characteristic of the murine response to polysaccharide antigens. the goal of the present study was to produce subclass switch variants of the γ ...201323637599
a single-dose plga encapsulated protective antigen domain 4 nanoformulation protects mice against bacillus anthracis spore challenge.bacillus anthracis, the etiological agent of anthrax, is a major bioterror agent. vaccination is the most effective prophylactic measure available against anthrax. currently available anthrax vaccines have issues of the multiple booster dose requirement, adjuvant-associated side effects and stability. use of biocompatible and biodegradable nanoparticles to deliver the antigens to immune cells could solve the issues associated with anthrax vaccines. we hypothesized that the delivery of a stable i ...201323637922
constructing droplet interface bilayers from the contact of aqueous droplets in oil.we describe a protocol for forming an artificial lipid bilayer by contacting nanoliter aqueous droplets in an oil solution in the presence of phospholipids. a lipid monolayer forms at each oil-water interface, and when two such monolayers touch, a bilayer is created. droplet interface bilayers (dibs) are a simple way to generate stable bilayers suitable for single-channel electrophysiology and optical imaging from a wide variety of preparations, ranging from purified proteins to reconstituted eu ...201323640169
prothera biologics, inc.: a novel immunomodulator and biomarker for life-threatening diseases.prothera biologics is a development stage bio-therapeutics company in east providence, rhode island. the company was founded in 2002 to focus on the critical role and commercial potential of inter-alpha inhibitor proteins (iaip) for treating acute life-threatening inflammatory diseases. the discovery research originated in the basic research laboratories of the co-founders, yow-pin lim, md, phd, and douglas c. hixson, phd, at rhode island hospital, a lifespan partner. the company is backed by th ...201323641420
human leukocyte antigens and cellular immune responses to anthrax vaccine adsorbed.interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (hla) and other gene families. this study examined associations between hla genotypes, haplotypes, and homozygosity and protective antigen (pa)-specific cellular immune responses in healthy subjects following immunization with anthrax vaccine adsorbed (ava). while limited associations were observed between individual hla alleles or haplotypes and variable ly ...201323649091
evaluation of immunogenicity and efficacy of anthrax vaccine adsorbed for postexposure prophylaxis.antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (pep). in a rabbit pep study, animals were subjected to lethal challenge with aerosolized bacillus ...201323658392
assay for peptidoglycan o-acetyltransferase: a potential new antibacterial target.the o-acetylation of peptidoglycan occurs at the c-6 hydroxyl group of muramoyl residues in many human pathogens, both gram positive and gram negative, such as staphylococcus aureus and species of campylobacter, helicobacter, neisseria, and bacillus, including bacillus anthracis. the process is a maturation event being catalyzed either by integral membrane o-acetylpeptidoglycan transferase (oat) of gram-positive bacteria or by a two-component peptidoglycan o-acetyltransferase system (pata/patb) ...201323660013
optimization of a novel potent and selective bacterial dna helicase inhibitor scaffold from a high throughput screening hit.benzobisthiazole derivatives were identified as novel helicase inhibitors through high throughput screening against purified staphylococcus aureus (sa) and bacillus anthracis (ba) replicative helicases. chemical optimization has produced compound 59 with nanomolar potency against the dna duplex strand unwinding activities of both b. anthracis and s. aureus helicases. selectivity index (si=cc50/ic50) values for 59 were greater than 500. kinetic studies demonstrated that the benzobisthiazole-based ...201323664213
studying the fate of non-volatile organic compounds in a commercial plasma air purifier.degradation of non-volatile organic compounds-environmental toxins (methyltriclosane and phenanthrene), bovine serum albumin, as well as bioparticles (legionella pneumophila, bacillus subtilis, and bacillus anthracis)-in a commercially available plasma air purifier based on a cold plasma was studied in detail, focusing on its efficiency and on the resulting degradation products. this system is capable of handling air flow velocities of up to 3.0m s(-1) (3200lmin(-1)), much higher than other plas ...201323669793
the use of colorimetric sensor arrays to discriminate between pathogenic bacteria.a colorimetric sensor array is a high-dimensional chemical sensor that is cheap, compact, disposable, robust, and easy to operate, making it a good candidate technology to detect pathogenic bacteria, especially potential bioterrorism agents like yersinia pestis and bacillus anthracis which feature on the center for disease control and prevention's list of potential biothreats. here, a colorimetric sensor array was used to continuously monitor the volatile metabolites released by bacteria in soli ...201323671629
proteomic analysis of the oxidative stress response induced by low-dose hydrogen peroxide in bacillus anthracis.anthrax is a bacterial disease caused by the aerobic sporeforming bacterium bacillus anthracis, which is an important pathogen owing to its ability to be used as a terror agent. b. anthracis spores can escape phagocytosis and initiate the germination process even in antimicrobial conditions, such as oxidative stress. to analyze the oxidative stress response in b. anthracis and thereby learn how to prevent antimicrobial resistance, we performed protein expression profiling of b. anthracis strain ...201323676920
[response and evaluation of the disinfection effects on an anthrax outbreak in human being and cattle in guizhou]. 201323678679
structure-based non-canonical amino acid design to covalently crosslink an antibody-antigen complex.engineering antibodies to utilize non-canonical amino acids (ncaa) should greatly expand the utility of an already important biological reagent. in particular, introducing crosslinking reagents into antibody complementarity determining regions (cdrs) should provide a means to covalently crosslink residues at the antibody-antigen interface. unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic ...201423680795
the potential impact of an anthrax attack on real estate prices and foreclosures in seattle.this article provides a methodology for the economic analysis of the potential consequences of a simulated anthrax terrorism attack on real estate within the seattle metropolitan area. we estimate spatially disaggregated impacts on median sales price of residential housing within the seattle metro area following an attack on the central business district (cbd). using a combination of longitudinal panel regression and gis analysis, we find that the median sales price in the cbd could decline by a ...201423682844
decontamination of materials contaminated with bacillus anthracis and bacillus thuringiensis al hakam spores using pes-solid, a solid source of peracetic acid.to develop test methods and evaluate survival of bacillus anthracis ames, b. anthracis ∆sterne and b. thuringiensis al hakam spores after exposure to pes-solid (a solid source of peracetic acid), including pes-solid formulations with bacteriostatic surfactants.201323692445
anthrax threat: a review of clinical and diagnostic measures.anthrax is the plague of the ancient world and its existence is confirmed by the roman poet virgil. also it is a threat in the modern world as it can be used in biological wars and bioterrorism. anthrax is caused by bacillus anthracis an unmovable, aerobic, gram-positive rod. it forms spores, which can survive for years in the environment. three clinical forms result after exposure to anthrax spores: cutaneous, respiratory, and gastro- intestinal. the cutaneous anthrax commonly prevails among hu ...201323697023
randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of anthrax vaccine adsorbed plus cpg 7909 (av7909) in healthy adult volunteers.a new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. this phase 1 study compared the safety and immunogenicity of 2 im doses (days 0 and 14) of 4 formulations of av7909 (ava plus cpg 7909) with 2 im doses of biothrax(®) (anthrax vaccine adsorbed) and 2 im doses of saline placebo administered on days 0 and 14. a total of 105 healthy adults 18-50 years of age were randomized ...201323701746
structure of the chlamydia trachomatis immunodominant antigen pgp3.chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. here we present the structure of the secreted c. trachomatis protein pgp3, an immunodominant antigen and putative virulence factor. the ∼84-kda pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular n- and c-terminal assemblies connected by a triple-helical coiled-coil. the c-terminal domains posses ...201323703617
cct chaperonin complex is required for efficient delivery of anthrax toxin into the cytosol of host cells.bacterial toxins have evolved successful strategies for coopting host proteins to access the cytosol of host cells. anthrax lethal factor (lf) enters the cytosol through pores in the endosomal membrane formed by anthrax protective antigen. although in vitro models using planar lipid bilayers have shown that translocation can occur in the absence of cellular factors, recent studies using intact endosomes indicate that host factors are required for translocation in the cellular environment. in thi ...201323716698
detection of biological warfare agents using ultra violet-laser induced fluorescence lidar.this review has been written to highlight the threat of biological warfare agents, their types and detection. bacterial biological agent bacillus anthracis (bacteria causing the disease anthrax) which is most likely to be employed in biological warfare is being discussed in detail. standoff detection of biological warfare agents in aerosol form using ultra violet-laser induced fluorescence (uv-lif) spectroscopy method has been studied. range-resolved detection and identification of biological ae ...201323719340
anthrax set protein: a potential virulence determinant that epigenetically represses nf-κb activation in infected macrophages.toxins play a major role in the pathogenesis of bacillus anthracis by subverting the host defenses. however, besides toxins, b. anthracis expresses effector proteins, whose role in pathogenesis are yet to be investigated. here we present that suppressor-of-variegation, enhancer-of-zeste, trithorax protein from b. anthracis (baset) methylates human histone h1, resulting in repression of nf-κb functions. notably, baset is secreted and undergoes nuclear translocation to enhance h1 methylation in b. ...201323720780
spatial modelling of bacillus anthracis ecological niche in zimbabwe.anthrax continues to cause significant mortalities in livestock, wildlife and humans worldwide. in zimbabwe, anthrax outbreaks have been reported almost annually over the past four decades. in this study we tested whether anthrax outbreak data and a set of environmental variables can be used to predict the ecological niche for bacillus anthracis using maximum entropy modelling for species geographical distribution (maxent). confirmed geo-referenced anthrax outbreaks data for the period 1995-2010 ...201323726015
assessment of delivery parameters with the multi-electrode array for development of a dna vaccine against bacillus anthracis.gene electrotransfer (get) enhances delivery of dna vaccines by increasing both gene expression and immune responses. our lab has developed the multi-electrode array (mea) for dna delivery to skin. the mea was used at constant pulse duration (150 ms) and frequency (6.67 hz). in this study, delivery parameters including applied voltage (5-45 v), amount of plasmid (100-300 μg), and number of treatments (2-3) were evaluated for delivery of a dna vaccine. mice were intradermally injected with plasmi ...201323727769
bacillus anthracis co-opts nitric oxide and host serum albumin for pathogenicity in hypoxic conditions.bacillus anthracis is a dangerous pathogen of humans and many animal species. its virulence has been mainly attributed to the production of lethal and edema toxins as well as the antiphagocytic capsule. recent data indicate that the nitric oxide (no) synthase (banos) plays an important pathogenic role at the early stage of disease by protecting bacteria from the host reactive species and s-nytrosylating the mitochondrial proteins in macrophages. in this study we for the first time present eviden ...201323730627
competency in chaos: lifesaving performance of care providers utilizing a competency-based, multi-actor emergency preparedness training curriculum.providing comprehensive emergency preparedness training (ept) to care providers is important to the future success of disaster operations in the us. few ept programs possess both competency-driven goals and metrics to measure performance during a multi-patient simulated disaster.201323731521
pandemic influenza planning, united states, 1978-2008.during the past century, 4 influenza pandemics occurred. after the emergence of a novel influenza virus of swine origin in 1976, national, state, and local us public health authorities began planning efforts to respond to future pandemics. several events have since stimulated progress in public health emergency planning: the 1997 avian influenza a(h5n1) outbreak in hong kong, china; the 2001 anthrax attacks in the united states; the 2003 outbreak of severe acute respiratory syndrome; and the 200 ...201323731839
bacillus anthracis peptidoglycan activates human platelets through fcγrii and complement.platelet activation frequently accompanies sepsis and contributes to the sepsis-associated vascular leakage and coagulation dysfunction. our previous work has implicated peptidoglycan (pgn) as an agent causing systemic inflammation in gram-positive sepsis. we used flow cytometry and fluorescent microscopy to define the effects of pgn on the activation of human platelets. pgn induced platelet aggregation, expression of the activated form of integrin αiibβ3, and exposure of phosphatidylserine (ps) ...201323733338
evaluation of ambulance decontamination using gaseous chlorine dioxide.we evaluated gaseous chlorine dioxide (clo2) decontamination of an ambulance using a variety of bacterial biological agents.201323734992
bacillus anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model.disseminated intravascular coagulation (dic) appears to be important in the pathogenesis of bacillus anthracis infection, but its causes are unclear. although lethal toxin (lt) and edema toxin (et) could contribute, b. anthracis cell wall peptidoglycan (pgn), not the toxins, stimulates inflammatory responses associated with dic.201323737601
systemic use of fluoroquinolone in children.fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. however, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. indications for fluoroquinolone use in patients younger than 18 years, as stated by the u.s. food and drug administration, include treatment of complicated urinary ...201323741232
genomic copy number variants: evidence for association with antibody response to anthrax vaccine adsorbed.anthrax and its etiologic agent remain a biological threat. anthrax vaccine is highly effective, but vaccine-induced igg antibody responses vary widely following required doses of vaccinations. such variation can be related to genetic factors, especially genomic copy number variants (cnvs) that are known to be enriched among genes with immunologic function. we have tested this hypothesis in two study populations from a clinical trial of anthrax vaccination.201323741398
mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of bacillus anthracis and cross-reacting with the homologous edema factor.the lethal toxin (lt) of bacillus anthracis, composed of the protective antigen (pa) and the lethal factor (lf), plays an essential role in anthrax pathogenesis. pa also interacts with the edema factor (ef, 20% identity with lf) to form the edema toxin (et), which has a lesser role in anthrax pathogenesis. the first recombinant antibody fragment directed against lf was scfv 2lf; it neutralizes lt by blocking the interaction between pa and lf. here, we report that scfv 2lf cross-reacts with ef an ...201323741517
the sepsis model: an emerging hypothesis for the lethality of inhalation anthrax.inhalation anthrax is often described as a toxin-mediated disease. however, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that l ...201323742651
thermal effects on surface structures and properties of bacillus anthracis spores on nanometer scales.bacterial spores, one of the hardiest forms of life known, can survive severe environmental stresses such as high temperature. using thermal atomic force microscopy (afm), we show that the surface structures and properties of bacillus anthracis spores when exposed to elevated temperatures undergo substantial changes on nanometer scales. thermal-blister-like nanostructures, which grow in size with increasing temperature, are formed on the spore surface when it is heated by a thermal tip. although ...201323742662
straight talk with... tom inglesby. interview by kevin jiang.when letters containing anthrax spores were mailed to several us senators and media offices in september 2001, just one week after the 9/11 attacks, bioterrorism catapulted to the national stage. political leaders and public health officials, desperate for guidance on this once-theoretical scenario, turned to experts including tom inglesby, then deputy director of the johns hopkins center for civilian biodefense strategies, a bioterrorism research and analysis think tank in baltimore. in the yea ...201323744137
cleavage of the junb transcription factor by caspases generates a carboxyl-terminal fragment that inhibits activator protein-1 transcriptional activity.the activator protein-1 (ap-1) family transcription factor, junb, is an important regulator of proliferation, apoptosis, differentiation, and the immune response. in this report, we show that junb is cleaved in a caspase-dependent manner in apoptotic anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma cell lines and that ectopically expressed junb is cleaved in murine raw 264.7 macrophage cells treated with the nalp1b inflammasome activator, anthrax lethal toxin. in both cases, w ...201323749999
characterization of bacillus anthracis persistence in vivo.pulmonary exposure to bacillus anthracis spores initiates inhalational anthrax, a life-threatening infection. it is known that dormant spores can be recovered from the lungs of infected animals months after the initial spore exposure. consequently, a 60-day course antibiotic treatment is recommended for exposed individuals. however, there has been little information regarding details or mechanisms of spore persistence in vivo. in this study, we investigated spore persistence in a mouse model. th ...201323750280
cross-functionalities of bacillus deacetylases involved in bacillithiol biosynthesis and bacillithiol-s-conjugate detoxification pathways.bshb, a key enzyme in bacillithiol biosynthesis, hydrolyses the acetyl group from n-acetylglucosamine malate to generate glucosamine malate. in bacillus anthracis, ba1557 has been identified as the n-acetylglucosamine malate deacetylase (bshb); however, a high content of bacillithiol (~70%) was still observed in the b. anthracis ∆ba1557 strain. genomic analysis led to the proposal that another deacetylase could exhibit cross-functionality in bacillithiol biosynthesis. in the present study, ba155 ...201323758290
transient lipopolysaccharide-induced resistance to aerosolized bacillus anthracis in new zealand white rabbits.previous studies have demonstrated that prior infection by various bacterial pathogens induces nonspecific resistance to subsequent infection by other gram-negative and gram-positive bacterial pathogens. in the present study, we evaluated whether underlying inflammation enhanced host resistance to inhalational bacillus anthracis infection in new zealand white rabbits (spf; bordetella- and pasteurella-free). accordingly, rabbits were pretreated with either the inflammagen bacterial lps (60,000 eu ...201323759528
total synthesis of the ribosomally synthesized linear azole-containing peptide plantazolicin a from bacillus amyloliquefaciens. 201323761292
live attenuated tularemia vaccines: recent developments and future goals.in the aftermath of the 2001 anthrax attacks in the u.s., numerous efforts were made to increase the level of preparedness against a biological attack both in the us and worldwide. as a result, there has been an increase in research interest in the development of vaccines and other countermeasures against a number of agents with the potential to be used as biological weapons. one such agent, francisella tularensis, has been the subject of a surge in the level of research being performed, leading ...201323764535
razor ex anthrax air detection system for detection of bacillus anthracis spores from aerosol collection samples: collaborative study.the razor ex anthrax air detection system was validated in a collaborative study for the detection of bacillus anthracis in aerosol collection buffer. phosphate-buffered saline was charged with 1 mg/ml standardized dust to simulate an authentic aerosol collection sample. the dust-charged buffer was spiked with either b. anthracis ames at 2000 spores/ml or bacillus cereus at 20 000 spores/ml. twelve collaborators participated in the study, with four collaborators at each of three sites. each coll ...201323767365
detection of protective antigen, an anthrax specific toxin in human serum by using surface plasmon resonance.in this study, surface plasmon resonance (spr) technology was used for the sensitive detection of protective antigen (pa), an anthrax specific toxin in spiked human serum samples. a monoclonal antibody raised against bacillus anthracis pa was immobilized on carboxymethyldextran-modified gold chip, and its interaction with pa was characterized in situ by spr. by using kinetic evaluation software, kd (equilibrium constant) and bmax (maximum binding capacity of analyte) were found to be 20 fm and 1 ...201323773677
small-molecule inhibitors of lethal factor protease activity protect against anthrax infection.bacillus anthracis, the causative agent of anthrax, manifests its pathogenesis through the action of two secreted toxins. the bipartite lethal and edema toxins, a combination of lethal factor or edema factor with the protein protective antigen, are important virulence factors for this bacterium. we previously developed small-molecule inhibitors of lethal factor proteolytic activity (lfis) and demonstrated their in vivo efficacy in a rat lethal toxin challenge model. in this work, we show that th ...201323774434
increased camp in monocytes augments notch signaling mechanisms by elevating rbp-j and transducin-like enhancer of split (tle).in cells of the innate immune system, pathological increases in intracellular camp attenuate immune responses and contribute to infections by bacteria such as bacillus anthracis. in this work, camp from b. anthracis edema toxin (et) is found to activate the notch signaling pathway in both mouse macrophages and human monocytes. et as well as a cell-permeable activator of pka induce notch target genes (hes1, hey1, il2ra, and il7r) and are able to significantly enhance the induction of these notch ...201323775085
anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete.licensed to kill: a new antibiotic, anthracimycin (see scheme), produced by a marine-derived actinomycete in saline culture, shows significant activity toward bacillus anthracis, the bacterial pathogen responsible for anthrax infections. chlorination of anthracimycin gives a dichloro derivative that retains activity against gram-positive bacteria, such as anthrax, but also shows activity against selected gram-negative bacteria.201323776159
differentiation of springtime vegetation indices associated with summer anthrax epizootics in west texas, usa, deer.anthrax outbreaks in white-tailed deer, odocoileus virginianus, are frequent in west texas, usa, particularly across the edwards plateau. however, the outbreak severity varies among years. we summarize the outbreak history in white-tailed deer at a ranch north of del rio, texas, from 2001 to 2010 and compare mortality rates to remotely sensed vegetation indices derived from moderate resolution imaging spectroradiometer satellite data. it has long been posited that the occurrence of mid- to high- ...201323778625
protective-antigen (pa) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection.an intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. protective antigen (pa)-based vaccines are most favored as immune responses directed against pa are singularly protective, although the actual protective mechanism remains to be unraveled. herein we show that contrary to the prevailing view, an efficacious pa-based vaccine confers protection against inhalation ...201323787486
zinc regulates the activity of kinase-phosphatase pair (basprkc/basprpc) in bacillus anthracis.bacillus anthracis ser/thr protein kinase prkc (basprkc) is important for virulence of the bacterium within the host. homologs of prkc and its cognate phosphatase prpc (basprpc) are the most conserved mediators of signaling events in diverse bacteria. basprkc homolog in bacillus subtilis regulates critical processes like spore germination and basprpc modulates the activity of basprkc by dephosphorylation. so far, biochemical and genetic studies have provided important insights into the roles of ...201323793375
immuno capture pcr for rapid and sensitive identification of pathogenic bacillus anthracis.immuno capture pcr (ipcr) is a technique capable of detecting the pathogens with high specificity and sensitivity. rapid and accurate detection of bacillus anthracis was achieved using anti-ea1 antibodies to capture the cells and two primer sets targeting the virulence factors of the pathogen i.e., protective antigen (pag) and capsule (cap) in an ipcr format. monoclonal antibodies specific to b. anthracis were generated against extractable antigen 1 protein and used as capture antibody onto 96 w ...201323793942
de novo asymmetric synthesis of oligo-rhamno di- and tri-saccharides related to the anthrax tetrasaccharide.an asymmetric synthesis of the di- and trisaccharide portion of the naturally occurring anthrax tetrasaccharide from acetylfuran has been developed. the construction of the di- and trisaccharide subunits is based upon our previously disclosed route to anthrax tetrasaccharide. the approach uses iterative diastereoselective palladium-catalyzed glycosylations, luche reductions, diastereoselective dihydroxylations, and regioselective protections for the assembly of the rhamno- di- and tri-saccharide ...201323794755
a preliminary study on the insect fauna of al-baha province, saudi arabia, with descriptions of two new species.a preliminary study was carried out on the insect fauna of al-baha province, south-western part of saudi arabia. a total number of 582 species and subspecies (few identified only to the genus level) belonging to 129 families and representing 17 orders were recorded. two of these species are described as new, namely: monomorium sarawatensis sharaf & aldawood, sp. n. [formicidae, hymenoptera] and anthrax alruqibi el-hawagry sp. n. [bombyliidae, diptera]. another eight species are recorded for the ...201323794807
suspect vector transmission of human cutaneous anthrax during an animal outbreak in southern italy.during an outbreak of sheep anthrax in basilicata, southern italy, the owner of a flock located about 3 km away from the affected farm developed skin lesions attributable to cutaneous anthrax. the dna extracted from the human scabs confirmed the diagnosis, and a 15-loci multiple locus variable number tandem repeat (vntr) analysis (mlva) following single-nucleotide repeat (snr) analysis yielded the same genotype as that found in the dead sheep. the breeder, who had not had contact with infected o ...201323808978
rapid detection and identification of bacillus anthracis in food using pyrosequencing technology.the development of advanced methodologies for the detection of bacillus anthracis has been evolving rapidly since the release of the anthrax spores in the mail in 2001. recent advances in detection and identification techniques could prove to be an essential component in the defense against biological attacks. sequence based such as pyrosequencing, which has the capability to determine short dna stretches in real-time using biotinylated pcr amplicons, has potential biodefense applications. using ...201323810955
rapid identification of bacillus anthracis spores in suspicious powder samples by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms).rapid and reliable identification of bacillus anthracis spores in suspicious powders is important to mitigate the safety risks and economic burdens associated with such incidents. the aim of this study was to develop and validate a rapid and reliable laboratory-based matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) analysis method for identifying b. anthracis spores in suspicious powder samples. a reference library containing 22 different bacillus sp. s ...201323811517
inhalational anthrax in a vaccinated soldier. 201323813313
analysis of the errors in the electrostatically embedded many-body expansion of the energy and the correlation energy for zn and cd coordination complexes with five and six ligands and use of the analysis to develop a generally successful fragmentation strategy.in the present paper, we apply the electrostatically embedded many-body expansion of the correlation energy (ee-mb-ce) to the calculation of zinc-ligand and cadmium-ligand bond dissociation energies, and we analyze the errors due to various fragmentation schemes in a variety of neutral, positively charged, and negatively charged zn(2+) and cd(2+) coordination complexes. as a result of the analysis, we are able to present a new, simple, and unambiguous fragmentation strategy. following this strat ...201323814509
3-substituted indole inhibitors against francisella tularensis fabi identified by structure-based virtual screening.in this study, we describe novel inhibitors against francisella tularensis schus4 fabi identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. two 3-substituted indoles, 54 and 57, preferentially bound the nad(+) form of the enzyme and inhibited growth of f. tularensis schus4 at concentrations near that of their measured ki. while 57 was species-specific, 54 showed a broader sp ...201323815100
cbrne tc3: a hybrid approach to casualty care in the cbrne environment.the implementation of tactical combat casualty care (tccc) guidelines for the operation enduring freedom and operation iraqi freedom contingency operations has dramatically reduced preventable combat deaths. a study of these principles and their application to medical treatment in the chemical, biological, radiological, nuclear, and high-yield explosives (cbrne), weapons of mass destruction (wmd) environment is presented as a potential readiness and force multiplier for units engaged in this are ...201323817878
direct proteolytic cleavage of nlrp1b is necessary and sufficient for inflammasome activation by anthrax lethal factor.inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the caspase-1 (casp1) protease. activated casp1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (nlr) or aim2-like receptor (alr) protein families. certain nlrs and alrs have been shown to function as direct re ...201323818853
genetic diversity of korean bacillus anthracis isolates from soil evaluated with a single nucleotide repeat analysis.bacillus (b.) anthracis, the etiological agent of anthrax, is one of the most genetically monomorphic bacteria species in the world. due to the very limited genetic diversity of this species, classification of isolates of this bacterium requires methods with high discriminatory power. single nucleotide repeat (snr) analysis is a type of variable-number tandem repeat assay that evaluates regions with very high mutation rates. to subtype a collection of 21 isolates that were obtained during a b. a ...201323820210
engineering unnatural variants of plantazolicin through codon reprogramming.plantazolicin (pzn) is a polyheterocyclic natural product derived from a ribosomal peptide that harbors remarkable antibiotic selectivity for the causative agent of anthrax, bacillus anthracis. to simultaneously establish the structure-activity relationship of pzn and the substrate tolerance of the biosynthetic pathway, an escherichia coli expression strain was engineered to heterologously produce pzn analogues. variant pzn precursor genes were produced by site-directed mutagenesis and later scr ...201323823732
a new murine model for gastrointestinal anthrax infection.the scientific community has been restricted by the lack of a practical and informative animal model of gastrointestinal infection with vegetative bacillus anthracis. we herein report the development of a murine model of gastrointestinal anthrax infection by gavage of vegetative sterne strain of bacillus anthracis into the complement-deficient a/j mouse strain. mice infected in this manner developed lethal infections in a dose-dependent manner and died 30 h-5 d following gavage. histological fin ...201323825096
biowarfare and bioterrorism.bioterrorism is not only a reality of the times in which we live but bioweapons have been used for centuries. critical care physicians play a major role in the recognition of and response to a bioterrorism attack. critical care clinicians must be familiar with the diagnosis and management of the most likely bioterrorism agents, and also be adequately prepared to manage a mass casualty situation. this article reviews the epidemiology, diagnosis, and treatment of the most likely agents of biowarfa ...201323830660
antxr1, a stem cell-enriched functional biomarker, connects collagen signaling to cancer stem-like cells and metastasis in breast cancer.cancer stem-like cells are thought to contribute to tumor recurrence. the anthrax toxin receptor 1 (antxr1) has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. primary stem cell-enriched basal cells (cd49f(+)/epcam(-)/lin(-)) expressed higher levels of antxr1 compared with mature luminal cells. cd49f(+)/epcam(-), cd44(+)/epcam(-), cd44(+)/cd24(-), or aldefluor-positive subpopulations of breast cancer cells were enriched for antxr1 expression. cd4 ...201323832666
new generation of oral mucosal vaccines targeting dendritic cells.as most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. both local mucosal immunity and robust systemic ...201323835515
the use of complementary and alternative medicine among dermatology outpatients in eastern turkey.over the past decade, complementary and alternative medicine (cam) has become increasingly popular around the world.201423836839
high temperature unfolding of a truncated hemoglobin by molecular dynamics simulation.heme containing proteins are associated with peroxidase activity. the proteins like hemoglobin, myoglobins, cytochrome c and micro-peroxidase other than peroxidases have been shown to exhibit weak peroxidase-like activity. this weak peroxidase-like activity in hemoglobin-like molecules is due to heme moiety. we conducted molecular dynamics (md) studies to decipher the unfolding path of ba-glb (a truncated hemoglobin from bacillus anthracis) and the role of heme moiety to its unfolding path. the ...201323839248
designed azolopyridinium salts block protective antigen pores in vitro and protect cells from anthrax toxin.several intracellular acting bacterial protein toxins of the ab-type, which are known to enter cells by endocytosis, are shown to produce channels. this holds true for protective antigen (pa), the binding component of the tripartite anthrax-toxin of bacillus anthracis. evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric pa63 binding/translocation component are r ...201323840407
novel strategies for enhanced removal of persistent bacillus anthracis surrogates and clostridium difficile spores from skin.removing spores of clostridium difficile and bacillus anthracis from skin is challenging because they are resistant to commonly used antimicrobials and soap and water washing provides only modest efficacy. we hypothesized that hygiene interventions incorporating a sporicidal electrochemically generated hypochlorous acid solution (vashe(®)) would reduce the burden of spores on skin.201323844234
inhibitors of bacillus anthracis edema factor.edema factor (ef) is a calmodulin (cam)-activated adenylyl cyclase (ac) toxin from bacillus anthracis that contributes to anthrax pathogenesis. anthrax is an important medical problem, but treatment of b. anthracis infections is still unsatisfying. thus, selective ef inhibitors could be valuable drugs in the treatment of anthrax infection, most importantly shock. the catalytic site of ef, the ef/cam interaction site and allosteric sites constitute potential drug targets. to this end, most effort ...201323850654
a human/murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro.human anthrax infection caused by exposure to bacillus anthracis cannot always be treated by antibiotics. this is mostly because of the effect of the remaining anthrax toxin in the body. lethal factor (lf) is a component of lethal toxin (letx), which is the major virulence of anthrax toxin. a murine igg monoclonal antibody (mab) against lf with blocking activity (coded lf8) was produced in a previous study. in this report, a human/murine chimeric fab mab (coded lf8-fab) was developed from lf8 by ...201323861692
constant domains influence binding of mouse-human chimeric antibodies to the capsular polypeptide of bacillus anthracis.our laboratory previously described the binding characteristics of the murine igg3 monoclonal antibody (muab) f26g3. this antibody binds the poly-glutamic acid capsule (pga) of bacillus anthracis, an essential virulence factor in the progression of anthrax. f26g3 igg3 muab binds pga with a relatively high functional affinity (10 nm), produces a distinct "rim" quellung reaction, and is protective in a murine model of pulmonary anthrax. this study engineered an igg subclass family of f26g3 mouse-h ...201323863605
ground anthrax bacillus refined isolation (gabri) method for analyzing environmental samples with low levels of bacillus anthracis contamination.in this work are reported the results of a qualitative analytical method capable of detecting bacillus anthracis spores when they are present in very low concentration in the soil. the ground anthrax bacillus refined isolation (gabri) method, assessed in our laboratory, was compared with the classic method. the comparison involved artificially anthrax-contaminated soil samples (500 spores/7.5 grams soil) and naturally contaminated soil samples collected in bangladesh during a field investigation ...201323865983
validation of potential inhibitors for srta against bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation.the development of srta inhibitors targeting the biothreat organism namely bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, adme, and molecular dynamics studies. in this study, experimentally reported ba-srta inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. the obtained aaahr hypothesis was a pure theoretical concept that accounts ...201423869520
optimizing snp microarray probe design for high accuracy microbial genotyping.microarrays to characterize single nucleotide polymorphisms (snps) provide a cost-effective and rapid method (under 24h) to genotype microbes as an alternative to sequencing. we developed a pipeline for snp discovery and microarray design that scales to 100's of microbial genomes. here we tested various snp probe design strategies against 8 sequenced isolates of bacillus anthracis to compare sequence and microarray data. the best strategy allowed probe length to vary within 32-40 bp to equalize ...201323871857
characterization of amiba2446, a novel bacteriolytic enzyme active against bacillus species.there continues to be a need for developing efficient and environmentally friendly treatments for bacillus anthracis, the causative agent of anthrax. one emerging approach for inactivation of vegetative b. anthracis is the use of bacteriophage endolysins or lytic enzymes encoded by bacterial genomes (autolysins) with highly evolved specificity toward bacterium-specific peptidoglycan cell walls. in this work, we performed in silico analysis of the genome of bacillus anthracis strain ames, using a ...201323872558
an electrochemiluminescence assay for the detection of bio threat agents in selected food matrices and in the screening of clostridium botulinum outbreak strains associated with type a botulism.specific screening methods for complex food matrices are needed that enable unambiguous and sensitive detection of bio threat agents (btas) such as bacillus anthracis spores and microbial toxins (e.g. staphylococcal enterotoxin b (seb) and clostridial botulinum neurotoxins (bonts)). the present study describes an image-based 96-well meso scale discovery (msd) electrochemiluminescence (ecl) assay for simultaneous detection of btas in dairy milk products.201423873138
transcriptomic and phenotypic analysis of paralogous spx gene function in bacillus anthracis sterne.spx of bacillus subtilis is a redox-sensitive protein, which, under disulfide stress, interacts with rna polymerase to activate genes required for maintaining thiol homeostasis. spx orthologs are highly conserved among low %gc gram-positive bacteria, and often exist in multiple paralogous forms. in this study, we used b. anthracis sterne, which harbors two paralogous spx genes, spxa1 and spxa2, to examine the phenotypes of spx null mutations and to identify the genes regulated by each spx paralo ...201323873705
engineering biomaterial-associated complement activation to improve vaccine efficacy.the complement system plays an important role in innate and adaptive immunity, which suggests that complement activation could be exploited as a potential strategy for vaccine adjuvants. here we explored the potential of chitosan-based microparticles (cs-nh2 mps) as a vaccine adjuvant with an active surface for complement activation due to the abundance of amino groups. in vaccination studies, using recombinant anthrax protective antigen as a model antigen, compared with the control microparticl ...201323875970
toxin inhibition of antimicrobial factors induced by bacillus anthracis peptidoglycan in human blood.here, we describe the capacity of bacillus anthracis peptidoglycan (bapgn) to trigger an antimicrobial response in human white blood cells (wbcs). analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not b and t cells, were highly responsive to bapgn and produced a variety of cytokines and chemokines. this bapgn-induced response was suppressed by anthrax lethal toxin (lt) and edema toxin (et), with the most pronounced effect on human monocytes, and this corres ...201323876807
structural and functional insight into an unexpectedly selective n-methyltransferase involved in plantazolicin biosynthesis.plantazolicin (pzn), a polyheterocyclic, n(α),n(α)-dimethylarginine-containing antibiotic, harbors remarkably specific bactericidal activity toward strains of bacillus anthracis, the causative agent of anthrax. previous studies demonstrated that genetic deletion of the s-adenosyl-l-methionine-dependent methyltransferase from the pzn biosynthetic gene cluster results in the formation of desmethylpzn, which is devoid of antibiotic activity. here we describe the in vitro reconstitution, mutational ...201323878226
in vitro and in vivo activities of recombinant anthrax protective antigen co-expressed with thioredoxin in escherichia coli.because of the central role it plays in the formation of lethal toxin and edema toxin, protective antigen (pa) is the principal target for the development of vaccines against anthrax. in the present study, we explored and compared the in vitro and in vivo activities of recombinant anthrax protective antigen (rpa) and receptor binding domain of protective antigen (pa4). as a result, the fully soluble rpa and pa4 proteins were successfully expressed in escherichia coli by co-expression with thiore ...201323880942
anthrax: has the clinical milieu changed since 2001?since the anthrax attacks of 2001 (amerithrax), several important improvements in the knowledge of bacillus anthracis and the clinical condition it causes have occurred. while much remains to be known about the optimal management of anthrax patients, several approaches that were not widely utilized, available, or known in 2001 would be used in the treatment of critically ill anthrax patients in 2012.201223882372
present-day conservative treatment retinopathy of prematurity.retinopathy of prematurity occurs in prematurely born babies. etiology of disease is multifactorial and frequency of retinopathy of prematurity diagnosis increases. retinopathy is one of causes for major loss of vision and amaurosis in newborns around the world. low efficacy of treatment leads to necessity for looking for new solutions and modern therapy use in treatment of this disease. so far, therapies used are: laser and cryotherapy and cases of retina detachment, the course is combined with ...201323882745
identification of a ligand on the wip1 bacteriophage highly specific for a receptor on bacillus anthracis.tectiviridae is a family of tailless bacteriophages with gram-negative and gram-positive hosts. the family model prd1 and its close relatives all infect a broad range of enterobacteria by recognizing a plasmid-encoded conjugal transfer complex as a receptor. in contrast, tectiviruses with gram-positive hosts are highly specific to only a few hosts within the same bacterial species. the cellular determinants that account for the observed specificity remain unknown. here we present the genome sequ ...201323893110
differentiation of strains from the bacillus cereus group by rflp-pfge genomic fingerprinting.bacillus mycoides, bacillus pseudomycoides, bacillus weihenstephanensis, bacillus anthracis, bacillus thuringiensis, and bacillus cereus belong to the b. cereus group. the last three species are characterized by different phenotype features and pathogenicity spectrum, but it has been shown that these species are genetically closely related. the macrorestriction analysis of the genomic dna with the noti enzyme was used to generate polymorphism of restriction profiles for 39 food-borne isolates (b ...201323893780
regulation of bacillus subtilis bacillithiol biosynthesis operons by spx.bacillithiol is the major low molecular mass thiol produced by many firmicutes bacteria, including the model organism bacillus subtilis and pathogens such as bacillus anthracis and staphylococcus aureus. we have previously shown that four genes (bsha, bshb1, bshb2 and bshc) are involved in bacillithiol biosynthesis. here, we report that these four genes are encoded within three, unlinked operons all expressed from canonical σ(a)-dependent promoters as determined by 5'race (rapid amplification of ...201323894131
assessing agreement of repeated binary measurements with an application to the cdc's anthrax vaccine clinical trial.cohen's kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. however, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. this study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions ...201323898025
reverse transcription-pcr-electrospray ionization mass spectrometry for rapid detection of biothreat and common respiratory pathogens.electrospray ionization mass spectrometry (esi-ms) analysis of reverse transcription (rt)-pcr amplicons from human respiratory samples allows for broad pathogen identification approximately 8 h after collection. we investigated the performance characteristics of a high-throughput rt-pcr-coupled esi-ms assay for distinguishing biothreat (bt) agents from common bacterial, fungal, and viral respiratory pathogens in bronchoalveolar lavage (bal) fluid specimens from subjects with suspected respirator ...201323903543
anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.anthrax lethal toxin (lt), secreted by bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. lt specifically cleaves the docking domains of mapkk (meks); thus, we hypothesized that lt directly impairs cardiac function through dysregulation of mapk signaling mechanisms.201323907041
investigation of an outbreak of cutaneous anthrax in banlu village, lianyungang, china, 2012.after notification of a suspected case of anthrax following the slaughtering of a sick cow in banlu village, an area that has not had any anthrax cases for decades, we aimed to confirm the outbreak, determine the transmission mechanism and implement control measures.201223908932
nucleotidyl cyclase activity of particulate guanylyl cyclase a: comparison with particulate guanylyl cyclases e and f, soluble guanylyl cyclase and bacterial adenylyl cyclases cyaa and edema factor.guanylyl cyclases (gcs) regulate many physiological processes by catalyzing the synthesis of the second messenger cgmp. the gc family consists of seven particulate gcs (pgcs) and a nitric oxide-activated soluble gc (sgc). rat sgc α1β1 possesses much broader substrate specificity than previously assumed. moreover, the exotoxins cyaa from bordetella pertussis and edema factor (ef) from bacillus anthracis possess nucleotidyl cyclase (nc) activity. pgc-a is a natriuretic peptide-activated homodimer ...201323922959
periocular cutaneous anthrax in jimma zone, southwest ethiopia: a case series.anthrax is a zoonotic disease caused by bacillus anthracis. naturally occurring human infection is rare and is generally the result of contact with anthrax-infected animals or animal products.201323924443
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