Publications

crosstalk between the coagulation and complement systems in sepsis.	sepsis is a potent activator of the hemostatic and complement systems. while local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects that lead to multiple organ failure and death. we have extensively studied the activation of complement and coagulation cascades in experimental sepsis using baboons challenged with live bacteria, such as gram-negative escherichia coli or gram-positive staphylococcus au ...	2014	24759136
age of bioterrorism: are you prepared? review of bioweapons and their clinical presentation for otolaryngologists.	this review on category a bioweapons is intended to help otolaryngologists (1) understand the concepts of bioterrorism, (2) identify a bioterrorism attack, and (3) recognize specific otolaryngologic symptoms and signs of category a bioweapons.	2014	24757076
reductive methylation and mutation of an anthrax toxin fusion protein modulates its stability and cytotoxicity.	we characterized an anti-cancer fusion protein consisting of anthrax lethal factor (lf) and the catalytic domain of pseudomonas exotoxin a by (i) mutating the n-terminal amino acids and by (ii) reductive methylation to dimethylate all lysines. dimethylation of lysines was achieved quantitatively and specifically without affecting binding of the fusion protein to pa or decreasing the enzymatic activity of the catalytic moiety. ubiquitination in vitro was drastically decreased for both the n-termi ...	2014	24755540
surveillance and diagnosis of plague and anthrax in tanzania and zambia.		2014	28235266
targeted silencing of anthrax toxin receptors protects against anthrax toxins.	anthrax spores can be aerosolized and dispersed as a bioweapon. current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (tem8) and capillary morphogenesis protein 2 (cmg2). we hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using rna interference (rna ...	2014	24742682
antxr2 is a potential causative gene in the genome-wide association study of the blood pressure locus 4q21.	hypertension is the most prevalent cardiovascular disease worldwide, but its genetic basis is poorly understood. recently, genome-wide association studies identified 33 genetic loci that are associated with blood pressure. however, it has been difficult to determine whether these loci are causative owing to the lack of functional analyses. of these 33 genome-wide association studies (gwas) loci, the 4q21 locus, known as the fibroblast growth factor 5 (fgf5) locus, has been linked to blood pressu ...	2014	24739539
high-throughput sequencing of bacillus anthracis in france: investigating genome diversity and population structure using whole-genome snp discovery.	single nucleotide polymorphisms (snps) are ideal signatures for subtyping monomorphic pathogens such as bacillus anthracis. here we report the use of next-generation sequencing technology to investigate the historical, geographic and genetic diversity of bacillus anthracis in france. 122 strains isolated over a 60-years period throughout the country were whole-genome sequenced and comparative analyses were carried out with a focus on snps discovery to discriminate regional sub-groups of strains.	2014	24734872
efficacy and safety of avp-21d9, an anthrax monoclonal antibody, in animal models and humans.	anthrax is an acute infectious disease caused by the spore-forming bacterium bacillus anthracis. timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. however, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. an anthrax antitoxin, avp-21d9, also known as thravixa (fully human anthrax monoclonal antibody), is being ...	2014	24733473
[knowledge of zoonoses transmission routes and of the species concerned among rural workers].	the aim of this study was to evaluate the level of awareness of zoonoses among rural workers and their potential associations with socio-demographic factors. a cross-sectional study was performed by holding personal interviews (n=110, n=94) using a structured questionnaire. the statistical analysis included the χ(2) test, the student's t test and pearson and spearman correlations. the highest level of awareness was found for trichinosis, rabies and scabies. species transmitting brucellosis, tube ...	2014	24721268
spectrally-resolved fluorescence cross sections of aerosolized biological live agents and simulants using five excitation wavelengths in a bsl-3 laboratory.	a system for measuring spectrally-resolved fluorescence cross sections of single bioaerosol particles has been developed and employed in a biological safety level 3 (bsl-3) facility at edgewood chemical and biological center (ecbc). it is used to aerosolize the slurry or solution of live agents and surrogates into dried micron-size particles, and to measure the fluorescence spectra and sizes of the particles one at a time. spectrally-resolved fluorescence cross sections were measured for (1) bac ...	2014	24718194
high-throughput screening of a crispr/cas9 library for functional genomics in human cells.	targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. in contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. here we report the development of a focused crispr/cas-based (clustered regularly interspaced short palindromic repeats/crispr-associated) lentiviral library in hum ...	2014	24717434
proteases as activators for cytotoxic prodrugs in antitumor therapy.	proteases are often overexpressed in tumor cells and/or the stromal compartment and can thus be exploited in tumor therapy to activate cytotoxic prodrugs as, for example, in cytolytic fusion proteins, and for tumor imaging. specifically, we discuss cathepsin b-activated prodrug conjugates, antibody-directed prodrug therapy, protease-activated peptide-thapsigargin conjugates, protease-activated cytotoxic receptor ligands and other cytotoxic proteins, protease-mediated activation of anthrax toxin, ...	2014	24709544
design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.	the design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. the ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. to that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding pept ...	2014	24706570
rapid detection of bacillus spore aerosol particles by direct in situ analysis using maldi-tof mass spectrometry.	accurate and rapid analytical methods are essential for the detection and identification of biological warfare agents (bwa). although various studies have investigated the use of maldi-tof ms for bacterial classification, only a few studies have examined the applicability of method for the identification of bwas. this study aimed to generate, collect and analyse bacillus spore aerosol particles of 2-10 μm, the optimal size of a bwa. bacillus spore aerosol particles of 2-10 μm were rapidly analys ...	2014	24702137
the planning, execution, and evaluation of a mass prophylaxis full-scale exercise in cook county, il.	increasing threats of bioterrorism and the emergence of novel disease agents, including the recent international outbreaks of h7n9 influenza and mers-cov, have stressed the importance and highlighted the need for public health preparedness at local, regional, and national levels. to test plans that were developed for mass prophylaxis scenarios, in april 2013 the cook country department of public health (ccdph) and the triple community (tripcom) medical reserve corps (mrc) executed a full-scale m ...	2014	24697783
standard method for deposition of dry, aerosolized, silica-coated bacillus spores onto inanimate surfaces.	to evaluate a standard aerosolization method for uniformly depositing threat-representative spores onto surfaces.	2014	24690070
anthrax lethal and edema toxins in anthrax pathogenesis.	the pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. b. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the usa. the exotoxins secreted by b. anthracis use capillary morphogenesis protein 2 (cmg2) as the major ...	2014	24684968
the il-23/th17 axis is involved in the adaptive immune response to bacillus anthracis in humans.	the neutralization of toxins is considered essential for protection against lethal infection with bacillus anthracis (ba), a select agent and bioterrorism threat. however, toxin-neutralizing activity alone would not be expected to provide sterile immunity. therefore, we hypothesized that the development of an adaptive immune response against ba is required for bacterial clearance. we found that human monocyte-derived dendritic cells (hdcs) kill germinated ba bacilli, but not nongerminated ba spo ...	2014	24643777
synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against bacillus anthracis.	due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. as a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against bacillus anthracis. the structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an n-acryloyl-substituted 1,2-dihydrophthalazine ring. vario ...	2014	24642909
a protective antigen mutation increases the ph threshold of anthrax toxin receptor 2-mediated pore formation.	anthrax toxin protective antigen (pa) binds cellular receptors and self-assembles into oligomeric prepores. a prepore converts to a protein translocating pore after it has been transported to an endosome where the low ph triggers formation of a membrane-spanning β-barrel channel. formation of this channel occurs after some pa-receptor contacts are broken to allow pore formation, while others are retained to preserve receptor association. the interaction between pa and anthrax toxin receptor 1 (a ...	2014	24641616
three eyelid localized cutaneous anthrax cases.	anthrax is primarily seen in the developing countries, but it can be a worldwide medical concern due to bioterrorism threats. palpebral anthrax is a rare form of cutaneous anthrax. untreated cutaneous anthrax can be lethal. patients with palpebral anthrax can develop complications including cicatrisation and ectropion. thus, anthrax should be considered in differential diagnosis for patients presenting with preseptal cellulitis in high-risk regions. herein, we report three anthrax cases (with di ...	2014	24641116
therapeutic potential of capillary morphogenesis gene 2 extracellular vwa domain in tumour‑related angiogenesis.	capillary morphogenesis gene 2 (cmg2) is a receptor of anthrax toxin and plays an important role in angiogenesis. it has been shown to be involved in the cell adhesion and motility of various cell types, including epithelia and endothelia. the present study aimed to examine the therapeutic potential of targeting cmg2 to prevent tumour‑related new vasculature. the full-length coding sequence of the human cmg2 gene and different fragments of the cmg2 vwa domain were amplified and constructed into ...	2014	24993339
antimicrobial properties of cuo nanorods and multi-armed nanoparticles against b. anthracis vegetative cells and endospores.	two different kinds of cuo nanoparticles (nps) namely cuo nanorods (ps2) and multi-armed nanoparticles (p5) were synthesized by wet and electrochemical routes, respectively. their structure, morphology, size and compositions were characterized by sem, edx and xrd. the nps demonstrated strong bactericidal potential against bacillus anthracis cells and endospores. ps2 killed 92.17% of 4.5 × 10(4) cfu/ml b. anthracis cells within 1 h at a dose of 1 mg/ml. whereas p5 showed a higher efficacy by kill ...	2014	24991516
serum adenosine deaminase activity in cutaneous anthrax.	adenosine deaminase (ada) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. the aim of this study was to investigate serum ada activity in patients with cutaneous anthrax.	2014	24997584
identification of peptide sequences as a measure of anthrax vaccine stability during storage.	the uk anthrax vaccine is an alum precipitate of a sterile filtrate of bacillus anthracis sterne culture (avp). an increase in shelf life of avp from 3 to 5 years prompted us to investigate the in vivo potency and the antigen content of 12 batches with a shelf life of 6.4 to 9.9 years and one bulk with a shelf life of 23.8 years. all batches, except for a 9.4-year-old batch, passed the potency test. mass spectrometry (ms) and in-gel difference 2-dimensional gel electrophoresis (dige) were used t ...	2014	24637775
structure determination of ba0150, a putative polysaccharide deacetylase from bacillus anthracis.	polysaccharide deacetylases are bacterial enzymes that catalyze the deacetylation of acetylated sugars on the membranes of gram-positive bacteria, allowing them to be unrecognized by host immune systems. inhibition of these enzymes would disrupt such pathogenic defensive mechanisms and therefore offers a promising route for the development of novel antibiotic therapeutics. here, the first x-ray crystal structure of ba0150, a putative polysaccharide deacetylase from bacillus anthracis, is reporte ...	2014	24637747
anti-inflammatory and anti-superbacterial properties of sulforaphane from shepherd's purse.	shepherd's purse, capsella bursa-pastoris (l.) medik., has been considered a health food for centuries in asia and is known to contain the isothiocyanate compound sulforaphane. in this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (scs) isolated from shepherd's purse. scs had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (no), cytokines (interleukin 1β [il-1β], il-6, and il-10), and prostagl ...	2014	24634594
prospects of bacterial and plant protein-based immunotoxins for treatment of cancer.	bacterial- and plant-derived immunotoxins have documented potential for treatment of cancer. we discuss anthrax toxin, ribosome inactivating-toxins, such as saporin and ricin, and adp-ribosylating toxins such as diphtheria toxin and pseudomonas exotoxin, with focus on the latter, which has been most thoroughly investigated. regarding their potential as anticancer agents, critical issues such as immunogenicity and toxicity are outlined. we describe different generations of immunotoxins, the pathw ...	2014	24633317
inflammasome sensor nlrp1 controls rat macrophage susceptibility to toxoplasma gondii.	toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. rats vary in their susceptibility to this parasite. the toxo1 locus conferring toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing nlrp1. this gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (lt) induced rapid cell death (pyroptosis). we show here that rat strain differences in toxoplasma infected macrophage sensi ...	2014	24626226
phase 3 trial evaluating the immunogenicity and safety of a three-dose biothrax® regimen for post-exposure prophylaxis in healthy adults.	this study was conducted to support licensure of a post-exposure prophylaxis indication for biothrax(®) (anthrax vaccine adsorbed) concurrent with antimicrobials for individuals exposed to aerosolized anthrax spores.	2014	24613523
cryo-em analysis of the organization of bcla and bxpb in the bacillus anthracis exosporium.	bacillus anthracis and other pathogenic bacillus species form spores that are surrounded by an exosporium, a balloon-like layer that acts as the outer permeability barrier of the spore and contributes to spore survival and virulence. the exosporium consists of a hair-like nap and a paracrystalline basal layer. the filaments of the nap are comprised of trimers of the collagen-like glycoprotein bcla, while the basal layer contains approximately 20 different proteins. one of these proteins, bxpb, f ...	2014	24607412
[epidemiologic situation on dangerous infectious diseases on the territory of republic of abkhazia].	data from literature and results of epizootological examination of the territory of republic of abkhazia in 2011 and 2012 that confirm the presence in the republic of natural foci of hemorrhagic fever with renal syndrome, west nile fever, crimean hemorrhagic fever, tick-borne encephalitis, q fever, tahyna, inkoo, bhanja, sindbis fever, anaplasmosis, tick-borne borreliosis, tularemia and leptospirosis are presented. rabies and anthrax are actual for abkhazia. spread of aedes aegypti mosquitos in ...	2014	24605653
genome sequence of a bacillus anthracis outbreak strain from zambia, 2011.	in august 2011, an anthrax outbreak occurred among hippopotamus amphibius hippopotamuses and humans in zambia. here, we report the draft genome sequence of the bacillus anthracis outbreak strain czc5, isolated from tissues of h. amphibius hippopotamuses that had died in the outbreak area.	2014	24604644
bacillus cereus certhrax adp-ribosylates vinculin to disrupt focal adhesion complexes and cell adhesion.	bacillus cereus is often associated with mild to moderate gastroenteritis; however, some recent isolates cause inhalational anthrax-like diseases and death. these potential emerging human pathogens express multiple virulence factors. b. cereus strain g9241 expresses anthrax toxin, several polysaccharide capsules, and the novel adp-ribosyltransferase, certhrax. in this study, we show that certhrax adp-ribosylates arg-433 of vinculin, a protein that coordinates actin cytoskeleton and extracellular ...	2014	24573681
microevolution during an anthrax outbreak leading to clonal heterogeneity and penicillin resistance.	anthrax is a bacterial disease primarily affecting grazing animals but it can also cause severe disease in humans. we have used genomic epidemiology to study microevolution of the bacterium in a confined outbreak in cattle which involved emergence of an antibiotic-resistant phenotype. at the time of death, the animals contained a heterogeneous population of single nucleotide variants (snvs), some being clonal but most being subclonal. we found that independent isolates from the same carcass had ...	2014	24551231
generation of protective immune response against anthrax by oral immunization with protective antigen plant-based vaccine.	in concern with frequent recurrence of anthrax in endemic areas and inadvertent use of its spores as biological weapon, the development of an effective anthrax vaccine suitable for both human and veterinary needs is highly desirable. a simple oral delivery through expression in plant system could offer promising alternative to the current methods that rely on injectable vaccines extracted from bacterial sources. in the present study, we have expressed protective antigen (pa) gene in indian musta ...	2014	24548460
the bifunctional cell wall hydrolase cwlt is needed for conjugation of the integrative and conjugative element icebs1 in bacillus subtilis and b. anthracis.	the mobile genetic element icebs1 is an integrative and conjugative element (ice) found in bacillus subtilis. one of the icebs1 genes, cwlt, encodes a cell wall hydrolase with two catalytic domains, a muramidase and a peptidase. we found that cwlt is required for icebs1 conjugation. we examined the role of each of the two catalytic domains and found that the muramidase is essential, whereas the peptidase is partially dispensable for transfer of icebs1. we also found that the putative signal pept ...	2014	24532767
enhanced early innate and t cell-mediated responses in subjects immunized with anthrax vaccine adsorbed plus cpg 7909 (av7909).	nuthrax™ (anthrax vaccine adsorbed with cpg 7909 adjuvant) (av7909) is in development. samples obtained in a phase ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of cpg 7909 (pf-03512676) on adaptive immunity. subjects received two intramuscular doses of commercial biothrax(®) (anthrax vaccine adsorbed, ava), or two intramuscular doses of one of four formulations of av7909. ip-10, il-6, and c-reactive protein (crp) levels were elevated 24-48 h after a ...	2014	24530403
responding to biological incidents--what are the current issues in remediation of the contaminated environment?	since 2000 there have been a number of biological incidents resulting in environmental contamination with bacillus anthracis, the causative agent of anthrax. these incidents include the us anthrax attacks in 2001, the us and uk drumming incidents in 2006-2008 and more recently, anthrax contamination of heroin in 2009/2010 and 2012/2013. remediation techniques used to return environments to normal have varied between incidents, with different decontamination technologies being employed. many fact ...	2014	24530001
whole-genome sequencing of the nonproteolytic bacillus anthracis v770-np1-r strain reveals multiple mutations in peptidase loci.	we report the draft whole-genome sequence of the nonproteolytic bacillus anthracis v770-np1-r strain. compared to those of other b. anthracis strains, the genome exhibits unique mutations in multiple targets potentially affecting proteolytic functions. one of these mutations is a deletion that disrupts the nprr quorum-sensing regulator of the npra protease.	2014	24526646
severe systemic bacillus anthracis infection in an intravenous drug user.	there has recently been an outbreak of injectional anthrax infection secondary to contaminated heroin use in the uk and europe. we present a case of a 37-year-old man presenting with pain and swelling in the groin following injection of heroin into the area. he was initially treated for severe cellulitis, however, he failed to respond to appropriate antimicrobial therapy. he went onto develop a widespread rash; it was then that a diagnosis of injectional anthrax infection was considered. appropr ...	2014	24526196
structural properties of prokaryotic promoter regions correlate with functional features.	the structural properties of the dna molecule are known to play a critical role in transcription. in this paper, the structural profiles of promoter regions were studied within the context of their diversity and their function for eleven prokaryotic species; escherichia coli, klebsiella pneumoniae, salmonella typhimurium, pseudomonas auroginosa, geobacter sulfurreducens helicobacter pylori, chlamydophila pneumoniae, synechocystis sp., synechoccocus elongates, bacillus anthracis, and the archaea ...	2014	24516674
rapid homogenous time-resolved fluorescence (htrf) immunoassay for anthrax detection.	infection with bacillus anthracsis spores induces an acute anthrax disease that can cause casualties and death in untreated cases. thus rapid diagnosis of anthrax at early stage of the disease is essential to allow an effective treatment. here we present the development of rapid and sensitive homogenous time-resolved fluorescence (htrf) immunoassays based on the energy transfer process of europium cryptate (euk) donor to alexafluor647 acceptor. the energy transfer process is limited to d < 10 nm ...	2014	24515915
the spectrum of post-vaccination inflammatory cns demyelinating syndromes.	a wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. a pubmed search from 1979 to 2013 revealed seventy one (71) documented cases. the most commonly reported vaccinations that were associated with cns demyelinating diseases included influenza (21 cases), human papilloma virus (hpv) (9 cases), hepatitis a or b (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax ...	2014	24514081
protective antigen and extractable antigen 1 based chimeric protein confers protection against bacillus anthracis in mouse model.	recombinant bivalent chimeric protein was generated comprising of domain 4 of protective antigen (pa4) and carboxy terminal region of extractable antigen 1 (ea1c) by overlap extension pcr. the immunogenicity and protective efficacy of recombinant chimeric protein (pe) and protein mixture (paea) along with the individual components, pa4 and ea1c were evaluated in this study. we found that pe and paea exhibited higher endpoint titer and elevated igg1 response. compared to pa4 and ea1c, the chimeri ...	2014	24513572
injectional anthrax infection due to heroin use induces strong immunological memory.		2014	24513100
characterization and in vitro inhibition studies of bacillus anthracis ftsz: a potential antibacterial target.	ftsz is an essential bacterial cell division protein that is an attractive target for the development of antibacterial agents. ftsz is a homologue of eukaryotic tubulin, has gtpase activity, and forms a ring-type structure to initiate cell division. in this study, the ftsz of bacillus anthracis was cloned into a bacterial expression vector and overexpressed into escherichia coli bl21 (de3) cells. the overexpressed b. anthracis ftsz was soluble and purified to homogeneity using ni-his-tag affinit ...	2014	24510482
inactivation and ultrastructure analysis of bacillus spp. and clostridium perfringens spores.	bacterial endospores are resistant to many environmental factors from temperature extremes to ultraviolet irradiation and are generally more difficult to inactivate or kill than vegetative bacterial cells. it is often considered necessary to treat spores or samples containing spores with chemical fixative solutions for prolonged periods of time (e.g., 1-21 days) to achieve fixation/inactivation to enable electron microscopy (em) examination outside of containment laboratories. prolonged exposure ...	2014	24503289
frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system.	few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. in addition, though most ecological immunology studies employ serological antibody assays, endpoint titre determination is usually based on subjective criteria and needs to be made more objective. despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found world-wide, its natural ecology is not well u ...	2014	24499424
virtual screening of lpxtg competitive srta inhibitors targeting signal transduction mechanism in bacillus anthracis: a combined experimental and theoretical study.	members of the sortase enzyme super family decorate the surfaces of bacillus anthracis cell wall with proteins that play key roles in microbial pathogenesis and its biofilm formation. bacillus anthracis sortase-a (ba-srta) is a potential target for new therapeutics as it is required for b. anthracis survival and replication within macrophages. an understanding of the binding site pocket and substrate recognition mechanism by srta enzymes may serve to be beneficial in the rational development of ...	2014	24490975
functional characterization of walrk: a two-component signal transduction system from bacillus anthracis.	two-component signal transduction systems (tcs), consisting of a sensor histidine protein kinase and its cognate response regulator, are an important mode of environmental sensing in bacteria. additionally, they have been found to regulate virulence determinants in several pathogens. bacillus anthracis, the causative agent of anthrax and a bioterrorism agent, harbours 41 pairs of tcs. however, their role in its pathogenicity has remained largely unexplored. here, we show that walrk of b. anthrac ...	2014	24490131
characterization of toll-like receptors 1-10 in spotted hyenas.	previous research has shown that spotted hyenas (crocuta crocuta) regularly survive exposure to deadly pathogens such as rabies, canine distemper virus, and anthrax, suggesting that they have robust immune defenses. toll-like receptors (tlrs) recognize conserved molecular patterns and initiate a wide range of innate and adaptive immune responses. tlr genes are evolutionarily conserved, and assessing tlr expression in various tissues can provide insight into overall immunological organization and ...	2014	24488231
single nucleotide repeat analysis of b. anthracis isolates in canada through comparison of pyrosequencing and sanger sequencing.	several technology platforms have been developed to resolve the phylogenetic placement of b. anthracis. however, these methods lack the resolution to identify differences between closely related strains within an outbreak due to the highly clonal nature of b. anthracis. single nucleotide repeats (snrs) are a type of rapidly evolving genetic marker that can be used to track epidemiological distribution in the event of an outbreak. four snr targets were used to detect and type 35 b. anthracis isol ...	2014	24485934
dances with anthrax: wolves (canis lupus) kill anthrax bacteremic plains bison (bison bison bison) in southwestern montana.	bacillus anthracis, the cause of anthrax, was recovered from two plains bison (bison bison bison) cows killed by wolves (canis lupus) in montana, usa, without associated wolf mortality in july 2010. this bison herd experienced an epizootic in summer 2008, killing ∼ 8% of the herd, the first documented in the region in several decades. no wolf deaths were associated with the 2008 event. surveillance has continued since 2008, with research, ranch, and wildlife personnel diligent during summer. as ...	2014	24484485
plant-derived monoclonal antibodies for prevention and treatment of infectious disease.	numerous monoclonal antibodies (mabs) that recognize and neutralize infectious pathogens have been isolated and developed over the years. the fact that infectious diseases can involve large populations of infected individuals is an important factor that has motivated the search for both cost-effective and scalable methods of antibody production. the current technologies for production of antibodies in plants allow for very rapid expression and evaluation that can also be readily scaled for multi ...	2014	26082108
platelet-activating factor contributes to bacillus anthracis lethal toxin-associated damage.	the lethal toxin (letx) of bacillus anthracis plays a central role in the pathogenesis of anthrax-associated shock. platelet-activating factor (paf) is a potent lipid mediator that has been implicated in endotoxin-associated shock. in this study, we examined the contribution of paf to the manifestations of lethal toxin challenge in wt mice. letx challenge resulted in transient increase in serum paf levels and a concurrent decrease in paf acetylhydrolase activity. inhibition of paf activity using ...	2014	24478317
two-photon intravital imaging of lungs during anthrax infection reveals long-lasting macrophage-dendritic cell contacts.	the dynamics of the lung immune system at the microscopic level are largely unknown because of inefficient methods of restraining chest motion during image acquisition. in this study, we developed an improved intravital method for two-photon lung imaging uniquely based on a posteriori parenchymal tissue motion correction. we took advantage of the alveolar collagen pattern given by the second harmonic generation signal as a reference for frame registration. we describe here for the first time a d ...	2014	24478099
large-scale investigation of leishmania interaction networks with host extracellular matrix by surface plasmon resonance imaging.	we have set up an assay to study the interactions of live pathogens with their hosts by using protein and glycosaminoglycan arrays probed by surface plasmon resonance imaging. we have used this assay to characterize the interactions of leishmania promastigotes with ~70 mammalian host biomolecules (extracellular proteins, glycosaminoglycans, growth factors, cell surface receptors). we have identified, in total, 27 new partners (23 proteins, 4 glycosaminoglycans) of procyclic promastigotes of six ...	2014	24478075
novel giant siphovirus from bacillus anthracis features unusual genome characteristics.	here we present vb_bans-tsamsa, a novel temperate phage isolated from bacillus anthracis, the agent responsible for anthrax infections in wildlife, livestock and humans. tsamsa phage is a giant siphovirus (order caudovirales), featuring a long, flexible and non-contractile tail of 440 nm (not including baseplate structure) and an isometric head of 82 nm in diameter. we induced tsamsa phage in samples from two different carcass sites in etosha national park, namibia. the tsamsa phage genome is th ...	2014	24475065
efficacy of sporicidal wipes for inactivation of a bacillus anthracis surrogate.	to evaluate five commercially available sporicidal wipes and two disinfecting wipes for their ability to inactivate bacillus atrophaeus spores deposited onto various material surfaces.	2014	25220421
the impact of inducing germination of bacillus anthracis and bacillus thuringiensis spores on potential secondary decontamination strategies.	decontamination and remediation of a site contaminated by the accidental or intentional release of fully virulent bacillus anthracis spores are difficult, costly and potentially damaging to the environment. development of novel decontamination strategies that have minimal environmental impacts remains a high priority. although ungerminated spores are amongst the most resilient organisms known, once exposed to germinants, the germinating spores, in some cases, become susceptible to antimicrobial ...	2014	25196092
creating a state medical response system for medical disaster management: the north carolina experience.	the purpose of this work was to examine the creation and evolution of the north carolina state medical response system (smrs). during the past 30 years, states and local communities have developed a somewhat incongruent patchwork of medical disaster response systems. several local or regional programs participated in the national disaster medical system; however, aside from the disaster medical assistance teams, most of these local resources lacked national standards and national direction. the ...	2014	25188616
delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition.	human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. single alanine mutagenesis has been used to identify determinants of anti-bacterial activity and binding to bacterial proteins such as anthrax lethal factor. similar analyses of α-defensin interactions with non-enveloped viruses are limited. we used a comprehensive set of human α-defensin 5 (hd5) and human neutrophil peptide 1 (hnp1) alanine scan mutants in a combination of binding an ...	2014	25188351
long-range stabilization of anthrax protective antigen upon binding to cmg2.	protective antigen (pa) mediates entry of edema factor (ef) and lethal factor (lf) into the cytoplasmic space of the cells through the formation of a membrane-spanning pore. to do this, pa must initially bind to a host cellular receptor. recent mass spectrometry analysis of pa using histidine hydrogen-deuterium exchange (his-hdx) has shown that binding of the von willebrand factor a (vwa) domain of the receptor capillary morphogenesis protein-2 (cmg2) lowers the exchange rates of the imidazole c ...	2014	25186975
comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques.	humoral and cell-mediated immune correlates of protection (cop) for inhalation anthrax in a rhesus macaque (macaca mulatta) model were determined. the immunological and survival data were from 114 vaccinated and 23 control animals exposed to bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. the vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (ava) (biothrax) at 0, 1, and 6 months. the immune responses were modula ...	2014	25185577
surface plasmon resonance-based bacterial aerosol detection.	in the area of bioaerosol research, rapid methods for precise detection attracted much interest over last decades. one of such technologies operating in nearly real-time mode without any specific labelling is known as surface plasmon resonance (spr). recently, we validated a spr protocol in conjunction with our earlier developed personal bioaerosol sampler for rapid detection of airborne viruses. considering that the biological interaction between targeted micro-organism and corresponding antibo ...	2014	25178863
photocatalytic and biocidal activities of novel coating systems of mesoporous and dense tio₂-anatase containing silver nanoparticles.	here we describe the development of novel nanostructured coating systems with improved photocatalytic and antibacterial activities. these systems comprise a layer of sio2 followed by a layer of mesoporous or dense tio2-anatase, and doping with silver nanoparticles (ag nps). the coatings were synthesized via a sol-gel technique by combining colloidal ag nps with tio2 and sio2 sols. the photocatalytic activity was studied through methyl orange decomposition under uv light. results showed a great i ...	2014	25175258
recent developments in anti-dotes against anthrax.	the etiologic agent of disease anthrax, bacillus anthracis, causes recurrent outbreaks among the livestock and intermittent infections in humans across the world. controlling animal infections by vaccination can minimize the incidence of disease in humans. prevention of anthrax in occupationally exposed personnel is achieved through vaccination with either live spores or precipitates of culture supernatants from attenuated strains of b. anthracis. however, anthrax vaccination of the large human ...	2014	25174439
ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (antxr2).	antxr2 variants have been associated with ankylosing spondylitis (as) in two previous genome-wide association studies (gwas) (p∼9×10(-8)). however, a genome-wide significant association (p<5×10(-8)) was not observed. we conducted a more comprehensive analysis of antxr2 in an independent uk sample to confirm and refine this association.	2014	25169729
development of a simple method for the rapid identification of organisms causing anthrax by coagglutination test.	a protective antigen (pa) based coagglutination test was optimized in the present study for the specific and sensitive identification of bacteria causing anthrax in a cost effective and less risky manner. the test showed 100% specificity and sensitivity up to 9 × 10(3) formalinized vegetative cells or 11 ng of pa. the optimized test also detected anthrax toxin directly from the serum as well as blood of anthrax infected animals indicating the potential application for direct diagnosis of anthrax ...	2014	25151655
john bartlett and bioterrorism.	until 1997, the subject of bioterrorism was not discussed within the medical community and deliberately ignored in national planning efforts. biological weapons were regarded as "morally repulsive." this complacency stemmed from a 1972 biological weapons convention where all countries agreed to cease offensive biological weapons research. in the 1990s, however, the soviet union was discovered to have an extensive bioweapons program and a japanese religious cult sought to launch an anthrax attack ...	2014	25151482
confirmed bacillus anthracis infection among persons who inject drugs, scotland, 2009-2010.	in scotland, the 2009 outbreak of bacillus anthracis infection among persons who inject drugs resulted in a 28% death rate. to compare nonsurvivors and survivors, we obtained data on 11 nonsurvivors and 16 survivors. time from b. anthracis exposure to symptoms or hospitalization and skin and limb findings at presentation did not differ between nonsurvivors and survivors. proportionately more nonsurvivors had histories of excessive alcohol use (p = 0.05) and required vasopressors and/or mechanica ...	2014	25148307
investigation and control of anthrax outbreak at the human-animal interface, bhutan, 2010.	in 2010, we investigated anthrax outbreak in bhutan. a total of 43 domestic animals died, and cutaneous anthrax developed in 9 persons, and 1 died. all affected persons had contact with the carcasses of infected animals. comprehensive preparedness and response guidelines are needed to increase public awareness of anthrax in bhutan.	2014	25147965
patent prospects toward therapeutics and diagnostics of anthrax.	anthrax is one of the deadly infectious disease as documented in the cdc website. in spite of the availability of appropriate antimicrobial agents, the mortality related with the anthrax remains high. the pathogenicity of b. anthracis is mainly accredited to the two foremost components: toxins and capsule. virulence component of b. anthracis includes protective antigen (pa) which plays a vital role in pathogenesis, virulence protein edema factor (ef) and lethal factor (lf). this search for novel ...	2014	25145329
evaluation of up-converting phosphor technology-based lateral flow strips for rapid detection of bacillus anthracis spore, brucella spp., and yersinia pestis.	bacillus anthracis, brucella spp., and yersinia pestis are zoonotic pathogens and biowarfare- or bioterrorism-associated agents that must be detected rapidly on-site from various samples (e.g., viscera and powders). an up-converting phosphor technology-based lateral flow (upt-lf) strip was developed as a point-of-care testing (poct) to satisfy the requirements of first-level emergency response. we developed upt-lf poct to quantitatively detect the three pathogens within 15 min. sample and operat ...	2014	25144726
humoral responses to independent vaccinations are correlated in healthy boosted adults.	roughly half of u.s. adults do not receive recommended booster vaccinations, but protective antibody levels are rarely measured in adults. demographic factors, vaccination history, and responses to other vaccinations could help identify at-risk individuals. we sought to characterize rates of seroconversion and determine associations of humoral responses to multiple vaccinations in healthy adults.	2014	25140930
antimicrobial light-activated materials: towards application for food and environmental safety.	to produce light-activated antimicrobial materials composed of the photodynamic dye phloxine b incorporated into paper or cellulose membranes and to investigate ability of these materials to decrease bacterial loads on their surfaces as well as on food surfaces that were in contact with these materials under illumination with regular white light.	2014	25139147
injectional anthrax - new presentation of an old disease.	bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. each of these can lead to secondary bacteraemia and anthrax meningitis. since 2009,anthrax has emerged among heroin users in europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout europe; before 2009 only one case was reported. during 2012 ...	2014	25139073
'the battle for life': pasteur, anthrax, and the first probiotics.		2014	25128557
protective antigen-specific memory b cells persist years after anthrax vaccination and correlate with humoral immunity.	anthrax vaccine adsorbed (ava) generates short-lived protective antigen (pa) specific igg that correlates with in vitro toxin neutralization and protection from bacillus anthracis challenge. animal studies suggest that when pa-specific igg has waned, survival after spore challenge correlates with an activation of pa-specific memory b cells. here, we characterize the quantity and the longevity of ava-induced memory b cell responses in humans. peripheral blood mononuclear cells (pbmcs) from indivi ...	2014	25123559
role of the water-metal ion bridge in mediating interactions between quinolones and escherichia coli topoisomerase iv.	although quinolones have been in clinical use for decades, the mechanism underlying drug activity and resistance has remained elusive. however, recent studies indicate that clinically relevant quinolones interact with bacillus anthracis (gram-positive) topoisomerase iv through a critical water-metal ion bridge and that the most common quinolone resistance mutations decrease drug activity by disrupting this bridge. as a first step toward determining whether the water-metal ion bridge is a general ...	2014	25115926
complete genome sequence of bacillus anthracis hyu01, isolated from soil samples in the korean peninsula.	bacillus anthracis is a gram-positive endospore-forming bacterium that causes the zoonotic disease anthrax. we report a complete genome sequence of b. anthracis strain hyu01, isolated from changnyung, which belongs to the b branch (b.br.) 001/002 canonical single nucleotide polymorphism (cansnp) group.	2014	25103761
screening for anthrax occurrence in soil of flooded rural areas in poland after rainfalls in spring 2010.	anthrax spores remain viable and infectious in soil for decades. flood water can percolate towards the surface the spores buried in soil. moreover, the flood water might transport spores to areas previously unaffected. after the water recedes the spores located on the surface of the ground can be consumed by grazing animals and cause outbreaks of anthrax.	2014	25292110
[travel-associated pneumonias].	respiratory infections are responsible for up to 11% of febrile infections in travellers or immigrants from tropical and subtropical regions. the main pathogens are the same as in temperate climate zones: streptococcus pneumoniae, haemophilus influenzae, mycoplasma pneumoniae, chlamydophila pneumoniae, influenza viruses, legionella pneumophila. however, some pulmonary diseases can be attributed to bacterial, parasitic, viral or fungal pathogens that are endemic in tropical and subtropical region ...	2014	25290923
water-driven micromotors for rapid photocatalytic degradation of biological and chemical warfare agents.	threats of chemical and biological warfare agents (cbwa) represent a serious global concern and require rapid and efficient neutralization methods. we present a highly effective micromotor strategy for photocatalytic degradation of cbwa based on light-activated tio2/au/mg microspheres that propel autonomously in natural water and obviate the need for external fuel, decontaminating reagent, or mechanical agitation. the activated tio2/au/mg micromotors generate highly reactive oxygen species respo ...	2014	25289459
[molecular aspects of anthrax pathogenesis].	a model of anthrax infection with the role determined for main pathogenicity factors of bacillus anthracis exotoxin and capsule is presented. after spore phagocytosis by macrophages, synthesis of the main exotoxin component begins - a protective antigen that in oligomeric form disrupts phagosome membrane. this accelerates the transition of the pathogen from phagosome into the macrophage cytoplasm. poly-d-glutamine capsule synthesized by the pathogen triggers the exit (exocytosis) of vegetative c ...	2014	25286538
[immunogenicity and safety of a prototype chemical anthrax vaccine in laboratory animal models].	evaluation of immune stimulating and toxic effects of a vaccine prototype protein components.	2014	25286524
lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge.	inhalational anthrax is caused by inhalation of bacillus anthracis spores. the ability of b. anthracis to cause anthrax is attributed to the plasmid-encoded a/b-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. to better understand the contribution of these toxins to the disease pathophysiology in vivo, we used b. anthracis ames strain and isogenic toxin deletion mutants derived from the ame ...	2014	25285720
fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites.	parasites can shape the foraging behaviour of their hosts through cues indicating risk of infection. when cues for risk co-occur with desired traits such as forage quality, individuals face a trade-off between nutrient acquisition and parasite exposure. we evaluated how this trade-off may influence disease transmission in a 3-year experimental study of anthrax in a guild of mammalian herbivores in etosha national park, namibia. at plains zebra (equus quagga) carcass sites we assessed (i) carcass ...	2014	25274365
[the experiments conducted by japanese on human guinea pigs, and the use of biological weapons during the sino-japanese war (1937-1945)].	starting from the end of the nineteenth century, and during the first four decades of the past century, japan showed considerable military expansion, on the back of a pan-asiatic and imperialistic ideology, comparable only to those expressed by wilhelmian and nazi germany. this growth led to japan playing an extremely important role in the asia-pacific continent, which unavoidably brought the country onto a collision course with the british empire and the united states of america. the japanese g ...	2014	25269971
splitmem: a graphical algorithm for pan-genome analysis with suffix skips.	genomics is expanding from a single reference per species paradigm into a more comprehensive pan-genome approach that analyzes multiple individuals together. a compressed de bruijn graph is a sophisticated data structure for representing the genomes of entire populations. it robustly encodes shared segments, simple single-nucleotide polymorphisms and complex structural variations far beyond what can be represented in a collection of linear sequences alone.	2014	25398610
inhibitory effects of single-walled carbon nanotubes on biofilm formation from bacillus anthracis spores.	this study reports the inhibitory effect of single walled carbon nanotubes (swcnts) on biofilm formation from bacillus anthracis spores. although the presence of 50 to 100 μg ml(-1) of swcnts in the suspension increased spore attachment in the wells of 96-well plates, the presence of 200 μg ml(-1) of swcnts in the germination solution decreased the germination percentage of the attached spores by 93.14%, completely inhibiting subsequent biofilm formation. the inhibition kinetics of 50 μg ml(-1) ...	2014	25389559
gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs.	most vertebrates experience coinfections, and many pathogen-pathogen interactions occur indirectly through the host immune system. these interactions are particularly strong in mixed micro-macroparasite infections because of immunomodulatory effects of helminth parasites. while these trade-offs have been examined extensively in laboratory animals, few studies have examined them in natural systems. additionally, many wildlife pathogens fluctuate seasonally, at least partly due to seasonal host im ...	2014	25388877
caspase-1 autoproteolysis is differentially required for nlrp1b and nlrp3 inflammasome function.	inflammasomes are caspase-1-activating multiprotein complexes. the mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (nlrp1b) inflammasome was identified as the sensor of bacillus anthracis lethal toxin (lt) in mouse macrophages from sensitive strains such as balb/c. upon exposure to lt, the nlrp1b inflammasome activates caspase-1 to produce mature il-1β and induce pyroptosis. both processes are believed to depend on autoproteolysed caspase-1. in contrast to human nlrp1 ...	2014	25404286
erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor is associated with reduced anthrax-lethal-toxin-induced mortality in mice.	anthrax lethal toxin (lt), one of the primary virulence factors of bacillus anthracis, causes anthrax-like symptoms and death in animals. experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering lt. in this study, the granulocyte colony-stimulating factor (g-csf) was used as a therapeutic agent to ameliorate anthrax-lt- and spore-induced mortality in c57bl/6j mice. we demonstrated that g-csf promoted the mobilization o ...	2014	25384016
specific activation of dendritic cells enhances clearance of bacillus anthracis following infection.	dendritic cells are potent activators of the immune system and have a key role in linking innate and adaptive immune responses. in the current study we have used ex vivo pulsed bone marrow dendritic cells (bmdc) in a novel adoptive transfer strategy to protect against challenge with bacillus anthracis, in a murine model. pre-pulsing murine bmdc with either recombinant protective antigen (pa) or cpg significantly upregulated expression of the activation markers cd40, cd80, cd86 and mhc-ii. passiv ...	2014	25380285
the central nervous system as target of bacillus anthracis toxin independent virulence in rabbits and guinea pigs.	infection of the central nervous system is considered a complication of anthrax and was reported in humans and non-human primates. previously we have reported that bacillus anthracis possesses a toxin-independent virulent trait that, like the toxins, is regulated by the major virulence regulator, atxa, in the presence of pxo2. this toxin-independent lethal trait is exhibited in rabbits and guinea pigs following significant bacteremia and organ dissemination. various findings, including meningiti ...	2014	25375158
immunopotentiation for bacterial biodefense.	activation of the innate immune system can enhance resistance to a variety of bacterial and viral infections. in situations where the etiological agent of disease is unknown, such as a bioterror attack, stimulation of innate immunity may be particularly useful as induced immune responses are often capable of providing protection against a broad range of pathogens. in particular, the threat of an intentional release of a highly virulent bacterial pathogen that is either intrinsically resistant to ...	2014	25373479
statistical analysis, optimization, and prioritization of virtual screening parameters for zinc enzymes including the anthrax toxin lethal factor.	the anthrax toxin lethal factor (lf) and matrix metalloproteinase-3 (mmp-3, stromelysin-1) are popular zinc metalloenzyme drug targets, with lf primarily responsible for anthrax-related toxicity and host death, while mmp-3 is involved in cancer- and rheumatic disease-related tissue remodeling. a number of in silico screening techniques, most notably docking and scoring, have proven useful for identifying new potential drug scaffolds targeting lf and mmp-3, as well as for optimizing lead compound ...	2014	25373478
elucidation of the bicarbonate binding site and insights into the carboxylation mechanism of (n(5))-carboxyaminoimidazole ribonucleotide synthase (purk) from bacillus anthracis.	structures of (n(5))-carboxyaminoimidazole ribonucleotide synthase (purk) from bacillus anthracis with various combinations of atp, adp, mg(2+), bicarbonate and aminoimidazole ribonucleotide (air) in the active site are presented. the binding site of bicarbonate has only been speculated upon previously, but is shown here for the first time. the binding involves interactions with the conserved residues arg272, his274 and lys348. these structures provide insights into each ligand in the active sit ...	2014	25372694