Publications

phemadb: a solution for storage, retrieval, and analysis of high throughput phenotype data.	abstract:	2011	21507258
charge requirements for proton gradient-driven translocation of anthrax toxin.	anthrax lethal toxin is used as a model system to study protein translocation. the toxin is composed of a translocase channel, called protective antigen (pa), and an enzyme, called lethal factor (lf). a proton gradient (δph) can drive lf unfolding and translocation through pa channels; however, the mechanism of δph- mediated force generation, substrate unfolding, and the establishment of directionality are poorly understood. one recent hypothesis suggests that the δph may act through changes in ...	2011	21507946
acr appropriateness criteria® acute respiratory illness in immunocompetent patients.	acute respiratory illness is defined as one or more of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). the workup of these patients depends on many factors, including clinical presentation and the suspected etiology. this study reviews the literature on the indications and usefulness of radiologic studies for the evaluation of acute respiratory illness in the immunocompetent patient. the following recommendations are the result of evidence-based consensus ...	2011	21508726
one-step synthesized silver micro-dendrites used as novel separation mediums and their applications in multi-dna analysis.	a new kind of silver micro-dendrites have been synthesized for the separation and multiplex detection of dna merely by earth gravity. through this approach, the dna strands of the sickle cell disease, human t-lymphotropic virus type i, the anthrax lethal factor can be detected down to 100 pm with the detection range from 100 pm to 100 nm at the same time.	2011	21512713
larvicidal, antimicrobial and brine shrimp activities of extracts from cissampelos mucronata and tephrosia villosa from coast region, tanzania.	abstract:	2011	21513544
mechanism of inhibition of bacillus anthracis spore outgrowth by the lantibiotic nisin.	the lantibiotic nisin inhibits growth of vegetative gram-positive bacteria by binding to lipid ii, which disrupts cell wall biosynthesis and facilitates pore formation. nisin also inhibits the outgrowth of bacterial spores, including spores of bacillus anthracis, whose structural and biochemical properties are fundamentally different from those of vegetative bacteria. the molecular basis of nisin inhibition of spore outgrowth had not been identified, as previous studies suggested that inhibition ...	2011	21517116
contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis.	bacillus anthracis is a gram-positive spore forming bacterium that causes anthrax disease in humans and animals. systemic infection is characterized by septicemia, toxemia, and meningitis, the main neurological complication associated with high mortality. we have shown previously that b. anthracis sterne is capable of blood-brain barrier (bbb) penetration establishing the classic signs of meningitis, and that infection is dependent on the expression of both major anthrax toxins, lethal toxin (lt ...	2011	21518787
anthrax vaccination induced anti-lethal factor igg: fine specificity and neutralizing capacity.	the efficacy biomarker of the currently licensed anthrax vaccine (ava) is based on quantity and neutralizing capacity of anti-protective antigen (anti-pa) antibodies. however, animal studies have demonstrated that antibodies to lethal factor (lf) can provide protection against in vivo bacterial spore challenges. improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin prepa ...	2011	21420416
therapeutic recommendations for the management of patients exposed to bacillus anthracis in natural settings.		2011	21420809
secondary cell wall polysaccharides from bacillus cereus strains g9241, 03bb87 and 03bb102 causing fatal pneumonia share similar glycosyl structures with the polysaccharides from bacillus anthracis.	secondary cell wall polysaccharides (scwps) are important structural components of the bacillus cell wall and contribute to the array of antigens presented by these organisms in both spore and vegetative forms. we previously found that antisera raised to bacillus anthracis spore preparations cross-reacted with scwps isolated from several strains of pathogenic b. cereus, but did not react with other phylogenetically related but nonpathogenic bacilli, suggesting that the scwp from b. anthracis and ...	2011	21421577
anthrax lethal factor activates k(+) channels to induce il-1ß secretion in macrophages.	anthrax lethal toxin (letx) is a virulence factor of bacilillus anthracis that is a bivalent toxin, containing lethal factor (lf) and protective ag proteins, which causes cytotoxicity and altered macrophage function. letx exposure results in early k(+) efflux from macrophages associated with caspase-1 activation and increased il-1ß release. the mechanism of this toxin-induced k(+) efflux is unknown. the goals of the current study were to determine whether letx-induced k(+) efflux from macrophage ...	2011	21421849
mechanism of reactant and product dissociation from the anthrax edema factor: a locally enhanced sampling and steered molecular dynamics study.	the anthrax edema factor is a toxin overproducing damaging levels of cyclic adenosine monophosphate (camp) and pyrophosphate (ppi) from atp. here, mechanisms of dissociation of atp and products (camp, ppi) from the active site are studied using locally enhanced sampling (les) and steered molecular dynamics simulations. various substrate conformations and ionic binding modes found in crystallographic structures are considered. les simulations show that ppi and camp dissociate through different so ...	2011	21425348
cys-cys cross-linking shows contact between the n-terminus of lethal factor and phe427 of the anthrax toxin pore.	electrophysiological studies of wild-type and mutated forms of anthrax protective antigen (pa) suggest that the phe clamp, a structure formed by the phe427 residues within the lumen of the oligomeric pa pore, binds the unstructured n-terminus of the lethal factor and the edema factor during initiation of translocation. we now show by electrophysiological measurements and gel shift assays that a single cys introduced into the phe clamp can form a disulfide bond with a cys placed at the n-terminus ...	2011	21425869
detection of ascitic fluid infections in patients with liver cirrhosis and ascites.	ascitic fluid infections (afis) are the frequent complications of advanced liver disease. bacterial translocation is considered a key step in the pathogenesis of gut-derived bacterial infections; mainly spontaneous bacterial peritonitis (sbp) in cirrhotic patients. bacterial dna (bactdna) in ascitic fluid and serum has been suggested as a surrogate marker for bacterial translocation. we attempted at the isolation and identification of bacteria in ascitic fluid in cirrhotic patients and the asses ...	2011	21429450
the early humoral immune response to bacillus anthracis toxins in patients infected with cutaneous anthrax.	bacillus anthracis, the causative agent of anthrax, produces a tripartite toxin composed of two enzymatically active subunits, lethal factor (lf) and edema factor (ef), which, when associated with a cell-binding component, protective antigen (pa), form lethal toxin and edema toxin, respectively. in this preliminary study, we characterized the toxin-specific antibody responses observed in 17 individuals infected with cutaneous anthrax. the majority of the toxin-specific antibody responses observe ...	2011	21401726
the anthrax toxin channel: a barrel of lfs.		2011	21402885
trapping a translocating protein within the anthrax toxin channel: implications for the secondary structure of permeating proteins.	anthrax toxin consists of three proteins: lethal factor (lf), edema factor (ef), and protective antigen (pa). this last forms a heptameric channel, (pa(63))(7), in the host cell's endosomal membrane, allowing the former two (which are enzymes) to be translocated into the cytosol. (pa(63))(7) incorporated into planar bilayer membranes forms a channel that translocates lf and ef, with the n terminus leading the way. the channel is mushroom-shaped with a cap containing the binding sites for ef and ...	2011	21402886
quantitative mass spectrometry for bacterial protein toxins--a sensitive, specific, high-throughput tool for detection and diagnosis.	matrix-assisted laser-desorption time-of-flight (maldi-tof) mass spectrometry (ms) is a valuable high-throughput tool for peptide analysis. liquid chromatography electrospray ionization (lc-esi) tandem-ms provides sensitive and specific quantification of small molecules and peptides. the high analytic power of ms coupled with high-specificity substrates is ideally suited for detection and quantification of bacterial enzymatic activities. as specific examples of the ms applications in disease dia ...	2011	21403598
scratching the surface: the history of skin, its diseases and their treatment--history of medicine unit, university of birmingham, october 29-30, 2010.		2011	21409964
a new peptide motif present in the protective antigen of anthrax toxin exerts its efficiency on the cellular uptake of liposomes and applications for a dual-ligand system.	protective antigen (pa) is a nontoxic protein present in anthrax toxin. domain 4 of pa (pa-d4) acts as a receptor binding site for tumor endothelial marker 8 (tem8). in this study, kynd motif from pa-d4 was utilized as a ligand against tem8. the efficiency of kynd motif on cellular association was assessed by evaluating the cellular uptake of pegylated liposomes (peg-lps) in tem8 positive and negative cells. the peptide was attached on the top of the peg of peg-lp. compared to peg-lp, kynd modif ...	2011	21414394
a practical liquid plug flow-through polymerase chain-reaction system based on a heat-resistant resin chip.	flow-through polymerase chain reaction (pcr) microfluidic systems for fast, small-volume dna amplification on a single chip are significantly impacting medical and bioanalytical research. we have fabricated an improved, practical flow-through pcr chip by weighting a pressure-sensitive polyolefin (psp) film onto a cyclo-olefin polymer (cop) substrate. the substrate was cut so as to produce microchannels, and was used to amplify dna using a small moving liquid plug, in contrast to conventional con ...	2011	21415501
mek2 is sufficient but not necessary for proliferation and anchorage-independent growth of sk-mel-28 melanoma cells.	mitogen-activated protein kinase kinases (mkk or mek) 1 and 2 are usually treated as redundant kinases. however, in assessing their relative contribution towards erk-mediated biologic response investigators have relied on tests of necessity, not sufficiency. in response we developed a novel experimental model using lethal toxin (letx), an anthrax toxin-derived pan-mkk protease, and genetically engineered protease resistant mkk mutants (mkkcr) to test the sufficiency of mek signaling in melanoma ...	2011	21365009
the role of hla-dr-dq haplotypes in variable antibody responses to anthrax vaccine adsorbed.	host genetic variation, particularly within the human leukocyte antigen (hla) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. we searched for associations between the immunoglobulin g antibody to protective antigen (abpa) response to anthrax vaccine adsorbed (ava) in humans, and polymorphisms at hla class i (hla-a, -b, and -c) and class ii (hla-drb1, -dqa1, -dqb1, -dpb1 ...	2011	21368772
purification development and characterization of the zinc-dependent metallo-ß-lactamase from bacillus anthracis.	metallo-ß-lactamase from bacillus anthracis (bla2) catalyzes the hydrolysis of ß-lactam antibiotics which are commonly prescribed to combat bacterial infections. bla2 contributes to the antibiotic resistance of this bacterium. an understanding of it is necessary to design potential inhibitors that can be introduced with current antibiotics for effective eradication of anthrax infections. we have purified bla2 using ni(2+)-affinity chromatography with over 140-fold increase in activity with a yie ...	2011	21369909
peptide-based fluorescence resonance energy transfer protease substrates for the detection and diagnosis of bacillus species.	we describe the development of a highly specific enzyme-based fluorescence resonance energy transfer (fret) assay for easy and rapid detection both in vitro and in vivo of bacillus spp., among which are the members of the b. cereus group. synthetic substrates for b. anthracis proteases were designed and exposed to secreted enzymes of a broad spectrum of bacterial species. the rational design of the substrates was based on the fact that the presence of d-amino acids in the target is highly specif ...	2011	21370823
two capsular polysaccharides enable bacillus cereus g9241 to cause anthrax-like disease.	bacillus cereus g9241 causes an anthrax-like respiratory illness in humans; however, the molecular mechanisms of disease pathogenesis are not known. genome sequencing identified two putative virulence plasmids proposed to provide for anthrax toxin (pbcxo1) and/or capsule expression (pbc218). we report here that b. cereus g9241 causes anthrax-like disease in immune-competent mice, which is dependent on each of the two virulence plasmids. pbcxo1 encodes paga1, the homologue of anthrax protective a ...	2011	21371137
analogues of peptide smap-29 with comparable antimicrobial potency and reduced cytotoxicity.	smap-29 (sheep myeloid antimicrobial peptide-29) is a peptide with potent antibacterial properties. however, it is also highly cytotoxic both to human red blood cells (hrbcs) and human embryonic kidney (hek) cells. in this study, some of the amino acids of smap-29 were changed in an attempt to reduce haemolytic activity whilst maintaining high antibacterial efficacy. these analogues, plus other analogues described in the literature with potent antimicrobial activity against gram-positive bacteri ...	2011	21377841
bacillus anthracis comparative genome analysis in support of the amerithrax investigation.	before the anthrax letter attacks of 2001, the developing field of microbial forensics relied on microbial genotyping schemes based on a small portion of a genome sequence. amerithrax, the investigation into the anthrax letter attacks, applied high-resolution whole-genome sequencing and comparative genomics to identify key genetic features of the letters' bacillus anthracis ames strain. during systematic microbiological analysis of the spore material from the letters, we identified a number of m ...	2011	21383169
bacillus anthracis spore interactions with mammalian cells: relationship between germination state and the outcome of in vitro.	during inhalational anthrax, internalization of bacillus anthracis spores by host cells within the lung is believed to be a key step for initiating the transition from the localized to disseminated stages of infection. despite compelling in vivo evidence that spores remain dormant within the bronchioalveolar spaces of the lungs, and germinate only after uptake into host cells, most in vitro studies of infection have been conducted under conditions that promote rapid germination of spores within ...	2011	21356113
cutting edge: primary innate immune cells respond efficiently to polymeric peptidoglycan, but not to peptidoglycan monomers.	the cell wall of bacteria induces proinflammatory cytokines in monocytes and neutrophils in human blood. the nature of the stimulating component of bacterial cell walls is not well understood. we have previously shown polymeric peptidoglycan (pgn) has this activity, and the cytokine response requires pgn internalization and trafficking to lysosomes. in this study, we demonstrate that peptidoglycan monomers such as muramyl dipeptide and soluble peptidoglycan fail to induce robust cytokine product ...	2011	21357534
subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis.	anthrax is extremely rare in the western world but is endemic to areas of south and central asia. in early 2010 an outbreak was identified in heroin-injecting intravenous drug users in the united kingdom and europe. afghanistan is currently the principal source of heroin which reaches the united kingdom. when anthrax occurs, cutaneous disease accounts for over 95% of cases. at least 47 cases with 13 deaths have been confirmed so far. we present three cases presenting during this time with marked ...	2011	21357967
analysis of bacillus anthracis nucleoside hydrolase via in silico docking with inhibitors and molecular dynamics simulation.	as the enzyme nucleoside hydrolase (nh) is widely found in nature but has not yet been detected in mammals, it is considered an ideal target in the development of chemotherapy against parasitic diseases and bacterial infections like anthrax. considering the risk that this biological warfare agent represents nowadays, the search for new drugs and new molecular targets in the development of chemotherapy against anthrax is imperative. on this basis, we performed docking studies of six known nh inhi ...	2011	21318235
evaluation of the effect of syringe surfaces on protein formulations.	packaging of drugs in prefillable syringes offers considerable advantages over conventional vials. almost all major biotech molecules are available on the market today in prefilled syringes, and are safe and efficacious. newer high-concentration liquid formulations, especially fusion proteins, however, can suffer from instability in prefilled syringes due to syringe components like silicone oil. to assess the effect of siliconized and modified syringe surfaces on protein formulations, the stabil ...	2011	21319164
the adenylate cyclase toxin of bacillus anthracis is a potent promoter of t(h)17 cell development.		2011	21310477
dna probe functionalized qcm biosensor based on gold nanoparticle amplification for bacillus anthracis detection.	the rapid detection of bacillus anthracis, the causative agent of anthrax disease, has gained much attention since the anthrax spore bioterrorism attacks in the united states in 2001. in this work, a dna probe functionalized quartz crystal microbalance (qcm) biosensor was developed to detect b. anthracis based on the recognition of its specific dna sequences, i.e., the 168 bp fragment of the ba813 gene in chromosomes and the 340 bp fragment of the pag gene in plasmid pxo1. a thiol dna probe was ...	2011	21315574
possibilities, intentions and threats: dual use in the life sciences reconsidered.	due to the terrorist attacks of 9/11 and the anthrax letters of a few weeks later, the concept of dual use has spread widely in the life sciences during the past decade. this article is aimed at a clarification of the dual use concept and its scope of application for the life sciences. such a clarification would greatly facilitate the work of policymakers seeking to ensure security while avoiding undesirable interventions of government in the conduct of science. the article starts with an overvi ...	2011	21327859
hyaline fibromatosis syndrome inducing mutations in the ectodomain of anthrax toxin receptor 2 can be rescued by proteasome inhibitors.	hyaline fibromatosis syndrome (hfs) is a human genetic disease caused by mutations in the anthrax toxin receptor 2 (or cmg2) gene, which encodes a membrane protein thought to be involved in the homeostasis of the extracellular matrix. little is known about the structure and function of the protein or the genotype–phenotype relationship of the disease. through the analysis of four patients, we identify three novel mutants and determine their effects at the cellular level. altogether, we show that ...	2011	21328543
anthrax investigation. science in ivins case not ironclad, nrc says.		2011	21330501
efficacy of liquid spray decontaminants for inactivation of bacillus anthracis spores on building and outdoor materials.	to obtain data on the efficacy of various liquid and foam decontamination technologies to inactivate bacillus anthracis ames and bacillus subtilis spores on building and outdoor materials.	2011	21332900
antidotes to anthrax lethal factor intoxication. part 2: structural modifications leading to improved in vivo efficacy.	new anthrax lethal factor inhibitors (lfis) were designed based upon previously identified potent inhibitors 1a and 2. combining the new core structures with modifications to the c2-side chain yielded analogs with improved efficacy in the rat lethal toxin model.	2011	21334206
delayed treatment with w1-mab, a chimpanzee-derived monoclonal antibody against protective antigen, reduces mortality from challenges with anthrax edema or lethal toxin in rats and with anthrax spores in mice.	w1-mab is a chimpanzee-derived monoclonal antibody to protective antigen that improved survival when administered before anthrax lethal toxin challenge in rats. to better define w1-mab's efficacy for anthrax, we administered it after initiation of 24-hr infusions of edema toxin and lethal toxin either alone or together in rats or following anthrax spore challenge in mice.	2011	21336113
modeling of the structure and interactions of the b. anthracis antitoxin, moxx: deletion mutant studies highlight its modular structure and repressor function.	our previous report on bacillus anthracis toxin-antitoxin module (moxxt) identified it to be a two component system wherein, pemk-like toxin (moxt) functions as a ribonuclease (agarwal s et al. jbc 285:7254-7270, 2010). the labile antitoxin (moxx) can bind to/neutralize the action of the toxin and is also a dna-binding protein mediating autoregulation. in this study, molecular modeling of moxx in its biologically active dimeric form was done. it was found that it contains a conserved ribbon-heli ...	2011	21336656
current physical and sds extraction methods do not efficiently remove exosporium proteins from bacillus anthracis spores.	biochemical studies of the outermost spore layers of the bacillus cereus family are hindered by difficulties in efficient dispersal of the external spore layers and difficulties in dissociating protein complexes that comprise the exosporium layer. detergent and physical methods have been utilized to disrupt the exosporium layer. herein we compare commonly used sds extraction buffers used to extract spore proteins and demonstrate the incomplete extractability of the exosporium layer by these meth ...	2011	21338631
the assembly state between magnetic nanosensors and their targets orchestrates their magnetic relaxation response.	the target-induced clustering of magnetic nanoparticles is typically used for the identification of clinically relevant targets and events. a decrease in the water proton transverse nmr relaxation time, or t(2), is observed upon clustering, allowing the sensitive and accurate detection of target molecules. we have discovered a new mechanistically unique nanoparticle-target interaction resulting in a t(2) increase and demonstrate herein that this increase, and its associated r(2) relaxivity decre ...	2011	21341659
investigation and analysis of a human orf outbreak among people living on the same farm.	human orf is a viral zoonotic infection caused by parapoxvirus. the skin lesions of human orf can be misdiagnosed as cutaneous anthrax leading to overtreatment and also fear. this study was conducted to analyze an outbreak which led to deaths among kids and lambs in the same flock, and skin lesions in some persons who were living on the same farm that were initially diagnosed as cutaneous anthrax by a practitioner. eight patients with skin lesions and eleven persons who had no skin lesion were c ...	2011	21344145
comparison of air sampling methods for aerosolized spores of b. anthracis sterne.	bacillus anthracis sterne spores were aerosolized within a chamber at concentrations ranging from 1 x 10³ to 1.7 x 104 spores per cubic meter of air (particles (p)/m³) to compare three different sampling methods: andersen samplers, gelatin filters, and polytetrafluoroethylene (ptfe) membrane filters. three samples of each type were collected during each of 19 chamber runs. chamber concentration was determined by an aerodynamic particle sizer (aps) for the size range of 1.114-1.596 µm. runs were ...	2011	21347959
function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size.	changes in effective population size impinge on patterns of molecular evolution. notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. this prediction has been validated empirically for several endosymbiont and island taxa. here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidate ...	2011	21349981
high-level production of a single chain antibody against anthrax toxin in escherichia coli by high cell density cultivation.	previously, we isolated the m18 scfv, which is an affinity matured antibody against the anthrax toxin pa, and observed that its single chain antibody (scab) form (m18 scab) exhibited superior stability compared to the scfv. here, we report high cell density cultivations for preparative scale production of m18 scab in a 3.5 l fermenter. briefly, a ph-stat feeding strategy was employed in fed-batch cultivation, and four different cell densities (od(600) of 40, 80, 120, and 150) were examined for t ...	2011	21350955
chemical dissection of protein translocation through the anthrax toxin pore.		2011	21351339
targeting the anthrax receptors, tem-8 and cmg-2, for anti-angiogenic therapy.	the anthrax toxin receptors tumor endothelial marker-8 (tem-8) and capillary morphogenesis gene-2 (cmg-2) are responsible for allowing entry of anthrax toxin into host cells. these receptors were first discovered due to their enhanced expression on endothelial cells undergoing blood vessel growth or angiogenesis in model systems. inhibition of angiogenesis is an important strategy for current anti-cancer therapies and treatment of retinal diseases. functional roles for tem-8 and cmg-2 in angioge ...	2011	21196249
progress and novel strategies in vaccine development and treatment of anthrax.	the lethal anthrax disease is caused by spores of the gram-positive bacillus anthracis, a member of the cereus group of bacilli. although the disease is very rare in the western world, development of anthrax countermeasures gains increasing attention due to the potential use of b. anthracis spores as a bio-terror weapon. protective antigen (pa), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into ...	2011	21198675
particle release from respirators, part i: determination of the effect of particle size, drop height, and load.	in late 2001, some u.s. postal service workers and a few members of congress were exposed to anthrax spores. this led to an increased effort to develop employable methods to protect workers from exposure to anthrax. some investigations focused on selection and use of respirators to protect workers against airborne anthrax. the present study evaluated the potential for several types of half-mask respirators to release deposited particles. four brands of the most commonly used filtering facepiece ...	2011	21132594
continuing challenge of infectious diseases in india.	in india, the range and burden of infectious diseases are enormous. the administrative responsibilities of the health system are shared between the central (federal) and state governments. control of diseases and outbreaks is the responsibility of the central ministry of health, which lacks a formal public health department for this purpose. tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, hiv infection, and childhood cluster of vaccine-preventable diseases are given priority ...	2011	21227500
monoclonal antibodies directed against protective antigen of bacillus anthracis enhance lethal toxin activity in vivo.	protective antigen (pa) from bacillus anthracis binds to cellular receptors, combines with lethal factor (lf) forming lethal toxin (letx), and facilitates the translocation of lf into the cytosol. letx is cytotoxic for j774a.1 cells, a murine macrophage cell line, and causes death of fisher 344 rats when injected intravenously. pa is also the major protective component in anthrax vaccines. antibody-dependent enhancement has been reported for several viral diseases, a bacterial infection, and for ...	2011	21231965
evaluation of cryptococcus neoformans galactoxylomannan-protein conjugate as vaccine candidate against murine cryptococcosis.	galactoxylomannan (galxm) is a complex polysaccharide produced by the human pathogenic fungus cryptococcus neoformans that mediates profound immunological derangements in murine models. galxm is essentially non-immunogenic and produces immune paralysis in mice. previous studies have attempted to enhance immunogenicity by conjugating galxm to a protein carrier, but only transient antibody responses were elicited. here we report the generation of two galxm conjugates with bovine serum albumin (bsa ...	2011	21238568
screening and characterization of high-affinity ssdna aptamers against anthrax protective antigen.	the protective antigen (pa) of bacillus anthracis is a secreted protein that functions as a critical virulence factor. protective antigen has been selected as a biomarker in detecting bacterial infection. the in vitro selection method, systematic evolution of ligands by exponential enrichment (selex), was used to find single-stranded dnas that were tightly bound to pa. after 8 rounds of the selex process with pa, 4 different oligonucleotides (referred to as aptamers) that contain a 30-residue ss ...	2011	21245470
a case of septicaemic anthrax in an intravenous drug user.	in 2000, ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. in 2008, there were 574 drug related deaths in scotland, of which 336 were associated with heroin and or morphine. we report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in scotland.	2011	21251266
anthrax letters in an open office environment: effects of selected cdc response guidelines on personal exposure and building contamination.	in 2001, letters filled with a powder containing anthrax (bacillus anthracis) spores were delivered by mail to a number of governmental and media locations within the united states. in response, the u.s. centers for disease control and prevention (cdc) provided guidelines for office personnel who might encounter a letter containing suspicious powder. these guidelines were developed during the crisis and in the absence of experimental data from laboratory or field investigations. an obvious need ...	2011	21253984
the co-dependence of bxpb/exsfa and bcla for proper incorporation into the exosporium of bacillus anthracis.	the outermost layer of the bacillus anthracis spore consists of an exosporium comprised of two distinct layers, an outer hair-like nap layer and an internal basal layer. the hair-like nap is primarily comprised of the glycosylated collagen-like protein bcla. bcla is found in a trimeric form in close association with many other exosporium proteins in high-molecular weight complexes. we previously had characterized an n-terminal sequence of bcla that is sufficient for incorporation into the exospo ...	2011	21255119
raising awareness about terror medicine.	terror medicine, which is related to emergency and disaster medicine, focuses on the constellation of medical issues uniquely related to terrorist attacks. it ranges from recognizing features of biologic and chemical agents such as bacillus anthracis (anthrax) and sarin to the treatment of multi-injury victims of suicide bombings. medical personnel will be involved in rescue, diagnosis, treatment and recovery from a terrorist attack. dermatologists could play a central role in diagnosis and trea ...	2011	21146738
symmetry complementarity-guided design of anthrax toxin inhibitors based on β-cyclodextrin: synthesis and relative activities of face-selective functionalized polycationic clusters.	three new series of potential anthrax toxin inhibitors based on the β-cyclodextrin (βcd) scaffold were developed by exploiting face-selective cu(i)-catalyzed azide-alkyne 1,3-cycloadditions, amine-isothiocyanate coupling, and allyl group hydroboration-oxidation/hydroxy → amine replacement reactions. the molecular design follows the "symmetry-complementarity" concept between homogeneously functionalized polycationic βcd derivatives and protective antigen (pa), a component of anthrax toxin known t ...	2011	21140396
design of new chemotherapeutics against the deadly anthrax disease. docking and molecular dynamics studies of inhibitors containing pyrrolidine and riboamidrazone rings on nucleoside hydrolase from bacillus anthracis.	anthrax is a disease caused by bacillus anthracis, a dangerous biological warfare agent already used for both military and terrorist purposes. an important selective target for chemotherapy against this disease is nucleoside hydrolase (nh), an enzyme still not found in mammals. having this in mind we have performed molecular docking studies, aiming to analyze the three-dimensional positioning of six known inhibitors of trypanosoma vivax nh (tvnh) in the active site of b. anthracis nh (banh). we ...	2011	21142217
mechanisms of iron import in anthrax.	during an infection, bacterial pathogens must acquire iron from the host to survive. however, free iron is sequestered in host proteins, which presents a barrier to iron-dependent bacterial replication. in response, pathogens have developed mechanisms to acquire iron from the host during infection. interestingly, a significant portion of the iron pool is sequestered within heme, which is further bound to host proteins such as hemoglobin. the copious amount of heme-iron makes hemoglobin an ideal ...	2011	21258843
structural insights into inhibition of bacillus anthracis sporulation by a novel class of non-heme globin sensor domains.	pathogenesis by bacillus anthracis requires coordination between two distinct activities: plasmid-encoded virulence factor expression (which protects vegetative cells from immune surveillance during outgrowth and replication) and chromosomally encoded sporulation (required only during the final stages of infection). sporulation is regulated by at least five sensor histidine kinases that are activated in response to various environmental cues. one of these kinases, ba2291, harbors a sensor domain ...	2011	21216948
anthrax edema toxin has camp-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model.	while anthrax edema toxin produces pronounced tachycardia and lethal toxin depresses left ventricular (lv) ejection fraction in in vivo models, whether these changes reflect direct cardiac effects as opposed to indirect ones related to preload or afterload alterations is unclear. in the present study, the effects of edema toxin and lethal toxin were investigated in a constant pressure isolated perfused rat heart model. compared with control hearts, edema toxin at doses comparable to or less than ...	2011	21217068
therapeutic immunization in hiv infected ugandans receiving stable antiretroviral treatment: a phase i safety study.	therapeutic immunizations in hiv infection may boost immunity during antiretroviral treatment. we report on the first therapeutic vaccine trial in uganda, africa. this open label phase i trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic hiv-1 vaccine candidate. thirty hiv positive volunteers receiving a stable regimen of antiretroviral therapy with cd4 counts >400 were recruited for the safety evaluation of lfn-p24c, a detoxified anthrax-derived polypeptid ...	2011	21211581
papillation in bacillus anthracis colonies: a tool for finding new mutators.	colonies of bacillus anthracis sterne allow the growth of papillation after 6 days of incubation at 30°c on luria-bertani medium. the papillae are due to mutations that allow the cells to overcome the barriers to continued growth. cells isolated from papillae display two distinct gross phenotypes (group a and group b). we determined that group a mutants have mutations in the nprr gene including frameshifts, deletions, duplications and base substitutions. we used papillation as a tool for finding ...	2011	21205011
interactions of anthrax lethal factor with protective antigen defined by site-directed spin labeling.	the protective antigen (pa) moiety of anthrax toxin forms oligomeric pores that translocate the enzymatic moieties of the toxin--lethal factor (lf) and edema factor (ef)--across the endosomal membrane of mammalian cells. here we describe site-directed spin-labeling studies that identify interactions of lf with the prepore and pore conformations of pa. our results reveal a direct interaction between the extreme n terminus of lf (residues 2-5) and the f-clamp, a structure within the lumen of the p ...	2011	21262847
antibiotics cure anthrax in animal models.	respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. this study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with bacillus anthracis vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. however, upon termination of treatment, the animals died from respiratory anthrax. combined ...	2011	21263056
a non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates from b. anthracis spore challenge.	the health and economic burden of infectious diseases in general and bioterrorism in particular necessitate the development of medical countermeasures. one proven approach to reduce the disease burden and spread of pathogen is treatment with monoclonal antibodies (mab). mabs can prevent or reduce severity of the disease by variety of mechanisms, including neutralizing pathogen growth, limiting its spread from infected to adjacent cells, or by inhibiting biological activity of toxins, such as ant ...	2011	21270531
mlva and snp analysis identified a unique genetic cluster in bulgarian bacillus anthracis strains.	a collection of 40 bacillus anthracis strains mostly isolated from soil in bulgaria between 1960 and 1980 were investigated. all strains were proven to be b. anthracis by culture and amplification of a b. anthracis-specific chromosomal marker. pcr demonstrated that in nine strains both virulence plasmids (px01+/px02+) and in four strains only one plasmid (px02+) were present, whereas the majority of strains (n = 27) lacked both plasmids (px01-/px02-). multi-locus-variable number of tandem repeat ...	2011	21279731
optimizing the response to surveillance alerts in automated surveillance systems.	although much research effort has been directed toward refining algorithms for disease outbreak alerting, considerably less attention has been given to the response to alerts generated from statistical detection algorithms. given the inherent inaccuracy in alerting, it is imperative to develop methods that help public health personnel identify optimal policies in response to alerts. this study evaluates the application of dynamic decision making models to the problem of responding to outbreak de ...	2011	21290402
modeling the host response to inhalation anthrax.	inhalation anthrax, an often fatal infection, is initiated by endospores of the bacterium bacillus anthracis, which are introduced into the lung. to better understand the pathogenesis of an inhalation anthrax infection, we propose a two-compartment mathematical model that takes into account the documented early events of such an infection. anthrax spores, once inhaled, are readily taken up by alveolar phagocytes, which then migrate rather quickly out of the lung and into the thoracic/mediastinal ...	2011	21295589
parameters affecting spore recovery from wipes used in biological surface sampling.	the need for the precise and reliable collection of potential biothreat contaminants has motivated research in developing a better understanding of the variability in biological surface sampling methods. in this context, the objective of this work was to determine parameters affecting the efficiency of extracting bacillus anthracis sterne spores from commonly used wipe sampling materials and to describe performance using the interfacial energy concept. in addition, surface thermodynamics was app ...	2011	21296945
autoregulatory characteristics of a bacillus anthracis serine/threonine kinase.	ba-stk1 is a serine/threonine kinase (stk) expressed by bacillus anthracis. in previous studies, we found that ba-stk1 activity is modulated through dephosphorylation by a partner phosphatase, ba-stp1. in this study, we identified critical phosphorylation regions of ba-stk1 and determined the contributions of these phosphodomains to autophosphorylation and substrate phosphorylation. the data indicate that ba-stk1 undergoes trans-autophosphorylation within a regulatory domain, referred to as the ...	2011	21296958
room temperature stabilization of oral, live attenuated salmonella enterica serovar typhi-vectored vaccines.	foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated salmonella typhi 'ty21a' bacterial vaccine. ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. the optimized ty21a ...	2011	21300096
structure-based design of a heptavalent anthrax toxin inhibitor.	the design of polyvalent molecules, consisting of multiple copies of a biospecific ligand attached to a suitable scaffold, represents a promising approach to inhibit pathogens and oligomeric microbial toxins. despite the increasing interest in structure-based drug design, few polyvalent inhibitors based on this approach have shown efficacy in vivo. here we demonstrate the structure-based design of potent biospecific heptavalent inhibitors of anthrax lethal toxin. specifically, we illustrate the ...	2011	21302959
comparison of maldi-tof-ms and hplc-esi-ms/ms for endopeptidase activity-based quantification of anthrax lethal factor in serum.	diagnosing and treating anthrax at the earliest stage of disease is critical. we developed a method to diagnose anthrax at early stages of infection by detecting anthrax lethal factor (lf) at the attomol/ml level in plasma or serum. this method uses antibody capture and quantification of lf endoproteinase activity by isotope dilution matrix-assisted laser-desorption ionization (maldi) time-of-flight (tof) mass spectrometry (ms). many public health laboratories do not use maldi-tof-ms; thus, we h ...	2011	21302970
evaluation of bacillus strains as model systems for the work on bacillus anthracis spores.	available strain collections of bacillus anthracis and bacillus cereus were screened for b. cereus strains sharing major genotypic characteristics with b. anthracis. based on the comparison of partial spoiiiab sequences, whole genome sequences and mlst, a strain set representing different lineages including candidate model strains for b. anthracis was compiled. spores from the selected strain set and two b. anthracis strains were prepared according to a newly optimized protocol transferable to b ...	2011	20800917
sampling port for real-time analysis of bioaerosol in whole body exposure system for animal aerosol model development.	multiple factors influence the viability of aerosolized bacteria. the delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. the madison chamber is widely used to expose small animals to infectious aerosols.	2011	20849964
bioinformatic tools for using whole genome sequencing as a rapid high resolution diagnostic typing tool when tracing bioterror organisms in the food and feed chain.	the rapid technological development in the field of parallel sequencing offers new opportunities when tracing and tracking microorganisms in the food and feed chain. if a bioterror organism is deliberately spread it is of crucial importance to get as much information as possible regarding the strain as fast as possible to aid the decision process and select suitable controls, tracing and tracking tools. a lot of efforts have been made to sequence multiple strains of potential bioterror organisms ...	2011	20826036
a multiplex real-time pcr for identifying and differentiating b. anthracis virulent types.	bacillus anthracis is closely related to the endospore forming bacteria bacillus cereus and bacillus thuringiensis. for accurate detection of the life threatening pathogen b. anthracis, it is essential to distinguish between these three species. here we present a novel multiplex real-time pcr for simultaneous specific identification of b. anthracis and discrimination of different b. anthracis virulence types. specific b. anthracis markers were selected by whole genome comparison and different se ...	2011	20826037
characterization of an environmental strain of bacillus thuringiensis from a hot spring in western himalayas.	bacillus anthracis, the etiological agent of anthrax, is responsible for a serious and often fatal disease of mammalian livestock and humans and is an important biological warfare agent. bacillus sp. akg was isolated from a hot spring in western himalayas and species-specific primers targeting gyrb gene identified the strain as b. anthracis within cereus-group. cloning, sequencing, and phylogenetic analysis of the partial gyrb sequence from strain akg indicated a close affiliation with b. anthra ...	2011	20737272
protein-centric data integration for functional analysis of comparative proteomics data.	high-throughput proteomic, microarray, protein interaction and other experimental methods all generate long lists of proteins and/or genes that have been identified or have varied in accumulation under the experimental conditions studied. these lists can be difficult to sort through for biologists to make sense of. here we describe a next step in data analysis--a bottom-up approach at data integration--starting with protein sequence identifications, mapping them to a common representation of the ...	2011	21082443
clostridial binary toxins: iota and c2 family portraits.	there are many pathogenic clostridium species with diverse virulence factors that include protein toxins. some of these bacteria, such as c. botulinum, c. difficile, c. perfringens, and c. spiroforme, cause enteric problems in animals as well as humans. these often fatal diseases can partly be attributed to binary protein toxins that follow a classic ab paradigm. within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-adp-ribosylation of globular actin by the a c ...	2011	22919577
rapid field detection assays for bacillus anthracis, brucella spp., francisella tularensis and yersinia pestis.	rapid detection is essential for timely initiation of medical post-exposure prophylactic measures in the event of intentional release of biological threat agents. we compared real-time pcr assay performance between the applied biosystems 7300/7500 and the razor instruments for specific detection of the causative agents of anthrax, brucellosis, tularemia and plague. furthermore, an assay detecting bacillus thuringiensis, a bacillus anthracis surrogate, was developed for field-training purposes. a ...	2011	20132255
the surgical management of injectional anthrax.		2011	20615773
characterizing the native codon usages of a genome: an axis projection approach.	codon usage can provide insights into the nature of the genes in a genome. genes that are "native" to a genome (have not been recently acquired by horizontal transfer) range in codon usage from a low-bias "typical" usage to a more biased "high-expression" usage characteristic of genes encoding abundant proteins. genes that differ from these native codon usages are candidates for foreign genes that have been recently acquired by horizontal gene transfer. in this study, we present a method for cha ...	2011	20679093
inter-α inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection.	human inter-α inhibitor proteins are endogenous human plasma proteins that function as serine protease inhibitors. inter-α inhibitor proteins can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin. inter-α inhibitor proteins administered on hour or up to 24 h after spore challenge with bacillus anthracis sterne strain protected mice from l ...	2011	20523269
anthrax--update on diagnosis and management.	human anthrax is difficult to contain. this is primarily because it is a zoonotic disease and the disease has never been contained in the livestock of india due to lack of adequate vaccination facilities. animal anthrax is very common in many parts of india. the problem of anthrax is further compounded by lack of awareness on the part of village folk who unwittingly handle the hide and share the dead animal meat and this causes cutaneous and gastrointestinal forms of anthrax respectively. hemorr ...	2011	22334971
the pore-forming protein cry5b elicits the pathogenicity of bacillus sp. against caenorhabditis elegans.	the soil bacterium bacillus thuringiensis is a pathogen of insects and nematodes and is very closely related to, if not the same species as, bacillus cereus and bacillus anthracis. the defining characteristic of b. thuringiensis that sets it apart from b. cereus and b. anthracis is the production of crystal (cry) proteins, which are pore-forming toxins or pore-forming proteins (pfps). although it is known that pfps are important virulence factors since their elimination results in reduced virule ...	2011	22216181
genetic variation and linkage disequilibrium in bacillus anthracis.	we performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 bacillus anthracis strains. we used an efficient algorithm contained within a custom software program, uniquemer, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. we discovered a total of 240 single nuc ...	2011	22355684
predictability of anthrax infection in the serengeti, tanzania.	anthrax is endemic throughout africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. however, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.we explored rec ...	2011	22318563
are we prepared for emerging and re-emerging diseases? experience and lessons from epidemics that occurred in tanzania during the last five decades.	this paper reviews preparedness for containing and controlling emerging and re-emerging diseases drawing lessons from disease events that occurred in animal and human populations in the last five decades (1961-2011). a comprehensive analysis based on retrieval and analysis of grey and published literature as well as reported cases was carried out to document type and trend of occurrence of emerging and re-emerging infectious diseases in different parts of tanzania. overall, the majority of disea ...	2011	26591993
anthrax: an update.	anthrax is a zoonotic disease caused by bacillus anthracis. it is potentially fatal and highly contagious disease. herbivores are the natural host. human acquire the disease incidentally by contact with infected animal or animal products. in the 18th century an epidemic destroyed approximately half of the sheep in europe. in 1900 human inhalational anthrax occured sporadically in the united states. in 1979 an outbreak of human anthrax occured in sverdlovsk of soviet union. anthrax continued to r ...	2011	23569822
real-time loop-mediated isothermal amplification assay for rapid and sensitive detection of anthrax spores in spiked soil and talcum powder.	loop-mediated isothermal amplification (lamp) assay is a powerful and innovative gene amplification technique that specifically amplifies the target gene under isothermal conditions with a high degree of sensitivity, rapidity and specificity. the major advantage of the lamp assay is monitoring of amplified products without the requirement of any sophisticated equipment. in the present study a real time lamp assay was employed for rapid and real time detection of bacillus anthracis spores spiked ...	2011	25187140
antibacterial and cytotoxic activities of terminalia stenostachya and terminalia spinosa.	plants that belong to the combretaceae family have long history of use in the traditional medicine systems of africa and asia for treatment of diseases and conditions associated with hiv/aids-opportunistic infections. the objective of this study was to investigate the biological activities of extracts of terminalia stenostachya engl. & diels and terminalia spinosa engl. (combretaceae), to verify the rationale for their use by traditional health practitioners in the treatment of hiv/aids patients ...	2011	25566609
swelling of face. cutaneous anthrax.		2011	23022827
incorporating retrospective clustering into a prospective cusum methodology for anthrax: evaluating the effects of disease expectation.	we analysed livestock anthrax in kazakhstan from 1960-2006, using a prospective cusum to examine the affects of expectation on the detection of spatio-temporal clusters. three methods for deriving baselines were used for cusum; a standard z-score, avg, a spatially-weighted z-score derived from local moran's i, lisa, and a moving-window average, mwa. lisa and avg elicited alarm signals in the second year that did not return below threshold during the 47-year period, while mwa signaled an alarm at ...	2011	22749547
pathogens: a new open access journal serving all those interested in infectious disease.	infection ranks alongside cardiovascular disease as the major cause of human death across the world. word health organization data for 2002 shows that 26% of all deaths, almost 15 million in number, were due to infectious disease with hiv/aids, tb and malaria being the top three responsible infections. a significant proportion of these deaths were due to lower respiratory infections and diarrheal diseases in children. the worldwide morbidity associated with infectious disease is incalculable. wh ...	2011	25436600