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decision theoretic analysis of improving epidemic detection.the potentially catastrophic impact of an epidemic specially these due to bioterrorist attack, makes developing effective detection methods essential for public health. current detection methods trade off reliability of alarms for early detection of outbreaks. the performance of these methods can be improved by disease-specific modeling techniques that take into account the potential costs and effects of an attack to provide optimal warnings and the cost and effectiveness of interventions. we st ...200718693857
naturally acquired anthrax antibodies in a cheetah (acinonyx jubatus) in botswana.an outbreak of anthrax in the jwana game reserve in jwaneng, botswana, was first observed when three cheetahs (acinonyx jubatus) died of the disease in november 2004. in the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (elisa), for antibodies to the protective antigen (pa) of bacillus anthracis. of the 23 cheetahs, 16 regularly accessed the reserve. antibodies to pa were detected in one cheetah col ...200818689661
bioterrorism. scientists seek answers, ponder future after anthrax case suicide. 200818687926
death renews biosecurity debate. 200818685659
solubility improvement of an anthrax toxin peptide inhibitor by rational amino acid randomization.we previously described a potent anthrax toxin inhibitor, based on a phage-library-selected peptide sequence, synthesized as a tetra-branched molecule on a lysine core and further modified for improvement of activity [pini et al., biochem. j., 2006, 395, 157]. this branched peptide had very low solubility because of several hydrophobic residues in the peptide sequence. this complicated molecule purification and manufacturing. here we report a rational modification of the peptide sequence, obtain ...200818680450
the anthrax vaccine adsorbed vaccine generates protective antigen (pa)-specific cd4+ t cells with a phenotype distinct from that of naive pa t cells.cellular immune responses against protective antigen (pa) of bacillus anthracis in subjects that received the anthrax vaccine adsorbed (ava) vaccine were examined. multiple cd4(+) t-cell epitopes within pa were identified by using tetramer-guided epitope mapping. pa-reactive cd4(+) t cells with a cd45ra(-) phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (pbmc) with pa-specific tetramers. surprisingly, pa-specific t cells were also detected in pbmc of ...200818678674
dual promoters control expression of the bacillus anthracis virulence factor atxa.the atxa virulence regulator of bacillus anthracis is required for toxin and capsule gene expression. atxa is a phosphotransferase system regulatory domain-containing protein whose activity is regulated by phosphorylation/dephosphorylation of conserved histidine residues. here we report that transcription of the atxa gene occurs from two independent promoters, p1 (previously described by dai et al. [z. dai, j. c. sirard, m. mock, and t. m. koehler, mol. microbiol. 16:1171-1181, 1995]) and p2, wh ...200818676674
towards on-site pathogen detection using antibody-based sensors.in this paper, the recent progress within biosensors for plant pathogen detection will be reviewed. bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. focus will be put on antibody surface-immobilisation strategies as well as the use of antibodies in the widely used sensors, quartz crystal microbalance, surface plasmon resonance and cantilevers. we will describe the available data on a ...200818675543
studies on the antifungal properties of n-thiolated beta-lactams.n-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including staphylococcus aureus and bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. we now have found that these lactams also possess antifungal activity against candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. the mode of action and str ...200818672374
heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin.anthrax lethal toxin (lt) rapidly kills macrophages from certain mouse strains in a mechanism dependent on the breakdown of unknown protein(s) by the proteasome, formation of the nalp1b (nlrp1b) inflammasome and subsequent activation of caspase-1. we report that heat-shocking lt-sensitive macrophages rapidly protects them against cytolysis by inhibiting caspase-1 activation without upstream effects on lt endocytosis or cleavage of the toxin's known cytosolic substrates (mitogen-activated protein ...200818671821
preliminary development of dna aptamer-fc conjugate opsonins.encapsulated bacteria such as virulent strains of bacillus anthracis impair phagocytosis with their capsules unless opsonized by antibodies. poly-gamma-d-glutamic acid (gamma-pdga) is the major component of the b. anthracis capsule. in this work, poly-alpha-d-glutamic acid (alpha-pdga)-coated magnetic beads (mbs) were used as surrogates to simulate vegetative b. anthracis cells and avoid the hazards of working with virulent bacteria. dna aptamers were developed against the alpha-linked pdga-mbs ...200918671260
intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters.the current model for virulence gene regulation in bacillus anthracis involves several trans-acting factors, the most important of which appears to be the anthrax toxin activator encoded by the atxa gene. atxa is a positive regulator of the toxin genes paga, cya and lef, and of a number of other plasmid- and chromosome-encoded genes. the atxa protein (56 kda) possesses a predicted winged-helix dna-binding domain and phosphotransferase system-regulated domains, but the mechanism for positive regu ...200818667583
early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.effective prophylaxis and treatment for infections caused by biological threat agents (bta) rely upon early diagnosis and rapid initiation of therapy. most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most bta are indistinguishable flu-like signs.200818667072
stable and potent polyvalent anthrax toxin inhibitors: raft-inspired domain formation in liposomes that contain pegylated lipids. 200818666271
[the strategic plan for preparedness and response to bioterrorism in korea].following the anthrax bioterrorism attacks in the us in 2001, the korean government established comprehensive countermeasures against bioterrorism. these measures included the government assuming management of all infectious agents that cause diseases, including smallpox, anthrax, plaque, botulism, and the causative agents of viral hemorrhagic fevers (ebola fever, marburg fever, and lassa fever) for national security. in addition, the korean government is reinforcing the ability to prepare and r ...200818664725
["remarks on the so-called spleen fire": an early medical-scientific document in liechtenstein]. 200118663830
design and synthesis of aryl ether inhibitors of the bacillus anthracis enoyl-acp reductase.the problem of increasing bacterial resistance to the current generation of antibiotics is well documented. known resistant pathogens such as methicillin-resistant staphylococcus aureus are becoming more prevalent, while the potential exists for developing drug-resistant pathogens for use as bioweapons, such as bacillus anthracis. the biphenyl ether antibacterial agent, triclosan, exhibits broad-spectrum activity by targeting the fatty acid biosynthetic pathway through inhibition of enoyl-acyl c ...200818663709
effect of bacillus anthracis virulence factors on human dendritic cell activation.bacillus anthracis possesses three primary virulence factors: capsule, lethal toxin (lt), and edema toxin (et). dendritic cells (dcs) are critical to innate and acquired immunity and represent potential targets for these factors. we examined the ability of b. anthracis spores and bacilli to stimulate human monocyte-derived dc (mddc), primary myeloid dc (mdc), and plasmacytoid dc (pdc) cytokine secretion. exposure of mddcs and mdcs to spores or vegetative bacilli of the genetically complete strai ...200818662733
characterization of the catalytic activity of the gamma-phage lysin, plyg, specific for bacillus anthracis.bacillus anthracis causes anthrax, a lethal disease affecting humans that has attracted attention due to its bioterrorism potential. plyg is a lysin of gamma-phage, which specifically infects b. anthracis and lyses its cell wall. plyg contains a t7 lysozyme-like amidase domain, which appears to be the catalytic domain, in the n-terminal region and has a high degree of sequence similarity with plyl, which is an n-acetylmuramoyl-l-alanine amidase encoded by the b. anthracis genome. here, we demons ...200818662316
protein expression pattern of murine macrophages treated with anthrax lethal toxin.anthrax lethal toxin (letx; a combination of protective antigen and lethal factor) secreted by the vegetative cells of bacillus anthracis is cytotoxic for certain macrophage cell lines. the role of letx in mediating these effects is complicated largely due to the difficulty in identifying and assigning functions to the affected proteins. to analyze the protein profile of murine macrophages treated with letx, we employed two-dimensional polyacrylamide gel electrophoresis and maldi-tof ms, and int ...200818657635
recombinant bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen.inactivated bacillus anthracis spores given with protective antigen (pa) contribute to immunity against anthrax in several animal models. antiserum raised against whole irradiated b. anthracis spores has been shown to have anti-germination and opsonic activities in vitro. based on these observations, we hypothesized that surface-exposed spore proteins might serve as supplemental components of a pa-based anthrax vaccine. the protective anti-spore serum was tested for reactivity with recombinant f ...200818657585
the response to a specific germinant by bacillus anthracis spores in primary mouse macrophages is modulated by a protein encoded on the pxo1 plasmid.a bacillus anthracis sterne pxo1 plasmid-encoded protein designated cot43 was found in coat extracts of purified spores. cot43 is a tetratricopeptide repeat domain protein related to those which function as phosphatases in the sporulation phosphorelay and as regulators of competence and pathogenic factors. the synthesis of cot43 began in the late exponential phase downstream from a sigmaa promoter (as mapped by race) and it was present at least until the formation of phase white endospores. ther ...200818654763
functional expression of bacillus anthracis protective antigen in e. coli.the protective antigen (pa) of bacillus anthracis is a potent immunogen and an important candidate vaccine. in addition, it is used in monitoring systems like enzyme-linked immunosorbent assay to assess antibodies against pa in immunized subjects. the low level of pa production in b. anthracis and the difficulty of separating it from other bacterial components have made the researchers do different studies with the aim of producing recombinant pa (rpa). in this study, to produce rpa as a recombi ...200918654743
nanotube-assisted protein deactivation.conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. however, remotely controlling the activity of proteins in these conjugates has never been demonstrated. here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. we designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can se ...200818654449
the behaviour of virulent bacillus anthracis strain ao843 in rabbits. 200918650035
a dual-purpose protein ligand for effective therapy and sensitive diagnosis of anthrax.this article reports the design of a bivalent protein ligand with dual use in therapy and diagnosis of anthrax caused by bacillus anthracis. the ligand specifically binds to pa and thereby blocks the intracellular delivery of lf and ef toxins that, respectively, cause cell lysis and edema. the ligand is a chimeric scaffold with two pa-binding domains (called vwa) linked to an igg-fc frame. molecular modeling and binding measurements reveal that the vwa-fc dimer binds to pa with high affinity (k( ...200818649128
the decline of antibiotic era--new approaches for antibacterial drug discovery.infectious diseases still remain the main cause of human premature deaths; especially in developing countries. the emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug-resistant strains) have created the need for the development of novel therapeutic agents. only two new classes of antibiotics of novel mechanisms of action (linezolid and daptomycin) have been introduced into the market during the last three decades. the recent progress in molecular biology and bact ...200818646395
sizing the bacillus anthracis pa63 channel with nonelectrolyte poly(ethylene glycols).nonelectrolyte polymers of poly(ethylene glycol) (peg) were used to estimate the diameter of the ion channel formed by the bacillus anthracis protective antigen 63 (pa(63)). based on the ability of different molecular weight pegs to partition into the pore and reduce channel conductance, the pore appears to be narrower than the one formed by staphylococcus aureus alpha-hemolysin. numerical integration of the peg sample mass spectra and the channel conductance data were used to refine the estimat ...200818645196
mechanistic modeling of emergency events: assessing the impact of hypothetical releases of anthrax.a modular system for source-to-dose-to-effect modeling analysis has been developed based on the modeling environment for total risk studies (mentor),((1)) and applied to study the impacts of hypothetical atmospheric releases of anthrax spores. the system, mentor-2e (mentor for emergency events), provides mechanistically consistent analysis of inhalation exposures for various release scenarios, while allowing consideration of specific susceptible subpopulations (such as the elderly) at the resolu ...200818643828
the type iii pantothenate kinase encoded by coax is essential for growth of bacillus anthracis.in bacillus anthracis, the novel type iii pantothenate kinase (pank(ba); encoded by coax) catalyzes the first committed step in coenzyme a biosynthesis. we have demonstrated by analyzing the growth characteristics of a conditional coax mutant that pank(ba) is an essential enzyme, thus contributing to its validation as a new antimicrobial target.200818641144
recovery efficiencies of anthrax spores and ricin from nonporous or nonabsorbent and porous or absorbent surfaces by a variety of sampling methods*.the 2001 anthrax letter cases brought into focus the need to establish the most effective environmental sampling procedures. results are presented from two studies aimed at establishing the best procedures for everyday surfaces likely to be contaminated after the release of environmentally stable bioaggressive agents, as exemplified by anthrax spores and ricin. with anthrax spores, contact plates, with mean retrieval rates of 28-54%, performed better than other methods by a wide margin for flat ...200818637873
controlled plasmonic nanostructures for surface-enhanced spectroscopy and sensing.after its discovery more than 30 years ago, surface-enhanced raman spectroscopy (sers) was expected to have major impact as a sensitive analytical technique and tool for fundamental studies of surface species. unfortunately, the lack of reliable and reproducible fabrication methods limited its applicability. in recent years, sers has enjoyed a renaissance, and there is renewed interest in both the fundamentals and applications of sers. new techniques for nanofabrication, the design of substrates ...200818630932
overview of the inactivation by 254 nm ultraviolet radiation of bacteria with particular relevance to biodefense.our goal was to ultimately predict the sensitivity of untested bacteria (including those of biodefense interest) to ultraviolet (uv) radiation. in this study, we present an overview and analysis of the relevant 254 nm data previously reported and available in the literature. the amount of variability in this data prevented us from determining an "average" response for any bacterium. therefore, we developed particular selection criteria to include the data in our analysis and suggested future gui ...200818627518
in vivo demonstration and quantification of intracellular bacillus anthracis in lung epithelial cells.inhalational anthrax is initiated by the entry of bacillus anthracis spores into the lung. a critical early event in the establishment of an infection is the dissemination of spores from the lung. using in vitro cell culture assays, we previously demonstrated that b. anthracis spores are capable of entering into epithelial cells of the lung and crossing a barrier of lung epithelial cells without apparent disruption of the barrier integrity, suggesting a novel portal for spores to disseminate fro ...200818625737
the crystal structure of ump kinase from bacillus anthracis (ba1797) reveals an allosteric nucleotide-binding site.uridine monophosphate (ump) kinase is a conserved enzyme that catalyzes the atp-driven conversion of uridylate monophosphate into uridylate diphosphate, an essential metabolic step. in prokaryotes, the enzyme exists as a homohexamer that is regulated by various metabolites. whereas the enzymatic mechanism of ump kinase (uk) is well-characterized, the molecular basis of its regulation remains poorly understood. here we report the crystal structure of uk from bacillus anthracis (ba1797) in complex ...200818625239
anthrax lethal toxin suppresses chemokine production in human neutrophil nb-4 cells.microarray analysis was used to investigate the effects of bacillus anthracis lethal toxin (lt) on human neutrophil-like nb-4 cells to identify markers of intoxication. genes down-regulated after a 2h lt exposure included those encoding chemokines and transcription factors. significant decreases in the mrna of interleukin-8, ccl20, ccl3 and ccl4, which are important chemoattractants for immune cells, were observed using real-time pcr (12.3, 4.0, 4.1 and 2.2-fold (p<0.05), respectively). the decr ...200818625197
amide bonds assemble pili on the surface of bacilli.pilin precursors are the building blocks of pili on the surface of gram-positive bacteria; however, the assembly mechanisms of these adhesive fibers are unknown. here, we describe the chemical bonds that assemble bcpa pilin subunits on the surface of bacillus cereus. sortase d cleaves bcpa precursor between the threonine (t) and the glycine (g) residues of its lpxtg sorting signal and catalyzes formation of an amide bond between threonine (t) of the sorting signal and lysine (k) in the ypkn moti ...200818621716
novel inhibitors of anthrax edema factor.several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema factor (ef) of bacillus anthracis. these disturb cellular metabolism by catalyzing production of excessive amounts of the regulatory molecule camp. here, a structure-based method, where a 3d-pharmacophore that fit the active site of ef was constructed from fragments, was used to identify non-nucleotide inhibitors of ef. a library of small molecule fragments was docked to the ef-active site in existing crystal structur ...200818620864
[vaccines, biotechnology and their connection with induced abortion].diploid cells (wi-38, mrc-5) vaccines have their origin in induced abortions. among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis a, chickenpox, and herpes zoster. nowadays, other abortion tainted vaccines cultivated on transformed cells (293, per.c6) are in the pipeline: flu, respiratory syncytial and parainfluenza viruses, hiv, west nile virus, ebola, marburg and lassa, hepatitis b and c, foot and mouth disease, japanese encephalitis, dengue ...200818611078
combating the threat of anthrax: a quantitative structure-activity relationship approach.bacterial agents or products more likely to be used as biological weapons of mass destruction are bacillus anthracis, francisella tularensis, yersinia pestis, and the neurotoxin of clostridium botulinum. anthrax is an acute infectious disease with a high mortality rate caused by bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. in this paper, we developed 7 qsar models on penicillin-based inhibitors of the class a and b beta-lactamases from b. anth ...200818611038
microbial forensics: dna fingerprinting of bacillus anthracis (anthrax). 200818609763
efficacy of oritavancin in a murine model of bacillus anthracis spore inhalation anthrax.the inhaled form of bacillus anthracis infection may be fatal to humans. the current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. the potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against b. anthracis (mic against ames strain, 0.015 microg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. in postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of or ...200818606841
real-time pcr system targeting a chromosomal marker specific for bacillus anthracis.specific identification of bacillus anthracis and differentiation from closely related bacillus cereus and bacillus thuringiensis strains is still a major diagnostic problem. commercially available diagnostic kits targeting plasmid-markers cannot differentiate between b. anthracis, non-anthracis bacillus species harbouring anthrax-specific virulence plasmids, and plasmidless b. anthracis strains. a taqman pcr assay was designed targeting sequences of gene locus ba_5345 of the b. anthracis strain ...200818602986
a fluorimetric assay for real-time monitoring of adenylyl cyclase activity based on terbium norfloxacin.adenylyl cyclases catalyze the production of the second messenger cyclic amp from atp. until now, there has been no fluorescent adenylyl cyclase assay known that is applicable to high-throughput screening and kinetic determinations that can directly monitor the turnover of the unmodified substrate atp. in this study, a fluorescence-based assay is described using the ca(ii)- and calmodulin-dependent adenylyl cyclase edema factor (ef) from bacillus anthracis and tb(iii)-norfloxacin as probe for th ...200818601890
the vaccines development forum. 200818600591
birth defects among infants born to women who received anthrax vaccine in pregnancy.in response to bioterrorism threats, anthrax vaccine has been used by the us military and considered for civilian use. concerns exist about the potential for adverse reproductive health effects among vaccine recipients. this retrospective cohort evaluated birth defects, in relation to maternal anthrax vaccination, among all infants born to us military service women between 1998 and 2004. department of defense databases defined maternal vaccination and infant diagnoses; multivariable regression m ...200818599489
genotyping of bacillus cereus strains by microarray-based resequencing.the ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. in this regard, bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the b. cereus group that can cause diverse diseases. we employed custom-designed resequencing arrays (ras) based on the genome sequence of bacillus anthr ...200818596941
zoonoses-with friends like this, who needs enemies?zoonoses are infections that are spread from animals to humans. most often, humans are "dead-end" hosts, meaning that there is no subsequent human-to-human transmission. if one considers most of the emerging infections that were recognized at the end of the last century and the beginning of this century, they would fall into the category of zoonoses. one of the most important common traits exhibited by infections that have been or can be eliminated from the face of the earth (e.g. smallpox, meas ...200818596867
toxicity of anthrax toxin is influenced by receptor expression.anthrax toxin protective antigen (pa) binds to its cellular receptor, and seven subunits self-associate to form a heptameric ring that mediates the cytoplasmic entry of lethal factor or edema factor. the influence of receptor type on susceptibility to anthrax toxin components was examined using chinese hamster ovary (cho) cells expressing the human form of one of two pa receptors: tem8 or cmg2. unexpectedly, pa alone, previously believed to only mediate entry of lethal factor or edema factor, wa ...200818596206
zoonosis update. anthrax. 200818593313
assessment of acute injuries, exposure to environmental toxins, and five-year health surveillance of new york police department working dogs following the september 11, 2001, world trade center terrorist attack.to determine deployment logistics of new york police department (nypd) working dogs that assisted in relief efforts at the world trade center (wtc) site following the september 11, 2001, terrorist attack; establish types and rates of related acute injuries and illnesses; identify environmental toxin exposures; and determine long-term (ie, 5-year) health effects of deployment.200818593312
identification and characterization of bacillus anthracis spores by multiparameter flow cytometry.in response to the need for methods that can rapidly detect potentially virulent bacillus anthracis spores, we developed a two-color flow cytometric assay capable of simultaneously identifying b. anthracis spores and the presence of spore-associated protective antigen, a virulence marker for strains harboring the pxo1 plasmid.200818586967
an in vivo passive protection assay for the evaluation of immunity in ava-vaccinated individuals.samples of human plasma from anthrax vaccine adsorbed (ava, biothrax)-vaccinated individuals were used to demonstrate passive protection of a/j mice from a lethal challenge with the sterne strain of anthrax bacteria. the maximum concentration of human anti-protective antigen igg in mouse sera 24 h after injection of 260 microg of anti-pa igg was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). mice showed significant survival (p<or=0.001) after injection of serial dilutions ...200818586363
protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently.calmodulin (cam), a eukaryotic calcium sensor that regulates diverse biological activities, consists of n- and c-terminal globular domains (n-cam and c-cam, respectively). cam serves as the activator of cyaa, a 188-kda adenylyl cyclase toxin secreted by bordetella pertussis, which is the etiologic agent for whooping cough. upon insertion of the n-terminal adenylyl cyclase domain (acd) of cyaa to its targeted eukaryotic cells, cam binds to this domain tightly ( approximately 200 pm affinity). thi ...200818583346
inhalation anthrax: dose response and risk analysis.the notion that inhalation of a single bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. the difficulty in ...200818582166
biosynthesis of the 3,4-dihydroxybenzoate moieties of petrobactin by bacillus anthracis.the biosynthesis of the 3,4-dihydroxybenzoate moieties of the siderophore petrobactin, produced by b. anthracis str. sterne, was probed by isotopic feeding experiments in iron-deficient media with a mixture of unlabeled and d-[(13)c6]glucose at a ratio of 5:1 (w/w). after isolation of the labeled siderophore, analysis of the isotopomers was conducted via one-dimensional (1)h and (13)c nmr spectroscopy, as well as (13)c-(13)c dqfcosy spectroscopy. isotopic enrichment and (13)c-(13)c coupling cons ...200818582113
antibacterial activity of labdane diterpenoids from stemodia foliosa.as part of a continuing interest in exploring the chemistry of brazilian medicinal plants, three new labdane diterpenoids, 6alpha-acetoxymanoyl oxide (1), 6alpha-malonyloxymanoyl oxide (2), and 6alpha-malonyloxy-n-butyl ester manoyl oxide (3), together with the known betulinic acid, lupeol, sitosterol, and stigmasterol, were isolated from the aerial parts of stemodia foliosa. the structures of 1-3 were established on the basis of interpretation of spectroscopic data, including hresims, and 1d an ...200818582112
[zoonoses with wildlife reservoirs: a threat to public health and the economy].the world is experiencing an increase in emergent infections as a result of anthropogenic changes of the biosphere and globalization. global warming unrestricted exploitation of natural resources such as forests and fisheries, urbanization, human migration, and industrialization of animal husbandry cause environmental destruction and fragmentation. these changes of the biosphere favor local emergence of zoonoses from their natural biotopes and their interaction with domestic animals and human po ...200818575667
imported tropical infectious ulcers in travelers.skin ulcers are a commonly encountered problem at departments of tropical dermatology in the western world. furthermore, the general dermatologist is likely to be consulted more often for imported chronic skin ulcers because of the ever-increasing travel to and from tropical countries. the most common cause of chronic ulceration throughout the world is probably pyoderma. however, in some parts of the world, cutaneous leishmaniasis is one of the most prevalent causes. mycobacterium ulcerans is an ...200818572973
[phage lytic enzymes--new hope in battle against bacterial infections].bacteriophage lytic enzymes are produced during phage replication cycle in bacterial cells. lysis of bacterial cell wall enables release of virus particles. bakteriophage enzymes activity are highly specific, therefore they are able to destroy selected bacterial species, also resistant to antibiotics. this creates new possibilities in therapy of bacterial infections.200718572503
analysis of suspicious powders following the post 9/11 anthrax scare.following the 9/11 terrorist attacks, set environmental, inc., a chicago-based environmental and hazardous materials management company received a large number of suspicious powders for analysis.200818570168
properties and applications of antimicrobial peptides in biodefense against biological warfare threat agents.recent advances in knowledge of the properties of antimicrobial peptides (amps) are reviewed. amps are typically small, positively charged, amphipathic peptides that interact electrostatically and non-stereospecifically with the bacterial cell membrane, resulting in its permeabilization and cell death. classes of amps, their mechanisms of action, hemolytic activity, and cytotoxicity towards host cells are discussed. a particular focus is amps with potential for use in defense against biological ...200818568863
groel as a molecular scaffold for structural analysis of the anthrax toxin pore.we analyzed the 440-kda transmembrane pore formed by the protective antigen (pa) moiety of anthrax toxin in the presence of groel by negative-stain electron microscopy. groel binds both the heptameric pa prepore and the pa pore. the latter interaction retards aggregation of the pore, prolonging its insertion-competent state. two populations of unaggregated pores were visible: groel-bound pores and unbound pores. this allowed two virtually identical structures to be reconstructed, at 25-a and 28- ...200818568038
multiplex pathogen detection based on spatially addressable microarrays of barcoded resins.suspension microsphere immunoassays are rapidly gaining recognition in antigen identification and infectious disease biodetection due to their simplicity, versatility and high-throughput multiplex screening. we demonstrate a multiplex assay based on antibody-functionalized barcoded resins (bcrs) to identify pathogen antigens in complex biological fluids. the binding event of a particular antibody on given bead (fluorescence) and the identification of the specific pathogen agent (vibrational fing ...200818566958
domain specificity of the human antibody response to bacillus anthracis protective antigen.protective antigen (pa) is the cell surface recognition moiety of the bacillus anthracis a-b toxin system, and the active immunogenic component in the currently licensed human anthrax vaccine (biothrax, or ava). the serum antibody response to the pa protein is polyclonal and complex both in terms of the antibody combining sites utilized to bind pa and the pa-associated epitopes recognized. we have cloned, sequenced, and expressed a large panel of pa-specific human monoclonal antibodies from seve ...200818565627
de novo asymmetric synthesis of anthrax tetrasaccharide and related tetrasaccharide.a de novo asymmetric approach to the natural product anthrax tetrasaccharide 1 and an analogue 2 with an anomeric hexyl azide group has been developed from acetylfuran. the construction of the tetrasaccharide was achieved by a traditional [3 + 1] glycosylation strategy. an iterative diastereoselective palladium-catalyzed glycosylation, luche reduction, diastereoselective dihydroxylation, and regioselective acylation were employed for the assembly of the l-rhamno-trisaccharide building block. the ...200818563936
the effect of salt and phage concentrations on the binding sensitivity of magnetoelastic biosensors for bacillus anthracis detection.this article presents an investigation of the effect of salt and phage concentrations on the binding affinity of magnetoelastic (me) biosensors. the sensors were fabricated by immobilizing filamentous phage on the me platform surface for the detection of bacillus anthracis spores. in response to the binding of spores to the phage on the me biosensor, a corresponding decrease occurs in resonance frequency. transmission electron microscopy (tem) was used to verify the structure of phage under diff ...200818563848
chemical synthesis and immunological properties of oligosaccharides derived from the vegetative cell wall of bacillus anthracis. 200818563773
the bioterrorism threat and dual-use biotechnological research: an israeli perspective.israel has a long history of concern with chemical and biological threats, since several hostile states in the middle east are likely to possess such weapons. the twin-tower terrorist attacks and anthrax envelope scares of 2001 were a watershed for public perceptions of the threat of unconventional terror in general and of biological terror in particular. new advances in biotechnology will only increase the ability of terrorists to exploit the burgeoning availability of related information to de ...201018563629
saccharides cross-reactive with bacillus anthracis spore glycoprotein as an anthrax vaccine component.bacillus anthracis is a spore-forming bacterium that causes anthrax in humans and in other mammals. the glycoprotein bcla (bacillus collagen-like protein of anthracis) is a major constituent of the exosporium, the outermost surface of b. anthracis spores. the glycosyl part of bcla is an oligosaccharide composed of 2-o-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-glucose, referred to as anthrose, and three rhamnose residues. a structure similar to anthrose, 4-(3-hydroxy-3-methylbutanamid ...200818562275
pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: application for treatment of diarrhea.acute secretory diarrhea induced by infection with enterotoxigenic strains of escherichia coli involves binding of stable toxin (sta) to its receptor on the intestinal brush border, guanylyl cyclase type c (gc-c). intracellular cgmp is elevated, inducing increase in chloride efflux and subsequent accumulation of fluid in the intestinal lumen. we have screened a library of compounds and identified a pyridopyrimidine derivatives {5-(3-bromophenyl)-1,3-dimethyl-5,11-dihydro-1h-indeno[2',1':5,6]pyri ...200818559851
application of carbohydrate microarray technology for the detection of burkholderia pseudomallei, bacillus anthracis and francisella tularensis antibodies.we developed a microarray platform by immobilizing bacterial 'signature' carbohydrates onto epoxide modified glass slides. the carbohydrate microarray platform was probed with sera from non-melioidosis and melioidosis (burkholderia pseudomallei) individuals. the platform was also probed with sera from rabbits vaccinated with bacillus anthracis spores and francisella tularensis bacteria. by employing this microarray platform, we were able to detect and differentiate b. pseudomallei, b. anthracis ...200818558401
modeling the incubation period of inhalational anthrax.ever since the pioneering work of philip sartwell, the incubation period distribution for infectious diseases is most often modeled using a lognormal distribution. theoretical models based on underlying disease mechanisms in the host are less well developed. this article modifies a theoretical model originally developed by brookmeyer and others for the inhalational anthrax incubation period distribution in humans by using a more accurate distribution to represent the in vivo bacterial growth pha ...200818556642
dose-response models for inhalation of bacillus anthracis spores: interspecies comparisons.because experiments with bacillus anthracis are costly and dangerous, the scientific, public health, and engineering communities are served by thorough collation and analysis of experiments reported in the open literature. this study identifies available dose-response data from the open literature for inhalation exposure to b. anthracis and, via dose-response modeling, characterizes the response of nonhuman animal models to challenges. two studies involving four data sets amenable to dose-respon ...200818554269
evaluation of two selective media for the isolation of bacillus anthracis.to evaluate two selective media, polymyxin, lysozyme, ethylenediaminetetraacetic acid, thallium acetate (plet) agar and r&f anthracis chromogenic agar (chra), for the isolation and selection of bacillus anthracis.200818554264
high-throughput, single-cell analysis of macrophage interactions with fluorescently labeled bacillus anthracis spores.the engulfment of bacillus anthracis spores by macrophages is an important step in the pathogenesis of inhalational anthrax. however, from a quantitative standpoint, the magnitude to which macrophages interact with and engulf spores remains poorly understood, in part due to inherent limitations associated with commonly used assays. to analyze phagocytosis of spores by raw264.7 macrophage-like cells in a high-throughput, nonsubjective manner, we labeled b. anthracis sterne 7702 spores prior to in ...200818552183
progressive and destructive hair follicle infections in a murine cutaneous anthrax model.hair follicles may allow pathogen entry because they represent potential barrier defects and because there is immunological privilege within actively growing follicles. experimental cutaneous bacillus anthracis infections in mice have previously shown prominent organism invasion and proliferation within hair follicles. for the present study, c57bl/6 mice were inoculated with b. anthracis (sterne) spores onto abraded skin with either anagen (actively growing) or telogen (inactive) hair follicles; ...200818551767
cutaneous anthrax associated with drum making using goat hides from west africa--connecticut, 2007.on august 29, 2007, the connecticut department of public health was notified by a physician of suspect cutaneous anthrax involving a drum maker and one of his three children. the drum maker had been working with untreated goat hides from guinea in west africa. this report summarizes results of the joint epidemiologic and environmental investigation conducted by public health officials, environmental agencies, and law enforcement authorities. the investigation revealed that the drum maker was exp ...200818551098
a bacillus thuringiensis strain producing a polyglutamate capsule resembling that of bacillus anthracis.bacillus thuringiensis serovar monterrey strain bgsc 4aj1 produced a microscopically visible capsule that reacted with a fluorescent antibody specific for the poly-gamma-d-glutamic acid (pga) capsule of bacillus anthracis. pga capsule biosynthesis genes with 75%, 81%, 72%, 65% and 63% similarity, respectively, to those of the b. anthracis capbcade cluster were present on a plasmid (paj1-1). strain bgsc 4aj1, together with five strains of bacillus cereus that hybridized to a pga cap gene probe, w ...200818549401
u.s. military service members' perceptions of the anthrax vaccine immunization program.this research identifies the perceptions of u.s. military service members regarding the department of defense anthrax vaccine immunization program (avip). the service members' perceptions were addressed in the dimensions of ethics, effectiveness, and safety, as well as the overall perceptions of the avip. the study, conducted in october 2004, randomly selected active duty service members from the uniformed services assigned to a caribbean military base who participated in the avip during the per ...200818543562
virulence gene expression is independent of resde-regulated respiration control in bacillus anthracis.the resde two-component system regulates the synthesis of several components of the aerobic and anaerobic respiratory pathways in bacilli. the resd response regulator transcription factor has been implicated in the regulation of virulence factors in a number of gram-positive species, including bacillus anthracis. the precise deletions of resd and rese in b. anthracis that retained the classical respiratory phenotypes did not affect the expression of the gene for the protective antigen of the ant ...200818539743
synthesis and screening of small molecule inhibitors of anthrax edema factor.the synthesis and development of a novel class of molecules that inhibit anthrax edema factor, an adenylyl cyclase, is reported. these molecules are derived from the initial discovery that histidine and imidazole adducts of the prostaglandin pge(2) reduce the net secretory response of cholera toxin-challenged mice and act directly on the action of anthrax edema factor, a calmodulin-dependent adenylyl cyclase. the simple enones examined in this letter were prepared by palladium-catalyzed suzuki r ...200818539457
nosocomial infection of serratia marcescens may induce a protective effect in monkeys exposed to bacillus anthracis.this study was originally designed to collect data on the natural history of inhalational anthrax in a new nonhuman primate model. an uncontrollable event created a new experimental condition which allowed us to retrospectively evaluate the power of the innate immune system to protect from an aerosol exposure of b. anthracis. five african green monkeys (agms) had intravenous catheters implanted. one catheter was accidentally pulled out, leaving four agms with catheters and one without. all were ...200818538851
detection of agar, by analysis of sugar markers, associated with bacillus anthracis spores, after culture.detection of small quantities of agar associated with spores of bacillus anthracis could provide key information regarding its source or growth characteristics. agar, widely used in growth of bacteria on solid surfaces, consists primarily of repeating polysaccharide units of 3,6-anhydro-l-galactose (agal) and galactose (gal) with sulfated and o-methylated galactoses present as minor constituents. two variants of the alditol acetate procedure were evaluated for detection of potential agar markers ...200818538426
dna microarrays in the clinic: infectious diseases.we argue that the most-promising area of clinical application of microarrays in the foreseeable future is the diagnostics and monitoring of infectious diseases. microarrays for the detection and characterization of human pathogens have already found their way into clinical practice in some countries. after discussing the persistent, yet often underestimated, importance of infectious diseases for public health, we consider the technologies that are best suited for the detection and clinical inves ...200818536036
genetic medicine strategies to protect against bioterrorism. 200618528482
unexplained deaths in connecticut, 2002-2003: failure to consider category a bioterrorism agents in differential diagnoses.recognition of bioterrorism-related infections by hospital and emergency department clinicians may be the first line of defense in a bioterrorist attack.200818525371
unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant staphylococcus aureus and bacillus anthracis.this study describes the antibacterial properties of synthetically produced mixed aryl-alkyl disulfide compounds as a means to control the growth of staphylococcus aureus and bacillus anthracis. some of these compounds exerted strong in vitro bioactivity. our results indicate that among the 12 different aryl substituents examined, nitrophenyl derivatives provide the strongest antibiotic activities. this may be the result of electronic activation of the arylthio moiety as a leaving group for nucl ...200818524602
mechanisms of substrate selectivity for bacillus anthracis thymidylate kinase.bacillus anthracis is well known in connection with biological warfare. the search for new drug targets and antibiotics is highly motivated because of upcoming multiresistant strains. thymidylate kinase is an ideal target since this enzyme is at the junction of the de novo and salvage synthesis of dttp, an essential precursor for dna synthesis. here the expression and characterization of thymidylate kinase from b. anthracis (ba-tmpk) is presented. the enzyme phosphorylated deoxythymidine-5'-mono ...200818523102
characterization of bacillus anthracis arginase: effects of ph, temperature, and cell viability on metal preference.arginase (rocf) hydrolyzes l-arginine to l-ornithine and urea. while previously characterized arginases have an alkaline ph optimum and require activation with manganese, arginase from helicobacter pylori is optimally active with cobalt at ph 6. the arginase from bacillus anthracis is not well characterized; therefore, this arginase was investigated by a variety of strategies and the enzyme was purified.200818522738
an ounce of prevention is worth a pound of cure: improving communication to reduce mortality during bioterrorism responses.to identify communication needs and evaluate the effectiveness of alternative communication strategies for bioterrorism responses.200818522248
survey of nursing knowledge on bioterrorism.with the aim of identifying intervention programmes within the framework of basic and permanent nursing training, we evaluated the knowledge of 187 nurses and nursing students concerning biological emergencies. a questionnaire was used to identify their knowledge of the pathogens that may be used in a terrorist attack and measures for containing them, and their perception of the danger to public health. analysis of the responses showed that the undergraduates studying for the triennial degree we ...200818519061
recent insights into the biology and biomedical applications of flock house virus.flock house virus (fhv) is a nonenveloped, icosahedral insect virus whose genome consists of two molecules of single-stranded, positive-sense rna. fhv is a highly tractable system for studies on a variety of basic aspects of rna virology. in this review, recent studies on the replication of fhv genomic and subgenomic rna are discussed, including a landmark study on the ultrastructure and molecular organization of fhv replication complexes. in addition, we show how research on fhv b2, a potent su ...200818516498
gamma irradiation can be used to inactivate bacillus anthracis spores without compromising the sensitivity of diagnostic assays.the use of bacillus anthracis as a biological weapon in 2001 heightened awareness of the need for validated methods for the inactivation of b. anthracis spores. this study determined the gamma irradiation dose for inactivating virulent b. anthracis spores in suspension and its effects on real-time pcr and antigen detection assays. strains representing eight genetic groups of b. anthracis were exposed to gamma radiation, and it was found that subjecting spores at a concentration of 10(7) cfu/ml t ...200818515484
cloning and development of synthetic internal amplification control for bacillus anthracis real-time polymerase chain reaction assays.an internal amplification control (iac) was developed for bacillus anthracis rpob gene detection using taqman assay. synthetic iac oligonucleotides were subcloned using vector pdg1730 for ectopic integration into host bacillus subtilis strain 1a772 genome. differentially labeled target and iac probes were used in real-time polymerase chain reaction (pcr) assays. there was no nonspecific cross-detection in single-well reactions. limit of detection for both target and iac dna was 5 fg correspondin ...200818513914
a nod2-nalp1 complex mediates caspase-1-dependent il-1beta secretion in response to bacillus anthracis infection and muramyl dipeptide.nod2, a nod-like receptor (nlr), is an intracellular sensor of bacterial muramyl dipeptide (mdp) that was suggested to promote secretion of the proinflammatory cytokine il-1beta. yet, the molecular mechanism by which nod2 can stimulate il-1beta secretion, and its biological significance were heretofore unknown. we found that nod2 through its n-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger il-1beta processing and secretion in mdp-stimulated macrophages, whe ...200818511561
anthrax-associated shock.recent events have brought attention to the potential of bacillus anthracis as an agent of bioterrorism. the shock like state of anthrax is invariably associated with high mortality, despite anti-microbial and supportive therapy. multi-system dysfunction is typical, including: enhanced vascular permeability, hemorrhage and inflammation. important questions concerning the pathophysiology of anthrax-associated shock remain unanswered, including the effects of b. anthracis infection on cardiac func ...200818508494
substrate cleavage analysis of furin and related proprotein convertases. a comparative study.we present the data and the technology, a combination of which allows us to determine the identity of proprotein convertases (pcs) related to the processing of specific protein targets including viral and bacterial pathogens. our results, which support and extend the data of other laboratories, are required for the design of effective inhibitors of pcs because, in general, an inhibitor design starts with a specific substrate. seven proteinases of the human pc family cleave the multibasic motifs ...200818505722
adrenal gland hemorrhage in patients with fatal bacterial infections.a wide spectrum of adrenal gland pathology is seen during bacterial infections. hemorrhage is particularly associated with meningococcemia, while abscesses have been described with several neonatal infections. we studied adrenal gland histopathology of 65 patients with bacterial infections documented in a variety of tissues by using immunohistochemistry. the infections diagnosed included neisseria meningitidies, group a streptococcus, rickettsia rickettsii, streptococcus pneumoniae, staphylococc ...200818500257
design and synthesis of 2-pyridones as novel inhibitors of the bacillus anthracis enoyl-acp reductase.enoyl-acp reductase (enr), the product of the fabi gene, from bacillus anthracis (baenr) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis. a number of novel 2-pyridone derivatives were synthesized and shown to be potent inhibitors of baenr.200818499454
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