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new insights into gastrointestinal anthrax infection.bacterial infections are the primary cause of gastrointestinal (gi) disorders in both developing and developed countries, and are particularly dangerous for infants and children. bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. importantly, there are more case reports of gi anthrax infection in children than inhalational disease. early diagnosis is difficult and widespread systemic disease develops rapid ...201525577136
regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.it is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. we demonstrate here that the matrix receptor anthrax toxin receptor 1 (antxr1), also known as tumor endothelial marker 8 (tem8), is an essential component of these mechanisms. loss of tem8 function in mice causes reduced synthesis of ...201525572963
a ratiometric fluorescent nanoprobe based on terbium functionalized carbon dots for highly sensitive detection of an anthrax biomarker.a ratiometric fluorescent nanoprobe based on terbium functionalized carbon dots (cds) was designed to detect dipicolinic acid (dpa) as an anthrax biomarker with high selectivity and sensitivity. cds were generated by one-step synthesis using an ethylenediaminetetraacetic acid precursor, and served as a scaffold for coordination with tb(3+) and a fluorescence reference.201525706307
using common spatial distributions of atoms to relate functionally divergent influenza virus n10 and n11 protein structures to functionally characterized neuraminidase structures, toxin cell entry domains, and non-influenza virus cell entry domains.the ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. we related structures of influenza a n10 and n11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. we identified atoms with common distributed spatial occupancy in pdb structures of n10 protein, n11 protein, an influenza a neuraminidase, an influenza b neuraminidase, and a bacterial neuraminid ...201525706124
clinical and epidemiological investigation of a fatal anthrax case in china.anthrax is a recessive infectious disease caused by the bacterium bacillus anthracis, and is primarily a zoonotic disease. until recently, bacillus anthracis infections were relatively infrequent and confined to agrarian communities in underdeveloped countries. no anthrax cases were reported in changchun city in the past few decades until a male patient from the inner mongolia autonomous region presented the anthrax disease manifestation. this paper describes an anthrax patient's diagnosis, isol ...201525699498
characterization of the activity of the spore cortex lytic enzyme cwlj1.the germination enzyme cwlj1 plays an important role in degrading the cortex during the germination of bacillus anthracis spores. however, the specific function and catalytic activity of cwlj1 remain elusive. here we report for the first time a detailed in vitro mechanistic study of cwlj1 expressed in escherichia coli and its activity against the spore cortical fragments of b. anthracis when added exogenously. cwlj1 was active on both decoated spores and spore cortical fragments. through liquid ...201525676066
efficacy and immunogenicity of single-dose advav intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.advav is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kda protective antigen (pa83) from bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized b. anthracis spores. a noninferiority study comparing the efficacy of advav to the currently licensed anthrax vaccine absorbed (ava; biothrax) was performed in new zealand white rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for su ...201525673303
a heterodimer of a vhh (variable domains of camelid heavy chain-only) antibody that inhibits anthrax toxin cell binding linked to a vhh antibody that blocks oligomer formation is highly protective in an anthrax spore challenge model.anthrax disease is caused by a toxin consisting of protective antigen (pa), lethal factor, and edema factor. antibodies against pa have been shown to be protective against the disease. variable domains of camelid heavy chain-only antibodies (vhhs) with affinity for pa were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. two classes of neutralizing vhhs were identified recognizing distinct, non-overlapping epitopes. one class recognize ...201525564615
neutrophils negatively regulate induction of mucosal iga responses after sublingual immunization.induction of mucosal immunoglobulin-a (iga) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. innate immune cells are known to play a central role in induction of iga responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. using an in vivo model of sublingual vaccination with bacillus anthracis edema toxin (edtx) ...201525563500
[chemical, physical and biological risks in law enforcement].chemical, physical and biological risks among public safety and security forces. law enforcement personnel, involved in routine tasks and in emergency situations, are exposed to numerous and several occupational hazards (chemical, physical and biological) whith likely health and security consequences. these risks are particularly high when the organization and preparation are inadequate, there is a lacking or insufficient coordination, information, education and communication and safety and pers ...201525558740
in silico genomic fingerprints of the bacillus anthracis group obtained by virtual hybridization.in this study we evaluate the capacity of virtual hybridization to identify between highly related bacterial strains. eight genomic fingerprints were obtained by virtual hybridization for the bacillus anthracis genome set, and a set of 15,264 13-nucleotide short probes designed to produce genomic fingerprints unique for each organism. the data obtained from each genomic fingerprint were used to obtain hybridization patterns simulating a dna microarray. two virtual hybridization methods were used ...201527600214
[a method for differentiation of bacillus anthracis strains and phylogenetically related species based on determination of the structural differencesbetween chromosomal genes for biosynthesis of flagellin and methionine].nucleotide sequence analysis of several genes responsible for the anthrax pathogen definitive properties--motility and penicillinase activity--determined a chromosomal locus promising for interspecies differentiation. we demonstrated that the gene flic encoding flagellin synthesis contains extended region, distinguishing b. anthracis strains from the majority of non-pathogenic and opportunistic bacilli. a novel method for the anthrax pathogen indication and identification based on determination ...201527192817
evaluation of inhaled versus deposited dose using the exponential dose-response model for inhalational anthrax in nonhuman primate, rabbit, and guinea pig.the application of the exponential model is extended by the inclusion of new nonhuman primate (nhp), rabbit, and guinea pig dose-lethality data for inhalation anthrax. because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. for this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. four nhp, three rabbit, and two guinea pig data sets were utilized. ...201525545587
forensic dna analysis of wheat flour as commonly used in white powder cases.in the wake of terrorist attacks using anthrax and ricin, white powder is often encountered in cases of malicious mischief and terrorist threats. wheat flour is a common white powder encountered in such criminal investigations. we used dna analysis to investigate wheat flour samples for identification and discrimination as trace evidence. species identification of commercially available wheat flour was carried out by sequencing a partial region of the ribulose bisphosphate carboxylase large subu ...201526174661
ion selectivity of the anthrax toxin channel and its effect on protein translocation.anthrax toxin consists of three ∼ 85-kd proteins: lethal factor (lf), edema factor (ef), and protective antigen (pa). pa63 (the 63-kd, c-terminal portion of pa) forms heptameric channels ((pa63)7) in planar phospholipid bilayer membranes that enable the translocation of lf and ef across the membrane. these mushroom-shaped channels consist of a globular cap domain and a 14-stranded β-barrel stem domain, with six anionic residues lining the interior of the stem to form rings of negative charges. ( ...201526170174
metal iodate-based energetic composites and their combustion and biocidal performance.the biological agents that can be weaponized, such as bacillus anthracis, pose a considerable potential public threat. bacterial spores, in particular, are highly stress resistant and cannot be completely neutralized by common bactericides. this paper reports on synthesis of metal iodate-based aluminized electrospray-assembled nanocomposites which neutralize spores through a combined thermal and chemical mechanism. here metal iodates (bi(io3)3, cu(io3)2, and fe(io3)3) act as a strong oxidizer to ...201526161906
molecular characterization of the circulating bacillus anthracis in jordan.to understand the biomolecular charcteristics of bacillus anthracis in jordan, 20 blood smear slides from dead animals with suspected anthrax were analyzed using conventional and molecular approaches. all slides were positive for b. anthracis by conventional staining but no growth of the organism on selective media was detected. however, of the 20 samples, 16 were b. anthracis dna-positive using polymerase chain reaction (pcr). seven samples provided enough quantity and quality of dna, and their ...201526156620
electrochemical immunosensor based on bismuth nanocomposite film and cadmium ions functionalized titanium phosphates for the detection of anthrax protective antigen toxin.bacillus anthracis is a bioterrorism agent classified by the centers for disease control and prevention (cdc). herein, a novel electrochemical immunosensor for the sensitive, specific and easy detection of anthrax protective antigen (pa) toxin in picogram concentration was developed. the immunosensor consists of (i) a nafion-multiwall carbon nanotubes-bismuth nanocomposite film modified glassy carbon electrodes (binps/nafion-mwcnts/gce) as a sensing platform and (ii) titanium phosphate nanoparti ...201526148674
phosphate starvation enhances the pathogenesis of bacillus anthracis.identifying the factors responsible for survival and virulence of bacillus anthracis within the host is prerequisite for the development of therapeutics against anthrax. host provides several stresses as well as many advantages to the invading pathogen. inorganic phosphate (pi) starvation within the host has been considered as one of the major contributing factors in the establishment of infection by pathogenic microorganisms. here, we report for the first time that pi fluctuation encountered by ...201526143397
lessons to be learned from recent biosafety incidents in the united states.during recent months, the centers for disease control and prevention (cdc) announced the occurrence of three major biosafety incidents, raising serious concern about biosafety and biosecurity guideline implementation in the most prestigious agencies in the united states: the cdc, the national institutes of health (nih) and the federal drug administration (fda). these lapses included: a) the mishandling of bacillus anthracis spores potentially exposing dozens of employees to anthrax; b) the shipm ...201526137650
a novel chimeric anti-pa neutralizing antibody for postexposure prophylaxis and treatment of anthrax.anthrax is a highly lethal infectious disease caused by the bacterium bacillus anthracis, and the associated shock is closely related to the lethal toxin (letx) produced by the bacterium. the central role played by the 63 kda protective antigen (pa63) region of letx in the pathophysiology of anthrax makes it an excellent therapeutic target. in the present study, a human/murine chimeric igg mab, hmpa6, was developed by inserting murine antibody variable regions into human constant regions using a ...201526134518
identification and characterization of a novel geobacillus thermoglucosidasius bacteriophage, gve3.the study of extremophilic phages may reveal new phage families as well as different mechanisms of infection, propagation and lysis to those found in phages from temperate environments. we describe a novel siphovirus, gve3, which infects the thermophile geobacillus thermoglucosidasius. the genome size is 141,298 bp (g+c 29.6%), making it the largest geobacillus spp-infecting phage known. gve3 appears to be most closely related to the recently described bacillus anthracis phage vb_bans_tsamsa, ra ...201526123922
immunization of mice with anthrax protective antigen limits cardiotoxicity but not hepatotoxicity following lethal toxin challenge.protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. in animal models, in vivo challenges with toxin and/or spores can also be performed. however, neither of these approaches considers toxin-induced damage to specific organ systems. it is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. we therefore ...201526120785
differences in the purification and solution properties of purc gene products from streptococcus pneumoniae and bacillus anthracis.4-(n-succino)-5-aminoimidazole-4-carboxamide ribonucleotide synthetase (purc) is a key enzyme in the de novo purine biosynthetic pathway of bacteria and an ideal target pathway for the discovery of antimicrobials. bacillus anthracis (ba) and streptococcus pneumoniae (sp) are two of the bacteria shown to be severe detriments to public health. to be able to carry out the experimentation that leads to drug discovery, high yields of pure soluble recombinant protein must first be obtained. we studied ...201526118696
genome sequence of bacillus anthracis attenuated vaccine strain a16r used for human in china.an attenuated bacillus anthracis vaccine strain for human use, a16r, was obtained in china after ultraviolet radiation treatment and continuous subculture of the wild-type strain a16. a16r can synthesize the exotoxin, but without a capsule. we sequenced and annotated the a16r genome to encourage the use of this strain. the genome sequencing of the wild-type strain a16 is underway and the genomic comparison between the two strains will help to illustrate the attenuating mechanism of the a16r vacc ...201526116813
the effect of prolonged storage on the virulence of isolates of bacillus anthracis obtained from environmental and animal sources in the kars region of turkey.the stability of the plasmid-mediated virulence factors of bacillus anthracis, a tripartite toxin located on pxo1 and an antiphagocytic capsule encoded by genes located on pxo2, following long-term storage was investigated. a collection of 159 isolates of b. anthracis were collected from the kars region of turkey between 2000 and 2013 and stored at -20°c in brucella broth supplemented with 20% glycerine. a total of 142 isolates were recovered of which one failed to express a capsule upon primary ...201526109359
the disulfide bond cys255-cys279 in the immunoglobulin-like domain of anthrax toxin receptor 2 is required for membrane insertion of anthrax protective antigen pore.anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, ph-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. we previously reported that reduction of the disulfide bonds in the immunoglobulin-like (ig) domain of the anthrax toxin receptor 2 (antxr2) inhibited the function of the protective antigen (pa) pore. in the present study, the disulfide linkage in the ig domain was identified as cys255-cys279 and cys230- ...201526107617
metal binding spectrum and model structure of the bacillus anthracis virulence determinant mnta.the potentially lethal human pathogen bacillus anthracis expresses a putative metal import system, mntbca, which belongs to the large family of abc transporters. mntbca is essential for virulence of bacillus anthracis: deletion of mnta, the system's substrate binding protein, yields a completely non-virulent strain. here we determined the metal binding spectrum of mnta. in contrast to what can be inferred from growth complementation studies we find no evidence that mnta binds fe(2+) or fe(3+). r ...201526106847
animal models for the pathogenesis, treatment, and prevention of infection by bacillus anthracis.this article reviews the characteristics of the major animal models utilized for studies on bacillus anthracis and highlights their contributions to understanding the pathogenesis and host responses to anthrax and its treatment and prevention. advantages and drawbacks associated with each model, to include the major models (murine, guinea pig, rabbit, nonhuman primate, and rat), and other less frequently utilized models, are discussed. although the three principal forms of anthrax are addressed, ...201526104551
structural basis of proline-proline peptide bond specificity of the metalloprotease zmp1 implicated in motility of clostridium difficile.clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. in common with other pathogenic bacteria, c. difficile secretes proteins involved in adhesion, colonization, and dissemination. the recently identified zmp1 is an extracellular metalloprotease showing a unique specificity for pro-pro peptide bonds. the endogenous substrates of zmp1 are two surface proteins implicated in adhesion of c. difficile to surface proteins of human cel ...201526211609
lab-on-a-chip-based pcr-rflp assay for the confirmed detection of short-length feline dna in food.wider availability but lack of legal market trades has given feline meat a high potential for use as an adulterant in common meat and meat products. however, mixing of feline meat or its derivatives in food is a sensitive issue, since it is a taboo in most countries and prohibited in certain religions such as islam and judaism. cat meat also has potential for contamination with of severe acute respiratory syndrome, anthrax and hepatitis, and its consumption might lead to an allergic reaction. we ...201526208950
anthrax pathogenesis.anthrax is caused by the spore-forming, gram-positive bacterium bacillus anthracis. the bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. these are encoded by two large plasmids, the former by pxo1 and the latter by pxo2. the expression of both is controlled by the bicarbonate-responsive transcriptional regulator, atxa. the anthrax toxins are three polypeptides-protective antigen (pa), lethal factor (lf), and edema factor (ef)-that com ...201526195305
acyl carrier protein is a bacterial cytoplasmic target of cationic antimicrobial peptide ll-37.in addition to membrane disruption, the cathelicidin antimicrobial peptide (amp) ll-37 translocates through the bacterial inner membrane to target intracellular molecules. the present study aims to identify an alternate mechanism and a cytoplasmic target of ll-37 in francisella. ll-37 binding proteins from francisella novicida u112 bacterial lysates were precipitated by using biotinylated ll-37 (b-ll-37) and neutravidin-agarose beads. bound proteins were identified by lc-ms/ms, validated and cha ...201526188040
the differential effects of heat-shocking on the viability of spores from bacillus anthracis, bacillus subtilis, and clostridium sporogenes after treatment with peracetic acid- and glutaraldehyde-based disinfectants.this study investigated (1) the susceptibility of bacillus anthracis (ames strain), bacillus subtilis (atcc 19659), and clostridium sporogenes (atcc 3584) spores to commercially available peracetic acid (paa)- and glutaraldehyde (ga)-based disinfectants, (2) the effects that heat-shocking spores after treatment with these disinfectants has on spore recovery, and (3) the timing of heat-shocking after disinfectant treatment that promotes the optimal recovery of spores deposited on carriers. suspen ...201526185111
unlocking the sporicidal potential of ethanol: induced sporicidal activity of ethanol against clostridium difficile and bacillus spores under altered physical and chemical conditions.due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. however, alcohols lack activity against bacterial spores produced by pathogens such as clostridium difficile and bacillus anthracis. we hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats.201526177038
application of pyrosequencing® in food biodefense.the perpetration of a bioterrorism attack poses a significant risk for public health with potential socioeconomic consequences. it is imperative that we possess reliable assays for the rapid and accurate identification of biothreat agents to make rapid risk-informed decisions on emergency response. the development of advanced methodologies for the detection of biothreat agents has been evolving rapidly since the release of the anthrax spores in the mail in 2001, and recent advances in detection ...201526103911
raxibacumab augments hemodynamic support and improves outcomes during shock with b. anthracis edema toxin alone or together with lethal toxin in canines.lethal and edema toxin contribute to shock and lethality with bacillus anthracis. we showed previously in a 96-h sedated canine model that raxibacumab, a monoclonal antibody against protective antigen, augmented hemodynamic support (hs) and improved survival with lethal toxin challenge. here we study raxibacumab further. using this model, we have now studied raxibacumab with 24 h edema toxin challenges (study 1), and lethal and edema toxin challenges together (study 2).201526097803
dormant bacillus spores protect their dna in crystalline nucleoids against environmental stress.bacterial spores of the genera bacillus and clostridium are extremely resistant against desiccation, heat and radiation and involved in the spread and pathogenicity of health relevant species such as bacillus anthracis (anthrax) or clostridium botulinum. while the resistance of spores is very well documented, underlying mechanisms are not fully understood. in this study we show, by cryo-electron microscopy of vitreous sections and particular resin thin section electron microscopy, that dormant b ...201526094877
bacillus anthracis infections--new possibilities of treatment.bacillus anthracis is one of biological agents which may be used in bioterrorism attacks. the aim of this study a review of the new treatment possibilities of anthrax, with particular emphasis on the treatment of pulmonary anthrax. abbreviated description of the state of knowledge. pulmonary anthrax, as the most dangerous clinical form of the disease, is also extremely difficult to treat. recently, considerable progress in finding new drugs and suitable therapy for anthrax has been achieved, for ...201526094508
reverse-phase microarray analysis reveals novel targets in lymph nodes of bacillus anthracis spore-challenged mice.anthrax is a frequently fatal infection of many animal species and men. the causative agent bacillus anthracis propagates through the lymphatic system of the infected host; however, the specific interactions of the host and microbe within the lymphatics are incompletely understood. we report the first description of the phosphoprotein signaling in the lymph nodes of dba/2 mice using a novel technique combining the reverse-phase microarray with the laser capture microdissection. mice were challen ...201526091359
draft genome sequences of bacillus anthracis strains stored for several decades in japan.we report the draft genome sequences of bacillus anthracis strains shikan-niid, 52-40-niah, and 44-niah stored in japan and belonging to the a3 cluster.201526089418
human infection with a zoonotic orthopoxvirus in the country of georgia.during 2013, cutaneous lesions developed in two men in the country of georgia after they were exposed to ill cows. the men had never received vaccination against smallpox. tests of lesion material with the use of a quantitative real-time polymerase-chain-reaction assay for non-variola virus orthopoxviruses were positive, and dna sequence analysis implicated a novel orthopoxvirus species. during the ensuing epidemiologic investigation, no additional human cases were identified. however, serologic ...201525806914
bacillus cereus from the environment is genetically related to the highly pathogenic b. cereus in zambia.to follow-up anthrax in zambia since the outbreak in 2011, we have collected samples from the environment and the carcasses of anthrax-suspected animals, and have tried to isolate bacillus anthracis. in the process of identification of b. anthracis, we collected two isolates, of which colonies were similar to b. anthracis; however, from the results of identification using the molecular-based methods, two isolates were genetically related to the highly pathogenic b. cereus, of which clinical mani ...201525797134
genome sequence of bacillus anthracis isolated from an anthrax burial site in pollino national park, basilicata region (southern italy).a bacillus anthracis strain was isolated from a burial-site in pollino national park where a bovine died of anthrax and was buried in 2004. we report the first genome sequence of b. anthracis isolated in the basilicata region (southern italy), which is the highest risk area of anthrax infection in italy.201525792059
applications of commercial biosensors in clinical, food, environmental, and biothreat/biowarfare analyses.the lack of specific, low-cost, rapid, sensitive, and easy detection of biomolecules has resulted in the development of biosensor technology. innovations in biosensor technology have enabled many biosensors to be commercialized and have enabled biomolecules to be detected onsite. moreover, the emerging technologies of lab-on-a-chip microdevices and nanosensors offer opportunities for the development of new biosensors with much better performance. biosensors were first introduced into the laborat ...201525790902
laboratory-acquired lethal infections by potential bioweapons pathogens including ebola in 2014.researchers studying both cellular and viral disease agents in the laboratory have become infected since the early days of microbiology 150 years ago. however, in the early 21st century, new concerns about bioweapons being used to generate terror and also with a series of newly emerging or newly understood disease-causing microbes have resulted in infections and deaths of workers studying these microbes in the laboratory, generally to gain understanding and to develop treatments and vaccines. he ...201525790490
generation and characterization of human monoclonal antibodies targeting anthrax protective antigen following vaccination with a recombinant protective antigen vaccine.the anthrax protective antigen (pa) is the central component of the three-part anthrax toxin, and it is the primary immunogenic component in the approved ava anthrax vaccine and the "next-generation" recombinant pa (rpa) anthrax vaccines. animal models have indicated that pa-specific antibodies (ab) are sufficient to protect against infection with bacillus anthracis. in this study, we investigated the pa domain specificity, affinity, mechanisms of neutralization, and synergistic effects of pa-sp ...201525787135
differential dependence on n-glycosylation of anthrax toxin receptors cmg2 and tem8.antxr 1 and 2, also known as tem8 and cmg2, are two type i membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. here we have analyzed the importance of n-glycosylation on folding, trafficking and ligand binding of these closely related proteins. we find that tem8 has a stringent dependence on n-glycosylation. the presence of at least one glycan on each of its two extracellular domains, the vwa and ig-li ...201525781883
atomic structure of anthrax protective antigen pore elucidates toxin translocation.anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of bacillus anthracis, an agent that causes high mortality in humans and animals. protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. protective antigen is not only a vaccine component and therapeutic target for ...201525778700
glutamate racemase mutants of bacillus anthracis.d-glutamate is an essential component of bacterial peptidoglycan and a building block of the poly-γ-d-glutamic acid (pdga) capsule of bacillus anthracis, the causative agent of anthrax. earlier work suggested that two glutamate racemases, encoded by race1 and race2, are each essential for growth of b. anthracis, supplying d-glutamic acid for the synthesis of peptidoglycan and pdga capsule. earlier work could not explain, however, why two enzymes that catalyze the same reaction may be needed for ...201525777674
added benefit of raxibacumab to antibiotic treatment of inhalational anthrax.although antibiotics treat bacteremia in inhalational anthrax, pathogenesis is mainly driven by bacterial exotoxins. raxibacumab, an igg1 monoclonal antibody, binds the protective antigen (pa) of bacillus anthracis, thus blocking toxin effects and leading to improved survival in the rabbit and monkey models of inhalational anthrax. to assess raxibacumab's added benefit over levofloxacin (lvx) alone, rabbits surviving to 84 h after a challenge with 200 times the median (50%) lethal dose of b. ant ...201525487792
using poly i:c as an adjuvant does not induce or exacerbate models of systemic lupus erythematosus.subunit vaccines are typically poorly immunogenic when administered alone, and require adjuvants for robust responses. triggering tlrs to boost antigen-specific adaptive immunity is an attractive approach to increase the potency and quality of vaccines. however, recent reports suggest that alterations in tlr expression are associated with the pathogenesis of inflammatory and autoimmune diseases. to compare genetic studies with adjuvant studies, we examined whether stimulation through a tlr agoni ...201525483245
mapping of major diseases and devising prevention and control regimen to common diseases in cattle and shoats in dassenech district of south omo zone, south-western ethiopia.livestock production system, particularly in pastoral areas, is mainly constrained by rampant livestock diseases and seasonal feed and water shortages. in areas like dassenech, bordering kenya and south sudan, this risks are pronounced due to the unavailability of appropriate prevention and control. the research was conducted with the objectives of identifying major rampant diseases and designing appropriate prevention and control strategies. a cross-sectional study was employed, conducted using ...201525480484
armies of pestilence: cns infections as potential weapons of mass destruction.infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. cns infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. viruses responsible for encephalitides can be highly infectious in aerosol form. cns involvement in anthrax is ominous but should change treatment. brucellosis, plague, q fever, and other bacteria can uncommonly manifest with meningoenceph ...201525477355
combination of two candidate subunit vaccine antigens elicits protective immunity to ricin and anthrax toxin in mice.in an effort to develop combination vaccines for biodefense, we evaluated a ricin subunit antigen, rivax, given in conjunction with an anthrax protective antigen, dni. the combination led to high endpoint titer antibody response, neutralizing antibodies, and protective immunity against ricin and anthrax lethal toxin. this is a natural combination vaccine, since both antigens are recombinant subunit proteins that would be given to the same target population.201525475957
fate of bacillus anthracis during production of laboratory-scale cream cheese and homemade-style yoghurt.the viability of bacillus anthracis during production and storage of cream cheese and yoghurt was evaluated. experimental cheeses were manufactured from whole milk inoculated with a suspension of b. anthracis vegetative cells and spores at a final concentration of 10(4) cfu/ml. lactic acid bacteria (lab) and lab ferment were used to induce milk ripening and milk coagulation. the ph-value of the contaminated milk dropped below 4.5 within the first 6 h and the amount of lab increased by approximat ...201525475304
efficient cell-specific uptake of binding proteins into the cytoplasm through engineered modular transport systems.through advances in protein scaffold engineering and selection technologies, highly specific binding proteins, which fold under reducing conditions, can be generated against virtually all targets. despite tremendous therapeutic opportunities, intracellular applications are hindered by difficulties associated with achieving cytosolic delivery, compounded by even correctly measuring it. here, we addressed cytosolic delivery systematically through the development of a biotin ligase-based assay that ...201525526701
structure-based design of bacterial nitric oxide synthase inhibitors.inhibition of bacterial nitric oxide synthase (bnos) has the potential to improve the efficacy of antimicrobials used to treat infections by gram-positive pathogens staphylococcus aureus and bacillus anthracis. however, inhibitor specificity toward bnos over the mammalian nos (mnos) isoforms remains a challenge because of the near identical nos active sites. one key structural difference between the nos isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent t ...201525522110
prevalence of antibiotic resistance genes and bacterial pathogens in long-term manured greenhouse soils as revealed by metagenomic survey.antibiotic resistance genes (args), human pathogenic bacteria (hpb), and hpb carrying args pose a high risk to soil ecology and public health. here, we used a metagenomic approach to investigate their diversity and abundance in chicken manures and greenhouse soils collected from guli, pulangke, and hushu vegetable bases with different greenhouse planting years in nanjing, eastern china. there was a positive correlation between the levels of antibiotics, args, hpb, and hpb carrying args in manure ...201525514174
production and cell surface display of recombinant anthrax protective antigen on the surface layer of attenuated bacillus anthracis.to investigate the surface display of the anthrax protective antigen (pa) on attenuated bacillus anthracis, a recombinant b. anthracis strain, named ap429 was constructed by integrating into the chromosome a translational fusion harboring the dna fragments encoding the cell wall-targeting domain of the s-layer protein ea1 and the anthrax pa. crerecombinase action at the loxp sites excised the antibiotic marker. western blot analysis, fluorescence-activated cell sorting and immunofluorescence ana ...201525504373
medical science and the cruelty to animals act 1876: a re-examination of anti-vivisectionism in provincial britain.the cruelty to animals act 1876 was an important but ambiguous piece of legislation. for researchers it stymied british science, yet ensured that vivisection could continue under certain restrictions. for anti-vivisection protestors it was positive proof of the influence of their campaigns, yet overly deferent to britain's scientific elite. in previous accounts of the act and the rise of anti-vivisectionism, scientific medicine central to these debates has been treated as monolithic rather than ...201525437634
modified 2,4-diaminopyrimidine-based dihydrofolate reductase inhibitors as potential drug scaffolds against bacillus anthracis.the current letter describes the synthesis and biological evaluation of dihydrophthalazine-appended 2,4-diaminopyrimidine (dap) inhibitors (1) oxidized at the methylene bridge linking the dap ring to the central aromatic ring and (2) modified at the central ring ether groups. structures 4a-b incorporating an oxidized methylene bridge showed a decrease in activity, while slightly larger alkyl groups (ch2ch3 vs ch3) on the central ring oxygen atoms (r(2) and r(3)) had a minimal impact on the inhib ...201525435253
quantitative analysis of the thermal stability of the gamma phage endolysin plyg: a biophysical and kinetic approach to assaying therapeutic potential.endolysins are lytic enzymes encoded by bacteriophage that represent an emerging class of protein therapeutics. considering macromolecular thermoresistance correlates with shelf life, plyg, a bacillus anthracis endolysin, was thermally characterized to further evaluate its therapeutic potential. results from a biophysical thermal analysis revealed full-length plyg and its isolated domains comprised thermal denaturation temperatures exceeding 63°c. in the absence of reducing agent, plyg was deter ...201525432575
lytr-cpsa-psr enzymes as determinants of bacillus anthracis secondary cell wall polysaccharide assembly.bacillus anthracis, the causative agent of anthrax, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. surface (s)-layer proteins and associated proteins (bsls) function as chain length determinants and bind to the secondary cell wall polysaccharide (scwp). in this study, we identified the b. anthracis lcpd mutant, which displays increased chain length and s-layer assembly defects due to diminished scwp attachment to peptidoglycan. in contrast, the b. ...201525384480
htrc is involved in proteolysis of ypeb during germination of bacillus anthracis and bacillus subtilis spores.bacterial endospores can remain dormant for decades yet can respond to nutrients, germinate, and resume growth within minutes. an essential step in the germination process is degradation of the spore cortex peptidoglycan wall, and the sleb protein in bacillus species plays a key role in this process. stable incorporation of sleb into the spore requires the ypeb protein, and some evidence suggests that the two proteins interact within the dormant spore. early during germination, ypeb is proteolyt ...201525384476
total syntheses of linear polythiazole/oxazole plantazolicin a and its biosynthetic precursor plantazolicin b.plantazolicin a, a linear decacyclic natural product, exhibits desirable selective activity against the causative agent of anthrax toxicity. the total synthesis of plantazolicin a and its biosynthetic precursor plantazolicin b was successfully achieved by an efficient, unified, and highly convergent route featuring dicyclizations to form 2,4-concatenated oxazoles and the mild synthesis of thiazoles from natural amino acids. this report represents the first synthesis of plantazolicin b and includ ...201525424526
cytochrome c551 and the cytochrome c maturation pathway affect virulence gene expression in bacillus cereus atcc 14579.loss of the cytochrome c maturation system in bacillus cereus results in increased transcription of the major enterotoxin genes nhe, hbl, and cytk and the virulence regulator plcr. increased virulence factor production occurs at 37°c under aerobic conditions, similar to previous findings in bacillus anthracis. unlike b. anthracis, much of the increased virulence gene expression can be attributed to loss of only c551, one of the two small c-type cytochromes. additional virulence factor expression ...201525422307
comparing electronic news media reports of potential bioterrorism-related incidents involving unknown white powder to reports received by the united states centers for disease control and prevention and the federal bureau of investigation: u.s.a., 2009-2011.there have been periodic electronic news media reports of potential bioterrorism-related incidents involving unknown substances (often referred to as "white powder") since the 2001 intentional dissemination of bacillus anthracis through the u.s. postal system. this study reviewed the number of unknown "white powder" incidents reported online by the electronic news media and compared them with unknown "white powder" incidents reported to the u.s. centers for disease control and prevention (cdc) a ...201525420771
influence of protein formulation and carrier solution on asymmetrical flow field-flow fractionation: a case study of the plant-produced recombinant anthrax protective antigen pp-pa83.asymmetrical flow field-flow fractionation (affff) was used to investigate the properties of a plant-produced anthrax toxin protective antigen, pp-pa83. the affff fractogram consisted of two main peaks with molar masses similar to the molecular mass of pp-pa83 monomer. affff carrier solutions strongly influenced the ratio and the intensity of the two main peaks. these differences indicate that conformation changes in the pp-pa83 molecule occurred during the affff analysis. similar fractograms we ...201525417936
crystal structure of bacillus anthracis virulence regulator atxa and effects of phosphorylated histidines on multimerization and activity.the bacillus anthracis virulence regulator atxa controls transcription of the anthrax toxin genes and capsule biosynthetic operon. atxa activity is elevated during growth in media containing glucose and co(2)/bicarbonate, and there is a positive correlation between the co(2)/bicarbonate signal, atxa activity and homomultimerization. atxa activity is also affected by phosphorylation at specific histidines. we show that atxa crystallizes as a dimer. distinct folds associated with predicted dna-bin ...201525402841
host immunity to bacillus anthracis lethal factor and other immunogens: implications for vaccine design.infections of humans with bacillus anthracis are an issue with respect to the biothreat both to civilians and military personnel, infections of individuals by infected livestock in endemic regions and, recently, infections of intravenous drug users injecting anthrax-contaminated heroin. existing vaccination regimens are reliant on protective antigen neutralization induced by repeated boosts with the ava or avp vaccines. however, there is ongoing interest in updated approaches in light of the int ...201525400140
multiplexed genotyping of bacillus anthracis by luminex xmap suspension array.the luminex® xtag technology is a medium to high throughput, open methodology able to test many single nucleotide polymorphisms (snps) in a single reaction and a minimum time. multiplex snps interrogation are conducted on the luminex xmap system, which uses lasers to read universal tag, color-coded microspheres that attach to specific nucleic acid sequences. the present method describes a multiplex oligonucleotide ligation-pcr procedure (mol-pcr) for the simultaneous interrogation of 13 phylogen ...201525399112
single-nucleotide polymorphism discrimination using high-resolution melting analysis for the genotyping of bacillus anthracis.high-resolution melting (hrm) is a post-pcr technique that determines with high precision the melt profile of pcr products using a new generation of double-stranded dna-binding dyes and accurate fluorescence data acquisition over small temperature increments. the method can be used to interrogate small sets of single-nucleotide polymorphisms (snps). here, we describe a simple and cost-effective hrm-based method for the screening of 14 phylogenetically informative snps within the genome of bacill ...201525399109
detection of bacillus anthracis spores by super-paramagnetic lateral-flow immunoassays based on "road closure".detection of bacillus anthracis in the field, whether as a natural infection or as a biothreat remains challenging. here we have developed a new lateral-flow immunochromatographic assay (lfia) for b. anthracis spore detection based on the fact that conjugates of b. anthracis spores and super-paramagnetic particles labeled with antibodies will block the pores of chromatographic strips and form retention lines on the strips, instead of the conventionally reported test lines and control lines in cl ...201525294802
potentiality of eisenia fetida to degrade disposable paper cups-an ecofriendly solution to solid waste pollution.the aim of the present study was to subject the post-consumer waste, namely paper cups for vermicomposting along with cow dung in three different ratios for a period of 90-140 days employing eisenia fetida. the post-consumer wastes are a menace in many developing countries including india. this waste was provided as feed for earthworms and was converted to vermicompost. vermicompost prepared with paper cup waste was analyzed for their physicochemical properties. based on the physicochemical prop ...201525220767
crossing institutional boundaries: mapping the policy process for improved control of endemic and neglected zoonoses in sub-saharan africa.the recent adoption of the world health assembly resolution 66.12 for neglected tropical diseases (ntds) in may 2013 is an important turning point for advocacy regarding a number of endemic zoonotic infections, defined by the world health organization as the neglected zoonotic diseases (nzds). in addition to ntd-listed zoonoses such as rabies, echinococcosis (hydatid disease), leishmaniasis, human african trypanosomiasis (sleeping sickness) and taenia solium cysticercosis, the nzds also include ...201525000963
ion conductance of the stem of the anthrax toxin channel during lethal factor translocation.the tripartite anthrax toxin consists of protective antigen, lethal factor (lf), and edema factor. pa63 (the 63-kda, c-terminal part of protective antigen) forms heptameric channels in cell membranes that allow for the transport of lf and edema factor into the cytosol. these channels are mushroom shaped, with a ring of seven phenylalanine residues (known as the phenylalanine clamp) lining the junction between the cap and the stem. it is known that when lf is translocated through the channel, the ...201524996036
structural basis of bacillus anthracis moxxt disruption and the modulation of moxt ribonuclease activity by rationally designed peptides.bacillus anthracis moxxt is a type ii proteic toxin-antitoxin (ta) module wherein moxt is a ribonuclease that cleaves rna specifically while moxx interacts with moxt and inhibits its activity. disruption of the ta interaction has been proposed as a novel antibacterial strategy. peptides, either based on antitoxin sequence or rationally designed, have previously been reported to disrupt the moxxt interaction but cause a decrease in moxt ribonuclease activity. in the present study, we report the c ...201524650157
a model of federal interagency cooperation: the national interagency confederation for biological research.the terrorist attacks of september 11 and the anthrax mailings a month later prompted a sweeping response by the federal government to improve the preparedness of the us to meet the potential threat posed by a terrorist using a biological agent. this response transcended traditional interagency boundaries, creating new opportunities while producing unique fiscal and leadership challenges. the national interagency confederation for biological research has made significant progress over the past 1 ...201524819736
molecular modeling toward selective inhibitors of dihydrofolate reductase from the biological warfare agent bacillus anthracis.in the present work, we applied docking and molecular dynamics techniques to study 11 compounds inside the enzymes dihydrofolate reductase (dhfr) from the biological warfare agent bacillus anthracis (badhfr) and homo sapiens sapiens (hssdhfr). six of these compounds were selected for a study with the mutant baf96idhfr. our results corroborated with experimental data and allowed the proposition of a new molecule with potential activity and better selectivity for badhfr.201524985033
unusual cause of fatal anthrax meningitis.we report the case of fatal anthrax meningoencephalitis in the province of muş located in eastern anatolia, turkey. the organism isolated from cerebrospinal fluid was identified as bacillus anthracis. the patient was treated with crystallized penicillin g (24 mu/day iv) and ciprofloxacin (2 × 400/day iv), but died 5 days after hospitalization. although it is a rare case, we consider that the patients who have skin, respiratory and neurological systems might also have hemorrhagic meningitis.201524678752
cutaneous anthrax in southeast anatolia of turkey.anthrax is a rare disease cause by bacillus anthracis, a gram-positive, rod-shaped endospore-forming capsuled bacterium. anthrax is manifest in three primary forms: cutaneous, respiratory, and gastrointestinal. cutaneous anthrax accounts for approximately 95% of all cases of anthrax in humans.201524678748
injectional anthrax at a scottish district general hospital.this retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (ia) since december 2009 at monklands hospital in central scotland and represents the largest series of ia cases to be described from a single location. twenty-one patients who fulfilled national anthrax control team standardized case definitions of confirmed, probable or possible ia are reported. all cases survived and ...201525078285
source tracking of an anthrax outbreak in northeastern china using complete genome analysis and mlva genotyping.anthrax is caused by bacillus anthracis, an etiological agent behind zoonotic diseases worldwide. b. anthracis is also one of the most dangerous bioterrorism agents. an anthrax outbreak took place in liaoning province in northeastern china in august 2012. it resulted in seven human infections and dozens of dead cows. one b. anthracis strain, named han, was isolated from a dead cow. this strain showed minor pathogenicity in mice and was suspected to be derived from the locally administered vaccin ...201525073769
a one health, participatory epidemiology assessment of anthrax (bacillus anthracis) management in western uganda.sporadic anthrax outbreaks have occurred in and around uganda's queen elizabeth national park (qenp) for years, affecting wildlife, domestic animals, and humans. reported outbreaks (2004-2005 and 2010) in qenp collectively killed over 500 wild animals and over 400 domestic animals. a 2011 outbreak in sheema district temporarily froze local markets while killing two humans and seven bovines. one health is multidisciplinary at its core, yet studies sometimes focus on the effects of animals on huma ...201525066946
residues involved in the pore-forming activity of the clostridium perfringens iota toxin.clostridium perfringens iota toxin is a binary toxin that is organized into enzyme (ia) and binding (ib) components. ib forms channels in lipid bilayers and mediates the transport of ia into the target cells. here we show that ib residues 334-359 contain a conserved pattern of alternating hydrophobic and hydrophilic residues forming two amphipathic β-strands involved in membrane insertion and channel formation. this stretch of amino acids shows remarkable structural and functional analogies with ...201525266274
combinations of various cpg motifs cloned into plasmid backbone modulate and enhance protective immunity of viral replicon dna anthrax vaccines.dna vaccines are generally weak stimulators of the immune system. fortunately, their efficacy can be improved using a viral replicon vector or by the addition of immunostimulatory cpg motifs, although the design of these engineered dna vectors requires optimization. our results clearly suggest that multiple copies of three types of cpg motifs or combinations of various types of cpg motifs cloned into a viral replicon vector backbone with strong immunostimulatory activities on human pbmc are effi ...201525265876
potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.dna vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. the efficacy of dna vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. in this study, we comprehensively evaluated the conventional non-viral dna, viral replicon dna or viral replicon particles (vrp) vaccines encoding different forms of anthrax protective antigen (pa) for specific immunity and protective potency against anthrax. our ...201525102364
clpc operon regulates cell architecture and sporulation in bacillus anthracis.the clpc operon is known to regulate several processes such as genetic competence, protein degradation and stress survival in bacteria. here, we describe the role of clpc operon in bacillus anthracis. we generated knockout strains of the clpc operon genes to investigate the impact of ctsr, mcsa, mcsb and clpc deletion on essential processes of b. anthracis. we observed that growth, cell division, sporulation and germination were severely affected in mcsb and clpc deleted strains, while none of d ...201524947607
colonic immune suppression, barrier dysfunction, and dysbiosis by gastrointestinal bacillus anthracis infection.gastrointestinal (gi) anthrax results from the ingestion of bacillus anthracis. herein, we investigated the pathogenesis of gi anthrax in animals orally infected with toxigenic non-encapsulated b. anthracis sterne strain (pxo1+ pxo2-) spores that resulted in rapid animal death. b. anthracis sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only b. anthracis, but also of commensals. disease progression signific ...201424945934
bacillus anthracis-like bacteria and other b. cereus group members in a microbial community within the international space station: a challenge for rapid and easy molecular detection of virulent b. anthracis.for some microbial species, such as bacillus anthracis, the etiologic agent of the disease anthrax, correct detection and identification by molecular methods can be problematic. the detection of virulent b. anthracis is challenging due to multiple virulence markers that need to be present in order for b. anthracis to be virulent and its close relationship to bacillus cereus and other members of the b. cereus group. this is especially the case in environments where build-up of bacillus spores can ...201424945323
nmr conformational properties of an anthrax lethal factor domain studied by multiple amino acid-selective labeling.nmr-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution nmr spectra and their subsequent analysis. especially for bigger proteins (>20 kda) selective labeling is a frequently used means of sequence-specific assignment. in this work we present the successful overexpression of a polypeptide of 233 residues, corresponding to the structured part of the n-terminal domain of anthrax lethal factor, using escherichia coli ex ...201424944022
characterization of bacillus strains and hoax agents by protein profiling using automated microfluidic capillary electrophoresis.in recent times, but especially since 2001, bioterrorism has been of increasing concern. in addition to the use of biological agents, including bacillus anthracis (anthrax), there have been numerous hoax white powder "scares." it is imperative to rapidly and accurately identify any suspicious powder as hazardous or hoax. classical methods for identification typically rely on time-consuming cultivation or highly specific molecular tests which are limited if the agent is unknown. faster and field ...201424943711
decontamination efficacy of three commercial-off-the-shelf (cots) sporicidal disinfectants on medium-sized panels contaminated with surrogate spores of bacillus anthracis.in the event of a wide area release and contamination of a biological agent in an outdoor environment and to building exteriors, decontamination is likely to consume the nation's remediation capacity, requiring years to cleanup, and leading to incalculable economic losses. this is in part due to scant body of efficacy data on surface areas larger than those studied in a typical laboratory (5×10-cm), resulting in low confidence for operational considerations in sampling and quantitative measureme ...201424940605
distinct regions of nlrp1b are required to respond to anthrax lethal toxin and metabolic inhibition.pattern recognition receptors monitor for signs of infection or cellular dysfunction and respond to these events by initiating an immune response. nlrp1b is a receptor that upon activation recruits multiple copies of procaspase-1, which promotes cytokine processing and a proinflammatory form of cell death termed pyroptosis. nlrp1b detects anthrax lethal toxin when the toxin cleaves an amino-terminal fragment from the protein. in addition, nlrp1b is activated when cells are deprived of glucose or ...201424935976
capillary morphogenesis gene 2 regulates adhesion and invasiveness of prostate cancer cells.capillary morphogenesis gene 2 (cmg2), also known as anthrax toxin receptor 2, has been indicated in the formation of new vasculature and in the internalisation of the anthrax toxin. anti-angiogenesis therapy that targets this molecule has been investigated. however, our recent studies of this molecule have indicated that this gene may also play certain roles in cancer cells. the present study aimed to examine the expression of cmg2 in prostate cancer tissues and cell lines, and also its impact ...201424932305
effect of inoculation method on the determination of decontamination efficacy against bacillus spores.decontamination studies investigating the effectiveness of products and processes for the inactivation of bacillus species spores have traditionally utilized metering viable spores in a liquid suspension onto test materials (coupons). the current study addresses the representativeness of studies using this type of inoculation method compared to when coupons are dosed with a metered amount of aerosolized spores. the understanding of this comparability is important in order to assess the represent ...201424928258
complete genome sequence of bacillus cereus sensu lato bacteriophage bcp1.bacillus cereus sensu lato organisms are an ecologically diverse group that includes etiologic agents of food poisoning, periodontal disease, and anthrax. the recently identified bcp1 bacteriophage infects b. cereus sensu lato and is being developed as a therapeutic decontamination agent and diagnostic countermeasure. we announce the complete genome sequence of bcp1.201424926042
cholesterol depletion induces antxr2-dependent activation of mmp-2 via erk1/2 phosphorylation in neuroglioma u251 cell.cholesterol is a critical component of lipid rafts implicated in regulating multiple signal transduction. the anthrax toxin receptor 2 (antxr2) is a type i membrane protein acting as the second receptor for the anthrax toxin. in this study, we first investigated the association between cholesterol and antxr2. we provided the evidence that cholesterol depletion by methyl-beta-cyclodextrin (mβcd) promoted antxr2 expression in u251 neuroglioma cell, which was reversed by cholesterol supplement. mβc ...201424924630
[pregnancy and vaccinoprevention].vaccinations protect woman and her fetus against different infectious diseases, but their application on pregnant should be extremely responsible. in this review i present information about some infectious diseases and vaccines during pregnancy. women, planning to get pregnant should be advised to do serological tests in order to find out their immune status against some infections, leading to fetal congenital malformations (rubella, chicken pox, hepatitis b) and if necessary to get vaccinated a ...201424919344
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