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bacterial stimulation of toll-like receptor 4 drives macrophages to hemophagocytose.during acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. salmonella enterica serovar typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. the mechanism(s) that triggers a macrophage to become hemophagocy ...201526459510
transposon mutagenesis identifies novel genes associated with staphylococcus aureus persister formation.pathogenic bacterial persisters are responsible for the recalcitrance of chronic and persistent infections to antimicrobial therapy. although the mechanisms of persister formation and survival have been widely studied in escherichia coli, persistence mechanisms in staphylococcus aureus remain largely unknown. here, we screened a transposon mutant library of a clinical methicillin-resistant staphylococcus aureus(mrsa)strain, usa500 (st8), under antibiotic pressure and identified 13 genes whose in ...201526779120
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
genetic characterization of bovine viral diarrhea virus strains in beijing, china and innate immune responses of peripheral blood mononuclear cells in persistently infected dairy cattle.to acquire epidemiological data on the bovine viral diarrhea virus (bvdv) and identify cattle persistently infected (pi) with this virus, 4,327 samples from holstein dairy cows were screened over a four-year period in beijing, china. eighteen bvd viruses were isolated, 12 from pi cattle. based on genetic analysis of their 5'-untranslated region (5'-utr), the 18 isolates were assigned to subgenotype bvdv-1m, 1a, 1d, 1q, and 1b. to investigate the innate immune responses in the peripheral-blood mo ...201526119170
immunization of balb/c mice with brucella abortus 2308δwbka confers protection against wild-type infection.brucellosis is a zoonotic disease that causes animal and human diseases. vaccination is a major measure for prevention of brucellosis, but it is currently not possible to distinguish vaccinated animals from those that have been naturally infected. therefore, in this study, we constructed the brucella (b.) abortus 2380 wbka mutant (2308δwbka) and evaluated its virulence. the survival of 2308δwbka was attenuated in murine macrophage (raw 264.7) and balb/c mice, and it induced high protective immun ...201526040616
genome sequences of 11 brucella abortus isolates from persistently infected italian regions.bovine brucellosis, typically caused by brucella abortus, has been eradicated from much of the developed world. however, the disease remains prevalent in southern italy, persisting as a public and livestock health concern. we report here the whole-genome sequences of 11 isolates from cattle (bos taurus) and water buffalo (bubalus bubalis) that are representative of the current genetic diversity of b. abortus lineages circulating in italy.201526679575
modulation of hepcidin to treat iron deregulation: potential clinical applications.the secreted peptide hormone hepcidin regulates systemic and local iron homeostasis through degradation of the iron exporter ferroportin. dysregulation of hepcidin leads to altered iron homeostasis and development of pathological disorders including hemochromatosis, and iron loading and iron restrictive anemias. therapeutic modulation of hepcidin is a promising method to ameliorate these conditions. several approaches have been taken to enhance or reduce the effects of hepcidin in vitro and in v ...201526669208
modulation of hepcidin to treat iron deregulation: potential clinical applications.the secreted peptide hormone hepcidin regulates systemic and local iron homeostasis through degradation of the iron exporter ferroportin. dysregulation of hepcidin leads to altered iron homeostasis and development of pathological disorders including hemochromatosis, and iron loading and iron restrictive anemias. therapeutic modulation of hepcidin is a promising method to ameliorate these conditions. several approaches have been taken to enhance or reduce the effects of hepcidin in vitro and in v ...201526669208
converging roles of caspases in inflammasome activation, cell death and innate immunity.inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. however, recent studies have revealed that these caspases have functions beyond their established roles. in addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (il-1β) and il-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. certain apoptotic caspases assem ...201526655628
converging roles of caspases in inflammasome activation, cell death and innate immunity.inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. however, recent studies have revealed that these caspases have functions beyond their established roles. in addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (il-1β) and il-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. certain apoptotic caspases assem ...201526655628
zepto-molar electrochemical detection of brucella genome based on gold nanoribbons covered by gold nanoblooms.gold nanoribbons covered by gold nanoblooms were sonoelectrodeposited on a polycrystalline gold surface at -1800 mv (vs. agcl) with the assistance of ultrasound and co-occurrence of the hydrogen evolution reaction. the nanostructure, as a transducer, was utilized to immobilize a brucella-specific probe and fabrication of a genosensor, and the process of immobilization and hybridization was detected by electrochemical methods, using methylene blue as a redox marker. the proposed method for detect ...201526657828
bioterrorism and the role of the clinical microbiology laboratory.regular review of the management of bioterrorism is essential for maintaining readiness for these sporadically occurring events. this review provides an overview of the history of biological disasters and bioterrorism. i also discuss the recent recategorization of tier 1 agents by the u.s. department of health and human services, the laboratory response network (lrn), and specific training and readiness processes and programs, such as the college of american pathologists (cap) laboratory prepare ...201526656673
bioterrorism and the role of the clinical microbiology laboratory.regular review of the management of bioterrorism is essential for maintaining readiness for these sporadically occurring events. this review provides an overview of the history of biological disasters and bioterrorism. i also discuss the recent recategorization of tier 1 agents by the u.s. department of health and human services, the laboratory response network (lrn), and specific training and readiness processes and programs, such as the college of american pathologists (cap) laboratory prepare ...201526656673
dendritic cell subtypes: a new way to study host-pathogen interaction. 201526646201
dendritic cell subtypes: a new way to study host-pathogen interaction. 201526646201
structural insight into how bacteria prevent interference between multiple divergent type iv secretion systems.prokaryotes use type iv secretion systems (t4sss) to translocate substrates (e.g., nucleoprotein, dna, and protein) and/or elaborate surface structures (i.e., pili or adhesins). bacterial genomes may encode multiple t4sss, e.g., there are three functionally divergent t4sss in some bartonella species (vir, vbh, and trw). in a unique case, most rickettsial species encode a t4ss (rvh) enriched with gene duplication. within single genomes, the evolutionary and functional implications of cross-system ...201526646013
typing discrepancy between phenotypic and molecular characterization revealing an emerging biovar 9 variant of smooth phage-resistant b. abortus strain 8416 in china.a newly isolated smooth colony morphology phage-resistant strain 8416 isolated from a 45-year-old cattle farm cleaner with clinical features of brucellosis in china was reported. the most unusual phenotype was its resistance to two brucella phages tbilisi and weybridge, but sensitive to berkeley 2, a pattern similar to that of brucella melitensis biovar 1. vitek 2 biochemical identification system found that both strain 8416 and b. melitensis strains shared positive ilatk, but negative in other ...201526696984
the ligands of neutrophil gelatinase-associated lipocalin.neutrophil gelatinase associated lipocalin (ngal), was originally identified in neutrophil granules as a heterodimer complex with gelatinase b (matrix metalloproteinase 9, mmp9), but more recently has been found to be secreted by damaged epithelial cells. ngal is a member of the lipocalin family and subsequently named as lipocalin 2 on the basis of structural similarity with other members of the lipocalin family and its potential association with hydrophobic retinol and cholesterol oleate more s ...201527617081
sting: infection, inflammation and cancer.the rapid detection of microbial agents is essential for the effective initiation of host defence mechanisms against infection. understanding how cells detect cytosolic dna to trigger innate immune gene transcription has important implications - not only for comprehending the immune response to pathogens but also for elucidating the causes of autoinflammatory disease involving the sensing of self-dna and the generation of effective antitumour adaptive immunity. the discovery of the sting (stimul ...201526603901
early experiences matter: a review of the effects of prenatal environment on offspring characteristics in poultry.early life experiences can be important in determining offspring phenotypes and may influence interaction with the environment and hence health, welfare, and productivity. the prenatal environment of poultry can be divided into the pre-lay environment and the egg storage/incubation environment, both of which can affect offspring outcomes. the ability to separate maternal and egg/incubation effects makes birds well suited to this type of research. there are many factors, including feeding and nut ...201526614679
early experiences matter: a review of the effects of prenatal environment on offspring characteristics in poultry.early life experiences can be important in determining offspring phenotypes and may influence interaction with the environment and hence health, welfare, and productivity. the prenatal environment of poultry can be divided into the pre-lay environment and the egg storage/incubation environment, both of which can affect offspring outcomes. the ability to separate maternal and egg/incubation effects makes birds well suited to this type of research. there are many factors, including feeding and nut ...201526614679
serosurvey of smooth brucella, leptospira spp. and toxoplasma gondii in free-ranging jaguars (panthera onca) and domestic animals from brazil.this study investigated the exposure of jaguar populations and domestic animals to smooth brucella, leptospira spp. and toxoplasma gondii in the cerrado, pantanal and amazon biomes of brazil. between february 2000 and january 2010, serum samples from 31 jaguars (panthera onca), 1,245 cattle (bos taurus), 168 domestic dogs (canis lupus familiaris) and 29 domestic cats (felis catus) were collected and analysed by rose bengal test for smooth brucella, microscopic agglutination test for leptospira s ...201526605787
serologic screening for 13 infectious agents in roe deer (capreolus capreolus) in flanders.in order to investigate the role of roe deer in the maintenance and transmission of infectious animal and human diseases in flanders, we conducted a serologic screening in 12 hunting areas.201526609692
inhibition of host cell translation elongation by legionella pneumophila blocks the host cell unfolded protein response.cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. one system that responds to these stimuli is the ire1 branch of the unfolded protein response (upr), a sensor of endoplasmic reticulum (er) stress. activation of ire1, in the context of toll-like receptor (tlr) signaling, induces strong proinflammatory cytokine induction. we show here that legionella pneumophila, an intravacuolar pathogen that replicates ...201526598709
eraizda: a model for holistic annotation of animal infectious and zoonotic diseases.there is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides m ...201526581408
cutaneous ulcers as initial presentation of localized granulomatosis with polyangiitis: a case report and review of the literature.background. granulomatosis with polyangiitis (gpa) is an anca associated small vessel vasculitis characterized by necrotizing granulomatous inflammation involving the upper and the lower respiratory tract and the kidneys. the disease has a broad clinical spectrum that ranges from limited/localized involvement of a single organ system to a generalized systemic vasculitis that affects several organs with evidence of end organ damage. atypical forms of the disease have been recognized with or witho ...201526664797
genome expression profiling-based identification and administration efficacy of host-directed antimicrobial drugs against respiratory infection by nontypeable haemophilus influenzae.therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. in this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable haemophilus influenza ...201526416856
draft genome sequence of the intermediate rough vaccine strain brucella abortus s19δper mutant.here, we report the genome sequence of the intermediate rough vaccine strain mutant, brucella abortus s19δper. the length of the draft genome was 3,271,238 bp, with 57.2% g+c content. a total of 3,204 protein-coding genes and 56 rna genes were predicted.201526564050
comparison of biological and immunological characterization of lipopolysaccharides from brucella abortus rb51 and s19.brucella abortus rb51 is a rough stable mutant strain, which has been widely used as a live vaccine for prevention of brucellosis in cattle instead of b. abortus strain s19. b. abortus lipopolysaccharide (lps) has unique properties in comparison to other bacterial lps.201526862376
chromatographic immunoassays: strategies and recent developments in the analysis of drugs and biological agents.a chromatographic immunoassay is a technique in which an antibody or antibody-related agent is used as part of a chromatographic system for the isolation or measurement of a specific target. various binding agents, detection methods, supports and assay formats have been developed for this group of methods, and applications have been reported that range from drugs, hormones and herbicides to peptides, proteins and bacteria. this review discusses the general principles and applications of chromato ...201526571109
high prevalence and genetic heterogeneity of rodent-borne bartonella species on heixiazi island, china.we performed genetic analysis of bartonella isolates from rodent populations from heixiazi island in northeast china. animals were captured at four sites representing grassland and brushwood habitats in 2011 and examined for the prevalence and genetic diversity of bartonella species, their relationship to their hosts, and geographic distribution. a high prevalence (57.7%) and a high diversity (14 unique genotypes which belonged to 8 clades) of bartonella spp. were detected from 71 rodents compri ...201526362983
iron and zinc exploitation during bacterial pathogenesis.ancient bacteria originated from metal-rich environments. billions of years of evolution directed these tiny single cell creatures to exploit the versatile properties of metals in catalyzing chemical reactions and biological responses. the result is an entire metallome of proteins that use metal co-factors to facilitate key cellular process that range from the production of energy to the replication of dna. two key metals in this regard are iron and zinc, both abundant on earth but not readily a ...201526497057
draft genome sequences of two brucella abortus strains isolated from cattle and pig.we report the draft genome sequences of two brucella abortus strains lmn1 and lmn2 isolated from cattle and pig. the lmn1 and lmn2 have the genome size of 3,395,952 bp and 3,334,792 bp, respectively. in addition to the conserved genes of brucella, few novel regions showing similarity to the phages were identified in both strains.201526816552
prevalence of asymptomatic brucellosis in children 7 to 12 years old.background. brucellosis is one of the most common diseases of humans and animals and its clinical manifestations differ from asymptomatic infection to chronic illness associated with recurrence of symptoms. this study aimed to evaluate the prevalence of brucellosis in asymptomatic children 7 to 12 years old in kahak, iran. methods. in this study, 186 children 7 to 12 years old were evaluated. demographic data and exposure to the brucellosis agent were recorded and blood samples for the wright, c ...201526576151
genetic characterization of the wboa gene from the predominant biovars of brucella isolates in iran.brucella spp. are gram-negative, facultative intracellular bacteria pathogens responsible for brucellosis, a zoonotic disease that can cause abortion, fetal death, and genital infections in animals and undulant fever in humans. lipopolysaccharide (lps) is known as a major virulence factor of brucella spp. the wboa gene is capable of encoding a glycosyltransferase that appears to play a major role in lps biosynthesis. hence, the characterization of this gene can help in the clarification of the p ...201526516446
inactivation of the mapk signaling pathway by listeria monocytogenes infection promotes trophoblast giant cell death.listeria monocytogenes has a well-characterized ability to cross the placental barrier, resulting in spontaneous abortion and fetal infections. however, the mechanisms resulting in infection-associated abortion are not fully understood. in this study, we demonstrate that the dephosphorylation of mapk family proteins caused by l. monocytogenes infection of trophoblast giant (tg) cells, which are placental immune cells, contributes to infectious abortion. dephosphorylation of c-jun, p38, and erk1/ ...201526528279
phospholipase a1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity.a subset of bacterial pathogens, including the zoonotic brucella species, are highly resistant against polymyxin antibiotics. bacterial polymyxin resistance has been attributed primarily to the modification of lipopolysaccharide; however, it is unknown what additional mechanisms mediate high-level resistance against this class of drugs. this work identified a role for the brucella melitensis gene bvea (bmeii0681), encoding a predicted esterase, in the resistance of b. melitensis to polymyxin b. ...201526282427
structural, functional, and immunogenic insights on cu,zn superoxide dismutase pathogenic virulence factors from neisseria meningitidis and brucella abortus.bacterial pathogens neisseria meningitidis and brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. mortality from acute n. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. cu,zn superoxide dismutases (sods) localized ...201526459556
ccl20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to brucella abortus infection.both ccl20 and human β-defensin 2 (hbd2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. they are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. whereas brucella spp. can infect humans through inhalation, their ability to induce ccl20 and hbd2 in lung cells is unknown. here we show that b. abortus induces ccl20 expression in human alveolar (a549) or bronchial (calu-6) epithelial cell lines, primary alveo ...201526448160
gesper: a statistical model for deconvoluting off-target-confounded rna interference screens.small interfering rnas (sirnas) exhibit strong off-target effects, which confound the gene-level interpretation of rna interference screens and thus limit their utility for functional genomics studies. here, we present gesper, a statistical model for reconstructing individual, gene-specific phenotypes. using 115,878 sirnas, single and pooled, from three companies in three pathogen infection screens, we demonstrate that deconvolution of image-based phenotypes substantially improves the reproducib ...201526445817
general stress signaling in the alphaproteobacteria.the alphaproteobacteria uniquely integrate features of two-component signal transduction and alternative σ factor regulation to control transcription of genes that ensure growth and survival across a range of stress conditions. research over the past decade has led to the discovery of the key molecular players of this general stress response (gsr) system, including the sigma factor σ(ecfg), its anti-σ factor nepr, and the anti-anti-σ factor phyr. the central molecular event of gsr activation ent ...201526442844
brucella canis is an intracellular pathogen that induces a lower proinflammatory response than smooth zoonotic counterparts.canine brucellosis caused by brucella canis is a disease of dogs and a zoonotic risk. b. canis harbors most of the virulence determinants defined for the genus, but its pathogenic strategy remains unclear since it has not been demonstrated that this natural rough bacterium is an intracellular pathogen. studies of b. canis outbreaks in kennel facilities indicated that infected dogs displaying clinical signs did not present hematological alterations. a virulent b. canis strain isolated from those ...201526438796
ontology-based representation and analysis of host-brucella interactions.biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. idobru is an ontology in the domain of brucella and brucellosis. brucella is a gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. in this study, idobru is ...201526445639
mntr(rv2788): a transcriptional regulator that controls manganese homeostasis in mycobacterium tuberculosis.the pathogenic mycobacterium mycobacterium tuberculosis encodes two members of the dtxr/mntr family of metalloregulators, ider and sirr. ider represses gene expression in response to ferrous iron, and we here demonstrate that sirr (rv2788), although also annotated as an iron-dependent repressor, functions instead as a manganese-dependent transcriptional repressor and is therefore renamed mntr. mntr regulates transporters that promote manganese import and genes that respond to metal ion deficienc ...201526337157
hepatotoxicity and nephrotoxicity of gallotannin-enriched extract isolated from galla rhois in icr mice.to evaluate the hepatotoxicity and nephrotoxicity of galla rhois (gr) toward the liver and kidney of icr mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration of 250, 500 and 1,000 mg/kg body weight/day of gallotannin-enriched extract of gr (gegr) for 14 days. gegr contained 68.7±2.5% of gallotannin, 25.3±0.9% of gallic acid and 4.4±0.1% of methyl gallate. also, the level of malond ...201526472962
isocitrate treatment of acute anemia of inflammation in a mouse model.acute and severe anemia of inflammation (ai) is a common complication of various clinical syndromes, including fulminant infections, critical illness with multiorgan failure, and exacerbations of autoimmune diseases. building on recent data showing beneficial results with isocitrate treatment for chronic low-grade ai in a rat model, we used a mouse model of acute and severe ai induced by intraperitoneal heat-killed brucella abortus to determine if isocitrate would be effective in this more strin ...201526603720
isocitrate treatment of acute anemia of inflammation in a mouse model.acute and severe anemia of inflammation (ai) is a common complication of various clinical syndromes, including fulminant infections, critical illness with multiorgan failure, and exacerbations of autoimmune diseases. building on recent data showing beneficial results with isocitrate treatment for chronic low-grade ai in a rat model, we used a mouse model of acute and severe ai induced by intraperitoneal heat-killed brucella abortus to determine if isocitrate would be effective in this more strin ...201526603720
dangerous liaisons: caspase-11 and reactive oxygen species crosstalk in pathogen elimination.recently, the focus of murine caspase-11 and human orthologs caspase-4, -5 research has been on their novel function to induce noncanonical inflammasome activation in direct response to gram-negative bacterial infection. on the other hand, a new role in anti-bacterial autophagy has been attributed to caspase-11, -4 and -5, which currently stands largely unexplored. in this review, we connect lately emerged evidence that suggests these caspases have a key role in anti-bacterial autophagy and disc ...201526426007
run and fyve domain-containing protein 4 enhances autophagy and lysosome tethering in response to interleukin-4.autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. here, we unravel the role of run and fyve domain-containing protein 4 (rufy4) as a positive molecular regulator of macroautophagy in primary dendritic cells (dcs). we show that exposure t ...201526416964
vaxvec: the first web-based recombinant vaccine vector database and its data analysis.a recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. to compare and better understand recombinant vectors and vaccines, we have generated vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vect ...201526403370
influence of the yjil-mdtm gene cluster on the antibacterial activity of proline-rich antimicrobial peptides overcoming escherichia coli resistance induced by the missing sbma transporter system.in view of increasing health threats from multiresistant pathogens, antimicrobial peptides (amps) and, specifically, proline-rich amps (pramps) have been investigated in animal models. pramps enter bacteria via the abc transporter sbma and inhibit intracellular targets. we used phage transduction (tn10 insertion) to screen by random mutagenesis for alternative uptake mechanisms for analogs of apidaecin 1b, a honeybee-derived pramp. all 24 apidaecin-resistant mutants had the tn10 insertion in the ...201526169420
in situ characterization of splenic brucella melitensis reservoir cells during the chronic phase of infection in susceptible mice.brucella are facultative intracellular gram-negative coccobacilli that chronically infect humans as well as domestic and wild-type mammals, and cause brucellosis. alternatively activated macrophages (m2a) induced by il-4/il-13 via stat6 signaling pathways have been frequently described as a favorable niche for long-term persistence of intracellular pathogens. based on the observation that m2a-like macrophages are induced in the spleen during the chronic phase of b. abortus infection in mice and ...201526376185
multiple-locus variable-number tandem-repeat analysis of brucella isolates from patients in xinjiang china.this study is to characterize and identify the human brucella strains in xinjiang, china with multiple-locus variable-number tandem-repeat (vntr) analysis (mlva) scheme.201526629067
human brucellosis: sero-prevalence and associated risk factors in agro-pastoral communities of kiboga district, central uganda.brucellosis remains a neglected zoonotic disease among agro-pastoral communities where unprocessed milk and milk products are consumed. a cross-sectional study was carried out in kiboga district to determine the seroprevalence and risk factors associated with human brucellosis in communities where livestock rearing in a common practice.201526374402
immune response of calves vaccinated with brucella abortus s19 or rb51 and revaccinated with rb51.brucella abortus s19 and rb51 strains have been successfully used to control bovine brucellosis worldwide; however, currently, most of our understanding of the protective immune response induced by vaccination comes from studies in mice. the aim of this study was to characterize and compare the immune responses induced in cattle prime-immunized with b. abortus s19 or rb51 and revaccinated with rb51. female calves, aged 4 to 8 months, were vaccinated with either vaccine s19 (0.6-1.2 x 1011 cfu) o ...201526352261
control of macrophage metabolism and activation by mtor and akt signaling.macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. they maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. the ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. while macrophage activation is well understood at the level of signal transduction and transcriptional regulat ...201526360589
lessons learned during the successful eradication of bovine tuberculosis from australia.there are very few international examples of the successful eradication of bovine tuberculosis (tb, caused by infection with mycobacterium bovis) from a national cattle population. this paper presents a brief overview of the successful tb eradication programme in australia from 1970, with primary emphasis on lessons of international relevance that were learned from the australian experience. the national brucellosis and tuberculosis eradication campaign ran for 27 years from 1970 to 1997 and has ...201526338937
prevalence of brucella spp in humans.to determine the seroprevalence of brucella spp in humans.201526487143
detection and discrimination of two brucella species by multiplex real-time pcr and high-resolution melt analysis curve from human blood and comparison of results using rflp.rapid and accurate detection of brucella abortus and brucella melitensis from clinical samples is so important because antibiotic treatment has major side effects. this study reveals a new method in detection of clinical samples of brucellosis using real-time pcr and high-resolution melt (hrm) curve analysis.201526523223
endoplasmic reticulum stress activates the inflammasome via nlrp3- and caspase-2-driven mitochondrial damage.endoplasmic reticulum (er) stress is observed in many human diseases, often associated with inflammation. er stress can trigger inflammation through nucleotide-binding domain and leucine-rich repeat containing (nlrp3) inflammasome, which might stimulate inflammasome formation by association with damaged mitochondria. how er stress triggers mitochondrial dysfunction and inflammasome activation is ill defined. here we have used an infection model to show that the ire1α er stress sensor regulates r ...201526341399
review of restricted experiment requests, division of select agents and toxins, centers for disease control and prevention, 2006-2013.the centers for disease control and prevention (cdc) division of select agents and toxins (dsat) regulates laboratories that possess, use, or transfer select agents and toxins in the united states. dsat also mitigates biosafety risks through the review of "restricted experiments," which under the select agent regulations are experiments that pose heightened biosafety risks. from january 2006 through december 2013, dsat received 618 requests from 109 entities to perform potentially restricted exp ...201526347984
molecular epidemiology of brucella abortus in northern ireland-1991 to 2012.brucellosis is the most common bacterial zoonoses worldwide. bovine brucellosis caused by brucella abortus has far reaching animal health and economic impacts at both the local and national levels. alongside traditional veterinary epidemiology, the use of molecular typing has recently been applied to inform on bacterial population structure and identify epidemiologically-linked cases of infection. multi-locus variable number tandem repeat vntr analysis (mlva) was used to investigate the molecula ...201526325586
annual trends of human brucellosis in pastoralist communities of south-western uganda: a retrospective ten-year study.human brucellosis is prevalent in both rural and urban uganda, yet most cases of the disease in humans go unnoticed and untreated because of inaccurate diagnosis, which is often due to the disease not manifesting in any symptoms. this study was undertaken to describe trends in laboratory-confirmed human brucellosis cases at three health facilities in pastoralist communities in south-western, uganda.201526337179
managing more than the mean: using quantile regression to identify factors related to large elk groups.animal group size distributions are often right-skewed, whereby most groups are small, but most individuals occur in larger groups that may also disproportionately affect ecology and policy. in this case, examining covariates associated with upper quantiles of the group size distribution could facilitate better understanding and management of large animal groups.we studied wintering elk groups in wyoming, where group sizes span several orders of magnitude, and issues of disease, predation and pr ...201527660373
pre-early functions of bacteriophage t5 and its relatives.coliphage t5 injects its dna in 2 steps: the first step transfer (fst) region 7.9% is injected and its genes are expressed and only then does the remainder (second step transfer, sst) of its dna enter the cell. in the fst region, only 2 essential genes (a1 and a2) have been identified and a third (dmp) non-essential gene codes for a deoxyribonucleotide 5' monophosphatase. thirteen additional putative orfs are present in the fst region. numerous properties have been attributed to fst region, incl ...201526904381
maintenance of brucellosis in yellowstone bison: linking seasonal food resources, host-pathogen interaction, and life-history trade-offs.the seasonal availability of food resources is an important factor shaping the life-history strategies of organisms. during times of nutritional restriction, physiological trade-offs can induce periods of immune suppression, thereby increasing susceptibility to infectious disease. our goal was to provide a conceptual framework describing how the endemic level bovine brucellosis (brucella abortus) may be maintained in yellowstone bison based on the seasonality of food resources and the life-histo ...201526380705
prevalence and spatial distribution of bovine brucellosis in san luis and la pampa, argentina.bovine brucellosis (bb) is a zoonotic disease caused by brucella abortus. bb is endemic in argentina, where vaccination with brucella abortus strain 19 is compulsory for 3-to-8 month-old heifers. the objectives of this study were to quantify the prevalence of bb and to identify factors associated with its occurrence, along with the spatial distribution of the disease, in the provinces of la pampa and san luis. a two-stage random sampling design was used to sample 8,965 cows (3,513 in la pampa an ...201526276733
boosting vaccine efficacy the natural (killer) way.coordination of the innate and adaptive immune systems is paramount to the development of protective humoral and cellular immunity following vaccination. natural killer (nk) cells are front-line soldiers of the innate immune system, and recent studies have revealed functions for nk cells in long-lived immune memory and the regulation of adaptive immune responses. these findings suggest that nk cells may play important roles in the development of efficacious vaccines, as well as, in some contexts ...201526272882
epidemiology of brucella infection in the human, livestock and wildlife interface in the katavi-rukwa ecosystem, tanzania.brucellosis is a zoonosis of public health importance worldwide. in tanzania, the disease is underreported due to insufficient awareness, inadequate diagnostic protocols, including lack of appropriate reagents for diagnosis. livestock and wildlife are considered potential sources of infection to humans; however, the role played by these carriers in the epidemiology of the disease in the ecosystems in tanzania is not fully understood. the objective of this study was to establish the prevalence of ...201526253151
strong association between human and animal brucella seropositivity in a linked study in kenya, 2012-2013.brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in kenya. a cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). a two-stage cluster sampling method with random selection of sublocations and households was conducted. blood samples ...201526101275
toll-like receptor 9 contributes to defense against acinetobacter baumannii infection.acinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. pattern recognition receptors, such as the toll-like receptors (tlrs), play a key role in pathogen detection and function to alert the immune system to infection. here, we examine the role for tlr9 signaling in response to a. baumannii infection. in a murine model of a. baumannii pneumonia, tlr9(-/-) mice exhibit significantly increased ...201526238713
optical whole-genome restriction mapping as a tool for rapidly distinguishing and identifying bacterial contaminants in clinical samples.optical restriction genome mapping is a technology in which a genome is linearized on a surface and digested with specific restriction enzymes, giving an arrangement of the genome with gaps whose order and size are unique for a given organism. current applications of this technology include assisting with the correct scaffolding and ordering of genomes in conjunction with whole-genome sequencing, observation of genetic drift and evolution using comparative genomics and epidemiological monitoring ...201526435946
mass spectrometry data from proteomics-based screening of immunoreactive proteins of fully virulent brucella strains using sera from naturally infected animals.here, we provide the dataset associated with our research article on comprehensive screening of brucella immunoreactive proteins using sera of naturally infected hosts published in biochemical and biophysical research communications wareth et al., 2015 [1]. whole-cell protein extracts were prepared from brucella abortus and brucella melitensis, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (sds-page) and subsequently western blotting was carried out using sera from bo ...201526322324
immune efficacy of five novel recombinant bordetella bronchiseptica proteins.the gram-negative pathogen bordetella bronchiseptica causes acute and chronic respiratory infection in a variety of animals. currently, there is no vaccine to prevent these infections. to identify useful candidate antigens for such a vaccine, five b. bronchiseptica genes including amino acid atp-binding cassette transporter substrate-binding protein (abc), lipoprotein (pl), outer membrane porin protein (ppp), leu/ile/val-binding protein (bpp), and conserved hypothetical protein (chp) were cloned ...201526223229
identification of recombination and positively selected genes in brucella.brucella is a facultative intracellular bacterium belongs to the class alpha proteobacteria. it causes zoonotic disease brucellosis to wide range of animals. brucella species are highly conserved in nucleotide level. here, we employed a comparative genomics approach to examine the role of homologous recombination and positive selection in the evolution of brucella. for the analysis, we have selected 19 complete genomes from 8 species of brucella. among the 1599 core genome predicted, 24 genes we ...201526543263
monoclonal antibody-defined specific c epitope of brucella o-polysaccharide revisited.the c epitope of brucella o-polysaccharide (o-ps) has so far lacked definitive structural identity. revised structures for this antigen revealed a unique capping perosamine tetrasaccharide consisting of a sequence of 1,2:1,3:1,2 interresidue linkages. here, using synthetic oligosaccharide glycoconjugates, the α-1,3 linkage of the o-ps is shown to be an integral structural requirement of this epitope. although a-dominant strains possess only one or two copies of the capping tetrasaccharide, this ...201526063236
structured and dynamic disordered domains regulate the activity of a multifunctional anti-σ factor.the anti-σ factor nepr plays a central role in regulation of the general stress response (gsr) in alphaproteobacteria. this small protein has two known interaction partners: its cognate extracytoplasmic function (ecf) σ factor and the anti-anti-σ factor, phyr. stress-dependent phosphorylation of phyr initiates a protein partner switch that promotes phospho-phyr binding to nepr, which frees ecf σ to activate transcription of genes required for cell survival under adverse or fluctuating conditions ...201526220965
the glycogen synthase kinase 3α and β isoforms differentially regulates interleukin-12p40 expression in endothelial cells stimulated with peptidoglycan from staphylococcus aureus.glycogen synthase kinase 3 (gsk3) is a constitutively active regulatory enzyme that is important in cancer, diabetes, and cardiovascular, neurodegenerative, and psychiatric diseases. while gsk3α is usually important in neurodegenerative and psychiatric diseases gsk3β is fundamental in the inflammatory response caused by bacterial components. peptidoglycan (pgn), one of the most abundant cell-wall structures of gram-positive bacteria, is an important inducer of inflammation. to evaluate whether i ...201526200352
first isolation, identification, phenotypic and genotypic characterization of brucella abortus biovar 3 from dairy cattle in tanzania.brucellosis is a disease of worldwide public health and economic importance. successful control is based on knowledge of epidemiology and strains present in an area. in developing countries, most investigations are based on serological assays. this study aimed at investigating a dairy herd experiencing abortions in order to establish within-herd seroprevalence to brucella spp., identify, characterize brucella strains by multiple loci variable number of tandem repeats analysis (mlva-vntr) and inv ...201526195218
the poly-γ-d-glutamic acid capsule surrogate of the bacillus anthracis capsule is a novel toll-like receptor 2 agonist.bacillus anthracis is a pathogenic gram-positive bacterium that causes a highly lethal infectious disease, anthrax. the poly-γ-d-glutamic acid (pga) capsule is one of the major virulence factors of b. anthracis, along with exotoxins. pga enables b. anthracis to escape phagocytosis and immune surveillance. our previous study showed that pga activates the human macrophage cell line thp-1 and human dendritic cells, resulting in the production of the proinflammatory cytokine interleukin-1β (il-1β) ( ...201526195551
dynamical localization of divl and plec in the asymmetric division cycle of caulobacter crescentus: a theoretical investigation of alternative models.cell-fate asymmetry in the predivisional cell of caulobacter crescentus requires that the regulatory protein divl localizes to the new pole of the cell where it up-regulates ccka kinase, resulting in a gradient of ctra~p across the cell. in the preceding stage of the cell cycle (the "stalked" cell), divl is localized uniformly along the cell membrane and maintained in an inactive form by divk~p. it is unclear how divl overcomes inhibition by divk~p in the predivisional cell simply by changing it ...201526186202
reduced susceptibility to rifampicin and resistance to multiple antimicrobial agents among brucella abortus isolates from cattle in brazil.this study aimed to determine the susceptibility profile of brazilian brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and mlva16-genotype of the strains. screening of 147 b. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (1.3 ...201526181775
description of the interaction between candida albicans and macrophages by mixed and quantitative proteome analysis without isolation.candida albicans is an opportunistic pathogen that causes fatal diseases in immunocompromised hosts. host resistance against c. albicans relies on ingestion of the pathogen by macrophages. analysis of the escaping behavior of c. albicans from macrophages is required to understand the onset of systemic candidiasis. in this study, native interactions of c. albicans with macrophages were investigated by proteome analysis using high efficiency of long monolithic silica capillary column. using this s ...201526179440
nk cells inhibit humoral immunity by reducing the abundance of cd4+ t follicular helper cells during a chronic virus infection.there is a need to understand better how to improve b cell responses and immunity to persisting virus infections, which often cause debilitating illness or death. people with chronic virus infection show evidence of improved virus control when there is a strong neutralizing antibody response, and conversely, b cell dysfunction is associated with higher viral loads. we showed previously that nk cells inhibit cd4(+) and cd8(+) t cell responses to disseminating lcmv infection and that depletion of ...201525986014
entry of francisella tularensis into murine b cells: the role of b cell receptors and complement receptors.francisella tularensis, the etiological agent of tularemia, is an intracellular pathogen that dominantly infects and proliferates inside phagocytic cells but can be seen also in non-phagocytic cells, including b cells. although protective immunity is known to be almost exclusively associated with the type 1 pathway of cellular immunity, a significant role of b cells in immune responses already has been demonstrated. whether their role is associated with antibody-dependent or antibody-independent ...201526161475
undiagnosed systemic lupus erythematosus presenting as hemophagocytic lymphohistiocytosis.hemophagocytic lymphohistiocytosis (hlh) is rarely diagnosed in adults. incidence is reported as one case per million persons per year. it can be triggered by conditions that affect immune homeostasis as infections, malignancies, and rheumatologic disorders. the following case demonstrates a rare instance in which undiagnosed systemic lupus erythematosus (sle) presented as hlh. a 28-year-old male presented with progressive weakness and recurrent fevers for 2 months. vital signs were within norma ...201526236531
recent advances in brucella abortus vaccines.brucella abortus vaccines play a central role in bovine brucellosis control/eradication programs and have been successfully used worldwide for decades. strain 19 and rb51 are the approved b. abortus vaccines strains most commonly used to protect cattle against infection and abortion. however, due to some drawbacks shown by these vaccines much effort has been undertaken for the development of new vaccines, safer and more effective, that could also be used in other susceptible species of animals. ...201526155935
recombinant salmonella expressing burkholderia mallei lps o antigen provides protection in a murine model of melioidosis and glanders.burkholderia pseudomallei and burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. these bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. both species are considered potential agents of biological warfare; they are classified as category b priority pathogens. currently there are no human or veterinary vaccines available against these pathogens. consequently efforts are directed towards ...201526148026
diversity of bartonella spp. in bats, southern vietnam. 201526079810
a pterin-dependent signaling pathway regulates a dual-function diguanylate cyclase-phosphodiesterase controlling surface attachment in agrobacterium tumefaciens.the motile-to-sessile transition is an important lifestyle switch in diverse bacteria and is often regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-gmp). in general, high c-di-gmp concentrations promote attachment to surfaces, whereas cells with low levels of signal remain motile. in the plant pathogen agrobacterium tumefaciens, c-di-gmp controls attachment and biofilm formation via regulation of a unipolar polysaccharide (upp) adhesin. the levels of c-di-gm ...201526126849
identification of burkholderia pseudomallei near-neighbor species in the northern territory of australia.identification and characterization of near-neighbor species are critical to the development of robust molecular diagnostic tools for biothreat agents. one such agent, burkholderia pseudomallei, a soil bacterium and the causative agent of melioidosis, is lacking in this area because of its genomic diversity and widespread geographic distribution. the burkholderia genus contains over 60 species and occupies a large range of environments including soil, plants, rhizospheres, water, animals and hum ...201526121041
ohr protects corynebacterium glutamicum against organic hydroperoxide induced oxidative stress.ohr, a bacterial protein encoded by the organic hydroperoxide resistance (ohr) gene, plays a critical role in resistance to organic hydroperoxides. in the present study, we show that the cys-based thiol-dependent ohr of corynebacterium glutamicum decomposes organic hydroperoxides more efficiently than hydrogen peroxide. replacement of either of the two cys residues of ohr by a ser residue resulted in drastic loss of activity. the electron donors supporting regeneration of the peroxidase activity ...201526121694
reversing tolerance in isotype switch-competent anti-insulin b lymphocytes.autoreactive b lymphocytes that escape central tolerance and mature in the periphery are a liability for developing autoimmunity. igg insulin autoantibodies that predict type 1 diabetes and complicate insulin therapies indicate that mechanisms for tolerance to insulin are flawed. to examine peripheral tolerance in anti-insulin b cells, we generated c57bl/6 mice that harbor anti-insulin vdjh-125 site directed to the native igh locus (vh125(sd)). class switch-competent anti-insulin b cells fail to ...201526109644
the impact of immunosenescence on pulmonary disease.the global population is aging with significant gains in life expectancy particularly in the developed world. consequently, greater focus on understanding the processes that underlie physiological aging has occurred. key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. immunosenescence and its associated chronic low grade systemic "inflamm-aging" contribute to the development and progression of ...201526199462
protection provided by an encapsulated live attenuated δabcba strain of brucella ovis against experimental challenge in a murine model.this study aimed to evaluate the brucella ovis δabcba strain as a vaccine candidate in the murine model. balb/c mice were subcutaneously or intraperitoneally immunized with a single dose or three doses of the b. ovis δabcba strain and then were challenged with wild-type b. ovis. single or multiple immunizations provided only mild protection, with significantly smaller numbers of wild-type b. ovis cfu in the livers of immunized mice but not in the spleens. encapsulation of b. ovis δabcba signific ...201525947146
26postoperative diagnosis and outcome in patients with revision arthroplasty for aseptic loosening.the most common cause of implant failure is aseptic loosening (al), followed by prosthetic joint infection (pji). this study evaluates the incidence of pji among patients operated with suspected al and whether the diagnosis of pji was predictive of subsequent implant failure including re-infection, at 2 years of follow up.201526084830
layered evolution in the immune system: a view from history.although much had still to be learned, evidence indicating that b-1a lymphocytes very likely belonged to a distinct lineage was largely in place by the time of the first large b-1a conference in 1991. the widely respected group of immunologists attending that meeting (including tasuko honjo and klaus rajewsky) developed and ultimately published the b-1a notation still in use today. here, i briefly review some of the early b-1a findings that underlie current studies. i close with a brief summary ...201526096553
induction murine models of chronic fatigue syndrome by brucella abortus antigen injections: is anemia induced or not?to investigate whether brucella abortus (ba) antigen injections lead to anemia, and to establish an appropriate chronic fatigue syndrome (cfs) animal model by ba injections, 6 repeated injections of ba antigen were fulfilled every 2 weeks. at a high dose of 1∗10(10) particles/mouse, anemia was induced within 2 weeks and then recovered a lot at the end of the research, while at a moderate dose of 1∗10(8) (3 injections) shifting to 1∗10(9)/mouse (3 injections) anemia was absent. in both groups run ...201526171388
the role of autophagy in intracellular pathogen nutrient acquisition.following entry into host cells intracellular pathogens must simultaneously evade innate host defense mechanisms and acquire energy and anabolic substrates from the nutrient-limited intracellular environment. most of the potential intracellular nutrient sources are stored within complex macromolecules that are not immediately accessible by intracellular pathogens. to obtain nutrients for proliferation, intracellular pathogens must compete with the host cell for newly-imported simple nutrients or ...201526106587
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