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Sample records for heterodimers alter borrelia

  1. Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosis

    NARCIS (Netherlands)

    Hovius, Joppe W. R.; Li, Xin; Ramamoorthi, Nandhini; van Dam, Alje P.; Barthold, Stephen W.; van der Poll, Tom; Speelman, Peter; Fikrig, Erol

    2007-01-01

    Ixodes ricinus ticks and mice can be infected with both Borrelia burgdorferi sensu stricto and Borrelia garinii. The effect of coinfection with these two Borrelia species on the development of murine Lyme borreliosis is unknown. Therefore, we investigated whether coinfection with the

  2. Whole-Genome Sequences of Borrelia bissettii Borrelia valaisiana and Borrelia spielmanii

    Energy Technology Data Exchange (ETDEWEB)

    Schutzer S. E.; Dunn J.; Fraser-Liggett C. M.; Qiu W.-G.; Kraiczy P.; Mongodin E. F.; Luft B. J.; Casjens S. R.

    2012-01-01

    It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

  3. Coexistence of Phases in a Protein Heterodimer

    Science.gov (United States)

    Krokhotin, Andrey; Liwo, Adam; Niemi, Antti J.; Scheraga, Harold A.

    2012-07-01

    A heterodimer consisting of two or more different kinds of proteins can display an enormous number of distinct molecular architectures. The conformational entropy is an essential ingredient in the Helmholtz free energy and, consequently, these heterodimers can have a very complex phase structure. Here, it is proposed that there is a state of proteins, in which the different components of a heterodimer exist in different phases. For this purpose, the structures in the protein data bank (PDB) have been analyzed, with radius of gyration as the order parameter. Two major classes of heterodimers with their protein components coexisting in different phases have been identified. An example is the PDB structure 3DXC. This is a transcriptionally active dimer. One of the components is an isoform of the intra-cellular domain of the Alzheimer-disease related amyloid precursor protein (AICD), and the other is a nuclear multidomain adaptor protein in the Fe65 family. It is concluded from the radius of gyration that neither of the two components in this dimer is in its own collapsed phase, corresponding to a biologically active protein. The UNRES energy function has been utilized to confirm that, if the two components are separated from each other, each of them collapses. The results presented in this work show that heterodimers whose protein components coexist in different phases, can have intriguing physical properties with potentially important biological consequences.

  4. Recombinant constructs of Borrelia burgdorferi

    Energy Technology Data Exchange (ETDEWEB)

    Dattwyler, Raymond J. (Setauket, NY); Gomes-Solecki, Maria J. C. (New York, NY); Luft, Benjamin J. (East Setauket, NY); Dunn, John J.(Bellport, NY)

    2007-02-20

    Novel chimeric nucleic acids, encoding chimeric Borrelia proteins comprising OspC or an antigenic fragment thereof and OspA or an antigenic fragment thereof, are disclosed. Chimeric proteins encoded by the nucleic acid sequences are also disclosed. The chimeric proteins are useful as vaccine immunogens against Lyme borreliosis, as well as for immunodiagnostic reagents.

  5. The formation of heterodimers by vancomycin group antibiotics

    DEFF Research Database (Denmark)

    Staroske, T; O'Brien, DP; Jørgensen, Thomas J. D.

    2000-01-01

    The formation of heterodimers in mixtures of glycopeptide antibiotics has been detected by electrospray ionization mass spectrometry (ESI-MS), and dimerization constants have been determined. By using NMR spectroscopy, it has been shown that these heterodimers indeed exist in aqueous solution...

  6. Use of CFSE staining of borreliae in studies on the interaction between borreliae and human neutrophils

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    Hytönen Jukka

    2006-10-01

    Full Text Available Abstract Background Species of the tick-transmitted spirochete group Borrelia burgdorferi sensu lato (B. burgdorferi cause Lyme borreliosis. Acute borrelial infection of the skin has unusual characteristics with only a mild local inflammatory response suggesting that the interaction between borreliae and the cells of the first-line defence might differ from that of other bacteria. It has been reported that human neutrophils phagocytose motile borreliae through an unconventional mechanism (tube phagocytosis which is not observed with non-motile borreliae. Therefore, it would be of great interest to visualise the bacteria by a method not affecting motility and viability of borreliae to be able to study their interaction with the cells of the innate immunity. Carboxyfluorescein diacetate, succinimidyl ester (CFSE labelling has been previously used for studying the adhesion of labelled bacteria to host cells and the uptake of labelled substrates by various cells using flow cytometry. Results In this study, CFSE was shown to efficiently stain different genospecies of B. burgdorferi without affecting bacterial viability or motility. Use of CFSE staining allowed subsequent quantification of borreliae associated with human neutrophils with flow cytometry and confocal microscopy. As a result, no difference in association between different borrelial genospecies (Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii, or between borreliae and the pyogenic bacterium Streptococcus pyogenes, with neutrophils could be detected. Borrelial virulence, on the other hand, affected association with neutrophils, with significantly higher association of a non-virulent mutant B. burgdorferi sensu stricto strain compared to the parental virulent wild type strain. Conclusion These results suggest that the flow cytometric assay using CFSE labelled borreliae is a valuable tool in the analysis of the interaction between borreliae and human neutrophils. The

  7. Delineation of a New Species of the Borrelia burgdorferi Sensu Lato Complex, Borrelia americana sp. nov

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Lin, T.; Gao, L.; Grubhoffer, Libor; Oliver, J. H., Jr.

    2009-01-01

    Roč. 47, č. 12 (2009), s. 3875-3880 ISSN 0095-1137 R&D Projects: GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : multilocus sequence analysis * B. burgdorferi sl complex * new borrelia species * Borrelia americana Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 4.162, year: 2009

  8. Infection of Ixodes ricinus by Borrelia burgdorferi sensu lato in peri-urban forests of France.

    Directory of Open Access Journals (Sweden)

    Axelle Marchant

    Full Text Available Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. In Europe, it is transmitted by Ixodes ticks that carry bacteria belonging to the Borrelia burgdorferi sensu lato complex. The objective of this work was to explore eco-epidemiological factors of Lyme borreliosis in peri-urban forests of France (Sénart, Notre-Dame and Rambouillet. We investigated whether the introduction of Tamias sibiricus in Sénart could alter the density of infected ticks. Moreover, the density and tick infection were investigated according to the tree species found in various patches of Sénart forest. For this purpose, ticks were sampled during 3 years. In the Sénart forest, the density of nymph and adult ticks showed no significant difference between 2008, 2009 and 2011. The nymph density varied significantly as a function of the month of collection. Regarding the nymphs, a higher rate of infection and infected density were found in 2009. Plots with chipmunks (C presented a lower density of both nymphs and adult ticks than plots without chipmunks (NC did. A higher rate of infection of nymphs with Borrelia was seen in C plots. The prevalence of the various species of Borrelia was also found to vary between C and NC plots with the year of the collect. The presence of chestnut trees positively influenced the density of both nymphs and adults. The infected nymph density showed a significant difference depending on the peri-urban forest studied, Sénart being higher than Rambouillet. The prevalence of Borrelia species also differed between the various forests studied. Concerning the putative role that Tamias sibiricus may play in the transmission of Borrelia, our results suggest that its presence is correlated with a higher rate of infection of questing ticks by Borrelia genospecies and if its population increases, it could play a significant role in the risk of transmission of Lyme borreliosis.

  9. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    Energy Technology Data Exchange (ETDEWEB)

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  10. Borrelia sp. phylogenetically different from Lyme disease- and relapsing fever-related Borrelia spp. in Amblyomma varanense from Python reticulatus.

    Science.gov (United States)

    Trinachartvanit, Wachareeporn; Hirunkanokpun, Supanee; Sudsangiem, Ronnayuth; Lijuan, Wanwisa; Boonkusol, Duangjai; Baimai, Visut; Ahantarig, Arunee

    2016-06-24

    Species of the genus Borrelia are causative agents of Lyme disease and relapsing fever. Lyme disease is the most commonly reported vector-borne disease in the northern hemisphere. However, in some parts of the world Lyme borreliosis and relapsing fever may be caused by novel Borrelia genotypes. Herein, we report the presence of a Borrelia sp. in an Amblyomma varanense collected from Python reticulatus. Ticks were collected from snakes, identified to species level and examined by PCR for the presence of Borrelia spp. flaB and 16S rRNA genes. Phylogenetic trees were constructed using the neighbour-joining method. Three A. varanense ticks collected from P. reticulatus were positive for a unique Borrelia sp., which was phylogenetically divergent from both Lyme disease- and relapsing fever-associated Borrelia spp. The results of this study suggest for the first time that there is a Borrelia sp. in A. varanense tick in the snake P. reticulatus that might be novel.

  11. Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov. prevail in diverse enzootic transmission cycles.

    Science.gov (United States)

    Margos, Gabriele; Lane, Robert S; Fedorova, Natalia; Koloczek, Johannes; Piesman, Joseph; Hojgaard, Andrias; Sing, Andreas; Fingerle, Volker

    2016-03-01

    Two species of the genus Borrelia , Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov., were first described by Postic and co-workers on the basis of genetic analyses of several loci. Multilocus sequence analysis of eight housekeeping loci confirmed that these two Borrelia genomospecies are distinct members of the Borrelia burgdorferi sensu lato complex. B. bissettiae sp. nov. was initially described in transmission cycles involving Neotoma fuscipes wood rats and Ixodes pacificus ticks in California, and Neotoma mexicana and Ixodes spinipalpis in Colorado. The preferred host of B. californiensis sp. nov. appears to be the California kangaroo rat, Dipodomys californicus ; Ixodes jellisoni , I. spinipalipis and I. pacificus ticks are naturally infected with it. Thus, the ecological associations of the two genomospecies and their genetic distance from all other known Borrelia genomospecies species justify their description as separate genomospecies: B. bissettiae sp. nov. (type strain DN127 T  = DSM 17990 T  =  CIP 109136 T ) and B. californiensis (type strain CA446 T  = DSM 17989 T  = ATCC BAA-2689 T ).

  12. Enzyme activities of Borrelia burgdorferi sensu lato

    Czech Academy of Sciences Publication Activity Database

    Heroldová, M.; Němec, M.; Hubálek, Zdeněk; Halouzka, Jiří

    2001-01-01

    Roč. 46, č. 3 (2001), s. 179-182 ISSN 0015-5632 R&D Projects: GA ČR GA206/00/1204 Institutional research plan: CEZ:AV0Z6093917 Keywords : Borrelia burgdorferi * Lyme disease Subject RIV: EE - Microbiology, Virology Impact factor: 0.776, year: 2001

  13. Molecular detection of Borrelia burgdorferi sensu lato

    DEFF Research Database (Denmark)

    Lager, Malin; Faller, Maximilian; Wilhelmsson, Peter

    2017-01-01

    the protocols using 16S rRNA as the target gene, however, this concordance was mainly related to cDNA as the type of template. When comparing cDNA and DNA as the type of template the analytical sensitivity was in general higher for the protocols using DNA as template regardless of the use of target gene...... molecular detection by polymerase chain reaction (PCR) may serve as a complement. Aim: The purpose of this study was to evaluate the analytical sensitivity, analytical specificity and concordance of eight different real-time PCR methods at five laboratories in Sweden, Norway and Denmark. Method: Each...... participating laboratory was asked to analyse three different sets of samples (reference panels; all blinded) i) cDNA extracted and transcribed from water spiked with cultured Borrelia strains, ii) cerebrospinal fluid spiked with cultured Borrelia strains, and iii) DNA dilution series extracted from cultured...

  14. Borrelia infection and risk of celiac disease.

    Science.gov (United States)

    Alaedini, Armin; Lebwohl, Benjamin; Wormser, Gary P; Green, Peter H; Ludvigsson, Jonas F

    2017-09-15

    Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease. Biopsy reports from all of Sweden's pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease. Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06-2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40-2.35), with the risk of disease being highest in the first year of follow-up. Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

  15. Novel insights about the MDM2/MDM4 heterodimer

    OpenAIRE

    Moretti, Fabiola

    2015-01-01

    MDM2 (mouse double minute 2 homolog) and MDM4 (double minute 4 human homolog, also known as MDMX) inhibit the activity of tumor protein p53 (TP53, best known as p53) through their heterodimerization. New evidence indicates that under stress conditions the heterodimer is modified, leading to different activities of the single molecules. In particular, following lethal DNA damage, MDM2 and MDM4 dissociate and MDM4 promotes the stabilization of homeodomain-interacting protein kinase 2 (HIPK2) an...

  16. SdAb heterodimer formation using leucine zippers

    Science.gov (United States)

    Goldman, Ellen R.; Anderson, George P.; Brozozog-Lee, P. Audrey; Zabetakis, Dan

    2013-05-01

    Single domain antibodies (sdAb) are variable domains cloned from camel, llama, or shark heavy chain only antibodies, and are among the smallest known naturally derived antigen binding fragments. SdAb derived from immunized llamas are able to bind antigens with high affinity, and most are capable of refolding after heat or chemical denaturation to bind antigen again. We hypothesized that the ability to produce heterodimeric sdAb would enable reagents with the robust characteristics of component sdAb, but with dramatically improved overall affinity through increased avidity. Previously we had constructed multimeric sdAb by genetically linking sdAb that bind non-overlapping epitopes on the toxin, ricin. In this work we explored a more flexible approach; the construction of multivalent binding reagents using multimerization domains. We expressed anti-ricin sdAb that recognize different epitopes on the toxin as fusions with differently charged leucine zippers. When the initially produced homodimers are mixed the leucine zipper domains will pair to produce heterodimers. We used fluorescence resonance energy transfer to confirm heterodimer formation. Surface plasmon resonance, circular dichroism, enzyme linked immunosorbent assays, and fluid array assays were used to characterize the multimer constructs, and evaluate their utility in toxin detection.

  17. Excitation dynamics and relaxation in a molecular heterodimer

    International Nuclear Information System (INIS)

    Balevičius, V.; Gelzinis, A.; Abramavicius, D.; Mančal, T.; Valkunas, L.

    2012-01-01

    Highlights: ► Dynamics of excitation within a heterogenous molecular dimer. ► Excited states can be swapped due to different reorganization energies of monomers. ► Conventional excitonic basis becomes renormalized due to interaction with the bath. ► Relaxation is independent of mutual positioning of monomeric excited states. -- Abstract: The exciton dynamics in a molecular heterodimer is studied as a function of differences in excitation and reorganization energies, asymmetry in transition dipole moments and excited state lifetimes. The heterodimer is composed of two molecules modeled as two-level systems coupled by the resonance interaction. The system-bath coupling is taken into account as a modulating factor of the molecular excitation energy gap, while the relaxation to the ground state is treated phenomenologically. Comparison of the description of the excitation dynamics modeled using either the Redfield equations (secular and full forms) or the Hierarchical quantum master equation (HQME) is demonstrated and discussed. Possible role of the dimer as an excitation quenching center in photosynthesis self-regulation is discussed. It is concluded that the system-bath interaction rather than the excitonic effect determines the excitation quenching ability of such a dimer.

  18. Recyclable magnetite-silver heterodimer nanocomposites with durable antibacterial performance

    Directory of Open Access Journals (Sweden)

    Chunyan Yong

    2018-03-01

    Full Text Available There is a significant need for magnetite-silver nanocomposites that exhibit durable and recyclable antimicrobial activity. In this study, magnetic iron oxide nanoparticles (Fe3O4 NPs coated with ethylenediamine-modified chitosan/polyacrylic acid copolymeric layer (Fe3O4@ECS/PAA were fabricated. Subsequently, directly deposited silver (Ag NPs procedure was carried out to form the antibacterial heterodimers of Fe3O4@ECS/PAA-Ag NPs. The composition and morphology of the resultant nanostructures were confirmed by FT-IR, XRD, TEM and TGA. The overall length of the heterodimers was approximately 45 nm, in which the mean diameter of Fe3O4@ECS/PAA NPs reached up to 35 nm, and that of Ag NPs was around 15 nm. The mass fraction of silver NPs in the nanocomposites was about 63.1%. The obtained Fe3O4@ECS/PAA NPs exhibited good colloidal stability, and excellent response to additional magnetic field, making the NPs easy to recover after antibacterial tests. In particular, the Fe3O4@ECS/PAA-Ag NPs retained nearly 100% biocidal efficiency (106–107 CFU/mg nanoparticles for both Gram-negative bacteria E. coli and Gram-positive bacteria S. aureus throughout ten cycles without washing with any solvents or water, exhibiting potent and durable antibacterial activity.

  19. Measuring Borrelia burgdorferi Motility and Chemotaxis.

    Science.gov (United States)

    Zhang, Kai; Li, Chunhao

    2018-01-01

    Swimming plate, cell motion tracking, and capillary tube assays are very useful tools to quantitatively measure bacterial motility and chemotaxis. These methods were modified and applied to study Borrelia burgdorferi motility and chemotaxis. By using these methods, numerous motility and chemotaxis mutants have been characterized and several chemoattractants were identified. With the assistance of these tools, the role of motility and chemotaxis in the pathogenicity of B. burgdorferi has been established. In addition, these tools also facilitate the study of motility and chemotaxis in other spirochetes.

  20. Multispacer sequence typing relapsing fever Borreliae in Africa.

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    Haitham Elbir

    Full Text Available BACKGROUND: In Africa, relapsing fevers are neglected arthropod-borne infections caused by closely related Borrelia species. They cause mild to deadly undifferentiated fever particularly severe in pregnant women. Lack of a tool to genotype these Borrelia organisms limits knowledge regarding their reservoirs and their epidemiology. METHODOLOGY/PRINCIPAL FINDINGS: Genome sequence analysis of Borrelia crocidurae, Borrelia duttonii and Borrelia recurrentis yielded 5 intergenic spacers scattered between 10 chromosomal genes that were incorporated into a multispacer sequence typing (MST approach. Sequencing these spacers directly from human blood specimens previously found to be infected by B. recurrentis (30 specimens, B. duttonii (17 specimens and B. crocidurae (13 specimens resolved these 60 strains and the 3 type strains into 13 species-specific spacer types in the presence of negative controls. B. crocidurae comprised of 8 spacer types, B. duttonii of 3 spacer types and B. recurrentis of 2 spacer types. CONCLUSIONS/SIGNIFICANCE: Phylogenetic analyses of MST data suggested that B. duttonii, B. crocidurae and B. recurrentis are variants of a unique ancestral Borrelia species. MST proved to be a suitable approach for identifying and genotyping relapsing fever borreliae in Africa. It could be applied to both vectors and clinical specimens.

  1. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models*

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-01-01

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. PMID:26912662

  2. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-05-06

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Synthesis, morphological control, and antibacterial properties of hollow/solid Ag2S/Ag heterodimers

    KAUST Repository

    Pang, Maolin; Hu, Jiangyong; Zeng, Huachun

    2010-01-01

    of this highly asymmetric dipolar composite, photocatalytic inactivation of Escherichia coli K-12 in the presence of the as-prepared Ag 2S/Ag heterodimers has been carried out under UV irradiation. The added Ag2S/Ag heterodimers show good chemical stability under

  4. Convergent Synthesis of Two Fluorescent Ebselen-Coumarin Heterodimers

    Directory of Open Access Journals (Sweden)

    Jim Küppers

    2016-07-01

    Full Text Available The organo-seleniumdrug ebselen exhibits a wide range of pharmacological effects that are predominantly due to its interference with redox systems catalyzed by seleno enzymes, e.g., glutathione peroxidase and thioredoxin reductase. Moreover, ebselen can covalently interact with thiol groups of several enzymes. According to its pleiotropic mode of action, ebselen has been investigated in clinical trials for the prevention and treatment of different ailments. Fluorescence-labeled probes containing ebselen are expected to be suitable for further biological and medicinal studies. We therefore designed and synthesized two coumarin-tagged activity-based probes bearing the ebselen warhead. The heterodimers differ by the nature of the spacer structure, for which—in the second compound—a PEG/two-amide spacer was introduced. The interaction of this probe and of ebselen with two cysteine proteases was investigated.

  5. Convergent Synthesis of Two Fluorescent Ebselen-Coumarin Heterodimers.

    Science.gov (United States)

    Küppers, Jim; Schulz-Fincke, Anna Christina; Palus, Jerzy; Giurg, Mirosław; Skarżewski, Jacek; Gütschow, Michael

    2016-07-08

    The organo-seleniumdrug ebselen exhibits a wide range of pharmacological effects that are predominantly due to its interference with redox systems catalyzed by seleno enzymes, e.g., glutathione peroxidase and thioredoxin reductase. Moreover, ebselen can covalently interact with thiol groups of several enzymes. According to its pleiotropic mode of action, ebselen has been investigated in clinical trials for the prevention and treatment of different ailments. Fluorescence-labeled probes containing ebselen are expected to be suitable for further biological and medicinal studies. We therefore designed and synthesized two coumarin-tagged activity-based probes bearing the ebselen warhead. The heterodimers differ by the nature of the spacer structure, for which-in the second compound-a PEG/two-amide spacer was introduced. The interaction of this probe and of ebselen with two cysteine proteases was investigated.

  6. Borrelia infection and risk of non-Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Schollkopf, C.; Melbye, M.; Munksgaard, L.

    2008-01-01

    Reports of the presence of Borrelia burgdorferi DNA in malignant lymphomas have raised the hypothesis that infection with B. burgdorferi may be causally related to non-Hodgkin lymphoma (NHL) development. We conducted a Danish-Swedish case-control study including 3055 NHL patients and 3187.......9-2.0]). However, in analyses of NHL subtypes, self-reported history of B. burgdorferi infection (OR = 2.5 [1.2-5.1]) and seropositivity for anti-Borrelia antibodies (OR = 3.6 [1.8-7.4]) were both associated with risk of mantle cell lymphoma. Notably, this specific association was also observed in persons who did...... not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 [2.0-8.9]). Our observations suggest a previously unreported association between B. burgdorferi infection and risk of mantle cell lymphoma Udgivelsesdato: 2008/6/15...

  7. Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

    Energy Technology Data Exchange (ETDEWEB)

    Angel, Thomas E.; Luft, Benjamin J.; Yang, Xiaohua; Nicora, Carrie D.; Camp, David G.; Jacobs, Jon M.; Smith, Richard D.

    2010-11-02

    We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism’s life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals.

  8. Antimicrobial Activity of Bee Venom and Melittin against Borrelia burgdorferi

    OpenAIRE

    Kayla M. Socarras; Priyanka A. S. Theophilus; Jason P. Torres; Khusali Gupta; Eva Sapi

    2017-01-01

    Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known f...

  9. Does RecA have a role in Borrelia recurrentis?

    OpenAIRE

    Cutler, S.J.; Rinky, I.J.; Bonilla, E.M.

    2011-01-01

    Genomic sequencing of two relapsing fever spirochaetes showed truncation of recA in Borrelia recurrentis, but not in Borrelia duttonii. RecA has an important role among bacteria; we investigated whether this characteristic was representative of B. recurrentis, or an artefact following in vitro cultivation. We sequenced recA directly from samples of patient with louse-borne relapsing fever (B. recurrentis) or tick-borne relapsing fever (B. duttonii). We confirmed the premature stop codon in se...

  10. Characterization of biofilm formation by Borrelia burgdorferi in vitro.

    Directory of Open Access Journals (Sweden)

    Eva Sapi

    Full Text Available Borrelia burgdorferi, the causative agent of Lyme disease, has long been known to be capable of forming aggregates and colonies. It was recently demonstrated that Borrelia burgdorferi aggregate formation dramatically changes the in vitro response to hostile environments by this pathogen. In this study, we investigated the hypothesis that these aggregates are indeed biofilms, structures whose resistance to unfavorable conditions are well documented. We studied Borrelia burgdorferi for several known hallmark features of biofilm, including structural rearrangements in the aggregates, variations in development on various substrate matrices and secretion of a protective extracellular polymeric substance (EPS matrix using several modes of microscopic, cell and molecular biology techniques. The atomic force microscopic results provided evidence that multilevel rearrangements take place at different stages of aggregate development, producing a complex, continuously rearranging structure. Our results also demonstrated that Borrelia burgdorferi is capable of developing aggregates on different abiotic and biotic substrates, and is also capable of forming floating aggregates. Analyzing the extracellular substance of the aggregates for potential exopolysaccharides revealed the existence of both sulfated and non-sulfated/carboxylated substrates, predominately composed of an alginate with calcium and extracellular DNA present. In summary, we have found substantial evidence that Borrelia burgdorferi is capable of forming biofilm in vitro. Biofilm formation by Borrelia species might play an important role in their survival in diverse environmental conditions by providing refuge to individual cells.

  11. Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection

    NARCIS (Netherlands)

    Wagemakers, A.; Mason, L. M. K.; Oei, A.; de Wever, B.; van der Poll, T.; Bins, A. D.; Hovius, J. W. R.

    2014-01-01

    Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method

  12. Heterogeneity of Borrelia burgdorferi sensu lato and their reflection on immune response

    Czech Academy of Sciences Publication Activity Database

    Stefančíková, A.; Derdáková, M.; Tresová, Gabriela; Peťko, B.; Szestáková, E.; Škardová, I.; Čisláková, L.

    2005-01-01

    Roč. 12, č. 2 (2005), s. 211-216 ISSN 1232-1966 Institutional research plan: CEZ:AV0Z60220518 Keywords : horses * ELISA * SDS-PAGE * IgG * seroprevalence * Borrelia burgdorferi * Borrelia garinii * Borrelia afzelii Subject RIV: EC - Immunology Impact factor: 1.051, year: 2005

  13. Evidence for frequent OspC gene transfer between Borrelia valaisiana sp. nov. and other Lyme disease spirochetes

    NARCIS (Netherlands)

    Wang, G.; van Dam, A. P.; Dankert, J.

    1999-01-01

    Molecular polymorphism of the ospC gene has been reported in Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii, the spirochetes causing human Lyme borreliosis. To assess the genetic relationship between ospC genes from the recently described Borrelia valaisiana sp. nov. and

  14. Genome-Wide Mutagenesis in Borrelia burgdorferi.

    Science.gov (United States)

    Lin, Tao; Gao, Lihui

    2018-01-01

    Signature-tagged mutagenesis (STM) is a functional genomics approach to identify bacterial virulence determinants and virulence factors by simultaneously screening multiple mutants in a single host animal, and has been utilized extensively for the study of bacterial pathogenesis, host-pathogen interactions, and spirochete and tick biology. The signature-tagged transposon mutagenesis has been developed to investigate virulence determinants and pathogenesis of Borrelia burgdorferi. Mutants in genes important in virulence are identified by negative selection in which the mutants fail to colonize or disseminate in the animal host and tick vector. STM procedure combined with Luminex Flex ® Map™ technology and next-generation sequencing (e.g., Tn-seq) are the powerful high-throughput tools for the determination of Borrelia burgdorferi virulence determinants. The assessment of multiple tissue sites and two DNA resources at two different time points using Luminex Flex ® Map™ technology provides a robust data set. B. burgdorferi transposon mutant screening indicates that a high proportion of genes are the novel virulence determinants that are required for mouse and tick infection. In this protocol, an effective signature-tagged Himar1-based transposon suicide vector was developed and used to generate a sequence-defined library of nearly 4800 mutants in the infectious B. burgdorferi B31 clone. In STM, signature-tagged suicide vectors are constructed by inserting unique DNA sequences (tags) into the transposable elements. The signature-tagged transposon mutants are generated when transposon suicide vectors are transformed into an infectious B. burgdorferi clone, and the transposable element is transposed into the 5'-TA-3' sequence in the B. burgdorferi genome with the signature tag. The transposon library is created and consists of many sub-libraries, each sub-library has several hundreds of mutants with same tags. A group of mice or ticks are infected with a mixed

  15. Temporomandibular joint involvement caused by Borrelia Burgdorferi.

    Science.gov (United States)

    Lesnicar, Gorazd; Zerdoner, Danijel

    2007-12-01

    Lyme borreliosis is an endemic disease in Slovenia with an incidence of around 150 patients per 100,000 inhabitants. Although the large joints are most typically affected in Lyme borreliosis, there are also periods of disease activity with arthritis or arthralgias involving smaller joints, including the temporo-mandibular joint. During the years between 2000 and 2003, two patients with Lyme borreliosis affecting the temporo-mandibular joints were treated. The patients presented with fatigue and pain in diverse muscle groups accompanied by arthralgia, which was most pronounced in the temporomandibular joint area. None of the patients were febrile or had joint effusions. Both patients were examined by means of biochemical and serological examinations for Borrelia burgdorferi using ELISA assay and Western blot test (both for IgM and IgG), plain radiographs, MR and CT scans, and scinti-scan of the temporo-mandibular joints They both had positive serum markers for an acute B. burgdorferi infection and were treated with intravenous ceftriaxone. None of the patients had clinical or laboratory signs of chronic Lyme disease activity two and four years following therapy, respectively. Roentgenographic and nuclear magnetic resonance imaging of the temporo-mandibular joints had not shown any persistent sign of acute inflammation. There are only few reports of patients with manifest temporo-mandibular joint involvement of Lyme borreliosis in the literature. This report emphasizes the importance of differential diagnosis of acute temporo-mandibular joint arthralgia, of early diagnosis of Lyme borreliosis, and of the necessity for prompt antibiotic treatment.

  16. Population dynamics of Borrelia burgdorferi in Lyme disease

    Directory of Open Access Journals (Sweden)

    Sebastian Christoph Binder

    2012-03-01

    Full Text Available Many chronic inflammatory diseases are known to be caused by persistent bacterial or viral infections. A well-studied example is the tick-borne infection by the gram-negative Spirochaetes of the genus Borrelia in humans and other mammals, causing severe symptoms of chronic inflammation and subsequent tissue damage (Lyme Disease, particularly in large joints and the central nervous system, but also in the heart and other tissues of untreated patients. Although killed efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably high infectivity in mice and men. In experimentally infected mice, the first immune response almost clears the infection. However, approximately one week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase. We developed a mathematical model describing the bacterial growth and the immune response against Borrelia burgdorferi in the C3H mouse strain that has been established as an experimental model for Lyme disease. The peculiar dynamics of the infection exclude two possible mechanistic explanations for the regrowth of the almost cleared bacteria. Neither the hypothesis of bacterial dissemination to different tissue nor a limitation of phagocytic capacity were compatible with experiment. The mathematical model predicts that Borrelia recovers from the strong initial immune response by the regrowth of an immune-resistant sub-population of the bacteria. The chronic phase appears as an equilibration of bacterial growth and adaptive immunity. This result has major implications for the development of the chronic phase of Borrelia infections as well as on potential protective clinical interventions.

  17. Synthesis, morphological control, and antibacterial properties of hollow/solid Ag2S/Ag heterodimers

    KAUST Repository

    Pang, Maolin

    2010-08-11

    Ag2S and Ag are important functional materials that have received considerable research interest in recent years. In this work, we develop a solution-based synthetic method to combine these two materials into hollow/solid Ag2S/Ag heterodimers at room temperature. Starting from monodisperse Cu2O solid spheres, CuS hollow spheres can be converted from Cu2O through a modified Kirkendall process, and the obtained CuS can then be used as a solid precursor for preparation of the Ag2S/Ag heterodimers through ion exchange and photo-assisted reduction. We have found that formation of the Ag2S/Ag heterodimers is instantaneous, and the size of Ag nanocrystals on the hollow spheres of Ag2S can be controlled by changing the concentration and power of reducing agents in the synthesis. The growth of Ag nanoparticles on hollow spheres of Ag2S in the dimers is along the [111] direction of the silver crystal; the light absorption properties have also been investigated. Furthermore, coupling or tripling of Ag2S/Ag heterodimers into dumbbell-like trimers ((Ag 2S)2/Ag, linear) and triangular tetramers ((Ag 2S)3/Ag, coplanar) can also be attained at 60°C by adding the bidentate ligand ethylenediamine as a cross-linking agent. To test the applicability of this highly asymmetric dipolar composite, photocatalytic inactivation of Escherichia coli K-12 in the presence of the as-prepared Ag 2S/Ag heterodimers has been carried out under UV irradiation. The added Ag2S/Ag heterodimers show good chemical stability under prolonged UV irradiation, and no appreciable solid dissolution is found. Possible mechanisms regarding the enhanced antibacterial activity have also been addressed. © 2010 American Chemical Society.

  18. Whole genome sequence of an unusual Borrelia burgdorferi sensu lato isolate

    Energy Technology Data Exchange (ETDEWEB)

    Casjens, S.R.; Dunn, J.; Fraser-Liggett, C. M.; Mongodin, E. F.; Qiu, W. G.; Luft, B. J.; Schutzer, S. E.

    2011-03-01

    Human Lyme disease is caused by a number of related Borrelia burgdorferi sensu lato species. We report here the complete genome sequence of Borrelia sp. isolate SV1 from Finland. This isolate is to date the closest known relative of B. burgdorferi sensu stricto, but it is sufficiently genetically distinct from that species that it and its close relatives warrant its candidacy for new-species status. We suggest that this isolate should be named 'Borrelia finlandensis.'

  19. Bistable optical response of a nanoparticle heterodimer : Mechanism, phase diagram, and switching time

    NARCIS (Netherlands)

    Nugroho, Bintoro; Iskandar, Alexander; Malyshev, V.A.; Knoester, Jasper

    2013-01-01

    We conduct a theoretical study of the bistable optical response of a nanoparticle heterodimer comprised of a closely spaced semiconductor quantum dot and a metal nanoparticle. The bistable nature of the response results from the interplay between the quantum dot's optical nonlinearity and its

  20. Spectral Sensitization of TiO2 Substrates by Monolayers of Porphyrin Heterodimers

    NARCIS (Netherlands)

    Koehorst, R.B.M.; Boschloo, G.K.; Savenije, T.J.; Goossens, A.; Schaafsma, T.J.

    2000-01-01

    Photoelectrochemical cells have been constructed by depositing monolayers of oriented covalently linked zinc/free base porphyrin heterodimers onto ~30 nm nonporous layers of TiO2 on ITO, deposited by metal-organic chemical vapor deposition (MO-CVD), and onto ~100 nm porous, nanostructured TiO2

  1. Plasmonic Heterodimers with Binding Site-Dependent Hot Spot for Surface-Enhanced Raman Scattering.

    Science.gov (United States)

    Tian, Yuanyuan; Shuai, Zhenhua; Shen, Jingjing; Zhang, Lei; Chen, Shufen; Song, Chunyuan; Zhao, Baomin; Fan, Quli; Wang, Lianhui

    2018-05-07

    A novel plasmonic heterodimer nanostructure with a controllable self-assembled hot spot is fabricated by the conjugation of individual Au@Ag core-shell nanocubes (Au@Ag NCs) and varisized gold nanospheres (GNSs) via the biotin-streptavidin interaction from the ensemble to the single-assembly level. Due to their featured configurations, three types of heterogeneous nanostructures referred to as Vertice, Vicinity, and Middle are proposed and a single hot spot forms between the nanocube and nanosphere, which exhibits distinct diversity in surface plasmon resonance effect. Herein, the calculated surface-enhanced Raman scattering enhancement factors of the three types of heterodimers show a narrow distribution and can be tuned in orders of magnitude by controlling the size of GNSs onto individual Au@Ag NCs. Particularly, the Vertice heterodimer with unique configuration can provide extraordinary enhancement of the electric field for the single hot spot region due to the collaborative interaction of lightning rod effect and interparticle plasmon coupling effect. This established relationship between the architecture and the corresponding optical properties of the heterodimers provides the basis for creating controllable platforms which can be exploited in the applications of plasmonic devices, electronics, and biodetection. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Perpetuation of the Lyme Disease Spirochete Borrelia lusitaniae by Lizards

    Science.gov (United States)

    Richter, Dania; Matuschka, Franz-Rainer

    2006-01-01

    To determine whether the Lyme disease spirochete Borrelia lusitaniae is associated with lizards, we compared the prevalence and genospecies of spirochetes present in rodent- and lizard-associated ticks at a site where this spirochete frequently infects questing ticks. Whereas questing nymphal Ixodes ricinus ticks were infected mainly by Borrelia afzelii, one-half of the infected adult ticks harbored B. lusitaniae at our study site. Lyme disease spirochetes were more prevalent in sand lizards (Lacerta agilis) and common wall lizards (Podarcis muralis) than in small rodents. Although subadult ticks feeding on rodents acquired mainly B. afzelii, subadult ticks feeding on lizards became infected by B. lusitaniae. Genetic analysis confirmed that the spirochetes isolated from ticks feeding on lizards are members of the B. lusitaniae genospecies and resemble type strain PotiB2. At our central European study site, lizards, which were previously considered zooprophylactic for the agent of Lyme disease, appear to perpetuate B. lusitaniae. PMID:16820453

  3. Does RecA have a role in Borrelia recurrentis?

    Science.gov (United States)

    Cutler, S J; Rinky, I J; Bonilla, E M

    2011-02-01

    Genomic sequencing of two relapsing fever spirochaetes showed truncation of recA in Borrelia recurrentis, but not in Borrelia duttonii. RecA has an important role among bacteria; we investigated whether this characteristic was representative of B. recurrentis, or an artefact following in vitro cultivation. We sequenced recA directly from samples of patient with louse-borne relapsing fever (B. recurrentis) or tick-borne relapsing fever (B. duttonii). We confirmed the premature stop codon in seven louse-borne relapsing fever samples, and its absence from three tick-borne relapsing fever samples. Furthermore, specific signature polymorphisms were found that could differentiate between these highly similar spirochaetes. © 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  4. Presence of Borrelia spp. DNA in ticks, but absence of Borrelia spp. and of Leptospira spp. DNA in blood of fever patients in Madagascar.

    Science.gov (United States)

    Hagen, Ralf Matthias; Frickmann, Hagen; Ehlers, Julian; Krüger, Andreas; Margos, Gabriele; Hizo-Teufel, Cecilia; Fingerle, Volker; Rakotozandrindrainy, Raphael; Kalckreuth, Vera von; Im, Justin; Pak, Gi Deok; Jeon, Hyon Jin; Rakotondrainiarivelo, Jean Philibert; Heriniaina, Jean Noël; Razafindrabe, Tsiry; Konings, Frank; May, Jürgen; Hogan, Benedikt; Ganzhorn, Jörg; Panzner, Ursula; Schwarz, Norbert Georg; Dekker, Denise; Marks, Florian; Poppert, Sven

    2018-01-01

    The occurrence of tick-borne relapsing fever and leptospirosis in humans in Madagascar remains unclear despite the presence of their potential vectors and reservoir hosts. We screened 255 Amblyomma variegatum ticks and 148 Rhipicephalus microplus ticks from Zebu cattle in Madagascar for Borrelia-specific DNA. Borrelia spp. DNA was detected in 21 Amblyomma variegatum ticks and 2 Rhipicephalus microplus ticks. One Borrelia found in one Rhipicephalus microplus showed close relationship to Borrelia theileri based on genetic distance and phylogenetic analyses on 16S rRNA and flaB sequences. The borreliae from Amblyomma variegatum could not be identified due to very low quantities of present DNA reflected by high cycle threshold values in real-time-PCR. It is uncertain whether these low numbers of Borrelia spp. are sufficient for transmission of infection from ticks to humans. In order to determine whether spirochaete infections are relevant in humans, blood samples of 1009 patients from the highlands of Madagascar with fever of unknown origin were screened for Borrelia spp. - and in addition for Leptospira spp. - by real-time PCR. No target DNA was detected, indicating a limited relevance of these pathogens for humans in the highlands of Madagascar. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Borreliae in Ixodes ricinus ticks feeding on humans

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk; Halouzka, Jiří; Juřicová, Zina

    2004-01-01

    Roč. 18, č. 3 (2004), s. 228-231 ISSN 0269-283X R&D Projects: GA ČR GA206/03/0726; GA AV ČR IBS6093007 Institutional research plan: CEZ:AV0Z6093917 Keywords : Borrelia burgdorferi * Ixodes ricinus * Lyme disease Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.405, year: 2004

  6. Longitudinal surveillance of the tick Ixodes ricinus for borreliae

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk; Halouzka, Jiří; Juřicová, Zina

    2003-01-01

    Roč. 17, č. 1 (2003), s. 46-51 ISSN 0269-283X R&D Projects: GA ČR GA206/00/1204; GA AV ČR IBS6093007 Institutional research plan: CEZ:AV0Z6093917 Keywords : Borrelia burgdorferi * Ixodes ricinus * Lyme disease Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.040, year: 2003

  7. Spirochetes, including Borrelia burgdorferi sensu lato, in mosquitoes

    Czech Academy of Sciences Publication Activity Database

    Sanogo, Yibayiri Osée; Halouzka, Jiří; Hubálek, Zdeněk

    2000-01-01

    Roč. 62, 3 Suppl. (2000), s. 288-289 ISSN 0002-9637. [Annual meeting of the American Society of Tropical Medicine and Hygiene /49./. Houston, 29.10.2000-02.11.2000] R&D Projects: GA ČR GA206/00/1234 Institutional research plan: CEZ:AV0Z6093917 Keywords : Borrelia burgdorferi Subject RIV: EE - Microbiology, Virology Impact factor: 1.765, year: 2000

  8. Does Host Complement Kill Borrelia burgdorferi within Ticks?

    OpenAIRE

    Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M.

    2003-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within ...

  9. Detection of Borrelia burgdorferi DNA in Lizards from Southern Maryland

    OpenAIRE

    SWANSON, KATHERINE I.; NORRIS, DOUGLAS E.

    2007-01-01

    Lizards serve as hosts for Ixodes ticks in the western and southeastern United States and may affect the transmission cycles of Borrelia burgdorferi in these regions. In Maryland, the role of lizards in the maintenance and transmission cycle of this pathogen has not been examined. We tested 29 lizards (Sceloporus undulatus and Eumeces spp.) and 21 ticks from these lizards for the presence of B. burgdorferi. Eight lizards were positive by polymerase chain reaction (PCR) for at least one B. bur...

  10. Antimicrobial Activity of Bee Venom and Melittin against Borrelia burgdorferi.

    Science.gov (United States)

    Socarras, Kayla M; Theophilus, Priyanka A S; Torres, Jason P; Gupta, Khusali; Sapi, Eva

    2017-11-29

    Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi . In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use.

  11. Occurrence of multiple infections with different Borrelia burgdorferi genospecies in Danish Ixodes ricinus nymphs

    DEFF Research Database (Denmark)

    Andersen, Jean Vennestrøm; Egholm, H.; Mikkelsen, Per Jensen

    2008-01-01

    The pathogen Borrelia burgdorferi causes Lyme Borreliosis in human and animals world-wide. In Europe the pathogen is transmitted to the host by the vector Ixodes ricinus. The nymph is the primary instar for transmission to humans. We here study the infection rate of five Borrelia genospecies: B...

  12. Borrelia burgdorferi sensu lato in humans in a rural area of Paraná State, Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Dib Gonçalves

    2015-06-01

    Full Text Available This study describes the detection of Borrelia garinii and Borrelia burgdorferi sensu stricto (s.s. in Brazilian individuals using PCR and DNA sequencing. Our results suggest that these species are emerging pathogens in this country, and additional studies are necessary to determine the epidemiological characteristics of this disease in Brazil.

  13. The ecology of Lyme borreliosis risk : interactions between lxodes ricinus, rodents and Borrelia burgdorferi sensu lato

    NARCIS (Netherlands)

    Duijvendijk, van Gilian

    2016-01-01

    The sheep tick (Ixodes ricinus) is widespread throughout Europe and can transmit Borrelia burgdorferi sensu lato (s.l.), which can cause Lyme borreliosis and B. miyamotoi, the agent of Borrelia miyamotoi disease in humans.

  14. Larvae of Ixodes ricinus transmit Borrelia afzelii and B. miyamotoi to vertebrate hosts

    NARCIS (Netherlands)

    van Duijvendijk, Gilian; Coipan, Claudia; Wagemakers, Alex; Fonville, Manoj; Ersöz, Jasmin; Oei, Anneke; Földvári, Gábor; Hovius, Joppe; Takken, Willem; Sprong, Hein

    2016-01-01

    Lyme borreliosis is the most common tick-borne human disease and is caused by Borrelia burgdorferi sensu lato (s.l.). Borrelia miyamotoi, a relapsing fever spirochaete, is transmitted transovarially, whereas this has not been shown for B. burgdorferi (s.l). Therefore, B. burgdorferi (s.l) is

  15. Larvae of Ixodes ricinus transmit Borrelia afzelii and B. miyamotoi to vertebrate hosts

    NARCIS (Netherlands)

    Duijvendijk, van Gilian; Coipan, Claudia; Wagemakers, Alex; Fonville, Manoj; Ersöz, Jasmin; Oei, Anneke; Földvári, Gábor; Hovius, Joppe; Takken, Willem; Sprong, Hein

    2016-01-01

    Background: Lyme borreliosis is the most common tick-borne human disease and is caused by Borrelia burgdorferi sensu lato (s.l.). Borrelia miyamotoi, a relapsing fever spirochaete, is transmitted transovarially, whereas this has not been shown for B. burgdorferi (s.l). Therefore, B. burgdorferi

  16. Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva

    NARCIS (Netherlands)

    Hovius, J. W.; Schuijt, T. J.; de Groot, K. A.; Roelofs, J. J. T. H.; Oei, G. A.; Marquart, J. A.; de Beer, R.; van 't Veer, C.; van der Poll, T.; Ramamoorthi, N.; Fikrig, E.; van Dam, A. P.

    2008-01-01

    BACKGROUND: Ixodes ticks are the main vectors for Borrelia burgdorferi sensu lato. In the United States, B. burgdorferi is the sole causative agent of Lyme borreliosis and is transmitted by Ixodes scapularis. In Europe, 3 Borrelia species-B. burgdorferi, B. garinii, and B. afzelii-are prevalent,

  17. Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.

    Science.gov (United States)

    Perederina, Anna; Khanova, Elena; Quan, Chao; Berezin, Igor; Esakova, Olga; Krasilnikov, Andrey S

    2011-10-01

    Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein components, as well as multiple features of their catalytic RNA moieties, but have distinct substrate specificities. While RNase P is practically universally found in all three domains of life, RNase MRP is essential in eukaryotes. The structural organizations of eukaryotic RNase P and RNase MRP are poorly understood. Here, we show that Pop5 and Rpp1, protein components found in both RNase P and RNase MRP, form a heterodimer that binds directly to the conserved area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed.

  18. Nanoparticle heterodimers: The role of size and interparticle gap distance on the optical response

    Science.gov (United States)

    Mokkath, Junais Habeeb

    2018-05-01

    Composite plasmonic nanostructures with controlled size, shape and relative arrangement is a subject of significant current research interest. Much of this is stimulated by the prospects by generating enormous near-field enhancements of the surface and interparticle gap regions for potential applications in surface-enhanced spectroscopies. In this manuscript, using time-dependent density functional theory (TDDFT) calculations, we investigate how the optical response in size matched homodimers and size mismatched heterodimers composed of Aluminum modify while varying the size and interparticle gap distances in the sub-nanometer range. Both systems show interesting optical response evolution. In particular, the size mismatched heterodimers show even more complex optical response evolution due to a symmetry-breaking in the system.

  19. Fano resonance assisting plasmonic circular dichroism from nanorice heterodimers for extrinsic chirality

    Science.gov (United States)

    Hu, Li; Huang, Yingzhou; Fang, Liang; Chen, Guo; Wei, Hua; Fang, Yurui

    2015-11-01

    In this work, the circular dichroisms (CD) of nanorice heterodimers consisting of two parallel arranged nanorices with the same size but different materials are investigated theoretically. Symmetry-breaking is introduced by using different materials and oblique incidence to achieve strong CD at the vicinity of Fano resonance peaks. We demonstrate that all Au-Ag heterodimers exhibit multipolar Fano resonances and strong CD effect. A simple quantitative analysis shows that the structure with larger Fano asymmetry factor has stronger CD. The intensity and peak positions of the CD effect can be flexibly tuned in a large range by changing particle size, shape, the inter-particle distance and surroundings. Furthermore, CD spectra exhibit high sensitivity to ambient medium in visible and near infrared regions. Our results here are beneficial for the design and application of high sensitive CD sensors and other related fields.

  20. Borrelia carolinensis sp. nov., a new (14th) member of the Borrelia burgdorferi Sensu Lato complex from the southeastern region of the United States

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Grubhoffer, Libor; Oliver, J. H., Jr.

    2009-01-01

    Roč. 47, č. 1 (2009), s. 134-141 ISSN 0095-1137 R&D Projects: GA MŠk(CZ) LC06009; GA ČR(CZ) GA524/06/1479 Institutional research plan: CEZ:AV0Z60220518 Keywords : multilocus sequence analysis * B. burgdorferi sl complex * new borrelia species * Borrelia carolinensis Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 4.162, year: 2009

  1. Plasmon-mediated binding forces on gold or silver homodimer and heterodimer

    International Nuclear Information System (INIS)

    Liaw, Jiunn-Woei; Kuo, Ting-Yu; Kuo, Mao-Kuen

    2016-01-01

    This study theoretically investigates plasmon-mediated optical binding forces, which are exerted on metal homo or heterodimers, induced by the normal illumination of a linearly polarized plane wave or Gaussian beam. Using the multiple multipole method, we analyzed the optical force in terms of Maxwell's stress tensor for various interparticle distance at some specific wavelengths. Numerical results show that for a given wavelength there are several stable equilibrium distances between two nanoparticles (NPs) of a homodimer, which are slightly shorter than some integer multiples of the wavelength in medium, such that metal dimer acts as bonded together. At these specific interparticle distances, the optical force between dimer is null and serves a restoring force, which is repulsive and attractive, respectively, as the two NPs are moving closer to and away from each other. The spring constant of the restoring force at the first stable equilibrium is always the largest, indicating that the first stable equilibrium distance is the most stable one. Moreover, the central line (orientation) of a dimer tends to be perpendicular to the polarization of light. For the cases of heterodimers, the phenomenon of stable equilibrium interparticle distance still exists, except there is an extra net photophoretic force drifting the heterodimer as one. Moreover, gradient force provided by a Gaussian beam may reduce the stability of these equilibriums, so larger NPs are preferred to stabilize a dimer under illumination of Gaussian beam. The finding may pave the way for using optical manipulation on the gold or silver colloidal self-assembly. - Highlights: • Optical binding force on Au/Ag dimer by linearly polarized light is studied. • For a wavelength several stable equilibriums for homodimer bound together exist. • The central line of a dimer tends to be perpendicular to the polarization of light. • For a heterodimer, stable equilibriums still exist with a net photophoretic

  2. Activation of RXR–PPAR heterodimers by organotin environmental endocrine disruptors

    Science.gov (United States)

    le Maire, Albane; Grimaldi, Marina; Roecklin, Dominique; Dagnino, Sonia; Vivat-Hannah, Valérie; Balaguer, Patrick; Bourguet, William

    2009-01-01

    The nuclear receptor retinoid X receptor-α (RXR-α)–peroxisome proliferator-activated receptor-γ (PPAR-γ) heterodimer was recently reported to have a crucial function in mediating the deleterious effects of organotin compounds, which are ubiquitous environmental contaminants. However, because organotins are unrelated to known RXR-α and PPAR-γ ligands, the mechanism by which these compounds bind to and activate the RXR-α–PPAR-γ heterodimer at nanomolar concentrations has remained elusive. Here, we show that tributyltin (TBT) activates all three RXR–PPAR-α, -γ, -δ heterodimers, primarily through its interaction with RXR. In addition, the 1.9 Å resolution structure of the RXR-α ligand-binding domain in complex with TBT shows a covalent bond between the tin atom and residue Cys 432 of helix H11. This interaction largely accounts for the high binding affinity of TBT, which only partly occupies the RXR-α ligand-binding pocket. Our data allow an understanding of the binding and activation properties of the various organotins and suggest a mechanism by which these tin compounds could affect other nuclear receptor signalling pathways. PMID:19270714

  3. Binary Toxin Subunits of Lysinibacillus sphaericus Are Monomeric and Form Heterodimers after In Vitro Activation.

    Directory of Open Access Journals (Sweden)

    Wahyu Surya

    Full Text Available The binary toxin from Lysinibacillus sphaericus has been successfully used for controlling mosquito-transmitted diseases. An activation step shortens both subunits BinA and BinB before their interaction with membranes and internalization in midgut cells, but the precise role of this activation step is unknown. Herein, we show conclusively using three orthogonal biophysical techniques that protoxin subunits form only monomers in aqueous solution. However, in vitro activated toxins readily form heterodimers. This oligomeric state did not change after incubation of these heterodimers with detergent. These results are consistent with the evidence that maximal toxicity in mosquito larvae is achieved when the two subunits, BinA and BinB, are in a 1:1 molar ratio, and directly link proteolytic activation to heterodimerization. Formation of a heterodimer must thus be necessary for subsequent steps, e.g., interaction with membranes, or with a suitable receptor in susceptible mosquito species. Lastly, despite existing similarities between BinB C-terminal domain with domains 3 and 4 of pore-forming aerolysin, no aerolysin-like SDS-resistant heptameric oligomers were observed when the activated Bin subunits were incubated in the presence of detergents or lipidic membranes.

  4. Ni@Fe2O3 heterodimers: controlled synthesis and magnetically recyclable catalytic application for dehalogenation reactions

    Science.gov (United States)

    Nakhjavan, Bahar; Tahir, Muhammad Nawaz; Natalio, Filipe; Panthöfer, Martin; Gao, Haitao; Dietzsch, Michael; Andre, Rute; Gasi, Teuta; Ksenofontov, Vadim; Branscheid, Robert; Kolb, Ute; Tremel, Wolfgang

    2012-07-01

    Ni@Fe2O3 heterodimer nanoparticles (NPs) were synthesized by thermal decomposition of organometallic reactants. After functionalization, these Ni@Fe2O3 heterodimers became water soluble. The pristine heterodimeric NPs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Mössbauer spectroscopy and magnetic susceptibility measurements. A special advantage of the heterodimers lies in the fact that nanodomains of different composition can be used as catalysts for the removal of environmentally hazardous halogenated pollutants.Ni@Fe2O3 heterodimer nanoparticles (NPs) were synthesized by thermal decomposition of organometallic reactants. After functionalization, these Ni@Fe2O3 heterodimers became water soluble. The pristine heterodimeric NPs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Mössbauer spectroscopy and magnetic susceptibility measurements. A special advantage of the heterodimers lies in the fact that nanodomains of different composition can be used as catalysts for the removal of environmentally hazardous halogenated pollutants. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr12121b

  5. Whole-Genome Sequences of Thirteen Isolates of Borrelia burgdorferi

    Energy Technology Data Exchange (ETDEWEB)

    Schutzer S. E.; Dunn J.; Fraser-Liggett, C. M.; Casjens, S. R.; Qiu, W.-G.; Mongodin, E. F.; Luft, B. J.

    2011-02-01

    Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single genome sequence is not sufficient to understand the relationship between genotypic and geographic variation and disease phenotype, we determined the whole-genome sequences of 13 additional B. burgdorferi isolates that span the range of natural variation. These sequences should allow improved understanding of pathogenesis and provide a foundation for novel detection, diagnosis, and prevention strategies.

  6. Lyme borreliosis: insights into tick- / host-borrelia relations

    Czech Academy of Sciences Publication Activity Database

    Grubhoffer, Libor; Golovchenko, Maryna; Vancová, Marie; Zacharovová, Klára; Rudenko, Natalia; Oliver, J. H., Jr.

    2005-01-01

    Roč. 52, č. 4 (2005), s. 279-294 ISSN 0015-5683 R&D Projects: GA ČR GA524/03/1326; GA ČR GA206/03/1323 Grant - others:National Institutes of Health(US) R37 AI-24899; Science and Technology Collaboration AVCR-NRC Canada(CZ) Z60220518/58-8500 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia spirochetes * ticks * lectins * glycoproteins Subject RIV: EE - Microbiology, Virology Impact factor: 1.138, year: 2005

  7. Relapsing fever causative agent in Southern Iran is a closely related species to East African borreliae.

    Science.gov (United States)

    Naddaf, Saied Reza; Ghazinezhad, Behnaz; Kazemirad, Elham; Cutler, Sally Jane

    2017-10-01

    We obtained two blood samples from relapsing fever patients residing in Jask County, Hormozgan Province, southern Iran in 2013. Sequencing of a partial fragment of glpQ from two samples, and further characterization of one of them by analyzing flaB gene, and 16S-23S spacer (IGS) revealed the greatest sequence identity with East African borreliae, Borrelia recurrentis, and Borrelia duttonii, and Borrelia microti from Iran. Phylogenetic analyses of glpQ, flaB, and concatenated sequences (glpQ, flab, and IGS) clustered these sequences amongst East African Relapsing fever borreliae and B. microti from Iran. However, the more discriminatory IGS disclosed a unique 8-bp signature (CAGCCTAA) separating these from B. microti and indeed other relapsing fever borreliae. In southern Iran, relapsing fever cases are mostly from localities in which O. erraticus ticks, the notorious vector of B. microti, prevail. There are chances that this argasid tick serves as a host and vector of several closely related species or ecotypes including the one we identified in the present study. The distribution of this Borrelia species remains to be elucidated, but it is assumed to be endemic to lowland areas of the Hormozgan Province, as well as Sistan va Baluchistan in the southeast and South Khorasan (in Persian: Khorasan-e Jonobi) in the east of Iran. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

    Directory of Open Access Journals (Sweden)

    Hye-Ji Choi

    Full Text Available Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A with mutations in one CH3 domain (CH3A on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B with mutations in the other CH3 domain (CH3B. In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90% with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-π interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display.

  9. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

    Directory of Open Access Journals (Sweden)

    Marianne J. Middelveen

    2018-04-01

    Full Text Available Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

  10. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

    Science.gov (United States)

    Middelveen, Marianne J; Sapi, Eva; Burke, Jennie; Filush, Katherine R; Franco, Agustin; Fesler, Melissa C; Stricker, Raphael B

    2018-04-14

    Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi , in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

  11. Differentiated THP-1 Cells Exposed to Pathogenic and Nonpathogenic Borrelia Species Demonstrate Minimal Differences in Production of Four Inflammatory Cytokines.

    Science.gov (United States)

    Stokes, John V; Moraru, Gail M; McIntosh, Chelsea; Kummari, Evangel; Rausch, Keiko; Varela-Stokes, Andrea S

    2016-11-01

    Tick-borne borreliae include Lyme disease and relapsing fever agents, and they are transmitted primarily by ixodid (hard) and argasid (soft) tick vectors, respectively. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering vertebrate host skin is with local antigen-presenting cells, regardless of whether the tick-associated Borrelia sp. is pathogenic. In this study, we performed a basic comparison of cytokine responses in THP-1-derived macrophages after exposure to selected borreliae, including a nonpathogen. By using THP-1 cells, differentiated to macrophages, we eliminated variations in host response and reduced the system to an in vitro model to evaluate the extent to which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi (B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides (LPS) (activated) or media (no treatment) controls. Intracellular and secreted interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured using flow cytometric and Luminex-based assays, respectively, at 6, 24, and 48 h postexposure time points. Using a general linear model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no treatment) had a significant effect on secreted TNF-α only. Time point had a significant effect on intracellular IFN-γ, TNF-α and IL-6. However, we did not see significant differences in selected cytokines among Borrelia spp. Thus, in this model, we were unable to distinguish pathogenic from nonpathogenic borreliae using the limited array of selected cytokines. While unique immune profiles may be detectable in an in vitro model and may reveal predictors for pathogenicity in borreliae

  12. Two ways of experimental infection of Ixodes ricinus ticks (Acari: Ixodidae) with spirochetes of Borrelia burgdorferi sensu lato complex

    Czech Academy of Sciences Publication Activity Database

    Fišerová, Lenka; Černá, Kateřina; Horká, Helena; Kopecký, Jan

    2008-01-01

    Roč. 55, č. 2 (2008), s. 150-154 ISSN 0015-5683 R&D Projects: GA ČR GA524/05/0811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Lyme disease spirochete * Borrelia burgdorferi * Borrelia baronii * Borrelia afzelii * tick * Ixodes ricinus Subject RIV: EC - Immunology Impact factor: 1.307, year: 2008

  13. Characterization of the UV-crosslinked heterodimer of histones H2B and H4

    International Nuclear Information System (INIS)

    Johnson, E.R.; Brown, D.M.; DeLange, R.J.

    1986-01-01

    At relatively high salt concentrations (1.2 M), histone 2B (H2B) and histone 4 (H4) can be covalently crosslinked by irradiation with ultraviolet light to yield a mixture of the three possible dimers: H2B-H2B, H4-H4, and H2B-H4. The formation of the H2B-H4 heterodimer was found to be favored at lower histone concentrations (> 90% H2B-H4 at 0.1 mg/ml total histone protein). CNBr cleavage of the H2B-H4 dimer produced three fragments which were separated by reverse phase HPLC. These fragments were identified by amino acid compositional analysis to be H4(85-102), H2B(62-125), and the crosslinked N-terminal regions H2B(1-59)-H4(1-84). Amino acid sequence analysis of the crosslinked fragment indicated that tyrosine-40 of H2B is likely involved in the covalent crosslinkage which joins the histone monomers to form the heterodimer

  14. Lipid exchange between Borrelia burgdorferi and host cells.

    Directory of Open Access Journals (Sweden)

    Jameson T Crowley

    2013-01-01

    Full Text Available Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or (3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

  15. Zinc is the metal cofactor of Borrelia burgdorferi peptide deformylase.

    Science.gov (United States)

    Nguyen, Kiet T; Wu, Jen-Chieh; Boylan, Julie A; Gherardini, Frank C; Pei, Dehua

    2007-12-15

    Peptide deformylase (PDF, E.C. 3.5.1.88) catalyzes the removal of N-terminal formyl groups from nascent ribosome-synthesized polypeptides. PDF contains a catalytically essential divalent metal ion, which is tetrahedrally coordinated by three protein ligands (His, His, and Cys) and a water molecule. Previous studies revealed that the metal cofactor is a Fe2+ ion in Escherichia coli and many other bacterial PDFs. In this work, we found that PDFs from two iron-deficient bacteria, Borrelia burgdorferi and Lactobacillus plantarum, are stable and highly active under aerobic conditions. The native B. burgdorferi PDF (BbPDF) was purified 1200-fold and metal analysis revealed that it contains approximately 1.1 Zn2+ ion/polypeptide but no iron. Our studies suggest that PDF utilizes different metal ions in different organisms. These data have important implications in designing PDF inhibitors and should help address some of the unresolved issues regarding PDF structure and catalytic function.

  16. Borrelia burgdorferi-specific IgA in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Christina D'Arco

    2017-05-01

    Full Text Available The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223-modVlsE(275-291, a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8% from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

  17. Borrelia burgdorferi-specific IgA in Lyme Disease.

    Science.gov (United States)

    D'Arco, Christina; Dattwyler, Raymond J; Arnaboldi, Paul M

    2017-05-01

    The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi

    OpenAIRE

    Miller, Christine L.; Rajasekhar Karna, S. L.; Seshu, J.

    2013-01-01

    The RpoS transcription factor of Borrelia burgdorferi is a “gatekeeper” because it activates genes required for spirochetes to transition from tick to vertebrate hosts. However, it remains unknown how RpoS becomes repressed to allow the spirochetes to transition back from the vertebrate host to the tick vector. Here we show that a putative carbohydrate-responsive regulatory protein, designated BadR (Borrelia host adaptation Regulator), is a transcriptional repressor of rpoS. BadR levels are e...

  19. Geographical and genospecies distribution of Borrelia burgdorferi sensu lato DNA detected in humans in the USA.

    Science.gov (United States)

    Clark, Kerry L; Leydet, Brian F; Threlkeld, Clifford

    2014-05-01

    The present study investigated the cause of illness in human patients primarily in the southern USA with suspected Lyme disease based on erythema migrans-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. The study also included some patients from other states throughout the USA. Several PCR assays specific for either members of the genus Borrelia or only for Lyme group Borrelia spp. (Borrelia burgdorferi sensu lato), and DNA sequence analysis, were used to identify Borrelia spp. DNA in blood and skin biopsy samples from human patients. B. burgdorferi sensu lato DNA was found in both blood and skin biopsy samples from patients residing in the southern states and elsewhere in the USA, but no evidence of DNA from other Borrelia spp. was detected. Based on phylogenetic analysis of partial flagellin (flaB) gene sequences, strains that clustered separately with B. burgdorferi sensu stricto, Borrelia americana or Borrelia andersonii were associated with Lyme disease-like signs and symptoms in patients from the southern states, as well as from some other areas of the country. Strains most similar to B. burgdorferi sensu stricto and B. americana were found most commonly and appeared to be widely distributed among patients residing throughout the USA. The study findings suggest that human cases of Lyme disease in the southern USA may be more common than previously recognized and may also be caused by more than one species of B. burgdorferi sensu lato. This study provides further evidence that B. burgdorferi sensu stricto is not the only species associated with signs and/or symptoms consistent with Lyme borreliosis in the USA.

  20. Molecular Typing of Borrelia burgdorferi Sensu Lato by Randomly Amplified Polymorphic DNA Fingerprinting Analysis

    Science.gov (United States)

    Wang, Guiqing; van Dam, Alje P.; Spanjaard, Lodewijk; Dankert, Jacob

    1998-01-01

    To study whether pathogenic clusters of Borrelia burgdorferi sensu lato strains occur, we typed 136 isolates, cultured from specimens from patients (n = 49) with various clinical entities and from ticks (n = 83) or dogs (n = 4) from different geographic regions, by randomly amplified polymorphic DNA (RAPD) fingerprinting with four arbitrary primers. The RAPD patterns were reproducible up to the 95% similarity level as shown in duplicate experiments. In these experiments the purified DNAs prepared on different days, from different colonies, and after various passages were used as templates. With an intergroup difference of 55%, the 136 strains could be divided into seven genetic clusters. Six clusters comprised and corresponded to the established species B. burgdorferi sensu stricto (n = 23), Borrelia garinii (n = 39), Borrelia afzelii (n = 59), Borrelia japonica (n = 1), Borrelia valaisiana (n = 12), and genomic group DN127 (n = 1). One strain from a patient with erythema migrans (EM) did not belong to any of the species or genomic groups known up to now. The RAPD types of B. burgdorferi sensu stricto, B. garinii, and B. afzelii isolates, which may give rise to human Lyme borreliosis (LB), were associated with their geographic origins. A high degree of genetic diversity was observed among the 39 B. garinii strains, and six subgroups could be recognized. One of these comprised eight isolates from patients with disseminated LB only and no tick isolates. B. afzelii strains from patients with EM or acrodermatitis chronica atrophicans were not clustered in particular branches. Our study showed that RAPD analysis is a powerful tool for discriminating different Borrelia species as well as Borrelia isolates within species. PMID:9508310

  1. Divergence of Borrelia burgdorferi sensu lato spirochetes could be driven by the host: diversity of Borrelia strains isolated from ticks feeding on a single bird

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Belfiore, N. M.; Grubhoffer, Libor; Oliver, J. H., Jr.

    2014-01-01

    Roč. 7, JAN 2014 (2014), s. 4 ISSN 1756-3305 Institutional support: RVO:60077344 Keywords : Borrelia burgdorferi sensu lato * Ixodes minor * bird migration * bird reservoir host * multilocus sequence analysis * multilocus sequence typing * recombinant genotypes * Southeastern United States Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.430, year: 2014

  2. Cytotoxic xanthone-anthraquinone heterodimers from an unidentified fungus of the order Hypocreales (MSX 17022).

    Science.gov (United States)

    Ayers, Sloan; Graf, Tyler N; Adcock, Audrey F; Kroll, David J; Shen, Qi; Swanson, Steven M; Matthew, Susan; Carcache de Blanco, Esperanza J; Wani, Mansukh C; Darveaux, Blaise A; Pearce, Cedric J; Oberlies, Nicholas H

    2012-01-01

    Two new xanthone-anthraquinone heterodimers, acremoxanthone C (5) and acremoxanthone D (2), have been isolated from an extract of an unidentified fungus of the order Hypocreales (MSX 17022) by bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Two known related compounds, acremonidin A (4) and acremonidin C (3) were also isolated, as was a known benzophenone, moniliphenone (1). The structures of these isolates were determined via extensive use of spectroscopic and spectrometric tools in conjunction with comparisons to the literature. All compounds (1-5) were evaluated against a suite of biological assays, including those for cytotoxicity, inhibition of the 20S proteasome, mitochondrial transmembrane potential and nuclear factor-κB.

  3. Response regulator heterodimer formation controls a key stage in Streptomyces development.

    Directory of Open Access Journals (Sweden)

    Mahmoud M Al-Bassam

    2014-08-01

    Full Text Available The orphan, atypical response regulators BldM and WhiI each play critical roles in Streptomyces differentiation. BldM is required for the formation of aerial hyphae, and WhiI is required for the differentiation of these reproductive structures into mature spores. To gain insight into BldM function, we defined the genome-wide BldM regulon using ChIP-Seq and transcriptional profiling. BldM target genes clustered into two groups based on their whi gene dependency. Expression of Group I genes depended on bldM but was independent of all the whi genes, and biochemical experiments showed that Group I promoters were controlled by a BldM homodimer. In contrast, Group II genes were expressed later than Group I genes and their expression depended not only on bldM but also on whiI and whiG (encoding the sigma factor that activates whiI. Additional ChIP-Seq analysis showed that BldM Group II genes were also direct targets of WhiI and that in vivo binding of WhiI to these promoters depended on BldM and vice versa. We go on to demonstrate that BldM and WhiI form a functional heterodimer that controls Group II promoters, serving to integrate signals from two distinct developmental pathways. The BldM-WhiI system thus exemplifies the potential of response regulator heterodimer formation as a mechanism to expand the signaling capabilities of bacterial cells.

  4. A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

    International Nuclear Information System (INIS)

    Grum, Daniel; Boom, Johannes van den; Neumann, Daniel; Matena, Anja; Link, Nina M.; Mueller, Jonathan W.

    2010-01-01

    3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Foerster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that - in spite of its low quantum yield - is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.

  5. Association of Borrelia and Rickettsia spp. and bacterial loads in Ixodes ricinus ticks.

    Science.gov (United States)

    Raulf, Marie-Kristin; Jordan, Daniela; Fingerle, Volker; Strube, Christina

    2018-01-01

    In recent years, awareness of coinfections has increased as synergistic or antagonistic effects on interacting bacteria have been observed. To date, several reports on coinfections of ticks with Rickettsia and Borrelia spp. are available. However, associations are rarely described and studies are based on rather low sample sizes. In the present study, coinfections of Ixodes ricinus with these pathogens were investigated by determining their association in a meta-analysis. A total of 5079 tick samples examined for Rickettsia and Borrelia spp. via probe-based quantitative real-time PCR in previous prevalence studies or as submitted diagnostic material were included. In Borrelia-positive ticks, genospecies were determined by Reverse Line Blot. Determination of bacterial loads resulted in an increase between developmental tick stages with highest mean bacterial loads in female ticks (7.96×10 4 in Borrelia single-infected, 4.87×10 5 in Rickettsia single-infected and 3.22×10 5 in Borrelia-Rickettsia coinfected females). The determined Borrelia-Rickettsia tick coinfection rate was 12.3% (626/5079) with a significant difference to the expected coinfection rate of 9.0% (457/5079). A significant slight association as well as correlation between Borrelia and Rickettsia were determined. In addition, a significant interrelation of the bacterial load in coinfected ticks was shown. At the level of Borrelia genospecies, significant weak associations with Rickettsia spp. were detected for B. afzelii, B. garinii/bavariensis, B. valaisiana and B. lusitaniae. The positive association provides evidence for interactions between Borrelia and Rickettsia spp. in the tick vector, presumably resulting in higher bacterial replication rates in the tick vector and possibly the reservoir host. However, coinfection may impact the vector negatively as indicated by an absent increase in coinfection rates from nymphs to adults. Future studies are needed to investigate the underlying mechanisms of

  6. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Vancová, Marie; Clark, K.; Grubhoffer, Libor; Oliver, J. H., Jr.

    2016-01-01

    Roč. 22, č. 3 (2016), 267.e9-267.e15 ISSN 1198-743X EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : antibiotic treatment * live Borrelia burgdorferi * live Borrelia bissettii * Lyme borreliosis * recovery of live spirochaetes Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 5.292, year: 2016

  7. Identification of Borrelia burgdorferi genospecies isolated from Ixodes ricinus ticks in the South Moravian region of the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Bonczek, Ondřej; Žákovská, A.; Vargová, L.; Šerý, Omar

    2015-01-01

    Roč. 22, č. 4 (2015), s. 642-646 ISSN 1232-1966 Institutional support: RVO:67985904 Keywords : Borrelia burgdorferi s. I. * Borrelia spielmanii * Ixodes ricinus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.895, year: 2015

  8. Does host complement kill Borrelia burgdorferi within ticks?

    Science.gov (United States)

    Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M

    2003-02-01

    The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within the vector. The Lyme disease outer surface protein A (OspA) vaccine is a transmission-blocking vaccine that targets spirochetes in the vector. In experiments with mice hyperimmunized with OspA, complement was not required to kill spirochetes within nymphs and to block transmission from nymphs to the vaccinated host. However, host complement did enhance the ability of OspA antibody to block larvae from acquiring spirochetes. Thus, the effects of OspA antibody on nymphal transmission and larval acquisition appear to be based on different mechanisms.

  9. Borrelia spirochetes in Russia: Genospecies differentiation by real-time PCR.

    Science.gov (United States)

    Mukhacheva, T A; Kovalev, S Y

    2014-10-01

    Spirochetes of the Borrelia burgdorferi sensu lato complex are the causative agent of Lyme borreliosis which is widespread in Russia. Nowadays, three clinically important B. burgdorferi s.l. genospecies, B. afzelii, B. garinii, B. bavariensis sp. nov., can be found in Russia, as well as B. miyamotoi, which belongs to the tick-borne relapsing fever group of spirochetes. Several techniques have been developed to differentiate Borrelia genospecies. However, most of them do not allow detection of all of these genospecies simultaneously. Also, no method based on the RT-PCR TaqMan approach has been proposed to differentiate the genetically closely related species B. bavariensis and B. garinii. In the present paper, we investigated two species of ticks, I. persulcatus and I. pavlovskyi (1343 and 92 adults, respectively). Two sets of primers and probes for RT-PCR, with uvrA, glpQ and nifS genes as targets, were designed to detect four Borrelia genospecies in positive samples. The average prevalence of Borrelia sp. was about 40%, with B. afzelii as the most prevalent genospecies. Mixed infections of B. bavariensis and B. garinii were found to be extremely rare. While B. bavariensis was predominant in I. persulcatus, I. pavlovskyi ticks were infected exclusively by B. garinii. The proposed technique proved to be efficient in selection of individual Borrelia species for further genetic analysis, in particular, for multilocus sequence typing. Also, it could be applied for the differentiation of Borrelia genospecies in clinical material. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Selective Assembly of Na,K-ATPase α2β2 Heterodimers in the Heart

    Science.gov (United States)

    Habeck, Michael; Tokhtaeva, Elmira; Nadav, Yotam; Ben Zeev, Efrat; Ferris, Sean P.; Kaufman, Randal J.; Bab-Dinitz, Elizabeta; Kaplan, Jack H.; Dada, Laura A.; Farfel, Zvi; Tal, Daniel M.; Katz, Adriana; Sachs, George; Vagin, Olga; Karlish, Steven J. D.

    2016-01-01

    The Na,K-ATPase α2 subunit plays a key role in cardiac muscle contraction by regulating intracellular Ca2+, whereas α1 has a more conventional role of maintaining ion homeostasis. The β subunit differentially regulates maturation, trafficking, and activity of α-β heterodimers. It is not known whether the distinct role of α2 in the heart is related to selective assembly with a particular one of the three β isoforms. We show here by immunofluorescence and co-immunoprecipitation that α2 is preferentially expressed with β2 in T-tubules of cardiac myocytes, forming α2β2 heterodimers. We have expressed human α1β1, α2β1, α2β2, and α2β3 in Pichia pastoris, purified the complexes, and compared their functional properties. α2β2 and α2β3 differ significantly from both α2β1 and α1β1 in having a higher K0.5K+ and lower K0.5Na+ for activating Na,K-ATPase. These features are the result of a large reduction in binding affinity for extracellular K+ and shift of the E1P-E2P conformational equilibrium toward E1P. A screen of perhydro-1,4-oxazepine derivatives of digoxin identified several derivatives (e.g. cyclobutyl) with strongly increased selectivity for inhibition of α2β2 and α2β3 over α1β1 (range 22–33-fold). Molecular modeling suggests a possible basis for isoform selectivity. The preferential assembly, specific T-tubular localization, and low K+ affinity of α2β2 could allow an acute response to raised ambient K+ concentrations in physiological conditions and explain the importance of α2β2 for cardiac muscle contractility. The high sensitivity of α2β2 to digoxin derivatives explains beneficial effects of cardiac glycosides for treatment of heart failure and potential of α2β2-selective digoxin derivatives for reducing cardiotoxicity. PMID:27624940

  11. First insights in the variability of Borrelia recurrentis genomes.

    Directory of Open Access Journals (Sweden)

    Durdica Marosevic

    2017-09-01

    Full Text Available Borrelia recurrentis is the causative agent of louse-borne relapsing fever, endemic to the Horn of Africa. New attention was raised in Europe, with the highest number of cases (n = 45 reported among migrants in 2015 in Germany and sporadically from other European countries. So far only one genome was sequenced, hindering the development of specific molecular diagnostic and typing tools. Here we report on modified culture conditions for B. recurrentis and the intraspecies genome variability of six isolates isolated and cultured in different years in order to explore the possibility to identify new targets for typing and examine the molecular epidemiology of the pathogen.Two historical isolates from Ethiopia and four isolates from migrants from Somalia (n = 3 and Ethiopia (n = 1 obtained in 2015 were cultured in MPK-medium supplemented with 50% foetal calf serum. Whole DNA was sequenced using Illumina MiSeq technology and analysed using the CLC Genomics Workbench and SPAdes de novo assembler. Compared to the reference B. recurrentis A1 29-38 SNPs were identified in the genome distributed on the chromosome and plasmids. In addition to that, plasmids of differing length, compared to the available reference genome were identified.The observed low genetic variability of B. recurrentis isolates is possibly due to the adaptation to a very conserved vector-host (louse-human cycle, or influenced by the fastidious nature of the pathogen and their resistance to in vitro growth. Nevertheless, isolates obtained in 2015 were bearing the same chromosomal SNPs and could be distinguished from the historical isolates by means of whole genome sequencing, but not hitherto used typing methods. This is the first study examining the molecular epidemiology of B. recurrentis and provides the necessary background for the development of better diagnostic tools.

  12. Babesia microti, human babesiosis, and Borrelia burgdorferi in Connecticut.

    Science.gov (United States)

    Anderson, J F; Mintz, E D; Gadbaw, J J; Magnarelli, L A

    1991-12-01

    Babesia microti was isolated from a white-footed mouse (Peromyscus leucopus) that was captured in southeastern Connecticut in 1988, when the first human case of babesiosis acquired in Connecticut was recognized. To date, 13 cases of babesiosis have been reported in Connecticut, the largest number of human cases reported on the mainland United States. Two of nine patients quiried remembered a prior tick bite. Since Babesia parasites are known to be vectored only by ticks, we surmise that 12 of these infections were acquired via tick bites; 1 was obtained by blood transfusion (the patient was 46 years of age) from an endemically infected donor. The ages of the patients with tick-acquired babesiosis ranged from 61 to 95 years. Two patients died with active infections, and one patient died from chronic obstructive pulmonary disease soon after treatment with clindamycin and quinine. Indirect fluorescent-antibody titers of blood samples drawn at the time of hospitalization for 11 patients and at the time of active infection for 1 asymptomatic person ranged from 1:1,024 to 1:4,096. Five of eight patients with babesiosis also had significant immunoglobulin G or immunoglobulin M titers (1:640 to 1:5,120) to Borrelia burgdorferi. B. microti was isolated in Syrian hamsters inoculated with blood from 7 of 12 patients tested and was also isolated from mice captured in six towns. The peridomestic nature of the disease was demonstrated by isolating the parasite from white-footed mice captured in or near the yards of eight different patients. Of 59 mice tested, 27 were positive and 25 were coinfected with B. burgdorferi. The isolation of B. microti from a white-footed mouse captured in north-central Connecticut (West Hartford), away from the focus of human infections in southeastern Connecticut, suggests that this pathogen may spread into other areas where Ixodes dammini, the tick vector, becomes established.

  13. MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Vahid Ezzatizadeh

    Full Text Available Friedreich ataxia (FRDA, the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions.To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription.Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.

  14. MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia

    Science.gov (United States)

    Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Anjomani-Virmouni, Sara; Al-Mahdawi, Sahar; Pook, Mark A.

    2014-01-01

    Background Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. PMID:24971578

  15. The Ku heterodimer and the metabolism of single-ended DNA double-strand breaks.

    Science.gov (United States)

    Balestrini, Alessia; Ristic, Dejan; Dionne, Isabelle; Liu, Xiao Z; Wyman, Claire; Wellinger, Raymund J; Petrini, John H J

    2013-06-27

    Single-ended double-strand breaks (DSBs) are a common form of spontaneous DNA break, generated when the replisome encounters a discontinuity in the DNA template. Given their prevalence, understanding the mechanisms governing the fate(s) of single-ended DSBs is important. We describe the influence of the Ku heterodimer and Mre11 nuclease activity on processing of single-ended DSBs. Separation-of-function alleles of yku70 were derived that phenocopy Ku deficiency with respect to single-ended DSBs but remain proficient for NHEJ. The Ku mutants fail to regulate Exo1 activity, and bypass the requirement for Mre11 nuclease activity in the repair of camptothecin-induced single-ended DSBs. Ku mutants exhibited reduced affinity for DNA ends, manifest as both reduced end engagement and enhanced probability of diffusing inward on linear DNA. This study reveals an interplay between Ku and Mre11 in the metabolism of single-ended DSBs that is distinct from repair pathway choice at double-ended DSBs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The Ku Heterodimer and the Metabolism of Single-Ended DNA Double-Strand Breaks

    Directory of Open Access Journals (Sweden)

    Alessia Balestrini

    2013-06-01

    Full Text Available Single-ended double-strand breaks (DSBs are a common form of spontaneous DNA break, generated when the replisome encounters a discontinuity in the DNA template. Given their prevalence, understanding the mechanisms governing the fate(s of single-ended DSBs is important. We describe the influence of the Ku heterodimer and Mre11 nuclease activity on processing of single-ended DSBs. Separation-of-function alleles of yku70 were derived that phenocopy Ku deficiency with respect to single-ended DSBs but remain proficient for NHEJ. The Ku mutants fail to regulate Exo1 activity, and bypass the requirement for Mre11 nuclease activity in the repair of camptothecin-induced single-ended DSBs. Ku mutants exhibited reduced affinity for DNA ends, manifest as both reduced end engagement and enhanced probability of diffusing inward on linear DNA. This study reveals an interplay between Ku and Mre11 in the metabolism of single-ended DSBs that is distinct from repair pathway choice at double-ended DSBs.

  17. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency

    Science.gov (United States)

    Tapia, Natalia; MacCarthy, Caitlin; Esch, Daniel; Gabriele Marthaler, Adele; Tiemann, Ulf; Araúzo-Bravo, Marcos J.; Jauch, Ralf; Cojocaru, Vlad; Schöler, Hans R.

    2015-01-01

    The transcription factors OCT4 and SOX2 are required for generating induced pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs). OCT4 and SOX2 associate and bind to DNA in different configurations depending on the arrangement of their individual DNA binding elements. Here we have investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and inducing pluripotency. To this end, we have generated SOX2 mutants that interfere with specific OCT4-SOX2 heterodimer configurations and assessed their ability to generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical element with juxtaposed individual binding sites, plays a more critical role in the induction and maintenance of pluripotency than any other OCT4-SOX2 configuration. Overall, the results of this study provide new insight into the protein interactions required to establish a de novo pluripotent network and to maintain a true pluripotent cell fate. PMID:26314899

  18. Absence of Intramolecular Singlet Fission in Pentacene-Perylenediimide Heterodimers: The Role of Charge Transfer State.

    Science.gov (United States)

    Wang, Long; Wu, Yishi; Chen, Jianwei; Wang, Lanfen; Liu, Yanping; Yu, Zhenyi; Yao, Jiannian; Fu, Hongbing

    2017-11-16

    A new class of donor-acceptor heterodimers based on two singlet fission (SF)-active chromophores, i.e., pentacene (Pc) and perylenediimide (PDI), was developed to investigate the role of charge transfer (CT) state on the excitonic dynamics. The CT state is efficiently generated upon photoexcitation. However, the resulting CT state decays to different energy states depending on the energy levels of the CT state. It undergoes extremely rapid deactivation to the ground state in polar CH 2 Cl 2 , whereas it undergoes transformation to a Pc triplet in nonpolar toluene. The efficient triplet generation in toluene is not due to SF but CT-mediated intersystem crossing. In light of the energy landscape, it is suggested that the deep energy level of the CT state relative to that of the triplet pair state makes the CT state actually serve as a trap state that cannot undergoes an intramolecular singlet fission process. These results provide guidance for the design of SF materials and highlight the requisite for more widely applicable design principles.

  19. Borrelia carolinensis sp. nov., a novel species of the Borrelia burgclorferi sensu lato complex isolated from rodents and a tick from the south-eastern USA

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Grubhoffer, Libor; Oliver, J. H., Jr.

    2011-01-01

    Roč. 61, č. 2 (2011), 381-383 ISSN 1466-5026 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA206/09/1782 Institutional research plan: CEZ:AV0Z60220518 Keywords : MULTILOCUS SEQUENCE-ANALYSIS * FRAGMENT-LENGTH-POLYMORPHISM * LYME -DISEASE * RIBOSOMAL-RNA * Borrelia carolinensis sp. nov. * phylogeny Subject RIV: EE - Microbiology, Virology Impact factor: 2.268, year: 2011

  20. Controlled synthesis of PbS-Au nanostar-nanoparticle heterodimers and cap-like Au nanoparticles

    Science.gov (United States)

    Zhao, Nana; Li, Lianshan; Huang, Teng; Qi, Limin

    2010-11-01

    Uniform PbS-Au nanostar-nanoparticle heterodimers consisting of one Au nanoparticle grown on one horn of a well-defined six-horn PbS nanostar were prepared using the PbS nanostars as growth substrates for the selective deposition of Au nanoparticles. The size of the Au nanoparticles on the horns of the PbS nanostars could be readily adjusted by changing the PbS concentration for the deposition of Au nanoparticles. An optimum cetyltrimethylammonium bromide concentration and temperature were essential for the selective deposition of uniform Au nanoparticles on single horns of the PbS nanostars. Unusual PbS-Au nanoframe-nanoparticle heterodimers were obtained by etching the PbS-Au nanostar-nanoparticle heterodimers with oxalic acid while novel cap-like Au nanoparticles were obtained by etching with hydrochloric acid. The obtained heterodimeric nanostructures and cap-like nanoparticles are promising candidates for anisotropic nanoscale building blocks for the controllable assembly of useful, complex architectures.

  1. Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection.

    Science.gov (United States)

    Wagemakers, A; Mason, L M K; Oei, A; de Wever, B; van der Poll, T; Bins, A D; Hovius, J W R

    2014-12-01

    Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.

  2. Detection of relapsing fever Borrelia spp., Bartonella spp. and Anaplasmataceae bacteria in argasid ticks in Algeria.

    Science.gov (United States)

    Lafri, Ismail; El Hamzaoui, Basma; Bitam, Idir; Leulmi, Hamza; Lalout, Reda; Mediannikov, Oleg; Chergui, Mohamed; Karakellah, Mohamed; Raoult, Didier; Parola, Philippe

    2017-11-01

    Argasid ticks (soft ticks) are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks. Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis) nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus. The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation.

  3. Analysis of the lipidated recombinant outer surface protein A from Borrelia burgdorferi by mass spectrometry

    NARCIS (Netherlands)

    Bouchon, B.; Klein, Michele; Bischoff, Rainer; Van Dorsselaer, A.; Roitsch, C.

    1997-01-01

    The outer surface protein A, OspA, from the spirochete Borrelia burgdorferi is a lipoprotein of 25 kDa. The recombinant OspA (rOspA) expressed in Escherichia coli has been purified and analyzed by electrospray mass spectrometry (ESMS). A heterogenous spectrum gave a measured mass of 28,462 +/- 9 Da

  4. Differential expression of Ixodes ricinus tick genes induced by blood feeding or Borrelia burgdorferi infection

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Edwards, M. J.; Grubhoffer, Libor

    2005-01-01

    Roč. 42, č. 1 (2005), s. 36-41 ISSN 0022-2585 R&D Projects: GA AV ČR IAA6022306 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * Borrelia burgdorferi * subtractive hybridization Subject RIV: EE - Microbiology, Virology Impact factor: 1.489, year: 2005

  5. Lectin-binding characteristics of a Lyme borreliosis spirochete Borrelia burgdorferi sensu stricto

    Czech Academy of Sciences Publication Activity Database

    Vancová, M.; Nebesářová, J.; Grubhoffer, Libor

    2005-01-01

    Roč. 50, č. 3 (2005), s. 229-238 ISSN 0015-5632 R&D Projects: GA ČR GA206/03/1323; GA AV ČR KSK6005114 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi * electron microscopy * lectin binding Subject RIV: EE - Microbiology, Virology Impact factor: 0.918, year: 2005

  6. Prevalence of borreliae in ixodid ticks from a floodplain forest ecosystem

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk; Stünzner, D.; Halouzka, Jiří; Sixl, W.; Wendelin, I.; Juřicová, Zina; Sanogo, Yibayiri Osée

    2003-01-01

    Roč. 115, 3-4 (2003), s. 121-124 ISSN 0043-5325 R&D Projects: GA MŠk ME 229; GA ČR GA206/00/1204 Institutional research plan: CEZ:AV0Z6093917 Keywords : Lyme disease * Borrelia burgdorferi * floodplain forest Subject RIV: EE - Microbiology, Virology Impact factor: 0.774, year: 2003

  7. Molecular typing of Borrelia burgdorferi sensu lato by randomly amplified polymorphic DNA fingerprinting analysis

    NARCIS (Netherlands)

    Wang, G.; van Dam, A. P.; Spanjaard, L.; Dankert, J.

    1998-01-01

    To study whether pathogenic clusters of Borrelia burgdorferi sensu lato strains occur, we typed 136 isolates, cultured from specimens from patients (n = 49) with various clinical entities and from ticks (n = 83) or dogs (n = 4) from different geographic regions, by randomly amplified polymorphic DNA

  8. A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

    NARCIS (Netherlands)

    Larsson, C.; Lundqvist, J.; Rooijen, van N.; Bergstrom, S.

    2009-01-01

    Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been

  9. A Borrelia afzelii Infection Increases Larval Tick Burden on Myodes glareolus (Rodentia

    NARCIS (Netherlands)

    Duijvendijk, van Gilian; Andel, van Wouter; Fonville, Manoj; Gort, Gerrit; Hovius, Joppe W.; Sprong, Hein; Takken, Willem

    2017-01-01

    Several microorganisms have been shown to manipulate their host or vector to enhance their own transmission. Here we examined whether an infection with Borrelia afzelii affects its transmission between its bank vole (Myodes glareolus, Schreber, 1780) host and tick vector. Captive-bred bank voles

  10. Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes

    Czech Academy of Sciences Publication Activity Database

    Pechová, Jitka; Tresová, Gabriela; Kovář, Lubomír; Kopecký, Jan

    2002-01-01

    Roč. 49, č. 2 (2002), s. 153ů159 ISSN 0015-5683 R&D Projects: GA ČR GA524/02/0901 Institutional research plan: CEZ:AV0Z6022909 Keywords : Ixodes ricinus * salivary gland extract * Borrelia afzelii Subject RIV: EC - Immunology Impact factor: 0.515, year: 2002

  11. Phylogenetic analysis of the spirochete Borrelia microti, a potential agent of relapsing fever in Iran.

    Science.gov (United States)

    Naddaf, Saied Reza; Ghazinezhad, Behnaz; Bahramali, Golnaz; Cutler, Sally Jane

    2012-09-01

    We report a role for Borrelia microti as a cause of relapsing fever in Iran supported by robust epidemiological evidence. The molecular identity of this spirochete and its relation with other relapsing fever borreliae have, until now, been poorly delineated. We analyzed an isolate of B. microti, obtained from Ornithodoros erraticus ticks, by sequencing four loci (16S rRNA, flaB, glpQ, intragenic spacer [IGS]) and comparing these sequences with those of other relapsing fever borreliae. Phylogenetic analysis using concatenated sequences of 16S rRNA, flaB, and glpQ grouped B. microti alongside three members of the African group, B. duttonii, B. recurrentis, and B. crocidurae, which are distinct from B. persica, the most prevalent established cause of tick-borne relapsing fever in Iran. The similarity values for 10 concatenated sequences totaling 2,437 nucleotides ranged from 92.11% to 99.84%, with the highest homologies being between B. duttonii and B. microti and between B. duttonii and B. recurrentis. Furthermore, the more discriminatory IGS sequence analysis corroborated the close similarity (97.76% to 99.56%) between B. microti and B. duttonii. These findings raise the possibility that both species may indeed be the same and further dispel the one-species, one-vector theory that has been the basis for classification of relapsing fever Borrelia for the last 100 years.

  12. Effect of tick saliva on immune interactions between Borrelia afzelii and murine dendritic cells

    Czech Academy of Sciences Publication Activity Database

    Slámová, M.; Skallová, A.; Páleníková, J.; Kopecký, Jan

    2011-01-01

    Roč. 33, č. 12 (2011), 654-660 ISSN 0141-9838 R&D Projects: GA AV ČR IAA600960811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia * dendritic cell * immune modulation * Ixodes ricinus Subject RIV: EC - Immunology Impact factor: 2.601, year: 2011

  13. Tick sialostatins L and L2 differentially influence dendritic cell responses to Borrelia spirochetes

    Czech Academy of Sciences Publication Activity Database

    Lieskovská, Jaroslava; Páleníková, Jana; Langhansová, Helena; Chagas, A. C.; Calvo, E.; Kotsyfakis, Michalis; Kopecký, Jan

    2015-01-01

    Roč. 8, MAY 15 2015 (2015), s. 275 ISSN 1756-3305 R&D Projects: GA ČR GAP302/12/2208 Institutional support: RVO:60077344 Keywords : Dendritic cell s * Borrelia burgdorferi * Tick cystatin * Signalling Subject RIV: EC - Immunology Impact factor: 3.234, year: 2015

  14. Effect of tick saliva on mechanisms of innate immune response against Borrelia afzelii

    Czech Academy of Sciences Publication Activity Database

    Kýčková, Kateřina; Kopecký, Jan

    2006-01-01

    Roč. 43, č. 4 (2006), s. 1208-1214 ISSN 0022-2585 R&D Projects: GA ČR GA524/05/0811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * Borrelia afzelii * phagocytosis Subject RIV: EC - Immunology Impact factor: 1.950, year: 2006

  15. Detection of relapsing fever Borrelia spp., Bartonella spp. and Anaplasmataceae bacteria in argasid ticks in Algeria.

    Directory of Open Access Journals (Sweden)

    Ismail Lafri

    2017-11-01

    Full Text Available Argasid ticks (soft ticks are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks.Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus.The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation.

  16. Detection and identification of Anaplasma phagocytophilum, Borrelia burgdorferi, and Rickettsia helvetica in Danish Ixodes ricinus ticks

    DEFF Research Database (Denmark)

    Skarphédinsson, Sigurdur; Lyholm, Birgitte Fjendbo; Ljungberg, Marianne

    2007-01-01

    % of adult ticks. The difference in prevalence between Anaplasma and Borrelia in adult ticks supports the idea that their maintenance cycles in nature may be different. Ticks were also infected with Rickettsia helvetica. Our study indicates that A. phagocytophilum prevalence in ticks in Denmark is as high...

  17. Granuloma Annulare and Morphea: Correlation with Borrelia burgdorferi Infections and Chlamydia-related Bacteria

    Directory of Open Access Journals (Sweden)

    Lauri Tolkki

    2017-12-01

    Full Text Available A retrospective study of 109 skin biopsies with granuloma annulare (GA or morphea histology from patients with suspected tick bite was performed. Biopsies were tested for cutaneous Borrelia burgdorferi DNA using PCR. The same biopsies were analysed for tick-borne novel agents, Chlamydia-related bacteria (members of the Chlamydiales order, using a PCR-based method. Borrelia DNA was detected in 7/73 (9.6% biopsies with GA and in 1/36 (2.8 % biopsies with morphea, while Chlamydiales DNA was found in 53/73 (72.6% biopsies with GA and 25/34 (73.4% biopsies with morphea. All Borrelia DNA-positive GA samples were also positive for Chlamydiales DNA. The Chlamydiales sequences detected in GA were heterogeneous and contained Waddliaceae and Rhabdochlamydiaceae bacteria, which are also present in Ixodes ricinus ticks, while the Chlamydiales sequences detected in morphea closely resembled those found in healthy skin. In conclusion, tick-mediated infections can trigger GA in some cases, while correlation of either Borrelia or Chlamydiales with morphea is unlikely.

  18. Evidence of Borrelia in wild and domestic mammals from the state of Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Emmanuel Montandon

    Full Text Available The main of the study was to evaluate the presence of Borrelia burgdorferi infection in domestic and wild vertebrates and ectoparasites in endemic areas from the state of Minas Gerais, Brazil. A total of 445 serum samples were examined by ELISA, which used the Borrelia burgdorferi strain G39/40 U.S. source and 3,821 tick samples were tested by polymerase chain reaction (PCR. B. burgdorferi antibodies were found in 30 serum samples (6.74%; three in marsupials (7.69%, three in rodents (2.80%, nine in dogs (6.25%, and 15 in horses (9.68%. Nested-PCR performed in DNA samples obtained from collected ticks demonstrated negative results. Although attempts to amplify B. burgdorferi DNA from ticks had been not successful, the presence of seroreactive vertebrates suggests the possibility the Borrelia species circulating in these regions. Further research is required to provide information on the presence of Borrelia in Brazilian territory and its association with Baggio-Yoshinari syndrome.

  19. Human pathogenic borreliae in Ixodes ricinus ticks in natural and urban ecosystem (Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Venclíková, Kristýna; Betášová, Lenka; Šikutová, Silvie; Jedličková, Petra; Hubálek, Zdeněk; Rudolf, Ivo

    2014-01-01

    Roč. 59, č. 4 (2014), s. 717-720 ISSN 1230-2821 EU Projects: European Commission(XE) 261504 - EDENEXT Institutional support: RVO:68081766 Keywords : Ixodes ricinus * Borrelia burgdorgeri s.l. * genomic species * ixodid ticks Subject RIV: EE - Microbiology, Virology Impact factor: 0.905, year: 2014

  20. Tick saliva suppresses IFN signalling in dendritic cells upon Borrelia afzelii infection

    Czech Academy of Sciences Publication Activity Database

    Lieskovská, Jaroslava; Kopecký, Jan

    2012-01-01

    Roč. 34, č. 1 (2012), s. 32-39 ISSN 0141-9838 R&D Projects: GA MŠk(CZ) LC06009 Institutional support: RVO:60077344 Keywords : Borrelia * dendritic cells * interferon signalling * tick saliva Subject RIV: EC - Immunology Impact factor: 2.208, year: 2012

  1. First detection of Borrelia miyamotoi in Ixodes ricinus ticks from northern Italy.

    NARCIS (Netherlands)

    Ravagnan, Silvia; Tomassone, Laura; Montarsi, Fabrizio; Krawczyk, Aleksandra Iwona; Mastrorilli, Eleonora; Sprong, Hein; Milani, Adelaide; Rossi, Luca; Capelli, Gioia

    2018-01-01

    Borrelia miyamotoi is a spirochete transmitted by several ixodid tick species. It causes a relapsing fever in humans and is currently considered as an emerging pathogen. In Europe, B. miyamotoi seems to occur at low prevalence in Ixodes ricinus ticks but has a wide distribution. Here we report the

  2. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement

    NARCIS (Netherlands)

    Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J.; Oei, Anneke; Nijhof, Ard M.; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D.; Hovius, Joppe W. R.

    2016-01-01

    We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement

  3. Large scale spatial risk and comparative prevalence of Borrelia miyamotoi and Borrelia burgdorferi sensu lato in Ixodes pacificus.

    Directory of Open Access Journals (Sweden)

    Kerry Padgett

    Full Text Available Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia. There is limited understanding of large scale entomological risk patterns of B. miyamotoi and of Borreila burgdorferi sensu stricto (ss, the agent of Lyme disease, in western North America. In this study, B. miyamotoi, a relapsing fever spirochete, was detected in adult (n=70 and nymphal (n=36 Ixodes pacificus ticks collected from 24 of 48 California counties that were surveyed over a 13 year period. Statewide prevalence of B. burgdorferi sensu lato (sl, which includes B. burgdorferi ss, and B. miyamotoi were similar in adult I. pacificus (0.6% and 0.8%, respectively. In contrast, the prevalence of B. burgdorferi sl was almost 2.5 times higher than B. miyamotoi in nymphal I. pacificus (3.2% versus 1.4%. These results suggest similar risk of exposure to B. burgdorferi sl and B. miyamotoi from adult I. pacificus tick bites in California, but a higher risk of contracting B. burgdorferi sl than B. miyamotoi from nymphal tick bites. While regional risk of exposure to these two spirochetes varies, the highest risk for both species is found in north and central coastal California and the Sierra Nevada foothill region, and the lowest risk is in southern California; nevertheless, tick-bite avoidance measures should be implemented in all regions of California. This is the first study to comprehensively evaluate entomologic risk for B. miyamotoi and B. burgdorferi for both adult and nymphal I. pacificus, an important human biting tick in western North America.

  4. Monoinfections caused by Borrelia burgdorferi and Borrelia burgdorferi / Anaplasma phagocytophilum co-infections in forestry workers and farmers

    Directory of Open Access Journals (Sweden)

    Małgorzata Tokarska-Rodak

    2015-10-01

    Full Text Available Background: The presence of co-infections induced by tick-borne pathogens in humans is an important epidemiological phenomenon. This issue has attracted growing attention of doctors and people working under conditions of an increased risk of being exposed to tick bites. Material and Methods: The research group consisted of 93 individuals with current anti-immunoglobulin M/G (IgM/ IgG Borrelia burgdorferi or IgG anti-Anaplasma phagocytophilum. The respondents were identified during the screening survey in a group of farmers and foresters occupationally exposed to tick bites. The aim of the work was to analyse the frequency of antibodies to specific antigens of B. burgdorferi and the levels of cytokines in forestry workers and farmers with B. burgdorferi monoinfections and B. burgdorferi / A. phagocytophilum co-infections. Statistical analysis was performed using the Chi2, Mann-Whitney U and Kruskal-Wallis tests. Results: There is a stronger generation of IgG antibodies to B. burgdorferi antigens in patients with B. burgdorferi / A. phagocytophilum co-infections, such as variable major protein-like sequence expressed (VlsE (p < 0.05, p19 (p < 0.02, p17 (p < 0.05 and complement regulator-acquiring surface protein 3 (CRASP3 (p < 0.02 compared to persons with B. burgdorferi monoinfections. The discrepancies in the synthesis of cytokines interleukin 6 (IL-6, IL-10, and tumor necrosis factor α (TNF-α have not been found in persons with B. burgdorferi monoinfections and B. burgdorferi / A. phagocytophilum co-infection. Conclusions: The immune response directed against B. burgdorferi is stronger in patients co-infected with B. burgdorferi and A. phagocytophilum than in those with monoinfection. Med Pr 2015;66(5:645–651

  5. Natural foci of Borrelia lusitaniae in a mountain region of Central Europe.

    Science.gov (United States)

    Tarageľová, Veronika Rusňáková; Mahríková, Lenka; Selyemová, Diana; Václav, Radovan; Derdáková, Markéta

    2016-03-01

    Lyme borreliosis is the most prevalent tick-borne disease in Europe. It is caused by spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex and transmitted to humans by ticks of the genus Ixodes. Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana are the most common genospecies in Central Europe. In contrast, Borrelia lusitaniae predominates in Mediterranean countries such as Portugal, Morocco, and Tunisia. In Slovakia, its prevalence is low and restricted to only a few sites. The aim of our research was to study the expansion of ticks into higher altitudes in the ecosystem of the Malá Fatra mountains (north Slovakia) and their infection with B. burgdorferi s.l. pathogens. Questing ticks were collected by flagging in seven years (2004, 2006-2011) at three different altitudes: low (630-660 m above sea level (ASL)), intermediate (720-750 m ASL), and high (1040-1070 m ASL). Tick abundance was highest at the lowest altitude and lowest at the highest altitude. The average infection prevalence of B. burgdorferi s.l. in nymphs and adults was 16.8% and 36.2%, respectively. The number of infected ticks decreased from 38.5% at the lowest altitude to 4.4% at the highest altitude. B. lusitaniae was the most frequently found genospecies (>60% of the ticks found positive for B. burgdorferi s.l.) in all sites in all the studied years with the exception of 2008 when B. afzelii predominated (62%). Our study confirms the spread of Ixodes ricinus ticks to higher altitudes in Slovakia. The discovery that our mountain study sites were a natural foci of B. lusitaniae was unexpected because this genospecies is usually associated with lizards and xerothermic habitats. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. The polar 2e/12c bond in phenalenyl-azaphenalenyl hetero-dimers: Stronger stacking interaction and fascinating interlayer charge transfer

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Rong-Lin; Li, Zhi-Ru, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); Xu, Hong-Liang, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Functional Material Chemistry, Faculty of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China)

    2016-08-07

    An increasing number of chemists have focused on the two-electron/multicenter bond (2e/mc) that was first introduced to interpret the bonding mechanism of radical dimers. Herein, we report the polar two-electron/twelve center (2e/12c) bonding character in a series of phenalenyl-azaphenalenyl radical hetero-dimers. Interestingly, the bonding energy of weaker polar hetero-dimer (P-TAP) is dominated by the overlap of the two different singly occupied molecular orbital of radicals, while that of stronger polar hetero-dimer (P-HAP) is dominated by the electrostatic attraction. Results show that the difference between the electronegativity of the monomers plays a prominent role in the essential attribution of the polar 2e/12c bond. Correspondingly, a stronger stacking interaction in the hetero-dimer could be effectively achieved by increasing the difference of nitrogen atoms number between the monomers. It is worthy of note that an interesting interlayer charge transfer character is induced in the polar hetero-dimers, which is dependent on the difference between the electronegativity of the monomers. It is our expectation that the new knowledge about the bonding nature of radical hetero-dimers might provide important information for designing radical based functional materials with various applications.

  7. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    International Nuclear Information System (INIS)

    Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

  8. The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates▿

    OpenAIRE

    Schuijt, Tim J.; Hovius, Joppe W. R.; van Burgel, Nathalie D.; Ramamoorthi, Nandhini; Fikrig, Erol; van Dam, Alje P.

    2008-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is transmitted by ticks. During transmission from the tick to the host, spirochetes are delivered with tick saliva, which contains the salivary protein Salp15. Salp15 has been shown to protect spirochetes against B. burgdorferi-specific antibodies. We now show that Salp15 from both Ixodes ricinus and Ixodes scapularis protects serum-sensitive isolates of Borrelia burgdorferi sensu lato against complement-mediated killing. I. ricinus Salp15 show...

  9. Characterization of the β-barrel assembly machine accessory lipoproteins from Borrelia burgdorferi.

    Science.gov (United States)

    Dunn, Joshua P; Kenedy, Melisha R; Iqbal, Henna; Akins, Darrin R

    2015-03-24

    Like all diderm bacteria studied to date, Borrelia burgdorferi possesses a β-barrel assembly machine (BAM) complex. The bacterial BAM complexes characterized thus far consist of an essential integral outer membrane protein designated BamA and one or more accessory proteins. The accessory proteins are typically lipid-modified proteins anchored to the inner leaflet of the outer membrane through their lipid moieties. We previously identified and characterized the B. burgdorferi BamA protein in detail and more recently identified two lipoproteins encoded by open reading frames bb0324 and bb0028 that associate with the borrelial BamA protein. The role(s) of the BAM accessory lipoproteins in B. burgdorferi is currently unknown. Structural modeling of B. burgdorferi BB0028 revealed a distinct β-propeller fold similar to the known structure for the E. coli BAM accessory lipoprotein BamB. Additionally, the structural model for BB0324 was highly similar to the known structure of BamD, which is consistent with the prior finding that BB0324 contains tetratricopeptide repeat regions similar to other BamD orthologs. Consistent with BB0028 and BB0324 being BAM accessory lipoproteins, mutants lacking expression of each protein were found to exhibit altered membrane permeability and enhanced sensitivity to various antimicrobials. Additionally, BB0028 mutants also exhibited significantly impaired in vitro growth. Finally, immunoprecipitation experiments revealed that BB0028 and BB0324 each interact specifically and independently with BamA to form the BAM complex in B. burgdorferi. Combined structural studies, functional assays, and co-immunoprecipitation experiments confirmed that BB0028 and BB0324 are the respective BamB and BamD orthologs in B. burgdorferi, and are important in membrane integrity and/or outer membrane protein localization. The borrelial BamB and BamD proteins both interact specifically and independently with BamA to form a tripartite BAM complex in B

  10. [Using the polymerase chain reaction to Borrelia burgdorferi infection in localized scleroderma injure (morphea), in Venezuelan patients].

    Science.gov (United States)

    Espinoza-León, Fabiola; Arocha, Francisco; Hassanhi, Manzur; Arévalo, Julio

    2010-09-01

    Borrelia burgdorferi is the causative agent of Lyme Borreliosis, an infectious multisystemic disease transmitted to humans by the Ixodes ticks bite. A possible association of Borrelia burgdorferi with localized scleroderma has been postulated. However, published data do not provide unequivocal results. Previous serologic analysis of patients with localized scleroderma in South American countries (including Venezuela), have been reported as yielding some reactivity. The present study looked for evidence of Borrelia burgdorferi infection in venezuelan patients with localized scleroderma, using the polymerase chain reaction to analyze 21 skin samples of patients with this skin condition. The results were negative in all the samples studied. Our data do not support an association of Borrelia burgdorferi infection and the sclerotic lesions of localized scleroderma; but do not rule out the possibility of a relationship between localized scleroderma and an unknown geno-specie of Borrelia burgdorferi sensu lato complex, a different Borrelia specie or a different spirochetal organism, as the etiological agents of the skin lesions in this area.

  11. Self-assembly of Hydrazide-based Heterodimers Driven by Hydrogen Bonding and Donor-Acceptor Interaction

    Institute of Scientific and Technical Information of China (English)

    FENG,Dai-Jun; WANG,Peng; LI,Xiao-Qiang; LI,Zhan-Ting

    2006-01-01

    A new series of hydrogen bonding-driven heterodimers have been self-assembled in chloroform from hydrazide-based monomers. Additional intermolecular donor-acceptor interaction between the electron-rich bis(p-phenylene)-34-crown-10 unit and the electron-deficient naphthalene diimide unit has been utilized to increase the stability of the dimmers, and pronounced cooperativity of the two discrete non-covalent forces to stabilize the dimer has been revealed by the quantitative 1H (2D) NMR and UV-Vis experiments.

  12. [Recombinant OspC identification and antigenicity detection from Borrelia burgdorferi PD91 in China].

    Science.gov (United States)

    Chen, Jian; Wan, Kang-Lin

    2003-10-01

    To recombine OspC gene from Borrelia burgdorferi PD91 of China and expressed it in E. coli for early diagnosis of Lyme disease. The OspC gene was amplified from the genome of Borrelia burgdorferi PD91 strain by polymerase chain reaction and recombined with plasmid PET-11D. The recombinant plasmid PET-11D-OspC was identified with PCR, restriction endonuclease analysis and sequencing. The antigenicity was verified with Western Blot. OspC gene was cloned correctly into vector PET-11D. The resultant sequence was definitely different from the published sequence. The recombinant OspC seemed to have had strong antigenicity. The findings laid basis for the studies on early diagnosis of Lyme disease.

  13. Reclassification of Borrelia spp. isolated in South Korea using Multilocus Sequence Typing.

    Science.gov (United States)

    Park, Kyung-Hee; Choi, Yeon-Joo; Kim, Jeoungyeon; Park, Hye-Jin; Song, Dayoung; Jang, Won-Jong

    2018-05-31

    Using Borrelia isolated from South Korea, we evaluated by MLST and three intergenic genes (16S rRNA, ospA, and 5S-23S IGS) typing to analyze the relationship between host and vector and molecular background. Using the MLST analysis, we identified B. afzelii, B. yangtzensis, B. garinii, and B. bavariensis. This study was first report of the identification of B. yangtzensis using the MLST in South Korea.

  14. Updates on Borrelia burgdorferi sensu lato complex with respect to public health

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Grubhoffer, Libor; Oliver, J. H., Jr.

    2011-01-01

    Roč. 2, č. 3 (2011), s. 123-128 ISSN 1877-959X R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA206/09/1782 Institutional research plan: CEZ:AV0Z60220518 Keywords : Spirochetes * Borrelia * Genetic diversity * Lyme borreliosis * Distribution * New species Subject RIV: EE - Microbiology, Virology Impact factor: 2.370, year: 2011

  15. A Case of Canine Borreliosis in Iran Caused by Borrelia persica

    OpenAIRE

    Shirani, Darush; Rakhshanpoor, Alaleh; Cutler, Sally J.; Ghazinezhad, Behnaz; Naddaf, Saied Reza

    2016-01-01

    Tick-borne relapsing fever is an endemic disease in Iran, with most cases attributed to infection by B. persica, which is transmitted by Ornithodoros tholozani soft ticks. Here, we report spirochetemia in blood of a puppy residing in Tehran, Iran. The causative species was identified by use of highly discriminative IGS sequencing; the 489 bp IGS sequence obtained in our study showed 99% identity (100% coverage) when compared with Borrelia persica sequences derived from clinical cases or from ...

  16. In silico evaluation of PCR - primers for detection of Lyme Borrelia

    OpenAIRE

    Sultan, Nasir

    2016-01-01

    Lyme borreliosis (LB) or Lyme disease is the most prevalent vector-borne disease in US and Europe. The etiologic is some species of tick-borne spirochetes Borrelia burgdorferi sensu lato (B. burgdorferi sl) complex. The most common clinical symptoms of LB is the erythema migrans (EM). The pathogen is transmitted to humans through the tick bite of Ixodes species, and spread to cause more severe manifestations such as Acrodermatitis Chronica Atrophicans (ACA), Lyme arthritis, and neuroborrelios...

  17. Borrelia burgdorferi infection and immunity in mice deficient in the fifth component of complement.

    OpenAIRE

    Bockenstedt, L K; Barthold, S; Deponte, K; Marcantonio, N; Kantor, F S

    1993-01-01

    When immunocompetent mice are inoculated with Borrelia burgdorferi, they develop acute arthritis and carditis that undergo spontaneous regression despite the persistence of infection. Specific T- and/or B-cell immunity appears to be necessary for resolution of disease manifestations. Humoral immune responses to B. burgdorferi are also important in prevention of B. burgdorferi infection, in that passive transfer of immune sera or protective monoclonal antibodies prevents the spirochete from es...

  18. Antibody responses to Borrelia burgdorferi detected by western blot vary geographically in Canada

    OpenAIRE

    Ogden, Nicholas H.; Arsenault, Julie; Hatchette, Todd F.; Mechai, Samir; Lindsay, L. Robbin

    2017-01-01

    Lyme disease is emerging in eastern and central Canada, and most cases are diagnosed using the two-tier serological test (Enzyme Immuno Assay [EIA] followed by Western blot [WB]). Simplification of this algorithm would be advantageous unless it impacts test performance. In this study, accuracy of individual proteins of the IgG WB algorithm in predicting the overall test result in samples from Canadians was assessed. Because Borrelia burgdorferi strains vary geographically in Canada, geographi...

  19. Exposed and hidden lectin-binding epitopes at the surface of Borrelia burgdorferi

    Czech Academy of Sciences Publication Activity Database

    Stoitsova, S. R.; Grubhoffer, Libor; Nebesářová, Jana

    2003-01-01

    Roč. 48, č. 5 (2003), s. 654-658 ISSN 0015-5632 R&D Projects: GA AV ČR IAA6022001 Grant - others:National Research Council at the Ministry of Education and Science(BG) K-709/97 Institutional research plan: CEZ:AV0Z6022909 Keywords : Borrelia burgdorferi * lectin-binding epitopes Subject RIV: EE - Microbiology, Virology Impact factor: 0.857, year: 2003

  20. Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection.

    Directory of Open Access Journals (Sweden)

    Rebecca A Elsner

    2015-07-01

    Full Text Available Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure

  1. Reptile-associated Borrelia species in the goanna tick (Bothriocroton undatum) from Sydney, Australia

    Czech Academy of Sciences Publication Activity Database

    Panetta, J. L.; Šíma, Radek; Calvani, N.E.D.; Hajdušek, Ondřej; Chandra, S.; Panuccio, J.; Šlapeta, J.

    2017-01-01

    Roč. 10, 20 December (2017), č. článku 616. ISSN 1756-3305 R&D Projects: GA ČR GA17-27393S; GA ČR GA17-27386S Institutional support: RVO:60077344 Keywords : Borrelia * Bothriocroton undatum * Coxiella burnetii * DNA extraction * Goanna tick * Illumina * Ixodidae * MiSeq Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.080, year: 2016

  2. Antibodies to Rickettsia spp. and Borrelia burgdorferi in Spanish Wild Red Foxes (Vulpes vulpes).

    Science.gov (United States)

    Lledó, Lourdes; Serrano, José Luis; Isabel Gegúndez, María; Giménez-Pardo, Consuelo; Saz, José Vicente

    2016-01-01

    We examined 314 red foxes (Vulpes vulpes) from the province of Soria, Spain, for Rickettsia typhi, Rickettsia slovaca, and Borrelia burgdorferi infection. Immunofluorescence assays showed 1.9% had antibodies to R. typhi, 6.7% had antibodies to R. slovaca, and 8.3% had antibodies to B. burgdorferi. Serostatus was not correlated with sex or age. Because red foxes can be infected by Rickettsiae and B. burgdorferi, presence of red foxes may be and indicator for the presence of these pathogens.

  3. Risk of occupational infections caused by Borrelia burgdorferi among forestry workers and farmers

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    Małgorzata Tokarska-Rodak

    2014-02-01

    Full Text Available Background: The aim of the work was to analyze the incidence of infection with Borrelia burgdorferi in forestry workers and farmers, major groups occupationally exposed to tick bites. Material and Methods: The study group included 275 workers (171 foresters and 104 farmers. The control group consisted of 45 people, who have not been occupationally exposed to tick bites. The screening Elisa and Wb tests for the presence of anti-Borrelia IgM/IgG antibodies were performed in all subjects of the study and control groups. Statistical analysis was performed using the Chi2 test. Results: The positive results denoting the presence of anti-Borrelia IgM/IgG antibodies were found in 55% of farmers and 28% of foresters occupationally exposed to Lyme borreliosis and coming from the area of South Podlasie Lowland and Lublin Polesie. The differences between the forestry workers and the control group (p ≤ 0.00001 and between farmers and the control group (p ≤ 0.001 were statistically significant. The species, such as B. spielmanii and B. bavariensis, which have not yet been reported in Poland, are significant etiologic agents of Lyme disease. Conclusion: The risk of occupational exposure to the B. burgdorferi infection is high for foresters and farmers, and the infection with spirochetes is frequently confirmed on the basis of positive results of the Wb test. The presence of specific antibodies against protein antigens of B. spielmanii and B. bavariensis suggest that these bacteria can cause Lyme disease both independently and in participation with other Borrelia species, which influences the development of the clinical manifestations of infection. Med Pr 2014;65(1:109–117

  4. Few vertebrate species dominate the Borrelia burgdorferi s.l. life cycle

    Science.gov (United States)

    Hofmeester, T. R.; Coipan, E. C.; van Wieren, S. E.; Prins, H. H. T.; Takken, W.; Sprong, H.

    2016-04-01

    Background. In the northern hemisphere, ticks of the Ixodidae family are vectors of diseases such as Lyme borreliosis, Rocky Mountain spotted fever and tick-borne encephalitis. Most of these ticks are generalists and have a three-host life cycle for which they are dependent on three different hosts for their blood meal. Finding out which host species contribute most in maintaining ticks and the pathogens they transmit, is imperative in understanding the drivers behind the dynamics of a disease. Methods. We performed a systematic review to identify the most important vertebrate host species for Ixodes ricinus and Borrelia burgdorferi s.l. as a well-studied model system for tick-borne diseases. We analyzed data from 66 publications and quantified the relative contribution for 15 host species. Review results. We found a positive correlation between host body mass and tick burdens for the different stages of I. ricinus. We show that nymphal burdens of host species are positively correlated with infection prevalence with B. burgdorferi s.l., which is again positively correlated with the realized reservoir competence of a host species for B. burgdorferi s.l. Our quantification method suggests that only a few host species, which are amongst the most widespread species in the environment (rodents, thrushes and deer), feed the majority of I. ricinus individuals and that rodents infect the majority of I. ricinus larvae with B. burgdorferi s.l. Discussion. We argue that small mammal-transmitted Borrelia spp. are maintained due to the high density of their reservoir hosts, while bird-transmitted Borrelia spp. are maintained due to the high infection prevalence of their reservoir hosts. Our findings suggest that Ixodes ricinus and Borrelia burgdorferi s.l. populations are maintained by a few widespread host species. The increase in distribution and abundance of these species, could be the cause for the increase in Lyme borreliosis incidence in Europe in recent decades.

  5. Comparative genome analysis: selection pressure on the Borrelia vls cassettes is essential for infectivity

    Directory of Open Access Journals (Sweden)

    Wilske Bettina

    2006-08-01

    Full Text Available Abstract Background At least three species of Borrelia burgdorferi sensu lato (Bbsl cause tick-borne Lyme disease. Previous work including the genome analysis of B. burgdorferi B31 and B. garinii PBi suggested a highly variable plasmid part. The frequent occurrence of duplicated sequence stretches, the observed plasmid redundancy, as well as the mainly unknown function and variability of plasmid encoded genes rendered the relationships between plasmids within and between species largely unresolvable. Results To gain further insight into Borreliae genome properties we completed the plasmid sequences of B. garinii PBi, added the genome of a further species, B. afzelii PKo, to our analysis, and compared for both species the genomes of pathogenic and apathogenic strains. The core of all Bbsl genomes consists of the chromosome and two plasmids collinear between all species. We also found additional groups of plasmids, which share large parts of their sequences. This makes it very likely that these plasmids are relatively stable and share common ancestors before the diversification of Borrelia species. The analysis of the differences between B. garinii PBi and B. afzelii PKo genomes of low and high passages revealed that the loss of infectivity is accompanied in both species by a loss of similar genetic material. Whereas B. garinii PBi suffered only from the break-off of a plasmid end, B. afzelii PKo lost more material, probably an entire plasmid. In both cases the vls gene locus encoding for variable surface proteins is affected. Conclusion The complete genome sequences of a B. garinii and a B. afzelii strain facilitate further comparative studies within the genus Borrellia. Our study shows that loss of infectivity can be traced back to only one single event in B. garinii PBi: the loss of the vls cassettes possibly due to error prone gene conversion. Similar albeit extended losses in B. afzelii PKo support the hypothesis that infectivity of Borrelia

  6. Low prevalence of Borrelia bavariensis in Ixodes ricinus ticks in southeastern Austria.

    Science.gov (United States)

    Glatz, Martin; Muellegger, Robert R; Hizo-Teufel, Cecilia; Fingerle, Volker

    2014-10-01

    Borrelia bavariensis was recently described as a distinct genospecies among the B. burgdorferi sensu lato complex. The prevalence of B. bavariensis in Austria, a highly endemic area for tick-transmitted pathogens, is scarcely characterized. To investigate the prevalence of B. bavariensis in Ixodes ricinus ticks we reevaluated the results of a study conducted in 518 ticks from southeastern Austria collected in 2002 and 2003. The presence of B. burgdorferi s.l.-specific DNA in ticks was analyzed by a PCR for the outer surface protein A (ospA) gene. Borrelia species were differentiated by restriction fragment length polymorphism (RFLP) analysis, and samples positive for B. bavariensis were further analyzed by multilocus sequence analysis. Two of 133 (1.5%) B. burgdorferi s.l.-positive I. ricinus ticks were infected with B. bavariensis. Both specimens were coinfected with the OspA serotype 5 of B. garinii. Borrelia bavariensis is present; however, seem to be rare in I. ricinus ticks in southeastern Austria. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. ThWRKY4 from Tamarix hispida Can Form Homodimers and Heterodimers and Is Involved in Abiotic Stress Responses

    Directory of Open Access Journals (Sweden)

    Liuqiang Wang

    2015-11-01

    Full Text Available WRKY proteins are a large family of transcription factors that are involved in diverse developmental processes and abiotic stress responses in plants. However, our knowledge of the regulatory mechanisms of WRKYs participation in protein–protein interactions is still fragmentary, and such protein–protein interactions are fundamental in understanding biological networks and the functions of proteins. In this study, we report that a WRKY protein from Tamarix hispida, ThWRKY4, can form both homodimers and heterodimers with ThWRKY2 and ThWRKY3. In addition, ThWRKY2 and ThWRKY3 can both bind to W-box motif with binding affinities similar to that of ThWRKY4. Further, the expression patterns of ThWRKY2 and ThWRKY3 are similar to that of ThWRKY4 when plants are exposed to abscisic acid (ABA. Subcellular localization shows that these three ThWRKY proteins are nuclear proteins. Taken together, these results demonstrate that ThWRKY4 is a dimeric protein that can form functional homodimers or heterodimers that are involved in abiotic stress responses.

  8. ThWRKY4 from Tamarix hispida Can Form Homodimers and Heterodimers and Is Involved in Abiotic Stress Responses.

    Science.gov (United States)

    Wang, Liuqiang; Zheng, Lei; Zhang, Chunrui; Wang, Yucheng; Lu, Mengzhu; Gao, Caiqiu

    2015-11-13

    WRKY proteins are a large family of transcription factors that are involved in diverse developmental processes and abiotic stress responses in plants. However, our knowledge of the regulatory mechanisms of WRKYs participation in protein-protein interactions is still fragmentary, and such protein-protein interactions are fundamental in understanding biological networks and the functions of proteins. In this study, we report that a WRKY protein from Tamarix hispida, ThWRKY4, can form both homodimers and heterodimers with ThWRKY2 and ThWRKY3. In addition, ThWRKY2 and ThWRKY3 can both bind to W-box motif with binding affinities similar to that of ThWRKY4. Further, the expression patterns of ThWRKY2 and ThWRKY3 are similar to that of ThWRKY4 when plants are exposed to abscisic acid (ABA). Subcellular localization shows that these three ThWRKY proteins are nuclear proteins. Taken together, these results demonstrate that ThWRKY4 is a dimeric protein that can form functional homodimers or heterodimers that are involved in abiotic stress responses.

  9. Borrelia persica infection in dogs and cats: clinical manifestations, clinicopathological findings and genetic characterization.

    Science.gov (United States)

    Baneth, Gad; Nachum-Biala, Yaarit; Halperin, Tamar; Hershko, Yizhak; Kleinerman, Gabriela; Anug, Yigal; Abdeen, Ziad; Lavy, Eran; Aroch, Itamar; Straubinger, Reinhard K

    2016-05-10

    Relapsing fever (RF) is an acute infectious disease caused by arthropod-borne spirochetes of the genus Borrelia. The disease is characterized by recurrent episodes of fever that concur with spirochetemia. The RF borrelioses include louse-borne RF caused by Borrelia recurrentis and tick-borne endemic RF transmitted by argasid soft ticks and caused by several Borrelia spp. such as B. crocidurae, B. coriaceae, B. duttoni, B. hermsii, B. hispanica and B. persica. Human infection with B. persica is transmitted by the soft tick Ornithodoros tholozani and has been reported from Iran, Israel, Egypt, India, and Central Asia. During 2003-2015, five cats and five dogs from northern, central and southern Israel were presented for veterinary care and detected with borrelia spirochetemia by blood smear microscopy. The causative infective agent in these animals was identified and characterized by PCR from blood and sequencing of parts of the flagellin (flab), 16S rRNA and glycerophosphodiester phosphodiestrase (GlpQ) genes. All animals were infected with B. persica genetically identical to the causative agent of human RF. Phylogenetic analysis indicated that DNA sequences from these pet carnivores clustered together with B. persica genotypes I and II from humans and O. tholozani ticks and distinctly from other RF Borrelia spp. The main clinical findings in cats included lethargy, anorexia, anemia in 5/5 cats and thrombocytopenia in 4/5. All dogs were lethargic and anorectic, 4/5 were febrile and anemic and 3/5 were thrombocytopenic. Three dogs were co-infected with Babesia spp. The animals were all treated with antibiotics and the survival rate of both dogs and cats was 80 %. The cat and dog that succumbed to disease died one day after the initiation of antibiotic treatment, while survival in the others was followed by the rapid disappearance of spirochetemia. This is the first report of disease due to B. persica infection in cats and the first case series in dogs. Infection was

  10. Development and optimization of an in vitro cultivation protocol allows for isolation of Borrelia miyamotoi from patients with hard tick-borne relapsing fever

    NARCIS (Netherlands)

    Koetsveld, Joris; Kolyasnikova, Nadezhda M.; Wagemakers, Alex; Toporkova, Marina G.; Sarksyan, Denis S.; Oei, Anneke; Platonov, Alexander E.; Hovius, Joppe W.

    2017-01-01

    Objectives: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; but clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a

  11. A divergent spirochete strain isolated from a resident of the southeastern United States was identified by multilocus sequence typing as Borrelia bissettii

    Czech Academy of Sciences Publication Activity Database

    Golovchenko, Maryna; Vancová, Marie; Clark, K.; Oliver, J. H., Jr.; Grubhoffer, Libor; Rudenko, Natalia

    2016-01-01

    Roč. 9, FEB 4 (2016), č. článku 68. ISSN 1756-3305 EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : Borrelia * Borrelia bissettii * MLST analysis * live spirochete * divergent strain Subject RIV: EG - Zoology Impact factor: 3.080, year: 2016

  12. Rexinoid Bexarotene Modulates Triglyceride but not Cholesterol Metabolism via Gene-Specific Permissivity of the RXR/LXR Heterodimer in the Liver

    DEFF Research Database (Denmark)

    Lalloyer, Fanny; Pedersen, Thomas Åskov; Gross, Barbara

    2009-01-01

    OBJECTIVE: Bexarotene (Targretin) is a clinically used antitumoral agent which exerts its action through binding to and activation of the retinoid-X-receptor (RXR). The most frequent side-effect of bexarotene administration is an increase in plasma triglycerides, an independent risk factor...... controlling cholesterol homeostasis. CONCLUSIONS: These findings demonstrate that the hypertriglyceridemic action of bexarotene occurs via the RXR/LXR heterodimer and show that RXR heterodimers can act with a selective permissivity on target genes of specific metabolic pathways in the liver....

  13. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Haijun Xu

    2010-09-01

    Full Text Available Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the σ(54-σ(S sigma factor cascade, plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl∼P, the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl∼P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl∼P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl∼P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl∼P can serve as a global signal in bacterial pathogenesis.

  14. Serological and molecular evidence for spotted fever group Rickettsia and Borrelia burgdorferi sensu lato co-infections in The Netherlands.

    Science.gov (United States)

    Koetsveld, Joris; Tijsse-Klasen, Ellen; Herremans, Tineke; Hovius, Joppe W R; Sprong, Hein

    2016-03-01

    Only a few reported cases indicate that Rickettsia helvetica and Rickettsia monacensis can cause disease in humans. Exposure to these two spotted fever group (SFG) rickettsiae occurs through bites of Ixodes ricinus, also the primary vector of Lyme borreliosis in Europe. To date, it is unclear how often exposure to these two microorganisms results in infection or disease. We show that of all the Borrelia burgdorferi s.l.-positive ticks, 25% were co-infected with rickettsiae. Predominantly R. helvetica was detected while R. monacensis was only found in approximately 2% of the ticks. In addition, exposure to tick-borne pathogens was compared by serology in healthy blood donors, erythema migrans (EM)-patients, and patients suspected of Lyme neuroborreliosis (LNB). As could be expected, seroreactivity against B. burgdorferi sensu lato was lower in blood donors (6%) compared to EM patients (34%) and suspected LNB cases (64%). Interestingly, seroreactivity against SFG Rickettsia antigens was not detected in serum samples from blood donors (0%), but 6% of the EM patients and 21% of the LNB suspects showed anti-rickettsial antibodies. Finally, the presence of B. burgdorferi s.l. and Rickettsia spp. in cerebrospinal fluid samples of a large cohort of patients suspected of LNB (n=208) was investigated by PCR. DNA of B. burgdorferi s.l., R. helvetica and R. monacensis was detected in seventeen, four and one patient, respectively. In conclusion, our data show that B. burgdorferi s.l. and SFG rickettsiae co-infection occurs in Dutch I. ricinus and that Lyme borreliosis patients, or patients suspected of Lyme borreliosis, are indeed exposed to both tick-borne pathogens. Whether SFG rickettsiae actually cause disease, and whether co-infections alter the clinical course of Lyme borreliosis, is not clear from our data, and warrants further investigation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Immunity against Ixodes scapularis salivary proteins expressed within 24 hours of attachment thwarts tick feeding and impairs Borrelia transmission.

    Directory of Open Access Journals (Sweden)

    Sukanya Narasimhan

    2007-05-01

    Full Text Available In North America, the black-legged tick, Ixodes scapularis, an obligate haematophagus arthropod, is a vector of several human pathogens including Borrelia burgdorferi, the Lyme disease agent. In this report, we show that the tick salivary gland transcriptome and proteome is dynamic and changes during the process of engorgement. We demonstrate, using a guinea pig model of I. scapularis feeding and B. burgdorferi transmission, that immunity directed against salivary proteins expressed in the first 24 h of tick attachment - and not later - is sufficient to evoke all the hallmarks of acquired tick-immunity, to thwart tick feeding and also to impair Borrelia transmission. Defining this subset of proteins will promote a mechanistic understanding of novel I. scapularis proteins critical for the initiation of tick feeding and for Borrelia transmission.

  16. Borrelia burgdorferi genospecies detection by RLB hybridization in Ixodes ricinus ticks from different sites of North-Eastern Poland.

    Science.gov (United States)

    Dunaj, Justyna; Zajkowska, Joanna Maria; Kondrusik, Maciej; Gern, Lise; Rais, Oliver; Moniuszko, Anna; Pancewicz, Sławomir; Świerzbińska, Renata

    2014-01-01

    RLB (Reverse Line Blot Hybridization) is a molecular biology technique that might be used for Borrelia burgdorferi sensu lato (sl) DNA detection with genospecies specification. Among B. burgdorferi sl genospecies at least 7 are regarded as pathogenic in Europe. The aim of the study was to evaluate the frequency of different Borrelia genospecies DNA detection in Ixodes ricinus ticks in the endemic area of North-Eastern Poland by using RLB. Ixodes ricinus ticks were collected in May - June, from 6 different sites in North-Eastern Poland (Jakubin, Kolno, Grajewo, Suwałki, Siemiatycze, Białowieża) by flagging. Extracted DNA was amplified by polymerase chain reaction (PCR) targeting the intergenic spacer 5S 23S of B. burgdorferi sl. PCR products were hybridised to 15 different oligonucleotide probes for 9 different Borrelia genospecies (B. burgdorferi sl, B. burgdorferi ss, B. garinii, B. afzelii, B. valaisiana, B. lusitaniae, B. spielmanii, B. bissettii and B. relapsing fever-like spirochetes (B. myamotoi)) by RLB. Borrelia genospecies DNA was detected in 205 Ixodes ricinus ticks. Among 14 infected with Borrelia ticks, 4 were identified as B. garinii and 10 as B. afzelii. Higher numbers of infected ticks were noticed in the eastern part of the research area, where large forest complexes dominate. Nymphs appeared to be the most frequently infected tick stage, which has an epidemiological meaning in the incidence of Lyme borreliosis. The study demonstrated that RLB might be easily used in Borrelia DNA detection with genospecies-identification, and indicated the domination of B. afzelii and B. garinii in ticks from North-Eastern Poland.

  17. Borreliacidal activity of Borrelia metal transporter A (BmtA binding small molecules by manganese transport inhibition

    Directory of Open Access Journals (Sweden)

    Wagh D

    2015-02-01

    Full Text Available Dhananjay Wagh,* Venkata Raveendra Pothineni,* Mohammed Inayathullah, Song Liu, Kwang-Min Kim, Jayakumar Rajadas Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA, USA *These authors contributed equally to this work  Abstract: Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA, a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 µg/mL (250 µM. Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.  Keywords: Lyme disease, BmtA, Borrelia burgdorferi, desloratadine, Bac Titer-Glo assay

  18. The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.

    Science.gov (United States)

    Ranjha, Lepakshi; Anand, Roopesh; Cejka, Petr

    2014-02-28

    MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis.

  19. The Saccharomyces cerevisiae Mlh1-Mlh3 Heterodimer Is an Endonuclease That Preferentially Binds to Holliday Junctions*

    Science.gov (United States)

    Ranjha, Lepakshi; Anand, Roopesh; Cejka, Petr

    2014-01-01

    MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis. PMID:24443562

  20. Association of HLA-DQ trans-heterodimers with prevalence of type 1 diabetes mellitus in Buryat ethnic group

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    Olga Nikolaevna Ivanova

    2012-09-01

    Full Text Available Aims. Search for the most pronounced HLA II markers of type 1 diabetes mellitus (T1DM in Buryat ethnic group and analysis ofHLA-DQ trans-heterodimers. Materials and methods. Case control design was applied for assessment of 74 patients with T1DM and 61 healthy individuals. Alleleidentification was performed with multi-primer allele-specific PCR technique. Association of genetic markers with pathology wasevaluated according to odds ratio (OR index. All calculations were performed with StatSoft and STATISTICA 6 software applications. Results. We show that regarding race-specific highly diabetogenic HLA class II haplotypes Buryat ethnic group holds intermediateposition between Mongoloids and Caucasians and none of those haplotypes are associated with T1DM. We revealed a statisticallysignificant association of T1DM with DQA1*0301+DQB1*0201+ phenotype represented by trans-coding alleles in 77% of cases. Onpopulation level DQA1*0301+DQB1*0302+ or *0201+ phenotype is found to be the most sensitive marker. It was registered in 43%of patients with T1DM against 11.5% of controls (OR 5.9; рс=0.0094. DQA1*0301+/DQВ1*0201 and DQВ1*0302 phenotype is themost specific marker, registered in 16% of patients, but not found in controls (OR 11.8; рс=0.047.Conclusions. HLA-mediated risk for development of T1DM in Buryat ethnic group is determined by HLA-DQ trans-heterodimers.

  1. S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

    Science.gov (United States)

    Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

    2017-01-25

    Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

  2. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation

    NARCIS (Netherlands)

    Wang, J.; Zheng, Y.; Zhao, J.; Liu, T.; Gao, L.; Gu, Z.; Wu, G.

    2012-01-01

    Objectives To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Material and Methods Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created

  3. Clinical characteristics associated with Borrelia burgdorferi sensu lato skin culture results in patients with erythema migrans.

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    Franc Strle

    Full Text Available Clinical characteristics associated with isolation of Borrelia burgdorferi sensu lato from skin have not been fully evaluated. To gain insight into predictors for a positive EM skin culture, we compared basic demographic, epidemiologic, and clinical data in 608 culture-proven and 501 culture-negative adult patients with solitary EM. A positive Borrelia spp. skin culture was associated with older age, a time interval of >2 days between tick bite and onset of the skin lesion, EM ≥ 5 cm in diameter, and location of the lesion on the extremities, whereas several other characteristics used as clinical case definition criteria for the diagnosis of EM (such as tick bite at the site of later EM, information on expansion of the skin lesion, central clearing were not. A patient with a 15-cm EM lesion had almost 3-fold greater odds for a positive skin culture than patients with a 5-cm lesion. Patients with a free time interval between the tick bite and onset of EM had the same probability of a positive skin culture as those who did not recall a tick bite (OR=1.02; however, the two groups had >3-fold greater odds for EM positivity than patients who reported a tick bite with no interval between the bite and onset of the lesion. In conclusion, several yet not all clinical characteristics used in EM case definitions were associated with positive Borrelia spp. skin culture. The findings are limited to European patients with solitary EM caused predominantly by B. afzelii but may not be valid for other situations.

  4. Evidence that two ATP-dependent (Lon proteases in Borrelia burgdorferi serve different functions.

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    James L Coleman

    2009-11-01

    Full Text Available The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. Borrelia spirochetes are unusual in that they code for two putative ATP-dependent Lon homologs, Lon-1 and Lon-2. Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted through the blood feeding of Ixodes ticks. Previous work in our laboratory reported that B. burgdorferi lon-1 is upregulated transcriptionally by exposure to blood in vitro, while lon-2 is not. Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. Phylogenetic analysis revealed that Lon-1 and Lon-2 cluster separately due to differences in the NH(2-terminal substrate binding domains that may reflect differences in substrate specificity. Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. We conclude that B. burgdorferi Lons -1 and -2 have distinct functional roles. Lon-2 functions in a manner consistent with canonical Lon, engaged in cellular homeostasis. Lon-1, by virtue of its blood induction, and as a unique feature of the Borreliae, may be important in host adaptation from the arthropod to a warm-blooded host.

  5. Expression of spoT in Borrelia burgdorferi during Serum Starvation

    OpenAIRE

    Concepcion, Marc B.; Nelson, David R.

    2003-01-01

    Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the tick Ixodes scapularis. A 2.9-kb fragment containing a putative spoT gene was isolated from B. burgdorferi genomic DNA by PCR amplification and cloned into a pBAD24 vector. The cloned gene complemented Escherichia coli mutant strain CF1693, which contains deletions of both the relA and spoT genes. The spoT gene in E. coli encodes a bifunctional enzyme capable of synthesizing and degrading (p)ppGpp, which mediates...

  6. A new (14th) member of Borrelia burgdorferi sensu lato complex

    Czech Academy of Sciences Publication Activity Database

    Oliver, J.; Rudenko, Natalia; Golovchenko, Maryna; Grubhoffer, Libor

    2008-01-01

    Roč. 14, S7 (2008), S110-S110 ISSN 1198-743X. [ECCMID /18./. 19.04.2008-22.04.2008, Barcelona] R&D Projects: GA ČR(CZ) GA524/06/1479; GA MŠk(CZ) LC06009 Grant - others:National Institutes of Health (NIH)(US) R37AI-24899; Centers for Disease Control and Prevention (CDC)(US) U50/CCU410282 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi s.l. complex * new member * multilocus sequence analysis Subject RIV: EC - Immunology

  7. Host association of Borrelia burgdorferi sensu lato--the key role of host complement.

    Science.gov (United States)

    Kurtenbach, Klaus; De Michelis, Simona; Etti, Susanne; Schäfer, Stefanie M; Sewell, Henna-Sisko; Brade, Volker; Kraiczy, Peter

    2002-02-01

    Borrelia burgdorferi sensu lato (s.l.), the tick-borne agent of Lyme borreliosis, is a bacterial species complex comprising 11 genospecies. Here, we discuss whether the delineation of genospecies is ecologically relevant. We provide evidence that B. burgdorferi s.l. is structured ecologically into distinct clusters that are host specific. An immunological model for niche adaptation is proposed that suggests the operation of complement-mediated selection in the midgut of the feeding tick. We conclude that vertebrate hosts rather than tick species are the key to Lyme borreliosis spirochaete diversity.

  8. Erythema migrans and serodiagnosis by enzyme immunoassay and immunoblot with three borrelia species.

    Science.gov (United States)

    Stanek, G; Breier, F; Menzinger, G; Schaar, B; Hafner, M; Partsch, H

    1999-12-10

    There is wide divergence of opinion between physicians regarding the use of serological measures for the diagnosis and treatment of erythema migrans, the hallmark of Lyme borreliosis. We studied the outcome of an enzyme immunoassay and immunoblot (Western blot) used on the sera of patients who had suffered tick bite and erythema migrans, and had been subsequently treated with various antibiotics. Ninety-nine consecutive patients presenting with erythema migrans after tick bite were prospectively recruited at the outpatient department of two Vienna City hospitals and at the consultation office for Lyme borreliosis of the Institute of Hygiene. University Vienna. Blood samples were taken before antibiotic treatment and 3 and 6 months thereafter. Blood samples from 100 blood donors served as controls. Antibodies against Borrelia burgdorferi sensu lato were determined by enzyme immunoassay (IgG and IgM EIA) and by IgG immunoblot. The latter was performed with isolates of B. alzelii (H2) B. burgdorferi sensu stricto (Le) and B. garinii (W) from Austrian patients. The 4 interpretation criteria for immunoblot results were: A (3 bands out of 8), B (2 bands out of 9), C and D (1 band out of 6). In all patients, the erythema resolved within the treatment period. No complications secondary to the borrelia infection were registered. After treatment there was no significant change in titre, nor was there a difference in the immunoblot pattern between the first, second and third serum samples. Serum antibodies to B. burgdorferi were positive by EIA in 22.9% (IgG) and 2.5% (IgM). Immunoblot results offered by borrelia species and by the interpretation criteria, ranging between 8.3% (criterion A, strain Le) and 44.2% (criterion D, strain H2). By EIA, control samples were IgG and IgM positive in 5% and 1%, respectively. Positive immunoblot results with strain H2 were found in 9%, 13%, 18%, and 20% by the criteria A through D respectively. After antibiotic treatment of erythema

  9. Seroprevalence of anti-Toxoplasma gondii and anti-Borrelia species antibodies in patients with schizophrenia: a case-control study from western Turkey.

    Science.gov (United States)

    Cevizci, Sibel; Celik, Merve; Akcali, Alper; Oyekcin, Demet Gulec; Sahin, Ozlem Oztürk; Bakar, Coskun

    2015-06-01

    We examined IgG antibody seroprevalence and risk factors for anti-Toxoplasma gondii and anti-Borrelia sp. in schizophrenic patients. This case-control study included 30 schizophrenic patients and 60 healthy individuals. Serological analyses were identified by using ELISA technique. In the case group the Toxoplasma seropositivity was 33.3% and Borrelia seropositivity was 13.3%, while in the control group the Toxoplasma positivity was 21.7% and Borrelia seropositivity was 15.0%. There was no significant difference with regard to seroprevalence between the groups (P = 0.232; P = 0.832, respectively). There was statistically significant difference between case and control groups related to hand and kitchen utensil hygiene after dealing with raw meat (P = 0.001). Our data showed the rate of Toxoplasma antibodies was higher in the case group, while the rate of Borrelia antibodies was higher in the control group. In both groups the high rates of seropositivity for Toxoplasma gondii and Borrelia sp. is thought to be due to neglect of personal hygiene. The present study also is the first to examine the association between Borrelia sp. and schizophrenia. Further studies are needed to determine whether there is an association between Borrelia sp. and schizophrenia or not.

  10. Establishment of a minor groove binder-probe based quantitative real time PCR to detect Borrelia burgdorferi sensu lato and differentiation of Borrelia spielmanii by ospA-specific conventional PCR

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    Strube Christina

    2010-08-01

    Full Text Available Abstract Background Borrelia burgdorferi sensu lato (sl, the causative agent of Lyme borreliosis, is transmitted by ticks of the genus Ixodes as vector. For identification of Borrelia infections in ticks a TaqMan™ minor groove binder (MGB probe-based quantitative real time PCR (qPCR was established targeting the 5S-23S intergenic spacer. Extension to a duplex qPCR included an Ixodes spp. positive control to verify successful DNA isolation. Besides qPCR, an ospA-specific conventional PCR for species-specific identification of B. spielmanii was established. Afterwards 1000 I. ricinus flagged in the city of Hanover, Germany, were investigated for B. burgdorferi sl infections followed by species identification. Furthermore, I. hexagonus ticks were investigated to proof applicability of the PCRs. Results Quantitative real time PCR (qPCR identifying B. burgdorferi sl in ticks was able to detect 1-10 copies per reaction. B. spielmanii ospA-specific conventional PCR was also highly specific and showed no cross reactions with the other tested Borrelia species. From 1000 hanoveranian ticks 24.3% were positive compared to only 7.4% positives by dark-field microscopy. Related to tick stage 1.7% larvae, 18.1% nymphs, and 34.6% adults were positive. The most frequent species was B. garinii, followed by B. afzelii, B. spielmanii, B. valaisiana and B. burgdorferi sensu stricto (ss. 70.6% of I. ricinus were mono-infected, whereas 28.0% and 1.4% were infected with two and three Borrelia species, respectively. From 232 I. hexagonus collected from hedgehogs in different sites of Germany, qPCR detected 5.7% to be infected with B. burgdorferi sl, which were identified as B. afzelii, B. garinii and B. spielmanii. Conclusions The evaluated qPCR to detect B. burgdorferi sl in Ixodes spp. is highly specific and sensitive. As a duplex qPCR including detection of Ixodes spp. DNA it is the first DNA based technique incorporating a control for successful DNA isolation from

  11. Tick Thioester-Containing Proteins and Phagocytosis Do Not Affect Transmission of Borrelia afzelii from the Competent Vector Ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Urbanová, V.; Hajdušek, O.; Hönig Mondeková, Helena; Šíma, R.; Kopáček, P.

    2017-01-01

    Roč. 7, MAR 16 (2017), s. 1-16, č. článku 73. ISSN 2235-2988 Institutional support: RVO:61388971 Keywords : Borrelia * complement * phagocytosis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.300, year: 2016

  12. Seroprevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus in zoo animal species in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Širmarová, J.; Tichá, L.; Golovchenko, Maryna; Salát, Jiří; Grubhoffer, L.; Rudenko, Natalia; Nowotny, N.; Růžek, Daniel

    2014-01-01

    Roč. 5, č. 5 (2014), s. 523-527 ISSN 1877-959X R&D Projects: GA ČR GAP502/11/2116 Institutional support: RVO:60077344 Keywords : Tick-borne encephalitis virus * Borrelia burgdorferi sensu lato * Lyme borreliosis * Seroprevalence * Zoo animals Subject RIV: EE - Microbiology, Virology Impact factor: 2.718, year: 2014

  13. Isolation, cultivation and identification of Borrelia burgdorferi genospecies from Ixodes ricinus ticks from the city of Brno, Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Pejchalová, K.; Žákovská, A.; Mejzlíková, M.; Halouzka, Jiří; Dendis, M.

    2007-01-01

    Roč. 14, č. 1 (2007), s. 75-79 ISSN 1232-1966 Institutional research plan: CEZ:AV0Z60930519 Keywords : Borrelia burgdorferi * cultivation * DFM method * Ixodes ricinus * Lyme Subject RIV: EE - Microbiology, Virology Impact factor: 1.074, year: 2007 http://www.aaem.pl/pdf/1475.pdf

  14. Borrelia-induced cytokine production is mediated by spleen tyrosine kinase (Syk) but is Dectin-1 and Dectin-2 independent

    NARCIS (Netherlands)

    Oosting, M.; Buffen, K.; Cheng, S.C.; Verschueren, I.C.; Koentgen, F.; Veerdonk, F.L. van de; Netea, M.G.; Joosten, L.A.B.

    2015-01-01

    Although it is known that Borrelia species express sugar-like structures on their outer surface, not much is known about the role of these structures in immune recognition by host cells. Fungi, like Candida albicans, are mainly recognized by C-type lectin receptors, in specific Dectin-1 and

  15. A tick gut protein with fibronectin III domains aids Borrelia burgdorferi congregation to the gut during transmission

    NARCIS (Netherlands)

    Narasimhan, Sukanya; Coumou, Jeroen; Schuijt, Tim J.; Boder, Eric; Hovius, Joppe W.; Fikrig, Erol

    2014-01-01

    Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized

  16. First detection of Borrelia burgdorferi sensu lato DNA in king penguins (Aptenodytes patagonicus halli).

    Science.gov (United States)

    Schramm, Frédéric; Gauthier-Clerc, Michel; Fournier, Jean-Charles; McCoy, Karen D; Barthel, Cathy; Postic, Danièle; Handrich, Yves; Le Maho, Yvon; Jaulhac, Benoît

    2014-10-01

    The hard tick Ixodes uriae parasitises a wide range of seabird species in the circumpolar areas of both Northern and Southern hemispheres and has been shown to be infected with Borrelia burgdorferi sensu lato, the bacterial agents of Lyme borreliosis. Although it is assumed that seabirds represent viable reservoir hosts, direct demonstrations of infection are limited to a single study from the Northern hemisphere. Here, the blood of 50 tick-infested adult king penguins (Aptenodytes patagonicus halli) breeding in the Crozet Archipelago (Southern Indian Ocean) was examined for B. burgdorferi sl exposure by serology and for spirochetemia by in vitro DNA amplification. Four birds were found positive by serology, whereas B. burgdorferi sl DNA was detected in two other birds. Our data therefore provide the first direct proof of Borrelia burgdorferi sl spirochetes in seabirds of the Southern hemisphere and indicate a possible reservoir role for king penguins in the natural maintenance of this bacterium. Although the bacterial genetic diversity present in these hosts and the infectious period for tick vectors remain to be elucidated, our results add to a growing body of knowledge on the contribution of seabirds to the complex epizootiology of Lyme disease and the global dissemination of B. burgdorferi sl spirochetes. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme disease group spirochete Borrelia bissettii.

    Science.gov (United States)

    Lane, R S; Mun, J; Eisen, L; Eisen, R J

    2006-08-01

    The western fence lizard, Sceloporus occidentalis, is refractory to experimental infection with Borrelia burgdorferi sensu stricto, one of several Lyme disease spirochetes pathogenic for humans. Another member of the Lyme disease spirochete complex, Borrelia bissettii, is distributed widely throughout North America and a similar, if not identical, spirochete has been implicated as a human pathogen in southern Europe. To determine the susceptibility of S. occidentalis to B. bissettii, 6 naïve lizards were exposed to the feeding activities of Ixodes pacificus nymphs experimentally infected with this spirochete. None of the lizards developed spirochetemias detectable by polymerase chain reaction for up to 8 wk post-tick feeding, infected nymphs apparently lost their B. bissettii infections within 1-2 wk after engorgement, and xenodiagnostic L. pacificus larvae that co-fed alongside infected nymphs did not acquire and maintain spirochetes. In contrast, 3 of 4 naïve deer mice (Peromyscus maniculatus) exposed similarly to feeding by 1 or more B. bissettii-infected nymphs developed patent infections within 4 wk. These and previous findings suggest that the complement system of S. occidentalis typically destroys B. burgdorferi sensu lato spirochetes present in tissues of attached and feeding I. pacificus nymphs, thereby potentially reducing the probability of transmission of these bacteria to humans or other animals by the resultant adult ticks.

  18. Seroprevalence against Rickettsia and Borrelia Species in Patients with Uveitis: A Prospective Survey

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    Kim B. Madsen

    2017-01-01

    Full Text Available Vector-borne diseases such as Lyme borreliosis and rickettsioses have been associated with ocular inflammation. Our aim was to study patients with diagnosed uveitis to evaluate serological signs of infection or exposure to these tick-borne agents. Forty-eight patients were prospectively examined with serology together with medical records and a questionnaire concerning previous exposure, diseases, and treatments. Seven patients (14.6% showed seroconversion to Rickettsia spp. between acute and convalescent phase sera, which provides support for a positive Rickettsia diagnosis according to guidelines. The specificity was confirmed by Western blot. Additional 28 patients had stationary titres of which eight (16.6% had 1 : 256 or higher titre in the first serum, and another 13 patients were seronegative. No epidemiological risk factor or marker could be identified. For Borrelia, only three patients showed moderate IgG titres. A control group of 100 blood donors, 60 patients with rheumatic disease, and 56 patients seeking medical care were tested of which 2.0–7.1% showed low anti-Rickettsia titres and 3.0–8.3% anti-Borrelia titres. The findings are indicative for an association between infection or exposure to Rickettsia spp. and uveitis with a seropositivity among patients with recurrent uveitis in concordance with the spread of rickettsial exposure in a tick-exposed population.

  19. Seroprevalence against Rickettsia and Borrelia Species in Patients with Uveitis: A Prospective Survey

    Science.gov (United States)

    Madsen, Kim B.; Wallménius, Katarina; Fridman, Åke; Påhlson, Carl

    2017-01-01

    Vector-borne diseases such as Lyme borreliosis and rickettsioses have been associated with ocular inflammation. Our aim was to study patients with diagnosed uveitis to evaluate serological signs of infection or exposure to these tick-borne agents. Forty-eight patients were prospectively examined with serology together with medical records and a questionnaire concerning previous exposure, diseases, and treatments. Seven patients (14.6%) showed seroconversion to Rickettsia spp. between acute and convalescent phase sera, which provides support for a positive Rickettsia diagnosis according to guidelines. The specificity was confirmed by Western blot. Additional 28 patients had stationary titres of which eight (16.6%) had 1 : 256 or higher titre in the first serum, and another 13 patients were seronegative. No epidemiological risk factor or marker could be identified. For Borrelia, only three patients showed moderate IgG titres. A control group of 100 blood donors, 60 patients with rheumatic disease, and 56 patients seeking medical care were tested of which 2.0–7.1% showed low anti-Rickettsia titres and 3.0–8.3% anti-Borrelia titres. The findings are indicative for an association between infection or exposure to Rickettsia spp. and uveitis with a seropositivity among patients with recurrent uveitis in concordance with the spread of rickettsial exposure in a tick-exposed population. PMID:29318041

  20. Positive IgG Western Blot for Borrelia burgdorferi in Colombia

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    Palacios Ricardo

    1999-01-01

    Full Text Available In order to evaluate the presence of specific IgG antibodies to Borrelia burgdorferi in patients with clinical manifestations associated with Lyme borreliosis in Cali, Colombia, 20 serum samples from patients with dermatologic signs, one cerebrospinal fluid (CSF sample from a patient with chronic neurologic and arthritic manifestations, and twelve serum samples from individuals without clinical signs associated with Lyme borreliosis were analyzed by IgG Western blot. The results were interpreted following the recommendations of the Centers for Diseases Control and Prevention (CDC for IgG Western blots. Four samples fulfilled the CDC criteria: two serum specimens from patients with morphea (localized scleroderma, the CSF from the patient with neurologic and arthritic manifestations, and one of the controls. Interpretation of positive serology for Lyme disease in non-endemic countries must be cautious. However these results suggest that the putative "Lyme-like" disease may correlate with positivity on Western blots, thus raising the possibility that a spirochete genospecies distinct from B. burgdorferi sensu stricto, or a Borrelia species other than B. burgdorferi sensu lato is the causative agent. Future work will focus on a survey of the local tick and rodent population for evidence of spirochete species that could be incriminated as the etiologic agent.

  1. Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in northern spotted owl

    Science.gov (United States)

    Thomas, N.J.; Bunikis, J.; Barbour, A.G.; Wolcott, M.J.

    2002-01-01

    Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.

  2. Survey of Borreliae in ticks, canines, and white-tailed deer from Arkansas, U.S.A.

    Directory of Open Access Journals (Sweden)

    Fryxell Rebecca T

    2012-07-01

    Full Text Available Abstract Background In the Eastern and Upper Midwestern regions of North America, Ixodes scapularis (L. is the most abundant tick species encountered by humans and the primary vector of B. burgdorferi, whereas in the southeastern region Amblyomma americanum (Say is the most abundant tick species encountered by humans but cannot transmit B. burgdorferi. Surveys of Borreliae in ticks have been conducted in the southeastern United States and often these surveys identify B. lonestari as the primary Borrelia species, surveys have not included Arkansas ticks, canines, or white-tailed deer and B. lonestari is not considered pathogenic. The objective of this study was to identify Borrelia species within Arkansas by screening ticks (n = 2123, canines (n = 173, and white-tailed deer (n = 228 to determine the identity and locations of Borreliae endemic to Arkansas using PCR amplification of the flagellin (flaB gene. Methods Field collected ticks from canines and from hunter-killed white-tailed were identified to species and life stage. After which, ticks and their hosts were screened for the presence of Borrelia using PCR to amplify the flaB gene. A subset of the positive samples was confirmed with bidirectional sequencing. Results In total 53 (21.2% white-tailed deer, ten (6% canines, and 583 (27.5% Ixodid ticks (252 Ixodes scapularis, 161 A. americanum, 88 Rhipicephalus sanguineus, 50 Amblyomma maculatum, 19 Dermacentor variabilis, and 13 unidentified Amblyomma species produced a Borrelia flaB amplicon. Of the positive ticks, 324 (22.7% were collected from canines (151 A. americanum, 78 R. sanguineus, 43 I. scapularis, 26 A. maculatum, 18 D. variabilis, and 8 Amblyomma species and 259 (37.2% were collected from white-tailed deer (209 I. scapularis, 24 A. maculatum, 10 A. americanum, 10 R. sanguineus, 1 D. variabilis, and 5 Amblyomma species. None of the larvae were PCR positive. A majority of the flaB amplicons were homologous with B

  3. The duplicated B-class heterodimer model: whorl-specific effects and complex genetic interactions in Petunia hybrida flower development.

    Science.gov (United States)

    Vandenbussche, Michiel; Zethof, Jan; Royaert, Stefan; Weterings, Koen; Gerats, Tom

    2004-03-01

    In both Antirrhinum (Antirrhinum majus) and Arabidopsis (Arabidopsis thaliana), the floral B-function, which specifies petal and stamen development, is embedded in a heterodimer consisting of one DEFICIENS (DEF)/APETALA3 (AP3)-like and one GLOBOSA (GLO)/PISTILLATA (PI)-like MADS box protein. Here, we demonstrate that gene duplications in both the DEF/AP3 and GLO/PI lineages in Petunia hybrida (petunia) have led to a functional diversification of their respective members, which is reflected by partner specificity and whorl-specific functions among these proteins. Previously, it has been shown that mutations in PhDEF (formerly known as GREEN PETALS) only affect petal development. We have isolated insertion alleles for PhGLO1 (FLORAL BINDING PROTEIN1) and PhGLO2 (PETUNIA MADS BOX GENE2) and demonstrate unique and redundant properties of PhDEF, PhGLO1, and PhGLO2. Besides a full homeotic conversion of petals to sepals and of stamens to carpels as observed in phglo1 phglo2 and phdef phglo2 flowers, we found that gene dosage effects for several mutant combinations cause qualitative and quantitative changes in whorl 2 and 3 meristem fate, and we show that the PHDEF/PHGLO1 heterodimer controls the fusion of the stamen filaments with the petal tube. Nevertheless, when the activity of PhDEF, PhGLO1, and PhGLO2 are considered jointly, they basically appear to function as DEF/GLO does in Antirrhinum and to a lesser extent as AP3/PI in Arabidopsis. By contrast, our data suggest that the function of the fourth B-class MADS box member, the paleoAP3-type PETUNIA HYBRIDA TM6 (PhTM6) gene, differs significantly from the known euAP3-type DEF/AP3-like proteins; PhTM6 is mainly expressed in the developing stamens and ovary of wild-type flowers, whereas its expression level is upregulated in whorls 1 and 2 of an A-function floral mutant; PhTM6 is most likely not involved in petal development. The latter is consistent with the hypothesis that the evolutionary origin of the higher eudicot

  4. Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

    Science.gov (United States)

    Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

    2016-01-01

    Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID:27412403

  5. Two-Step Hydrothermal Synthesis of Bifunctional Hematite-Silver Heterodimer Nanoparticles for Potential Antibacterial and Anticancer Applications

    Science.gov (United States)

    Trang, Vu Thi; Tam, Le Thi; Phan, Vu Ngoc; Van Quy, Nguyen; Huy, Tran Quang; Le, Anh-Tuan

    2017-06-01

    In recent years, the development of composite nanostructures containing noble metal and magnetic nanocrystals has attracted much interest because they offer a promising avenue for multifunctional applications in nanomedicine and pharmacotherapy. In this work, we present a facile two-step hydrothermal approach for the synthesis of bifunctional heterodimer nanoparticles (HDNPs) composed of hematite nanocubes (α-Fe2O3 NCs) and silver nanoparticles (Ag-NPs). The formation and magnetic property of α-Fe2O3-Ag HDNPs was analyzed by transmission electron microscopy, x-ray diffraction and vibrating sample magnetometer. Interestingly, the hydrothermal-synthesized α-Fe2O3-Ag HDNPs were found to display significant antibacterial activity against three types of infectious bacteria. The cytotoxicity of α-Fe2O3-Ag nanocomposite against lung cancer A549 cell line was investigated and compared with that of pure α-Fe2O3 NCs and Ag-NPs. The obtained results reveal that the α-Fe2O3-Ag nanocomposite exhibited higher anticancer performance than that of pure Ag-NPs, whereas pure α-Fe2O3 NCs were not cytotoxic to the tested cells. The inhibitory concentration (IC50) of the α-Fe2O3-Ag nanocomposite was found at 20.94 μg/mL. With the aforementioned properties, α-Fe2O3-Ag HDNPs showed a high potential as a multifunctional material for advanced biomedicine and nanotherapy applications.

  6. Structure of the Human Atg13-Atg101 HORMA Heterodimer: an Interaction Hub within the ULK1 Complex.

    Science.gov (United States)

    Qi, Shiqian; Kim, Do Jin; Stjepanovic, Goran; Hurley, James H

    2015-10-06

    The ULK1 complex, consisting of the ULK1 protein kinase itself, FIP200, Atg13, and Atg101, controls the initiation of autophagy in animals. We determined the structure of the complex of the human Atg13 HORMA (Hop1, Rev7, Mad2) domain in complex with the full-length HORMA domain-only protein Atg101. The two HORMA domains assemble with an architecture conserved in the Mad2 conformational heterodimer and the S. pombe Atg13-Atg101 HORMA complex. The WF finger motif that is essential for function in human Atg101 is sequestered in a hydrophobic pocket, suggesting that the exposure of this motif is regulated. Benzamidine molecules from the crystallization solution mark two hydrophobic pockets that are conserved in, and unique to, animals, and are suggestive of sites that could interact with other proteins. These features suggest that the activity of the animal Atg13-Atg101 subcomplex is regulated and that it is an interaction hub for multiple partners. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effects of coating molecules on the magnetic heating properties of Au-Fe3O4 heterodimer nanoparticles

    Science.gov (United States)

    Yamamoto, Y.; Ogasawara, J.; Himukai, H.; Itoh, T.

    2016-10-01

    In this paper, we report the heating properties of gold-magnetite (Au-Fe3O4) heterodimer nanoparticles (NPs) subjected to an alternating magnetic field. The Au-Fe3O4 NPs coated with oleic acid and oleylamine (OA) were synthesized through a method that combines seed mediation and high-temperature decomposition. The coating was replaced with dimercaptosuccinic acid (DMSA) by the ligand-exchange method. The specific absorption rates (SARs) for the OA- and DMSA-coated Au-Fe3O4 NPs coated with OA and DMSA at room temperature were determined through the calorimetric and magnetometric methods. SAR depended on the square of the magnetic field H up to an H value of 4 kA/m. The absolute value of the SAR for DMSA-coated NPs is about fivefold higher than that of the OA-coated NPs. The AC magnetic hysteresis measurements showed the recovery of the magnetic volume and the decrease in the magnetic anisotropy of the DMSA-coated NPs relative to those of the OA-coated NPs. These results suggest that the protective agent influences the magnetic properties of magnetite NPs via gold NPs.

  8. Polymorphism of 41 kD Flagellin Gene and Its Human B-Cell Epitope in Borrelia burgdorferi Strains of China

    Directory of Open Access Journals (Sweden)

    Huixin Liu

    2016-01-01

    Full Text Available The 41 kD flagellin of Borrelia burgdorferi (B. burgdorferi is a major component of periplasmic flagellar filament core and a good candidate for serodiagnosis in early stage of Lyme disease. Here, we chose 89 B. burgdorferi strains in China, amplified the gene encoding the 41 kD flagellin, and compared the sequences. The results showed that genetic diversity presented in the 41 kD flagellin genes of all 89 strains among the four genotypes of B. burgdorferi, especially in the genotype of B. garinii. Some specific mutation sites for each genotype of the 41 kD flagellin genes were found, which could be used for genotyping B. burgdorferi strains in China. Human B-cell epitope analysis showed that thirteen of 15 nonsynonymous mutations occurred in the epitope region of 41 kD flagellin and thirty of 42 B-cell epitopes were altered due to all 13 nonsynonymous mutations in the epitope region, which may affect the function of the antigen. Nonsynonymous mutations and changed human B-cell epitopes exist in 41 kD flagellin of B. burgdorferi sensu lato strains; these changes should be considered in serodiagnosis of Lyme disease.

  9. Automated purification of Borrelia burgdorferi s.l. PCR products with KingFisherTM magnetic particle processor prior to genome sequencing

    International Nuclear Information System (INIS)

    Maekinen, Johanna; Marttila, Harri; Viljanen, Matti K.

    2001-01-01

    Borrelia burgdorferi sensu lato genospecies were differentiated by PCR-based sequencing of the borrelial flagellin gene. To evaluate the usefulness of KingFisher TM magnetic particle processor in PCR product purification, borrelia PCR products were purified with KingFisher TM magnetic particle processor prior to cycle sequencing and the quality of the sequence data received was analyzed. KingFisher was found to offer a rapid and reliable alternative for borrelial PCR product purification

  10. Abundance of Ixodes ricinus and prevalence of Borrelia burgdorferi s.l. in the nature reserve Siebengebirge, Germany, in comparison to three former studies from 1978 onwards

    Czech Academy of Sciences Publication Activity Database

    Schwarz, Alexandra; Hönig, Václav; Vavrušková, Zuzana; Grubhoffer, Libor; Balczun, C.; Albring, A.; Schaub, G. A.

    2012-01-01

    Roč. 5, NOV 21 (2012) ISSN 1756-3305 R&D Projects: GA ČR GD206/09/H026; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Ixodes ricinus * Tick density * Borrelia prevalence * Borrelia lusitaniae * Multiple infections * Siebengebirge Subject RIV: EC - Immunology Impact factor: 3.246, year: 2012 http://www.parasitesandvectors.com/content/5/1/268

  11. Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor.

    Science.gov (United States)

    Thompson, P D; Hsieh, J C; Whitfield, G K; Haussler, C A; Jurutka, P W; Galligan, M A; Tillman, J B; Spindler, S R; Haussler, M R

    1999-12-01

    The vitamin D receptor (VDR) is a transcription factor believed to function as a heterodimer with the retinoid X receptor (RXR). However, it was reported [Schräder et al., 1994] that, on putative vitamin D response elements (VDREs) within the rat 9k and mouse 28k calcium binding protein genes (rCaBP 9k and mCaBP 28k), VDR and thyroid hormone receptor (TR) form heterodimers that transactivate in response to both 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and triiodothyronine (T(3)). We, therefore, examined associations of these receptors on the putative rCaBP 9k and mCaBP 28k VDREs, as well as on established VDREs from the rat osteocalcin (rOC) and mouse osteopontin (mOP) genes, plus the thyroid hormone response element (TRE) from the rat myosin heavy chain (rMHC) gene. In gel mobility shift assays, we found no evidence for VDR-TR heterodimer interaction with any tested element. Further, employing these hormone response elements linked to reporter genes in transfected cells, VDR and TR mediated responses to their cognate ligands only from the rOC/mOP and rMHC elements, respectively, while the CaBP elements were unresponsive to any combination of ligand(s). Utilizing the rOC and mOP VDREs, two distinct repressive actions of TR on VDR-mediated signaling were demonstrated: a T(3)-independent action, presumably via direct TR-RXR competition for DNA binding, and a T(3)-dependent repression, likely by diversion of limiting RXR from VDR-RXR toward the formation of TR-RXR heterodimers. The relative importance of these two mechanisms differed in a response element-specific manner. These results may provide a partial explanation for the observed association between hyperthyroidism and bone demineralization/osteoporosis. Copyright 1999 Wiley-Liss, Inc.

  12. Absence of sodA Increases the Levels of Oxidation of Key Metabolic Determinants of Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Maria D Esteve-Gassent

    Full Text Available Borrelia burgdorferi, the causative agent of Lyme disease, alters its gene expression in response to environmental signals unique to its tick vector or vertebrate hosts. B. burgdorferi carries one superoxide dismutase gene (sodA capable of controlling intracellular superoxide levels. Previously, sodA was shown to be essential for infection of B. burgdorferi in the C3H/HeN model of Lyme disease. We employed two-dimensional electrophoresis (2-DE and immunoblot analysis with antibodies specific to carbonylated proteins to identify targets that were differentially oxidized in the soluble fractions of the sodA mutant compared to its isogenic parental control strain following treatment with an endogenous superoxide generator, methyl viologen (MV, paraquat. HPLC-ESI-MS/MS analysis of oxidized proteins revealed that several proteins of the glycolytic pathway (BB0057, BB0020, BB0348 exhibited increased carbonylation in the sodA mutant treated with MV. Levels of ATP and NAD/NADH were reduced in the sodA mutant compared with the parental strain following treatment with MV and could be attributed to increased levels of oxidation of proteins of the glycolytic pathway. In addition, a chaperone, HtpG (BB0560, and outer surface protein A (OspA, BBA15 were also observed to be oxidized in the sodA mutant. Immunoblot analysis revealed reduced levels of Outer surface protein C (OspC, Decorin binding protein A (DbpA, fibronectin binding protein (BBK32, RpoS and BosR in the sodA mutant compared to the control strains. Viable sodA mutant spirochetes could not be recovered from both gp91/phox-⁄- and iNOS deficient mice while borrelial DNA was detected in multiple tissues samples from infected mice at significantly lower levels compared to the parental strain. Taken together, these observations indicate that the increased oxidation of select borrelial determinants and reduced levels of critical pathogenesis-associated lipoproteins contribute to the in vivo deficit of

  13. Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins

    DEFF Research Database (Denmark)

    Koetsveld, J.; Kolyasnikova, N. M.; Wagemakers, A.

    2018-01-01

    previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls. Methods: We assessed seroreactivity against GlpQ and four Vmps in a well-described, longitudinal......, and IgG between 21 and 50 days, after disease onset. Various combinations of GlpQ and Vmps increased sensitivity and/or specificity compared to single antigens. Notably, the GlpQ or variable large protein (Vlp)-15/16 combination yielded a sensitivity of 94.7% (95% CI: 75.4–99.7) 11–20 days after disease......Objectives: Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) has been performed experimentally but has not been extensively clinically validated. Because we had...

  14. Borrelia miyamotoi, Other Vector-Borne Agents in Cat Blood and Ticks in Eastern Maryland.

    Science.gov (United States)

    Shannon, Avery B; Rucinsky, Renee; Gaff, Holly D; Brinkerhoff, R Jory

    2017-12-01

    We collected blood and tick samples in eastern Maryland to quantify vector-borne pathogen exposure and infection in healthy cats and to assess occupational disease risk to veterinary professionals and others who regularly interact with household pets. Thirty-six percent of healthy cats parasitized by ticks at time of examination (9/25) were exposed to, and 14% of bloods (7/49) tested PCR-positive for, at least one vector-borne pathogen including several bloods and ticks with Borrelia miyamotoi, a recently recognized tick-borne zoonotic bacterium. There was no indication that high tick burdens were associated with exposure to vector-borne pathogens. Our results underscore the potential importance of cats to human vector-borne disease risk.

  15. Increasing RpoS expression causes cell death in Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Linxu Chen

    Full Text Available RpoS, one of the two alternative σ factors in Borrelia burgdorferi, is tightly controlled by multiple regulators and, in turn, determines expression of many critical virulence factors. Here we show that increasing RpoS expression causes cell death. The immediate effect of increasing RpoS expression was to promote bacterial division and as a consequence result in a rapid increase in cell number before causing bacterial death. No DNA fragmentation or degradation was observed during this induced cell death. Cryo-electron microscopy showed induced cells first formed blebs, which were eventually released from dying cells. Apparently blebbing initiated cell disintegration leading to cell death. These findings led us to hypothesize that increasing RpoS expression triggers intracellular programs and/or pathways that cause spirochete death. The potential biological significance of induced cell death may help B. burgdorferi regulate its population to maintain its life cycle in nature.

  16. Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and studies on taxonomic classification

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette

    2002-01-01

    Lyme borreliosis caused by the spirochete Borrelia burgdorferi is now the most common vectorborne disease in North America, Europe and Asia. It is a multisystemic infection which may cause skin, neurological, cardiac or rheumatologic disorders. The aims of the present thesis were: (i) to develop...... and different clinical presentations (dermatoborreliosis versus neuroborreliosis) and courses (self-limiting versus chronic disease). Furthermore, strain differences were of importance for selection of suitable antigens for diagnostic assays and for vaccine development. Since then, B. burgdorferi isolates have...... a histological B. burgdorferi specific immunophosphatase-staining method. The utility of the PCR was then tested for identification of B. burgdorferi DNA in skin biopsies from 31 patients with erythema migrans. The sensitivity of PCR was 71%, which was superior to culture and serology. Based on own and otherwise...

  17. Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement

    Science.gov (United States)

    Gardner, R.B.; Madigan, J.E.; Witonsky, S.G.; Bertone, J.J.; Swinebroad, E.L.; Schutzer, S.E.; Johnson, A.L.

    2018-01-01

    Borrelia burgdorferi infection is common in horses living in Lyme endemic areas and the geographic range for exposure is increasing. Morbidity after B. burgdorferi infection in horses is unknown. Documented, naturally occurring syndromes attributed to B. burgdorferi infection in horses include neuroborreliosis, uveitis, and cutaneous pseudolymphoma. Although other clinical signs such as lameness and stiffness are reported in horses, these are often not well documented. Diagnosis of Lyme disease is based on exposure to B. burgdorferi, cytology or histopathology of infected fluid or tissue and antigen detection. Treatment of Lyme disease in horses is similar to treatment of humans or small animals but treatment success might not be the same because of species differences in antimicrobial bioavailability and duration of infection before initiation of treatment. There are no approved equine label Lyme vaccines but there is strong evidence that proper vaccination could prevent infection in horses. PMID:29469222

  18. Borrelia burgdorferi antibodies in dogs from Cotia county, São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    JOPPERT Adriana Marques

    2001-01-01

    Full Text Available Dogs sera samples collected from Cotia County, São Paulo were tested using indirect immunoenzymatic test (ELISA in order to study Lyme disease serology in dogs. ELISA method was standardized and G39/40 North American strain of Borrelia burgdorferi was used as antigen. Positive results were confirmed employing the Western blotting technique. Because of the possibility of cross-reactions, sera were also tested for different serological strains of Leptospira interrogans and L. biflexa using microscopic sera agglutination test. Twenty-three of 237 (9.7% serum samples were positive in the ELISA; 20 of them (86.9% were confirmed by the Western blotting, what suggests that Cotia may be a risk area for Lyme disease. Although 4 samples (1.7% were positive for Lyme disease and leptospirosis, no correlation was found between the results (X² = 0.725; p = 0.394 what suggests absence of serological cross reactivity.

  19. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    Energy Technology Data Exchange (ETDEWEB)

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  20. Complement-mediated killing of Borrelia burgdorferi by nonimmune sera from sika deer.

    Science.gov (United States)

    Nelson, D R; Rooney, S; Miller, N J; Mather, T N

    2000-12-01

    Various species of cervid deer are the preferred hosts for adult, black-legged ticks (Ixodes scapularis and Ixodes pacificus) in the United States. Although frequently exposed to the agent of Lyme disease (Borrelia burgdorferi), these animals, for the most part, are incompetent as transmission reservoirs. We examined the borreliacidal activity of normal and B. burgdorferi-immune sera from sika deer (Cervus nippon) maintained in a laboratory setting and compared it to that of similar sera from reservoir-competent mice and rabbits. All normal deer sera (NDS) tested killed > 90% of B. burgdorferi cells. In contrast, normal mouse and rabbit sera killed feeding exhibited IFA titers of 1:256, whereas sera from mice and rabbits similarly exposed had titers of > 1:1,024. Heat treatment (56 C, 30 min) of NDS reduced borreliacidal activity, with complement-mediated killing. The chelators EGTA and EDTA were used to block the classical or both the classical and alternative complement pathways, respectively. Addition of 10 mM EGTA to NDS had a negligible effect on borreliacidal activity, with > 90% of the cells killed. Addition of 10 mM EDTA reduced the killing to approximately 30%, whereas the addition of Mg2+ (10 mM) restored borreliacidal activity to NDS. The addition of zymosan A, an activator of the alternative pathway, increased the survival of B. burgdorferi cells to approximately 80% in NDS. These data suggest that the alternative complement activation pathway plays a major role in the borreliacidal activity of NDS. Additionally, 10 mM EGTA had almost no effect on the killing activity of B. burgdorferi-exposed deer sera, suggesting that the classical pathway is not involved in Borrelia killing, even in sera from B. burgdorferi-exposed deer.

  1. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement.

    Science.gov (United States)

    Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J; Oei, Anneke; Nijhof, Ard M; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D; Hovius, Joppe W R

    2016-04-01

    We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI. We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro. We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing. We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.

  2. Stable Transmission of Borrelia burgdorferi Sensu Stricto on the Outer Banks of North Carolina.

    Science.gov (United States)

    Levine, J F; Apperson, C S; Levin, M; Kelly, T R; Kakumanu, M L; Ponnusamy, L; Sutton, H; Salger, S A; Caldwell, J M; Szempruch, A J

    2017-08-01

    The spirochaete (Borrelia burgdorferi) associated with Lyme disease was detected in questing ticks and rodents during a period of 18 years, 1991-2009, at five locations on the Outer Banks of North Carolina. The black-legged tick (Ixodes scapularis) was collected at varied intervals between 1991 and 2009 and examined for B. burgdorferi. The white-footed mouse (Peromyscus leucopus), house mouse (Mus musculus) marsh rice rat (Oryzomys palustris), marsh rabbit (Sylvilagus palustris), eastern cottontail (Sylvilagus floridanus) and six-lined racerunner (Cnemidophorus sexlineatus) were live-trapped, and their tissues cultured to isolate spirochaetes. Borrelia burgdorferi isolates were obtained from questing adult I. scapularis and engorged I. scapularis removed from P. leucopus, O. palustris and S. floridanus. The prevalence of B. burgdorferi infection was variable at different times and sites ranging from 7 to 14% of examined questing I. scapularis. Mitochondrial (16S) rRNA gene phylogenetic analysis from 65 adult I. scapularis identified 12 haplotypes in two major clades. Nine haplotypes were associated with northern/Midwestern I. scapularis populations and three with southern I. scapularis populations. Sixteen isolates obtained from tick hosts in 2005 were confirmed to be B. burgdorferi by amplifying and sequencing of 16S rRNA and 5S-23S intergenic spacer fragments. The sequences had 98-99% identity to B. burgdorferi sensu stricto strains B31, JD1 and M11p. Taken together, these studies indicate that B. burgdorferi sensu stricto is endemic in questing I. scapularis and mammalian tick hosts on the Outer Banks of North Carolina. © 2016 Blackwell Verlag GmbH.

  3. Crystal structure of the disintegrin heterodimer from saw-scaled viper (Echis carinatus) at 1.9 A resolution.

    Science.gov (United States)

    Bilgrami, Sameeta; Yadav, Savita; Kaur, Punit; Sharma, Sujata; Perbandt, Markus; Betzel, Christian; Singh, Tej P

    2005-08-23

    Disintegrins constitute a family of potent polypeptide inhibitors of integrins. Integrins are transmembrane heterodimeric molecules involved in cell-cell and cell-extracellular matrix interactions. They are involved in many diseases such as cancer and thrombosis. Thus, disintegrins have a great potential as anticancer and antithrombotic agents. A novel heterodimeric disintegrin was isolated from the venom of saw-scaled viper (Echis carinatus) and was crystallized. The crystals diffracted to 1.9 A resolution and belonged to space group P4(3)2(1)2. The data indicated the presence of a pseudosymmetry. The structure was solved by applying origin shifts to the disintegrin homodimer schistatin solved in space group I4(1)22 with similar cell dimensions. The structure refined to the final R(cryst)/R(free) factors of 0.213/0.253. The notable differences are observed between the loops, (Gln39-Asp48) containing the important Arg42-Gly43-Asp44, of the present heterodimer and schistatin. These differences are presumably due to the presence of two glycines at positions 43 and 46 that allow the molecule to adopt variable conformations. A comparative analysis of the surface-charge distributions of various disintegrins showed that the charge distribution on monomeric disintegrins occurred uniformly over the whole surface of the molecule, while in the dimeric disintegrins, the charge is distributed only on one face. Such a feature may be important in the binding of two integrins to a single dimeric disintegrin. The phylogenetic analysis developed on the basis of amino acid sequence and three-dimensional structures indicates that the protein diversification and evolution presumably took place from the medium disintegrins and both the dimeric and short disintegrins evolved from them.

  4. Small heterodimer partner (SHP deficiency protects myocardia from lipid accumulation in high fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    Full Text Available The small heterodimer partner (SHP regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO mice compared to those of wild-type (WT mice (nominal p value < 0.05. Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093. After 12 weeks of high fat diet (HFD, SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPARγ1 and PPARα were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.

  5. Detection of Lyme Disease Bacterium, Borrelia burgdorferi sensu lato, in Blacklegged Ticks Collected in the Grand River Valley, Ontario, Canada

    Science.gov (United States)

    Scott, John D.; Foley, Janet E.; Anderson, John F.; Clark, Kerry L.; Durden, Lance A.

    2017-01-01

    We document the presence of blacklegged ticks, Ixodes scapularis, in the Grand River valley, Centre Wellington, Ontario. Overall, 15 (36%) of 42 I. scapularis adults collected from 41 mammalian hosts (dogs, cats, humans) were positive for the Lyme disease bacterium, Borrelia burgdorferi sensu lato (s.l.). Using real-time PCR testing and DNA sequencing of the flagellin (fla) gene, we determined that Borrelia amplicons extracted from I. scapularis adults belonged to B. burgdorferi sensu stricto (s.s.), which is pathogenic to humans and certain domestic animals. Based on the distribution of I. scapularis adults within the river basin, it appears likely that migratory birds provide an annual influx of I. scapularis immatures during northward spring migration. Health-care providers need to be aware that local residents can present with Lyme disease symptoms anytime during the year. PMID:28260991

  6. Cinética do crescimento de Borrelia burgdorferi (Spirochaetaceae em diferentes meios de cultivo Cinetic growth of Borrelia burgdorferi (Spirochaetacease in different culture media

    Directory of Open Access Journals (Sweden)

    Angela de Oliveira

    2004-06-01

    Full Text Available Estudou-se a cinética de crescimento de Borrelia burgdorferi, por um período de 3 meses, utilizando os seguintes oito meios de cultivo : (1 BSK adicionado de soro de coelho, (2 BSK adicionado de soro de suíno, (3 BSK adicionado de soro de suíno + 5 fluorouracil, (4 PMR, (5 CTB, (6 Dubos, (7 Caldo Brucella e (8 BHI. Todos os meios foram preparados assepticamente e mantidos em tubos de ensaio com capacidade para 10 ml. Para cada meio, o inoculo foi padronizado para conter no início 10² espiroquetas para cada 0,1 ml de cultivo. O monitoramento do crescimento foi feito contando-se o total de espiroquetas em 0,1 ml do meio entre lâmina de microscopia e lamínula com dimen sões de 10x30mm, tendo sido utilizado microscópio de campo escuro. A contagem foi realizada durante 14 semanas, tendo sido diária nos primeiros 12 dias e semanal a partir desta data. Houve crescimento de B. burgdorferi em todos meios testados, com melhor performance para três deles: BSK adicionado de soro de coelho, BSK adicionado de soro de suíno + 5 fluorouracil e meio CTB. Observou-se crescimento de B. burgdorferi a partir da 4ª semana, atingindo o platô de crescimento entre a 8ª e 12ª semanas, quando começou a exaustão do meio de cultivo. Formas císticas de B. burgdorferi foram observadas em todos os meios testados.The cinetic of growth of Borrelia burgdorferi was studied during a 3-month period, using the following 8 culture media: (1 rabbit serum BSK, (2 swine serum BSK, (3 swine serum BSK+5 fluorouracil, (4 PMR, (5 CTB, (6 Dubos, (7 Brucella broth and (8 BHI. All media were prepared aseptically and were maintained in culture tubes of 10 ml capacity. For each medium, the inoculum was standardized to contain initially 10² spirochetes for each 0.1 ml of culture. The growth was monitorized by counting the total number of spirochetes in 0.1ml of medium in a dark field microscope, using a 10x30 mm cover slip. For the first 12 days, counting was done each 24

  7. Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients.

    Science.gov (United States)

    Middelveen, Marianne J; Bandoski, Cheryl; Burke, Jennie; Sapi, Eva; Filush, Katherine R; Wang, Yean; Franco, Agustin; Mayne, Peter J; Stricker, Raphael B

    2015-02-12

    Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin. Previously, spirochetes have been detected in the dermatological specimens from four MD patients, thus providing evidence of an infectious process. Based on culture, histology, immunohistochemistry, electron microscopy and molecular testing, we present corroborating evidence of spirochetal infection in a larger group of 25 MD patients. Irrespective of Lyme serological reactivity, all patients in our study group demonstrated histological evidence of epithelial spirochetal infection. Strength of evidence based on other testing varied among patients. Spirochetes identified as Borrelia strains by polymerase chain reaction (PCR) and/or in-situ DNA hybridization were detected in 24/25 of our study patients. Skin cultures containing Borrelia spirochetes were obtained from four patients, thus demonstrating that the organisms present in dermatological specimens were viable. Spirochetes identified by PCR as Borrelia burgdorferi were cultured from blood in seven patients and from vaginal secretions in three patients, demonstrating systemic infection. Based on these observations, a clinical classification system for MD is proposed. Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.

  8. Effect of salivary gland extract from Ixodes ricinus ticks on the proliferation of Borrelia burgdorferi sensu stricto in vivo

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Martina; Oborník, Miroslav; Kopecký, Jan

    2006-01-01

    Roč. 53, č. 2 (2006), s. 153-158 ISSN 0015-5683 R&D Projects: GA ČR GA524/05/0811 Grant - others:Studentská grantová agentura, Biologická fakulta Jihočeské univerzity(CZ) SGA2004/009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi * Ixodes ricinus * saliva-activated transmission Subject RIV: EC - Immunology Impact factor: 1.511, year: 2006

  9. Effect of forest clearing on the abundance of Ixodes ricinus ticks and the prevalence of Borrelia burgdorferi s.l

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk; Halouzka, Jiří; Juřicová, Zina; Šikutová, Silvie; Rudolf, Ivo

    2006-01-01

    Roč. 20, č. 2 (2006), s. 166-172 ISSN 0269-283X R&D Projects: GA ČR GA206/03/0726 EU Projects: European Commission(XE) 10284 - EDEN Institutional research plan: CEZ:AV0Z60930519 Keywords : Ixodes ricinus * Borrelia burgdorferi sensu lato * Lyme borreliosis risk Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.033, year: 2006

  10. Salivary gland extract from engorged Ixodes ricinus (Acari: Ixodidae) stimulates in vitro growth of Borrelia burgdorferi sensu lato

    Czech Academy of Sciences Publication Activity Database

    Rudolf, Ivo; Šikutová, Silvie; Kopecký, Jan; Hubálek, Zdeněk

    2010-01-01

    Roč. 50, č. 3 (2010), s. 294-298 ISSN 0233-111X R&D Projects: GA ČR GA206/03/0726; GA AV ČR IAA600960811 Institutional research plan: CEZ:AV0Z60930519; CEZ:AV0Z60220518 Keywords : salivary gland extract * Ixodes ricinus ticks * Borrelia burgdorferi sensu lato Subject RIV: EE - Microbiology, Virology Impact factor: 1.395, year: 2010

  11. In vitro susceptibility of Borrelia burgdorferi isolates to three antibiotics commonly used for treating equine Lyme disease.

    Science.gov (United States)

    Caol, Sanjie; Divers, Thomas; Crisman, Mark; Chang, Yung-Fu

    2017-09-29

    Lyme disease in humans is predominantly treated with tetracycline, macrolides or beta lactam antibiotics that have low minimum inhibitory concentrations (MIC) against Borrelia burgdorferi. Horses with Lyme disease may require long-term treatment making frequent intravenous or intramuscular treatment difficult and when administered orally those drugs may have either a high incidence of side effects or have poor bioavailability. The aim of the present study was to determine the in vitro susceptibility of three B. burgdorferi isolates to three antibiotics of different classes that are commonly used in practice for treating Borrelia infections in horses. Broth microdilution assays were used to determine minimum inhibitory concentration of three antibiotics (ceftiofur sodium, minocycline and metronidazole), for three Borrelia burgdorferi isolates. Barbour-Stoner-Kelly (BSK K + R) medium with a final inoculum of 10 6 Borrelia cells/mL and incubation periods of 72 h were used in the determination of MICs. Observed MICs indicated that all isolates had similar susceptibility to each drug but susceptibility to the tested antimicrobial agents varied; ceftiofur sodium (MIC = 0.08 μg/ml), minocycline hydrochloride (MIC = 0.8 μg/ml) and metronidazole (MIC = 50 μg/ml). The MIC against B. burgorferi varied among the three antibiotics with ceftiofur having the lowest MIC and metronidazole the highest MIC. The MIC values observed for ceftiofur in the study fall within the range of reported serum and tissue concentrations for the drug metabolite following ceftiofur sodium administration as crystalline-free acid. Minocycline and metronidazole treatments, as currently used in equine practice, could fall short of attaining MIC concentrations for B. burgdorferi.

  12. Europe-Wide Meta-Analysis of Borrelia burgdorferi Sensu Lato Prevalence in Questing Ixodes ricinus Ticks

    Czech Academy of Sciences Publication Activity Database

    Strnad, Martin; Hönig, Václav; Růžek, Daniel; Grubhoffer, Libor; Rego, Ryan O. M.

    2017-01-01

    Roč. 83, č. 15 (2017), č. článku e00609-17. ISSN 0099-2240 EU Projects: European Commission(XE) 278976 - ANTIGONE; European Commission(XE) 602272 - ANTIDotE Institutional support: RVO:60077344 Keywords : Borrelia burgdorferi sensu lato * tick * Ixodes ricinus * genospecies * meta-analysis * Lyme borreliosis * Lyme disease Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.807, year: 2016

  13. Prevalence of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Ixodes scapularis (Acari: Ixodidae) adults in New Jersey, 2000-2001.

    Science.gov (United States)

    Schulze, Terry L; Jordan, Robert A; Hung, Robert W; Puelle, Rose S; Markowski, Daniel; Chomsky, Martin S

    2003-07-01

    Using polymerase chain reaction, we analyzed 529 Ixodes scapularis Say adults collected from 16 of New Jersey's 21 counties for the presence of Borrelia burgdorferi, the etiological agent of Lyme disease. Overall, 261 (49.3%) were positive. B. burgdorferi was detected in ticks obtained from each county and from 53 of the 58 (93.1%) municipalities surveyed. The observed statewide prevalence in New Jersey is similar to those reported from other northeastern and mid-Atlantic states.

  14. Comparison of MKP and BSK-H media for the cultivation and isolation of Borrelia burgdorferi sensu lato.

    Directory of Open Access Journals (Sweden)

    Eva Ružić-Sabljić

    Full Text Available The isolation of B. burgdorferi sensu lato requires the use of complex cultivation media. The aim of the study was to compare the usefulness of BSK-H (a commercial medium produced by HiMedia, India and MKP medium. MKP and BSK-H media were prepared in accordance with the relevant protocols. Borrelia strains and skin culture biopsies were simultaneously inoculated into both media, incubated and checked for growth. Borrelial growth characteristics, isolation rates and characteristics of the isolated borreliae were analysed and compared. Initially, numbers of spirochaetes were higher in BSK-H than in MKP; however, in comparison with MKP, the strains subcultured in BSK-H medium were more frequently irregular, thin and non-motile, and rapidly died. In addition, the borrelial isolation rate from erythema migrans skin samples was higher in MKP than in BSK-H medium (108/171, 63.2% versus 70/171, 40.9%; p<0.0001. The far most frequently isolated species was Borrelia afzelii (92.9% and 97.2% strains isolated from BSK-H and MKP, respectively. Comparison of strains cultured from individual patients in both media showed differences in plasmid contents in 9/46 (19.6% strain pairs, and protein profiles differed in 30/43 (69.8% strain pairs, most often in the expression of OspC (in 27/28 patients OspC was expressed only in strains growing in MKP. BSK-H medium supports the growth of borrelial strains but MKP is superior with regard to the isolation rate, morphology and motility of strains. BSK-H medium supports fast initial growth of borreliae but this is followed by rapid deformation and death of the spirochaetes.

  15. Effect of tick saliva on signalling pathways activated by TLR-2 ligand and Borrelia afzelii in dendritic cells

    Czech Academy of Sciences Publication Activity Database

    Lieskovská, Jaroslava; Kopecký, Jan

    2012-01-01

    Roč. 35, č. 8-9 (2012), s. 421-429 ISSN 0141-9838 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GAP302/12/2208 Institutional support: RVO:60077344 Keywords : Borrelia * dendritic cells * tick saliva * Toll-like receptor signalling Subject RIV: EC - Immunology Impact factor: 2.208, year: 2012 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3024.2012.01375.x/abstract

  16. Serological studies on the infection of dogs in Ontario with Borrelia burgdorferi, the etiological agent of Lyme disease

    OpenAIRE

    Artsob, Harvey; Barker, Ian K.; Fister, Richard; Sephton, Gregory; Dick, Daryl; Lynch, John A.; Key, Doug

    1993-01-01

    A serological study was undertaken to determine whether dogs in Ontario are being exposed to Borrelia burgdorferi, the etiological agent of Lyme disease. This study consisted of a survey of randomly selected dogs and testing of diagnostic submissions from candidate Lyme disease cases. The survey of 1,095 dogs, bled between January 1988 and August 1989, revealed a total of 65 (5.9%) enzyme-linked immunosorbent assay (ELISA) reactors, of which 22 had immuno-fluorescent antibody assay (IFA) tite...

  17. A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host.

    Science.gov (United States)

    Purser, Joye E; Lawrenz, Matthew B; Caimano, Melissa J; Howell, Jerrilyn K; Radolf, Justin D; Norris, Steven J

    2003-05-01

    Borrelia burgdorferi, a spirochaete that causes Lyme borreliosis, contains 21 linear and circular plasmids thought to be important for survival in mammals or ticks. Our results demonstrate that the gene BBE22 encoding a nicotinamidase is capable of replacing the requirement for the 25 kb linear plasmid lp25 during mammalian infection. Transformation of B. burgdorferi lacking lp25 with a shuttle vector containing the lp25 gene BBE22 (pBBE22) restored infectivity in mice to a level comparable to that of wild-type Borrelia. This complementation also restored the growth and host adaptation of lp25-B. burgdorferi in dialysis membrane chambers (DMCs) implanted in rats. A single Cys to Ala conversion at the putative active site of BBE22 abrogated the ability of pBBE22 to re-establish infectivity or growth in DMCs. Additional Salmonella typhimurium complementation studies and enzymatic analysis demonstrated that the BBE22 gene product has nicotinamidase activity and is most probably required for the biosynthesis of NAD. These results indicate that some plasmid-encoded products fulfil physiological functions required in the enzootic cycle of pathogenic Borrelia.

  18. Spatial clustering of Borrelia burgdorferi sensu lato within populations of Allen's chipmunks and dusky-footed woodrats in northwestern California.

    Science.gov (United States)

    Hacker, Gregory M; Brown, Richard N; Fedorova, Natalia; Girard, Yvette A; Higley, Mark; Clueit, Bernadette; Lane, Robert S

    2018-01-01

    The ecology of Lyme borreliosis is complex in northwestern California, with several potential reservoir hosts, tick vectors, and genospecies of Borrelia burgdorferi sensu lato. The primary objective of this study was to determine the fine-scale spatial distribution of different genospecies in four rodent species, the California ground squirrel (Otospermophilus beecheyi), northern flying squirrel (Glaucomys sabrinus), dusky-footed woodrat (Neotoma fuscipes), and Allen's chipmunk (Neotamias senex). Rodents were live-trapped between June 2004 and May 2005 at the Hoopa Valley Tribal Reservation (HVTR) in Humboldt County, California. Ear-punch biopsies obtained from each rodent were tested by polymerase chain reaction (PCR) and sequencing analysis. The programs ArcGIS and SaTScan were used to examine the spatial distribution of genospecies. Multinomial log-linear models were used to model habitat and host-specific characteristics and their effect on the presence of each borrelial genospecies. The Akaike information criterion (AICc) was used to compare models and determine model fit. Borrelia burgdorferi sensu stricto was primarily associated with chipmunks and B. bissettiae largely with woodrats. The top model included the variables "host species", "month", and "elevation" (weight = 0.84). Spatial clustering of B. bissettiae was detected in the northwestern section of the HVTR, whereas B. burgdorferi sensu stricto was clustered in the southeastern section. We conclude that the spatial distribution of these borreliae are driven at least in part by host species, time-of-year, and elevation.

  19. Prevalence of ticks and tick-borne pathogens: Babesia and Borrelia species in ticks infesting cats of Great Britain.

    Science.gov (United States)

    Davies, Saran; Abdullah, Swaid; Helps, Chris; Tasker, Séverine; Newbury, Hannah; Wall, Richard

    2017-09-15

    In a study of tick and tick-borne pathogen prevalence, between May and October 2016, 278 veterinary practices in Great Britain examined 1855 cats. Six-hundred and one cats were found to have attached ticks. The most frequently recorded tick species was Ixodes ricinus (57.1%), followed by Ixodes hexagonus (41.4%) and Ixodes trianguliceps (1.5%). Male cats, 4-6 years of age living in rural areas were most likely to be carrying a tick; hair length and tick treatment history had no significant association with attachment. For cats that were parasitized by ticks in large urban areas, I. hexagonus was the most frequent species recorded. Molecular analysis was possible for 541 individual tick samples, others were too damaged for analysis; Babesia spp., and Borrelia burgdorferi sensu lato were identified in 1.1% (n=6) and 1.8% (n=10) of these, respectively. Babesia spp. included Babesia vulpes sp. nov./Babesia microti-like (n=4) in I. hexagonus and Babesia venatorum (n=2) in I. ricinus. Borrelia burgdorferi s.l. species included Borrelia garinii (n=6) and Borrelia afzelii (n=4). The majority of B. burgorferi s.l. cases were found in I. ricinus, with B. afzelii in one I. hexagonus nymph. No Borrelia or Babesia spp. were present in I. trianguliceps. To determine a true prevalence for ticks on cats, practices that only submitted questionnaires from cats with ticks and practices that submitted fewer than 5 returns per week were removed; amongst those considered to have adhered strictly to the collection protocol, feline tick prevalence amongst cats that had access to the outdoors was 6.6%. These results show that ticks can be found on cats throughout Great Britain, which harbour a range of species of Babesia and B. burgdorferi s.l. and that cats, particularly in green spaces within urban areas, may form an important host for I. hexagonus, a known vector of pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Selective association of outer surface lipoproteins with the lipid rafts of Borrelia burgdorferi.

    Science.gov (United States)

    Toledo, Alvaro; Crowley, Jameson T; Coleman, James L; LaRocca, Timothy J; Chiantia, Salvatore; London, Erwin; Benach, Jorge L

    2014-03-11

    Borrelia burgdorferi contains unique cholesterol-glycolipid-rich lipid rafts that are associated with lipoproteins. These complexes suggest the existence of macromolecular structures that have not been reported for prokaryotes. Outer surface lipoproteins OspA, OspB, and OspC were studied for their participation in the formation of lipid rafts. Single-gene deletion mutants with deletions of ospA, ospB, and ospC and a spontaneous gene mutant, strain B313, which does not express OspA and OspB, were used to establish their structural roles in the lipid rafts. All mutant strains used in this study produced detergent-resistant membranes, a common characteristic of lipid rafts, and had similar lipid and protein slot blot profiles. Lipoproteins OspA and OspB but not OspC were shown to be associated with lipid rafts by transmission electron microscopy. When the ability to form lipid rafts in live B. burgdorferi spirochetes was measured by fluorescence resonance energy transfer (FRET), strain B313 showed a statistically significant lower level of segregation into ordered and disordered membrane domains than did the wild-type and the other single-deletion mutants. The transformation of a B313 strain with a shuttle plasmid containing ospA restored the phenotype shared by the wild type and the single-deletion mutants, demonstrating that OspA and OspB have redundant functions. In contrast, a transformed B313 overexpressing OspC neither rescued the FRET nor colocalized with the lipid rafts. Because these lipoproteins are expressed at different stages of the life cycle of B. burgdorferi, their selective association is likely to have an important role in the structure of prokaryotic lipid rafts and in the organism's adaptation to changing environments. IMPORTANCE Lipid rafts are cholesterol-rich clusters within the membranes of cells. Lipid rafts contain proteins that have functions in sensing the cell environment and transmitting signals. Although selective proteins are present in

  1. The crystal structure of the AhRR-ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription.

    Science.gov (United States)

    Sakurai, Shunya; Shimizu, Toshiyuki; Ohto, Umeharu

    2017-10-27

    2,3,7,8-Tetrachlorodibenzo- p -dioxin and related compounds are extraordinarily potent environmental toxic pollutants. Most of the 2,3,7,8-tetrachlorodibenzo- p -dioxin toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix (bHLH) Per-ARNT-Sim (PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription. The control of AhR activation is critical for managing AhR-mediated diseases, but the mechanisms by which AhRR represses AhR activation remain poorly understood, because of the lack of structural information. Here, we determined the structure of the AhRR-ARNT heterodimer by X-ray crystallography, which revealed an asymmetric intertwined domain organization presenting structural features that are both conserved and distinct among bHLH-PAS family members. The structures of AhRR-ARNT and AhR-ARNT were similar in the bHLH-PAS-A region, whereas the PAS-B of ARNT in the AhRR-ARNT complex exhibited a different domain arrangement in this family reported so far. The structure clearly disclosed that AhRR competitively represses AhR binding to ARNT and target DNA and further suggested the existence of an AhRR-ARNT-specific repression mechanism. This study provides a structural basis for understanding the mechanism by which AhRR represses AhR-mediated gene transcription. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Atomic structure of the GaAs(001)-c(4x4) surface: first-principles evidence for diversity of heterodimer motifs.

    Science.gov (United States)

    Penev, E; Kratzer, P; Scheffler, M

    2004-10-01

    The GaAs(001)-c(4x4) surface was studied using ab initio atomistic thermodynamics based on density-functional theory calculations. We demonstrate that in a range of stoichiometries, between those of the conventional three As-dimer and the new three Ga-As-dimer models, there exists a diversity of atomic structures featuring Ga-As heterodimers. These results fully explain the experimental scanning tunneling microscopy images and are likely to be relevant also to the c(4x4)-reconstructed (001) surfaces of other III-V semiconductors.

  3. Lack of IgG antibody seropositivity to Borrelia burgdorferi in patients with Parry-Romberg syndrome and linear morphea en coup de sabre in Mexico.

    Science.gov (United States)

    Gutiérrez-Gómez, Claudia; Godínez-Hana, Ana L; García-Hernández, Marisela; Suárez-Roa, María de Lourdes; Toussaint-Caire, Sonia; Vega-Memije, Elisa; Gutiérrez-Mendoza, Daniela; Pérez-Dosal, Marcia; Medina-De la Garza, Carlos E

    2014-08-01

    Progressive hemifacial atrophy or Parry-Romberg Syndrome (PRS) is a rare, acquired, progressive dysplasia of subcutaneous tissue and bone characterized by unilateral facial involvement. Its etiology is unknown, but theories about its pathogenesis include infectious, degenerative, autoimmune, and traumatic causes among others. The causal relationship of PRS and linear morphea en coup de sabre (LMCS) with Borrelia burgdorferi infection remains controversial. Our goal was to serologically determine anti-B. burgdorferi antibodies in patients diagnosed with PRS and LMCS to establish a possible association as a causative agent. We conducted a serology study with patients belonging to a group of 21 individuals diagnosed with PRS, six with LMCS, and 21 matched controls. Anti-Borrelia IgG antibodies were determined by ELISA. A descriptive statistical analysis and Fischer's exact test were done. In serological tests, only two cases had borderline values and were further analyzed by Western blot with non-confirmatory results. For both the PRS and LMCS group, the association test was not significant, suggesting a lack of association between PRS or LMCS and the presence of anti-Borrelia antibodies. In Mexico there are no previous studies on Borrelia infection and its relationship between PRS or LMCS. Our result showed a lack of association of either clinical entities with anti-Borrelia-antibodies. Former reports of this association may suggest coincidental findings without causal relationship. © 2014 The International Society of Dermatology.

  4. Validate or falsify: Lessons learned from a microscopy method claimed to be useful for detecting Borrelia and Babesia organisms in human blood.

    Science.gov (United States)

    Aase, Audun; Hajdusek, Ondrej; Øines, Øivind; Quarsten, Hanne; Wilhelmsson, Peter; Herstad, Tove K; Kjelland, Vivian; Sima, Radek; Jalovecka, Marie; Lindgren, Per-Eric; Aaberge, Ingeborg S

    2016-01-01

    A modified microscopy protocol (the LM-method) was used to demonstrate what was interpreted as Borrelia spirochetes and later also Babesia sp., in peripheral blood from patients. The method gained much publicity, but was not validated prior to publication, which became the purpose of this study using appropriate scientific methodology, including a control group. Blood from 21 patients previously interpreted as positive for Borrelia and/or Babesia infection by the LM-method and 41 healthy controls without known history of tick bite were collected, blinded and analysed for these pathogens by microscopy in two laboratories by the LM-method and conventional method, respectively, by PCR methods in five laboratories and by serology in one laboratory. Microscopy by the LM-method identified structures claimed to be Borrelia- and/or Babesia in 66% of the blood samples of the patient group and in 85% in the healthy control group. Microscopy by the conventional method for Babesia only did not identify Babesia in any samples. PCR analysis detected Borrelia DNA in one sample of the patient group and in eight samples of the control group; whereas Babesia DNA was not detected in any of the blood samples using molecular methods. The structures interpreted as Borrelia and Babesia by the LM-method could not be verified by PCR. The method was, thus, falsified. This study underlines the importance of doing proper test validation before new or modified assays are introduced.

  5. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening

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    Pothineni VR

    2016-04-01

    Full Text Available Venkata Raveendra Pothineni,1 Dhananjay Wagh,1 Mustafeez Mujtaba Babar,1 Mohammed Inayathullah,1 David Solow-Cordero,2 Kwang-Min Kim,1 Aneesh V Samineni,1 Mansi B Parekh,1 Lobat Tayebi,3 Jayakumar Rajadas1 1Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, 2Chemical & Systems Biology, Stanford University School of Medicine, Stanford, CA, 3Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI, USA Abstract: Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved that were screened are Library of Pharmacologically Active Compounds (LOPAC1280, the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150

  6. Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

    Science.gov (United States)

    Forselv, Kristine J N; Lorentzen, Åslaug R; Ljøstad, Unn; Mygland, Åse; Eikeland, Randi; Kjelland, Vivian; Noraas, Sølvi; Quarsten, Hanne

    2018-04-01

    Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples. Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls. Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases. We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.

  7. Molecular characterization of the Borrelia burgdorferi in vivo-essential protein PncA.

    Science.gov (United States)

    Jewett, Mollie W; Jain, Sunny; Linowski, Angelika K; Sarkar, Amit; Rosa, Patricia A

    2011-10-01

    The conversion of nicotinamide to nicotinic acid by nicotinamidase enzymes is a critical step in maintaining NAD(+) homeostasis and contributes to numerous important biological processes in diverse organisms. In Borrelia burgdorferi, the nicotinamidase enzyme, PncA, is required for spirochaete survival throughout the infectious cycle. Mammals lack nicotinamidases and therefore PncA may serve as a therapeutic target for Lyme disease. Contrary to the in vivo importance of PncA, the current annotation for the pncA ORF suggests that the encoded protein may be inactive due to the absence of an N-terminal aspartic acid residue that is a conserved member of the catalytic triad of characterized PncA proteins. Herein, we have used genetic and biochemical strategies to determine the N-terminal sequence of B. burgdorferi PncA. Our data demonstrate that the PncA protein is 24 aa longer than the currently annotated sequence and that pncA translation is initiated from the rare, non-canonical initiation codon AUU. These findings are an important first step in understanding the catalytic function of this in vivo-essential protein.

  8. Serologic evidence for Borrelia hermsii infection in rodents on federally owned recreational areas in California.

    Science.gov (United States)

    Fritz, Curtis L; Payne, Jessica R; Schwan, Tom G

    2013-06-01

    Tick-borne relapsing fever (TBRF) is endemic in mountainous regions of the western United States. In California, the principal agent is the spirochete Borrelia hermsii, which is transmitted by the argasid tick Ornithodoros hermsi. Humans are at risk of TBRF when infected ticks leave an abandoned rodent nest in quest of a blood meal. Rodents are the primary vertebrate hosts for B. hermsii. Sciurid rodents were collected from 23 sites in California between August, 2006, and September, 2008, and tested for serum antibodies to B. hermsii by immunoblot using a whole-cell sonicate and a specific antigen, glycerophosphodiester phosphodiesterase (GlpQ). Antibodies were detected in 20% of rodents; seroprevalence was highest (36%) in chipmunks (Tamias spp). Seroprevalence in chipmunks was highest in the Sierra Nevada (41%) and Mono (43%) ecoregions and between 1900 and 2300 meters elevation (43%). The serological studies described here are effective in implicating the primary vertebrate hosts involved in the maintenance of the ticks and spirochetes in regions endemic for TBRF.

  9. Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis

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    Scragg Ian G

    2002-10-01

    Full Text Available Abstract Background We report the characterisation of the variable large protein (vlp gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever. Methods The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1B. recurrentis A1 gene in both this and other isolates. Results This isolate was found to carry silent and expressed copies of the vlp1B. recurrentis A1 gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1B. recurrentis A17 on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters. Conclusion Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates.

  10. Seroprevalence of Borrelia burgdorferi antibodies in white-tailed deer from Texas

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    Shakirat A. Adetunji

    2016-08-01

    Full Text Available Lyme Disease is caused by the bacterial pathogen Borrelia burgdorferi, and is transmitted by the tick-vector Ixodes scapularis. It is the most prevalent arthropod-borne disease in the United States. To determine the seroprevalence of B. burgdorferi antibodies in white-tailed deer (Odocoileus virginianus from Texas, we analyzed serum samples (n = 1493 collected during the 2001–2015 hunting seasons, using indirect ELISA. Samples with higher sero-reactivity (0.803 and above than the negative control group (0.662 were further tested using a more specific standardized western immunoblot assay to rule out false positives. Using ELISA, 4.7% of the samples were sero-reactive against B. burgdorferi, and these originated in two eco-regions in Texas (Edwards Plateau and South Texas Plains. However, only 0.5% of the total samples were sero-reactive by standardized western immunoblot assay. Additionally, both ELISA and standardized western immunoblot assay results correlated with an increased incidence in human Lyme Disease cases reported in Texas. This is the first longitudinal study to demonstrate fluctuation in sero-reactivity of white-tailed deer to B. burgdorferi sensu stricto antigens in southern United States. Future ecological and geographical studies are needed to assess the environmental factors governing the prevalence of Lyme Disease in non-endemic areas of the southern United States.

  11. A case of canine borreliosis in Iran caused by Borrelia persica.

    Science.gov (United States)

    Shirani, Darush; Rakhshanpoor, Alaleh; Cutler, Sally Jane; Ghazinezhad, Behnaz; Naddaf, Saied Reza

    2016-04-01

    Tick-borne relapsing fever is an endemic disease in Iran, with most cases attributed to infection by Borrelia persica, which is transmitted by Ornithodoros tholozani soft ticks. Here, we report spirochetemia in blood of a puppy residing in Tehran, Iran. The causative species was identified by use of highly discriminative IGS sequencing; the 489 bp IGS sequence obtained in our study showed 99% identity (100% coverage) when compared with B. persica sequences derived from clinical cases or from O. tholozani ticks. Our IGS sequence also showed 99% similarity over 414 bp (85% coverage) with a strain from a domestic dog, and 96% over 328 bp (69% coverage) with a strain from a domestic cat. Pet-keeping in cosmopolitan cities like Tehran has become increasingly popular in recent years. Animals are often transported into the city in cages or cardboard boxes that might also harbor minute tick larvae and/or early stages of the nymphs bringing them into the urban environment. This may pose a threat to household members who buy and keep these puppies and as a result may come into close contact with infected ticks. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Determination of Seroprevalence of Borrelia burgdorferi IgG in Adult Population Living in Trabzon.

    Science.gov (United States)

    Cora, Merve; Kaklıkkaya, Neşe; Topbaş, Murat; Çan, Gamze; Yavuzyılmaz, Asuman; Tosun, İlknur; Aydın, Faruk

    2017-01-01

    Lyme borreliosis is a tick-borne, multi-systemic infectious disease that is thought to be wide spread in Turkey even though studies on its seroprevalence are limited. To determine the seroprevalence of Lyme borreliosis in part of north-eastern Tur-key (in the city of Trabzon), and to identify possible relationships between seropositivity and various factors such as location, gender, age group, occupation, income, and educational level. Retrospective cross-sectional study. A total of 884 blood samples collected from provincial and district health centers serving a population of about 800,000 were included in this study. ELISA was used to determine the anti-Borrelia IgG antibody levels in the samples. Samples that yielded positive results by ELISA were further subjected to western blot (WB). IgG antibodies were found in 128 samples (14.5%). Statistical analysis revealed significant differences between age groups and educational levels in terms of the incidence of seropositivity, whereas location, gender, occupational group and income level had no effect (p<0.001, p<0.001, p=0.948, p=0.645, p=0.131, p=0.080 respectively). The risk of contracting Lyme borreliosis in Trabzon is high, and necessary measures need to be taken to avoid the spread of disease.

  13. Determination of Seroprevalence of Borrelia burgdorferi IgG in Adult Population Living in Trabzon

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    Merve Cora

    2017-02-01

    Full Text Available Background: Lyme borreliosis is a tick-borne, multi-systemic infectious disease that is thought to be wide spread in Turkey even though studies on its seroprevalence are limited. Aims: To determine the seroprevalence of Lyme borreliosis in part of north-eastern Tur-key (in the city of Trabzon, and to identify possible relationships between seropositivity and various factors such as location, gender, age group, occupation, income, and educational level. Study Design: Retrospective cross-sectional study. Methods: A total of 884 blood samples collected from provincial and district health centers serving a population of about 800,000 were included in this study. ELISA was used to determine the anti-Borrelia IgG antibody levels in the samples. Samples that yielded positive results by ELISA were further subjected to western blot (WB. Results: IgG antibodies were found in 128 samples (14.5%. Statistical analysis revealed significant differences between age groups and educational levels in terms of the incidence of seropositivity, whereas location, gender, occupational group and income level had no effect (p<0.001, p<0.001, p=0.948, p=0.645, p=0.131, p=0.080 respectively. Conclusions: The risk of contracting Lyme borreliosis in Trabzon is high, and necessary measures need to be taken to avoid the spread of disease

  14. Borrelia burgdorferi in ticks and dogs in the province of Vojvodina, Serbia*

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    Savić S.

    2010-12-01

    Full Text Available Lyme disease is a tick borne zoonotic infection, caused by Borrelia burgdorferi s.l. bacteria. For the transmission of the disease, the presence of ticks is a prerequisite. Lyme borreliosis mostly occurs in people and dogs, but it may occur in other animals. Ticks which carry B. burgdorferi s.l. in Serbia are of the Ixodes ricinus specis. In Serbia, Lyme disease was detected for the first time in the late ‘80-es. In dogs, clinical symptoms may occur even months after a tick bite, and include weakness, lymphadenopathy, fever, lameness, arthritis, etc. In our survey, we have observed tick and dog populations in the province of Vojvodina (northern part of Serbia. I. ricinus ticks were collected and examined for the presence of B. burgdorferi s.l. in several chosen locations. In addition, blood samples were collected from house dogs and pets from the same locations, and analyzed for the presence of antibodies specific for B. burgdorferi s.l. The results showed a mean infection of ticks of 22.12 %, and a mean seroprevalence of Lyme disease in dogs of 25.81 %. We conclude that in Vojvodina there is an actual risk of Lyme borreliosis for other animals and humans, because of the persistence of B. burgdorferi s.l. in both tick and dog populations.

  15. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

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    Elizabeth A. Novak

    2014-05-01

    Full Text Available In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

  16. Inefficient co-feeding transmission of Borrelia afzelii in two common European songbirds

    Science.gov (United States)

    Heylen, Dieter J. A.; Sprong, Hein; Krawczyk, Aleksandra; Van Houtte, Natalie; Genné, Dolores; Gomez-Chamorro, Andrea; van Oers, Kees; Voordouw, Maarten J.

    2017-01-01

    The spirochete bacterium Borrelia afzelii is the most common cause of Lyme borreliosis in Europe. This tick-borne pathogen can establish systemic infections in rodents but not in birds. However, several field studies have recovered larval Ixodes ricinus ticks infected with B. afzelii from songbirds suggesting successful transmission of B. afzelii. We reviewed the literature to determine which songbird species were the most frequent carriers of B. afzelii-infected I. ricinus larvae and nymphs. We tested experimentally whether B. afzelii is capable of co-feeding transmission on two common European bird species, the blackbird (Turdus merula) and the great tit (Parus major). For each bird species, four naïve individuals were infested with B. afzelii-infected I. ricinus nymphal ticks and pathogen-free larval ticks. None of the co-feeding larvae tested positive for B. afzelii in blackbirds, but a low percentage of infected larvae (3.33%) was observed in great tits. Transstadial transmission of B. afzelii DNA from the engorged nymphs to the adult ticks was observed in both bird species. However, BSK culture found that these spirochetes were not viable. Our study suggests that co-feeding transmission of B. afzelii is not efficient in these two songbird species. PMID:28054584

  17. Functional analysis of the Borrelia burgdorferi bba64 gene product in murine infection via tick infestation.

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    Toni G Patton

    Full Text Available Borrelia burgdorferi, the causative agent of Lyme borreliosis, is transmitted to humans from the bite of Ixodes spp. ticks. During the borrelial tick-to-mammal life cycle, B. burgdorferi must adapt to many environmental changes by regulating several genes, including bba64. Our laboratory recently demonstrated that the bba64 gene product is necessary for mouse infectivity when B. burgdorferi is transmitted by an infected tick bite, but not via needle inoculation. In this study we investigated the phenotypic properties of a bba64 mutant strain, including 1 replication during tick engorgement, 2 migration into the nymphal salivary glands, 3 host transmission, and 4 susceptibility to the MyD88-dependent innate immune response. Results revealed that the bba64 mutant's attenuated infectivity by tick bite was not due to a growth defect inside an actively feeding nymphal tick, or failure to invade the salivary glands. These findings suggested there was either a lack of spirochete transmission to the host dermis or increased susceptibility to the host's innate immune response. Further experiments showed the bba64 mutant was not culturable from mouse skin taken at the nymphal bite site and was unable to establish infection in MyD88-deficient mice via tick infestation. Collectively, the results of this study indicate that BBA64 functions at the salivary gland-to-host delivery interface of vector transmission and is not involved in resistance to MyD88-mediated innate immunity.

  18. The first case of imported Borrelia miyamotoi disease concurrent with Lyme disease.

    Science.gov (United States)

    Oda, Rentaro; Kutsuna, Satoshi; Sekikawa, Yoshiyuki; Hongo, Igen; Sato, Kozue; Ohnishi, Makoto; Kawabata, Hiroki

    2017-05-01

    Borrelia miyamotoi disease (BMD) is an emerging infectious disease caused by B. miyamotoi. Although BMD has been reported in the United States, Europe, and Japan, no case of imported BMD has been described in the world. Here, we report a 63-year-old American man living in Japan who presented with malaise, headache, myalgia, and arthralgia. We suspected Lyme disease because of his travel history to Minnesota and presence of erythema migrans. Serologic analysis supported our diagnosis, and doxycycline was administered for 14 days. However, we also suspected coinfection with BMD because of his fever, elevated liver function test results and his travel history. The patient was seropositive for the immunoglobulin M antibody to recombinant glycerophosphodiester phosphodiesterase, and was diagnosed with coinfection with BMD. This case suggests that BMD should be considered in febrile travelers returning from the Northeastern and Midwestern regions of the United States, and that BMD and Lyme disease coinfection should be considered to detect cases of imported BMD. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein.

    Science.gov (United States)

    Bykowski, Tomasz; Babb, Kelly; von Lackum, Kate; Riley, Sean P; Norris, Steven J; Stevenson, Brian

    2006-07-01

    The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. burgdorferi cells indicated that the spirochete controls vlsE transcription levels in response to environmental cues. Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production is controlled at the level of transcriptional initiation, and regions of 5' DNA involved in the regulation were identified. Electrophoretic mobility shift assays detected qualitative and quantitative changes in patterns of protein-DNA complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting the involvement of DNA-binding proteins in the regulation of vlsE, with at least one protein acting as a transcriptional activator.

  20. Outer surface protein B is critical for Borrelia burgdorferi adherence and survival within Ixodes ticks.

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    Girish Neelakanta

    2007-03-01

    Full Text Available Survival of Borrelia burgdorferi in ticks and mammals is facilitated, at least in part, by the selective expression of lipoproteins. Outer surface protein (Osp A participates in spirochete adherence to the tick gut. As ospB is expressed on a bicistronic operon with ospA, we have now investigated the role of OspB by generating an OspB-deficient B. burgdorferi and examining its phenotype throughout the spirochete life cycle. Similar to wild-type isolates, the OspB-deficient B. burgdorferi were able to readily infect and persist in mice. OspB-deficient B. burgdorferi were capable of migrating to the feeding ticks but had an impaired ability to adhere to the tick gut and survive within the vector. Furthermore, the OspB-deficient B. burgdorferi bound poorly to tick gut extracts. The complementation of the OspB-deficient spirochete in trans, with a wild-type copy of ospB gene, restored its ability to bind tick gut. Taken together, these data suggest that OspB has an important role within Ixodes scapularis and that B. burgdorferi relies upon multiple genes to efficiently persist in ticks.

  1. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Koc, Hasan; Schmitt, Mark E; Krasilnikov, Andrey S

    2007-10-01

    Pop6 and Pop7 are protein subunits of Saccharomyces cerevisiae RNase MRP and RNase P. Here we show that bacterially expressed Pop6 and Pop7 form a soluble heterodimer that binds the RNA components of both RNase MRP and RNase P. Footprint analysis of the interaction between the Pop6/7 heterodimer and the RNase MRP RNA, combined with gel mobility assays, demonstrates that the Pop6/7 complex binds to a conserved region of the P3 domain. Binding of these proteins to the MRP RNA leads to local rearrangement in the structure of the P3 loop and suggests that direct interaction of the Pop6/7 complex with the P3 domain of the RNA components of RNases MRP and P may mediate binding of other protein components. These results suggest a role for a key element in the RNase MRP and RNase P RNAs in protein binding, and demonstrate the feasibility of directly studying RNA-protein interactions in the eukaryotic RNases MRP and P complexes.

  2. Borrelia burgdorferi genospecies detection by RLB hybridization in Ixodes cinus ticks from different sites of North-Eastern Poland

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    Justyna Dunaj

    2014-06-01

    Full Text Available Introduction. RLB (Reverse Line Blot Hybridization is a molecular biology technique that might be used for [i]Borrelia burgdorferi [/i]sensu lato (sl DNA detection with genospecies specification. Among[i] B. burgdorferi[/i] sl genospecies at least 7 are regarded as pathogenic in Europe. objective. The aim of the study was to evaluate the frequency of different [i]Borrelia[/i] genospecies DNA detection in Ixodes ricinus ticks in the endemic area of North-Eastern Poland by using RLB. materials and method. Ixodes ricinus ticks were collected in May – June, from 6 different sites in North-Eastern Poland (Jakubin, Kolno, Grajewo, Suwałki, Siemiatycze, Białowieża by flagging. Extracted DNA was amplified by polymerase chain reaction (PCR targeting the intergenic spacer 5S 23S of [i]B. burgdorferi sl.[/i] PCR products were hybridised to 15 different oligonucleotide probes for 9 different [i]Borrelia [/i]genospecies ([i]B. burgdorferi sl, B. burgdorferi ss, B. garinii, B. afzelii, B. valaisiana, B. lusitaniae, B. spielmanii, B. bissettii and B. relapsing[/i] fever-like spirochetes (B. myamotoi by RLB. results. [i]Borrelia [/i]genospecies DNA was detected in 205 Ixodes ricinus ticks. Among 14 infected with [i]Borrelia[/i] ticks, 4 were identified as B. garinii and 10 as B. afzelii. Higher numbers of infected ticks were noticed in the eastern part of the research area, where large forest complexes dominate. Nymphs appeared to be the most frequently infected tick stage, which has an epidemiological meaning in the incidence of Lyme borreliosis. conclusions. The study demonstrated that RLB might be easily used in [i]Borrelia[/i] DNA detection with genospecies-identification, and indicated the domination of [i]B. afzelii and B. garinii [/i]in ticks from North-Eastern Poland.

  3. Borrelia burgdorferi genospecies detection by RLB hybridization in Ixodes cinus ticks from different sites of North-Eastern Poland

    OpenAIRE

    Justyna Dunaj; Joanna Maria Zajkowska; Maciej Kondrusik; Lise Gern; Oliver Rais; Anna Moniuszko; Sławomir Pancewicz; Renata Świerzbińska

    2014-01-01

    Introduction. RLB (Reverse Line Blot Hybridization) is a molecular biology technique that might be used for [i]Borrelia burgdorferi [/i]sensu lato (sl) DNA detection with genospecies specification. Among[i] B. burgdorferi[/i] sl genospecies at least 7 are regarded as pathogenic in Europe. objective. The aim of the study was to evaluate the frequency of different [i]Borrelia[/i] genospecies DNA detection in Ixodes ricinus ticks in the endemic area of North-Eastern Poland by using RLB. ...

  4. Distribution of Soft Ticks and Their Natural Infection with Borrelia in a Focus of Relapsing Fever in Iran

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    Z Aghighi

    2007-11-01

    Full Text Available Tick-borne diseases such as relapsing fever and Crimean-Congo Hemorrhagic Fever (CCHF are of public health impor¬tance in Iran. There are 471 reported cases of relapsing fever in 2003, according to the Ministry of Health of Iran.The num¬ber of cases has been increased in recent years. Its distribution is more or less prevalent in different parts of Iran. The aim of this study was to find out the fauna and natural infection of soft ticks with Borrelia in Qazvin Province, during their sea¬sonal activity. The province covers 15821 km² between 48-45 to 50-50 east of Greenwich Meridian of longitude and 35-37 to 36-45 north latitude of the equator. For this purpose a field study was carried out in the region. A total of 54 villages from 19 districts were selected ran¬domly and ticks were collected from their habitats according to the standard method. A total of 3197 Argasidae ticks were collected from human dwellings, poultry and animal shelters. They belonged to Argas and Or¬nithodoros genera which 36.8% were Argas persicus, 4% A. reflexus, 6.4% O. canestrini, 45.5% O. lahorensis and 7.3% O. tholozani. It should be noted that 12 ticks of O. erraticus were collected from 12 rodents borrows. We found that 8.82 % of O. tholozani ticks were infected with Borrelia persica and half of the O. erraticus were infected with Borrelia microti. All the people who are in¬volved with veterinary activities should be aware of disease transmission by the ticks. In the endemic area of the disease tick control is recommended.

  5. Seroprevalence of antibodies to Borrelia burgdorferi sensu lato in healthy adults from western Norway: risk factors and methodological aspects.

    Science.gov (United States)

    Hjetland, Reidar; Nilsen, Roy M; Grude, Nils; Ulvestad, Elling

    2014-11-01

    The aim of this study was to assess the seroprevalence of antibodies to Borrelia burgdorferi sensu lato in a healthy adult population from Sogn and Fjordane county in western Norway by different assays. Sera from 1213 blood donors at four different blood banks were analysed in Enzygnost Lyme link VlsE/IgG (IgG), Enzygnost Borreliosis IgM (IgM), and Immunetics C6 Lyme ELISA kit (C6). Sera showing positive or grey-zone reactivities were further examined with Borrelia-EUROLine-RN-AT IgG blot and Borrelia-EUROLine-RN-AT IgM blot. The seroprevalences were 9.6%, 8.2%, 8.4%, 6.4% and 5.7%, respectively. The seroprevalence for IgG was lower in the eastern part of the county and in owners of pet animals. It was higher in men, and increased with age and number of tick bites. C6 and IgG gave comparable results. IgM only was found in 4.5%, more often in women, did not increase with age, and showed no relationship with geography, and 56.4% were positive in IgM blot. In conclusion, antibodies to B. burgdorferi s.l. are common in blood donors in western Norway. The results may be used for evaluation of predictive values of test results in patients, as well as a basis for test algorithms in the laboratory. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  6. Borrelia burgdorferi sensu lato spirochetes in wild birds in northwestern California: associations with ecological factors, bird behavior and tick infestation.

    Science.gov (United States)

    Newman, Erica A; Eisen, Lars; Eisen, Rebecca J; Fedorova, Natalia; Hasty, Jeomhee M; Vaughn, Charles; Lane, Robert S

    2015-01-01

    Although Borrelia burgdorferi sensu lato (s.l.) are found in a great diversity of vertebrates, most studies in North America have focused on the role of mammals as spirochete reservoir hosts. We investigated the roles of birds as hosts for subadult Ixodes pacificus ticks and potential reservoirs of the Lyme disease spirochete B. burgdorferi sensu stricto (s.s.) in northwestern California. Overall, 623 birds representing 53 species yielded 284 I. pacificus larvae and nymphs. We used generalized linear models and zero-inflated negative binomial models to determine associations of bird behaviors, taxonomic relationships and infestation by I. pacificus with borrelial infection in the birds. Infection status in birds was best explained by taxonomic order, number of infesting nymphs, sampling year, and log-transformed average body weight. Presence and counts of larvae and nymphs could be predicted by ground- or bark-foraging behavior and contact with dense oak woodland. Molecular analysis yielded the first reported detection of Borrelia bissettii in birds. Moreover, our data suggest that the Golden-crowned Sparrow (Zonotrichia atricapilla), a non-resident species, could be an important reservoir for B. burgdorferi s.s. Of 12 individual birds (9 species) that carried B. burgdorferi s.l.-infected larvae, no birds carried the same genospecies of B. burgdorferi s.l. in their blood as were present in the infected larvae removed from them. Possible reasons for this discrepancy are discussed. Our study is the first to explicitly incorporate both taxonomic relationships and behaviors as predictor variables to identify putative avian reservoirs of B. burgdorferi s.l. Our findings underscore the importance of bird behavior to explain local tick infestation and Borrelia infection in these animals, and suggest the potential for bird-mediated geographic spread of vector ticks and spirochetes in the far-western United States.

  7. Europe-Wide Meta-Analysis of Borrelia burgdorferi Sensu Lato Prevalence in Questing Ixodes ricinus Ticks.

    Science.gov (United States)

    Strnad, Martin; Hönig, Václav; Růžek, Daniel; Grubhoffer, Libor; Rego, Ryan O M

    2017-08-01

    Lyme borreliosis is the most common zoonotic disease transmitted by ticks in Europe and North America. Despite having multiple tick vectors, the causative agent, Borrelia burgdorferi sensu lato , is vectored mainly by Ixodes ricinus in Europe. In the present study, we aimed to review and summarize the existing data published from 2010 to 2016 concerning the prevalence of B. burgdorferi sensu lato spirochetes in questing I. ricinus ticks. The primary focus was to evaluate the infection rate of these bacteria in ticks, accounting for tick stage, adult tick gender, region, and detection method, as well as to investigate any changes in prevalence over time. The data obtained were compared to the findings of a previous metastudy. The literature search identified data from 23 countries, with 115,028 ticks, in total, inspected for infection with B. burgdorferi sensu lato We showed that the infection rate was significantly higher in adults than in nymphs and in females than in males. We found significant differences between European regions, with the highest infection rates in Central Europe. The most common genospecies were B. afzelii and B. garinii , despite a negative correlation of their prevalence rates. No statistically significant differences were found among the prevalence rates determined by conventional PCR, nested PCR, and real-time PCR. IMPORTANCE Borrelia burgdorferi sensu lato is a pathogenic bacterium whose clinical manifestations are associated with Lyme borreliosis. This vector-borne disease is a major public health concern in Europe and North America and may lead to severe arthritic, cardiovascular, and neurological complications if left untreated. Although pathogen prevalence is considered an important predictor of infection risk, solitary isolated data have only limited value. Here we provide summarized information about the prevalence of B. burgdorferi sensu lato spirochetes among host-seeking Ixodes ricinus ticks, the principal tick vector of

  8. Tick thioester-containing proteins and phagocytosis do not affect transmission of Borrelia afzelii from the competent vector ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Urbanová, Veronika; Hajdušek, Ondřej; Hönig Mondeková, Helena; Šíma, Radek; Kopáček, Petr

    2017-01-01

    Roč. 7, MAR (2017), č. článku 73. ISSN 2235-2988 R&D Projects: GA ČR GJ15-12006Y; GA ČR GA13-11043S; GA ČR GA17-27386S; GA ČR GA17-27393S EU Projects: European Commission(XE) 602272 - ANTIDotE Institutional support: RVO:60077344 Keywords : Borrelia * complement * Ixodes * phagocytosis * thioester-containing proteins Subject RIV: EC - Immunology OBOR OECD: Immunology Impact factor: 4.300, year: 2016

  9. Molecular detection of Borrelia bissettii DNA in serum samples from patients in the Czech Republic with suspected borreliosis

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Růžek, Daniel; Piskunova, N.; Mallátová, N.; Grubhoffer, Libor

    2009-01-01

    Roč. 292, č. 2 (2009), s. 274-281 ISSN 0378-1097 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GD524/03/H133; GA ČR(CZ) GA524/06/1479 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia bissettii in human serum * causative agent * co-infection * co-detection of different species * phylogenetic analysis Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.199, year: 2009

  10. Predictive value of Borrelia burgdorferi IgG antibody levels in patients referred to a tertiary Lyme centre.

    Science.gov (United States)

    Zwerink, M; Zomer, T P; van Kooten, B; Blaauw, G; van Bemmel, T; van Hees, B C; Vermeeren, Y M; Landman, G W

    2018-03-01

    A two-step testing strategy is recommended in serological testing for Lyme borreliosis; positive and indeterminate enzyme-linked immunosorbent assay (ELISA) results are confirmed with immunoblots. Several ELISAs quantify the concentration of antibodies tested, however, no recommendation exists for an upper cut-off value at which an IgG ELISA is sufficient and the immunoblot can be omitted. The study objective was to determine at which IgG antibody level an immunoblot does not have any additional predictive value compared to ELISA results. Data of adult patients who visited a tertiary Lyme centre between 2008 and 2014 were analysed. Both an ELISA (Enzygnost Lyme link VlsE IgG) and immunoblot (recomLine blot Borrelia) were performed. Clinical data were extracted from the patient's digital medical record. Positive predictive values (PPVs) for either previous or active infection with Borrelia burgdorferi s.l. were calculated for different cut-off ELISA IgG antibody levels where the immunoblot was regarded as reference test. In total, 1454 patients were included. According to the two-step test strategy, 486 (33%), 69 (5%) and 899 (62%) patients had positive, indeterminate and negative Borrelia IgG serology, respectively. At IgG levels of 500 IU/ml and higher, all immunoblots were positive, resulting in a 100% PPV (95% CI: 97.0-100). At IgG levels of 200 IU/ml and higher, the PPV was 99.3% (95% CI: 97.4-99.8). In conclusion, at IgG levels of 200 IU/ml and higher, an ELISA was sufficient to detect antibodies to Borrelia burgdorferi s.l. At those IgG levels, a confirmatory immunoblot may be omitted in patients referred to a tertiary Lyme centre. Before these results can be implemented in routine diagnosis of Lyme borreliosis, confirmation of the results is necessary in other patient populations and using other quantitative ELISAs and immunoblots. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Culture and identification of Borrelia spirochetes in human vaginal and seminal secretions [version 3; referees: 2 approved, 2 not approved

    Directory of Open Access Journals (Sweden)

    Marianne J. Middelveen

    2015-04-01

    Full Text Available Background: Recent reports indicate that more than 300,000 cases of Lyme disease are diagnosed yearly in the USA. Preliminary clinical, epidemiological and immunological studies suggest that infection with the Lyme disease spirochete Borrelia burgdorferi (Bb could be transferred from person to person via intimate human contact without a tick vector. Failure to detect viable Borrelia spirochetes in vaginal and seminal secretions would argue against this hypothesis. Methods: Patients with and without a history of Lyme disease were selected for the study after informed consent was obtained. Serological testing for Bb was performed on all subjects. Semen or vaginal secretions were inoculated into BSK-H medium and cultured for four weeks. Examination of genital cultures and culture concentrates for the presence of spirochetes was performed using light and darkfield microscopy, and spirochete concentrates were subjected to Dieterle silver staining, anti-Bb immunohistochemical staining, molecular hybridization and PCR analysis for further characterization. Immunohistochemical and molecular testing was performed in three independent laboratories in a blinded fashion. Positive and negative controls were included in all experiments. Results: Control subjects who were asymptomatic and seronegative for Bb had no detectable spirochetes in genital secretions by PCR analysis. In contrast, spirochetes were observed in cultures of genital secretions from 11 of 13 subjects diagnosed with Lyme disease, and motile spirochetes were detected in genital culture concentrates from 12 of 13 Lyme disease patients using light and darkfield microscopy. Morphological features of spirochetes were confirmed by Dieterle silver staining and immunohistochemical staining of culture concentrates. Molecular hybridization and PCR testing confirmed that the spirochetes isolated from semen and vaginal secretions were strains of Borrelia, and all cultures were negative for treponemal

  12. Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis

    Science.gov (United States)

    Putschky, N; Schnarr, S; Wollenhaupt, J; Zeidler, H; Kuipers, J

    2001-01-01

    OBJECTIVE—Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis.
METHODS—Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined.
RESULTS—Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm3, 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only.
CONCLUSIONS—DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

 PMID:11350854

  13. Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.

    Directory of Open Access Journals (Sweden)

    Emir Hodzic

    Full Text Available The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.

  14. Antibody responses to Borrelia burgdorferi detected by western blot vary geographically in Canada.

    Science.gov (United States)

    Ogden, Nicholas H; Arsenault, Julie; Hatchette, Todd F; Mechai, Samir; Lindsay, L Robbin

    2017-01-01

    Lyme disease is emerging in eastern and central Canada, and most cases are diagnosed using the two-tier serological test (Enzyme Immuno Assay [EIA] followed by Western blot [WB]). Simplification of this algorithm would be advantageous unless it impacts test performance. In this study, accuracy of individual proteins of the IgG WB algorithm in predicting the overall test result in samples from Canadians was assessed. Because Borrelia burgdorferi strains vary geographically in Canada, geographic variations in serological responses were also explored. Metrics of relative sensitivity, specificity and the kappa statistic measure of concordance were used to assess the capacity of responses to individual proteins to predict the overall IgG WB result of 2524 EIA (C6)-positive samples from across Canada. Geographic and interannual variations in proportions of samples testing positive were explored by logistic regression. No one protein was highly concordant with the IgG WB result. Significant variations were found amongst years and geographic regions in the prevalence of samples testing positive using the overall IgG WB algorithm, and for individual proteins of the algorithm. In most cases the prevalence of samples testing positive were highest in Nova Scotia, and lower in samples from Manitoba westwards. These findings suggest that the current two tier test may not be simplified and continued use of the current two-tier test method and interpretation is recommended. Geographic and interannual variations in the prevalence of samples testing positive may be consistent with B. burgdorferi strain variation in Canada, and further studies are needed to explore this.

  15. Antibody responses to Borrelia burgdorferi detected by western blot vary geographically in Canada.

    Directory of Open Access Journals (Sweden)

    Nicholas H Ogden

    Full Text Available Lyme disease is emerging in eastern and central Canada, and most cases are diagnosed using the two-tier serological test (Enzyme Immuno Assay [EIA] followed by Western blot [WB]. Simplification of this algorithm would be advantageous unless it impacts test performance. In this study, accuracy of individual proteins of the IgG WB algorithm in predicting the overall test result in samples from Canadians was assessed. Because Borrelia burgdorferi strains vary geographically in Canada, geographic variations in serological responses were also explored. Metrics of relative sensitivity, specificity and the kappa statistic measure of concordance were used to assess the capacity of responses to individual proteins to predict the overall IgG WB result of 2524 EIA (C6-positive samples from across Canada. Geographic and interannual variations in proportions of samples testing positive were explored by logistic regression. No one protein was highly concordant with the IgG WB result. Significant variations were found amongst years and geographic regions in the prevalence of samples testing positive using the overall IgG WB algorithm, and for individual proteins of the algorithm. In most cases the prevalence of samples testing positive were highest in Nova Scotia, and lower in samples from Manitoba westwards. These findings suggest that the current two tier test may not be simplified and continued use of the current two-tier test method and interpretation is recommended. Geographic and interannual variations in the prevalence of samples testing positive may be consistent with B. burgdorferi strain variation in Canada, and further studies are needed to explore this.

  16. Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle.

    Directory of Open Access Journals (Sweden)

    Christopher J Pappas

    2011-07-01

    Full Text Available Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a vector-borne pathogen that cycles between a mammalian host and tick vector. This complex life cycle requires that the spirochete modulate its gene expression program to facilitate growth and maintenance in these diverse milieus. B. burgdorferi contains an operon that is predicted to encode proteins that would mediate the uptake and conversion of glycerol to dihydroxyacetone phosphate. Previous studies indicated that expression of the operon is elevated at 23°C and is repressed in the presence of the alternative sigma factor RpoS, suggesting that glycerol utilization may play an important role during the tick phase. This possibility was further explored in the current study by expression analysis and mutagenesis of glpD, a gene predicted to encode glycerol 3-phosphate dehydrogenase. Transcript levels for glpD were significantly lower in mouse joints relative to their levels in ticks. Expression of GlpD protein was repressed in an RpoS-dependent manner during growth of spirochetes within dialysis membrane chambers implanted in rat peritoneal cavities. In medium supplemented with glycerol as the principal carbohydrate, wild-type B. burgdorferi grew to a significantly higher cell density than glpD mutant spirochetes during growth in vitro at 25°C. glpD mutant spirochetes were fully infectious in mice by either needle or tick inoculation. In contrast, glpD mutants grew to significantly lower densities than wild-type B. burgdorferi in nymphal ticks and displayed a replication defect in feeding nymphs. The findings suggest that B. burgdorferi undergoes a switch in carbohydrate utilization during the mammal to tick transition. Further, the results demonstrate that the ability to utilize glycerol as a carbohydrate source for glycolysis during the tick phase of the infectious cycle is critical for maximal B. burgdorferi fitness.

  17. Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent

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    S.L. States

    2017-06-01

    Full Text Available Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R0, the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding – such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range.

  18. Borrelia burgdorferi Sensu Lato in Siberian chipmunks (Tamias sibiricus) introduced in suburban forests in France.

    Science.gov (United States)

    Vourc'h, Gwenaël; Marmet, Julie; Chassagne, Michelle; Bord, Séverine; Chapuis, Jean-Louis

    2007-01-01

    Numerous vertebrate reservoirs have been described for Borrelia burgdorferi sensu lato (sl), which includes the etiological agents of Lyme Borreliosis (LB). The Siberian chipmunk (Tamias sibiricus) is a rodent originating from Asia, where it is suspected to be a B. burgdorferi reservoir. It has been intentionally released into the wild in Europe since the 1970s, but has not yet been subject to any study regarding its association with the LB agent. In this paper we studied Siberian chipmunk infestation with the LB vector (Ixodes ricinus) and infection prevalence by LB spirochetes in a suburban introduced population. We compared these findings with known competent reservoir hosts, the bank vole (Myodes [clethrionomys] glareolus) and wood mouse (Apodemus sylvaticus). All Siberian chipmunks were infested with larvae and larval abundance was higher in this species (mean number of larvae [95% Confidence Interval]: 73.5 [46.0, 117.2]) than in the two other rodent species (bank voles: 4.4 [3.0, 6.3] and wood mice: 10.2 [4.9, 21.2]). Significant factors affecting abundance of larvae were host species and sampling season. Nymphs were most prevalent on chipmunks (86.2%, mean: 5.1 [3.3, 8.0]), one vole carried only two nymphs, and none of the mice had any nymphs. Nymph abundance in chipmunks was affected by sampling season and sex. Furthermore, the infection prevalence of B. burgdorferi sl in the Siberian chipmunk was the highest (33.3%) and predominantly of B. afzelii. The infection prevalence was 14.1% in bank voles, but no wood mouse was found to be infected. Our results suggest that the Siberian chipmunk may be an important reservoir host for LB.

  19. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie Feng

    2015-09-01

    Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy

  20. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-09-16

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive

  1. Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease.

    Science.gov (United States)

    Nadelman, R B; Pavia, C S; Magnarelli, L A; Wormser, G P

    1990-01-01

    Borrelia burgdorferi, the etiologic agent of Lyme disease, has rarely been successfully cultured from blood. We report on seven patients from Westchester County, New York, with B. burgdorferi bacteremia diagnosed between April 1987 and August 1987. One hundred thirty-two attempts to isolate spirochetes were made on blood specimens obtained from 104 patients. Twenty-two of these specimens were obtained from nine patients who had recently been bitten by Ixodes ticks but who were asymptomatic. Heparinized blood or serum specimens (0.2 to 0.4 mL) were inoculated onto 6 mL of modified Barbour-Stoenner-Kelly medium. Lyme serology was performed by enzyme-linked immunosorbent polyvalent, IgM, and IgG assays, fluorescent immunoassay, and microhemagglutination. Four of the seven patients had erythema migrans, two had facial nerve palsy, and one had a flu-like syndrome without rash. These patients represented 21% (four of 19) of all patients with the characteristic skin lesion who had blood cultures for B. burgdorferi, and 40% (two of five) of all those with facial nerve palsy. Serologic testing was frequently nonreactive; two patients had no detectable antibody on multiple sera by five different assays. All patients improved with antibiotic treatment, and had negative subsequent blood cultures, but five of seven had persistent complaints after completion of therapy. Culturing blood for B. burgdorferi may be useful in confirming the diagnosis of Lyme disease in selected patients. Use of spirochete blood cultures may facilitate a better understanding of the pathogenesis and natural history of Lyme disease.

  2. An enhanceosome containing the Jun B/Fra-2 heterodimer and the HMG-I(Y) architectural protein controls HPV 18 transcription.

    Science.gov (United States)

    Bouallaga, I; Massicard, S; Yaniv, M; Thierry, F

    2000-11-01

    Recent studies have reported new mechanisms that mediate the transcriptional synergy of strong tissue-specific enhancers, involving the cooperative assembly of higher-order nucleoprotein complexes called enhanceosomes. Here we show that the HPV18 enhancer, which controls the epithelial-specific transcription of the E6 and E7 transforming genes, exhibits characteristic features of these structures. We used deletion experiments to show that a core enhancer element cooperates, in a specific helical phasing, with distant essential factors binding to the ends of the enhancer. This core sequence, binding a Jun B/Fra-2 heterodimer, cooperatively recruits the architectural protein HMG-I(Y) in a nucleoprotein complex, where they interact with each other. Therefore, in HeLa cells, HPV18 transcription seems to depend upon the assembly of an enhanceosome containing multiple cellular factors recruited by a core sequence interacting with AP1 and HMG-I(Y).

  3. Tick-borne relapsing fever imported from West Africa: diagnosis by quantitative buffy coat analysis and in vitro culture of Borrelia crocidurae

    NARCIS (Netherlands)

    van Dam, A. P.; van Gool, T.; Wetsteyn, J. C.; Dankert, J.

    1999-01-01

    West African tick-borne relapsing fever (TBRF) is difficult to diagnose due to the low number of spirochetes in the bloodstream of patients. Previously, the causative microorganism, Borrelia crocidurae, had never been cultured in vitro. TBRF was rapidly diagnosed for two patients returning from

  4. IrC2/Bf - A yeast and Borrelia responsive component of the complement system from the hard tick Ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Urbanová, V.; Hajdušek, O.; Šíma, R.; Franta, Z.; Hönig Mondeková, Helena; Grunclová, L.; Bartošová-Sojková, P.; Jalovecká, M.; Kopáček, P.

    2018-01-01

    Roč. 76, FEB 2018 (2018), s. 86-94 ISSN 0145-305X Institutional support: RVO:61388971 Keywords : Borrelia * C3-complement convertase * Factor B Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.218, year: 2016

  5. Serological survey for antibodies to Borrelia burgdorferi in rodents and detection of spirochaetes in ticks and fleas in South Moravia (Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Juřicová, Zina; Halouzka, Jiří; Hubálek, Zdeněk

    2002-01-01

    Roč. 57, č. 3 (2002), s. 383-387 ISSN 0006-3088 R&D Projects: GA AV ČR IAA6087601; GA ČR GA206/00/1204 Institutional research plan: CEZ:AV0Z6093917 Keywords : Borrelia burgdorferi * Lyme disease Subject RIV: EE - Microbiology, Virology Impact factor: 0.169, year: 2002

  6. Prevalence of Borrelia burgdorferi sensu lato genospecies in host-seeking Ixodes ricinus ticks in selected South Bohemian locations (Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Danielová, V.; Daniel, M.; Rudenko, Natalia; Golovchenko, Maryna

    2004-01-01

    Roč. 12, č. 3 (2004), s. 151-156 ISSN 1210-7778 R&D Projects: GA ČR GA524/03/1326 Institutional research plan: CEZ:AV0Z6022909 Keywords : Ixodes ricinus * Borrelia * Czech Republic Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine

  7. Co-inoculation of Borrelia afzelii with tick salivary gland extract influences distribution of immunocompetent cells in the skin and lymph nodes of mice

    Czech Academy of Sciences Publication Activity Database

    Severinová, Jana; Salát, Jiří; Kročová, Z.; Řezníčková, Jana; Demová, Hana; Horká, Helena; Kopecký, Jan

    2005-01-01

    Roč. 50, č. 5 (2005), s. 457-463 ISSN 0015-5632 R&D Projects: GA ČR GA524/02/0901 Institutional research plan: CEZ:AV0Z6022909 Keywords : tick salivary gland extract * inflammation * Borrelia Subject RIV: EC - Immunology Impact factor: 0.918, year: 2005

  8. Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population.

    Science.gov (United States)

    Tschirren, Barbara; Andersson, Martin; Scherman, Kristin; Westerdahl, Helena; Mittl, Peer R E; Råberg, Lars

    2013-05-22

    The discovery of the key role of Toll-like receptors (TLRs) in initiating innate immune responses and modulating adaptive immunity has revolutionized our understanding of vertebrate defence against pathogens. Yet, despite their central role in pathogen recognition and defence initiation, there is little information on how variation in TLRs influences disease susceptibility in natural populations. Here, we assessed the extent of naturally occurring polymorphisms at TLR2 in wild bank voles (Myodes glareolus) and tested for associations between TLR2 variants and infection with Borrelia afzelii, a common tick-transmitted pathogen in rodents and one of the causative agents of human Lyme disease. Bank voles in our population had 15 different TLR2 haplotypes (10 different haplotypes at the amino acid level), which grouped in three well-separated clusters. In a large-scale capture-mark-recapture study, we show that voles carrying TLR2 haplotypes of one particular cluster (TLR2c2) were almost three times less likely to be Borrelia infected than animals carrying other haplotypes. Moreover, neutrality tests suggested that TLR2 has been under positive selection. This is, to our knowledge, the first demonstration of an association between TLR polymorphism and parasitism in wildlife, and a striking example that genetic variation at innate immune receptors can have a large impact on host resistance.

  9. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis.

    Science.gov (United States)

    Rudenko, N; Golovchenko, M; Vancova, M; Clark, K; Grubhoffer, L; Oliver, J H

    2016-03-01

    Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro

    Science.gov (United States)

    Theophilus, P. A. S.; Victoria, M. J.; Socarras, K. M.; Filush, K. R.; Gupta, K.; Luecke, D. F.; Sapi, E.

    2015-01-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi. PMID:26716015

  11. Direct Molecular Detection and Genotyping of Borrelia burgdorferi from Whole Blood of Patients with Early Lyme Disease

    Science.gov (United States)

    Eshoo, Mark W.; Crowder, Christopher C.; Rebman, Alison W.; Rounds, Megan A.; Matthews, Heather E.; Picuri, John M.; Soloski, Mark J.; Ecker, David J.; Schutzer, Steven E.; Aucott, John N.

    2012-01-01

    Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion. PMID:22590620

  12. Serological studies on the infection of dogs in Ontario with Borrelia burgdorferi, the etiological agent of Lyme disease

    Science.gov (United States)

    Artsob, Harvey; Barker, Ian K.; Fister, Richard; Sephton, Gregory; Dick, Daryl; Lynch, John A.; Key, Doug

    1993-01-01

    A serological study was undertaken to determine whether dogs in Ontario are being exposed to Borrelia burgdorferi, the etiological agent of Lyme disease. This study consisted of a survey of randomly selected dogs and testing of diagnostic submissions from candidate Lyme disease cases. The survey of 1,095 dogs, bled between January 1988 and August 1989, revealed a total of 65 (5.9%) enzyme-linked immunosorbent assay (ELISA) reactors, of which 22 had immuno-fluorescent antibody assay (IFA) titers ≥1:32. All but one of the IFA-positive and 10 of the ELISA-positive, IFA-negative sera were further tested by western blot. Eight western blot positive and three equivocal reactors were obtained. Three of the eight confirmed reactors had visited areas known to be endemic for Lyme disease, leaving five reactors that might have been infected in previously undocumented areas for B. burgdorferi activity in Ontario. Diagnostic submissions of sera from 223 dogs were received between August 1987 and February 1992. Test results revealed 21 (9.4%) IFA reactors, of which only six had significant titers (≥1:256) and were reactive by an immunodot Borrelia test. All six dogs had travelled to known Lyme endemic areas. Based on results obtained from this study, it seems likely that the agent of Lyme disease is not widespread in Ontario. PMID:17424284

  13. Evaluation of BSK-H Complete Medium Supplemented with Rabbit Serum and Sodium Bicarbonate for the Growth of Borrelia anserina

    Directory of Open Access Journals (Sweden)

    Bilal Aslam, Iftikhar Hussain*, Muhammad Shahid Mahmood and Ahrar Khan1

    2013-04-01

    Full Text Available The present study was conducted to compare the effect of 3 formulations Barbour-Stoenner-Kelly (BSK medium on the growth of Borrelia (B. anserina, the causative agent of avian borreliosis. Three different formulations of BSK medium (BSK-H, BSK-II and BSK-H complete medium were prepared. For the isolation of B. anserina, Argas ticks were inoculated in all the three (BSK-H, BSK-II and BSK-H complete formulations of BSK medium. All the samples were also observed for the impact of BSK medium on the growth (Generation time, Growth per hour, Specific growth rate of B. anserina. Phase contrast microscopy was performed for the observation of viable B. anserina cells, and additional confirmation of all the isolates was done by performing indirect immunofluorescence assay and PCR. BSK-H complete medium supplemented with 6% rabbit serum and sodium bicarbonate was found best when compared to two other formulations of BSK medium with respect to the isolation, generation time and growth rate of Borrelia spirochetes.

  14. The endosomal recycling of FgSnc1 by FgSnx41-FgSnx4 heterodimer is essential for polarized growth and pathogenicity in Fusarium graminearum.

    Science.gov (United States)

    Zheng, Wenhui; Lin, Yahong; Fang, Wenqin; Zhao, Xu; Lou, Yi; Wang, Guanghui; Zheng, Huawei; Liang, Qifu; Abubakar, Yakubu Saddeeq; Olsson, Stefan; Zhou, Jie; Wang, Zonghua

    2018-04-20

    Endosomal sorting machineries regulate the transport of their cargoes among intracellular compartments. However, the molecular nature of such intracellular trafficking processes in pathogenic fungal development and pathogenicity remains unclear. Here, we dissect the roles and molecular mechanisms of two sorting nexin proteins and their cargoes in endosomal recycling in Fusarium graminearum using high-resolution microscopy and high-throughput co-immunoprecipitation strategies. We show that the sorting nexins, FgSnx41 and FgSnx4, interact with each other and assemble into a functionally interdependent heterodimer through their respective BAR domains. Further analyses demonstrate that the dimer localizes to the early endosomal membrane and coordinates endosomal sorting. The small GTPase FgRab5 regulates the correct localization of FgSnx41-FgSnx4 and is consequently required for its trafficking function. The protein FgSnc1 is a cargo of FgSnx41-FgSnx4 and regulates the fusion of secreted vesicles with the fungal growing apex and plasma membrane. In the absence of FgSnx41 or FgSnx4, FgSnc1 is mis-sorted and degraded in the vacuole, and null deletion of either component causes defects in the fungal polarized growth and virulence. Overall, for the first time, our results reveal the mechanism of FgSnc1 endosomal recycling by FgSnx41-FgSnx4 heterodimer which is essential for polarized growth and pathogenicity in F. graminearum. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  15. T2 Magnetic Resonance Assay-Based Direct Detection of Three Lyme Disease-Related Borrelia Species in Whole-Blood Samples.

    Science.gov (United States)

    Snyder, Jessica L; Giese, Heidi; Bandoski-Gralinski, Cheryl; Townsend, Jessica; Jacobson, Beck E; Shivers, Robert; Schotthoefer, Anna M; Fritsche, Thomas R; Green, Clayton; Callister, Steven M; Branda, John A; Lowery, Thomas J

    2017-08-01

    In early Lyme disease (LD), serologic testing is insensitive and seroreactivity may reflect active or past infection. In this study, we evaluated a novel assay for the direct detection of three species of Borrelia spirochetes in whole blood. The T2 magnetic resonance (T2MR) assay platform was used to amplify Borrelia DNA released from intact spirochetes and to detect amplicon. Analytical sensitivity was determined from blood spiked with known concentrations of spirochetes, and the assay's limit of detection was found to be in the single-cell-per-milliliter range: 5 cells/ml for B. afzelii and 8 cells/ml for Borrelia burgdorferi and Borrelia garinii Clinical samples ( n = 66) from confirmed or suspected early LD patients were also analyzed. B. burgdorferi was detected using T2MR in 2/2 (100%) of blood samples from patients with confirmed early LD, based on the presence of erythema migrans and documentation of seroconversion or a positive real-time blood PCR. T2MR detected B. burgdorferi in blood samples from 17/54 (31%) of patients with probable LD, based on the presence of erythema migrans without documented seroconversion or of documented seroconversion in patients with a compatible clinical syndrome but without erythema migrans. Out of 21 clinical samples tested by real-time PCR, only 1 was positive and 13 were negative with agreement with T2MR. An additional 7 samples that were negative by real-time PCR were positive with T2MR. Therefore, T2MR enables a low limit of detection (LoD) for Borrelia spp. in whole blood samples and is able to detect B. burgdorferi in clinical samples. Copyright © 2017 American Society for Microbiology.

  16. Identification of host blood-meal sources and Borrelia in field-collected Ixodes ricinus ticks in north-western Poland

    Directory of Open Access Journals (Sweden)

    Beata Wodecka

    2015-12-01

    Full Text Available Forest animals play fundamental roles in the maintenance of [i]Ixodes ricinus[/i] and [i]Borrelia[/i] species in the forest biotope. To identify the forest vertebrate species that are host for I. ricinus and for the recognition of the reservoirs of [i]Borrelia[/i] species, the blood-meal of 325 [i]I. ricinus[/i] ticks collected at two forest sites in north-western Poland were analysed. Nested PCR was used to detect polymorphisms in a fragment of the mitochondrial 12S rRNA gene for the identification of the hosts species. The products were digested with the restriction enzymes, a combination that allows the identification of 60 vertebrate species, comprising 17 bird, 4 reptile and 39 mammalian species. Host DNA was detected in 244 (75%[i] I. ricinus[/i] individuals, with the species being detected and classified for 210 (86% samples. The restriction patterns resulted in the identification of 14 vertebrate species, including 2 species of birds, lizard, badger, rabbit, deer; most of the samples contained DNA from wild boar ([i]Sus scrofa[/i], red fox ([i]Vulpes vulpes[/i], red deer ([i]Cervus elaphus[/i] and roe deer ([i]Capreolus capreolus[/i]. Identification of Borrelia species was based on the flaB gene using nested PCR coupled to RFLP. This method allows the identification of all [i]Borrelia[/i] species transmitted by [i]I. ricinus [/i]in Europe, including [i]B. miyamotoi[/i] and 3 genetic variants of [i]B. garinii[/i]. In the studied isolates, 2 species belonging to [i]B. burgdorferi[/i] sensu lato were identified – B. [i]garinii [/i]and B. [i]afzelii[/i], and B. [i]miyamotoi,[/i] which are related to relapsing fever borreliae.

  17. Antibody profile to Borrelia burgdorferi in veterinarians from Nuevo León, Mexico, a non-endemic area of this zoonosis

    Directory of Open Access Journals (Sweden)

    Cassandra M. Skinner-Taylor

    2016-07-01

    Full Text Available Objectives: Lyme disease is a tick-borne disease caused by infections with Borrelia . Persons infected with Borrelia can be asymptomatic or can develop disseminated disease. Diagnosis and recognition of groups at risk of infection with Borrelia burgdorferi is of great interest to contemporary rheumatology. There are a few reports about Borrelia infection in Mexico, including lymphocytoma cases positive to B. burgdorferi sensu stricto by PCR and a patient with acrodermatitis chronica atrophicans. Veterinarians have an occupational risk due to high rates of tick contact. The aim of this work was to investigate antibodies to Borrelia in students at the Faculty of Veterinary Medicine and Zootechnics, at Nuevo León, Mexico, and determine the antibody profile to B. burgdorferi antigens. Material and methods: Sera were screened using a C6 ELISA, IgG and IgM ELISA using recombinant proteins from B. burgdorferi , B. gariniii and B. afzelii . Sera with positive or grey-zone values were tested by IgG Western blot to B. burgdorferi sensu stricto. Results : All volunteers reported tick exposures and 72.5% remembered tick bites. Only nine persons described mild Lyme disease related symptoms, including headaches, paresthesias, myalgias and arthralgias. None of the volunteers reported erythema migrans. Nine samples were confirmed by IgG Western blot. The profile showed 89% reactivity to OspA, 67% to p83, and 45% to BmpA. Conclusions : Positive sera samples shared antibody reactivity to the markers of late immune response p83 and BmpA, even if individuals did not present symptoms of Lyme arthritis or post-Lyme disease. The best criterion to diagnose Lyme disease in our country remains to be established, because it is probable that different strains coexist in Mexico. This is the first report of antibodies to B. burgdorferi in Latin American veterinarians. Veterinarians and high-risk people should be alert to take precautionary measures to prevent tick

  18. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends

    Energy Technology Data Exchange (ETDEWEB)

    Ti, Shih-Chieh; Pamula, Melissa C.; Howes, Stuart C.; Duellberg, Christian; Cade, Nicholas I.; Kleiner, Ralph E.; Forth, Scott; Surrey, Thomas; Nogales, Eva; Kapoor, Tarun M.

    2016-04-01

    The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. In this research, we have purified and characterized tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

  19. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  20. Complex Population Structure of Lyme Borreliosis Group Spirochete Borrelia garinii in Subarctic Eurasia

    Science.gov (United States)

    Comstedt, Pär; Asokliene, Loreta; Eliasson, Ingvar; Olsen, Björn; Wallensten, Anders; Bunikis, Jonas; Bergström, Sven

    2009-01-01

    Borrelia garinii, a causative agent of Lyme borreliosis in Europe and Asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. These bird groups associate with, correspondingly, Ixodes uriae and Ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. Studies of the overlap between these two natural cycles of B. garinii have been limited, in part due to the absence of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B

  1. Probable late lyme disease: a variant manifestation of untreated Borrelia burgdorferi infection

    Science.gov (United States)

    2012-01-01

    Background Lyme disease, a bacterial infection with the tick-borne spirochete Borrelia burgdorferi, can cause early and late manifestations. The category of probable Lyme disease was recently added to the CDC surveillance case definition to describe patients with serologic evidence of exposure and physician-diagnosed disease in the absence of objective signs. We present a retrospective case series of 13 untreated patients with persistent symptoms of greater than 12 weeks duration who meet these criteria and suggest a label of ‘probable late Lyme disease’ for this presentation. Methods The sample for this analysis draws from a retrospective chart review of consecutive, adult patients presenting between August 2002 and August 2007 to the author (JA), an infectious disease specialist. Patients were included in the analysis if their current illness had lasted greater than or equal to 12 weeks duration at the time of evaluation. Results Probable late Lyme patients with positive IgG serology but no history of previous physician-documented Lyme disease or appropriate Lyme treatment were found to represent 6% of our heterogeneous sample presenting with ≥ 12 weeks of symptom duration. Patients experienced a range of symptoms including fatigue, widespread pain, and cognitive complaints. Approximately one-third of this subset reported a patient-observed rash at illness onset, with a similar proportion having been exposed to non-recommended antibiotics or glucocorticosteroid treatment for their initial disease. A clinically significant response to antibiotics treatment was noted in the majority of patients with probable late Lyme disease, although post-treatment symptom recurrence was common. Conclusions We suggest that patients with probable late Lyme disease share features with both confirmed late Lyme disease and post-treatment Lyme disease syndrome. Physicians should consider the recent inclusion of probable Lyme disease in the CDC Lyme disease surveillance

  2. Stem loop sequences specific to transposable element IS605 are found linked to lipoprotein genes in Borrelia plasmids.

    Directory of Open Access Journals (Sweden)

    Nicholas Delihas

    Full Text Available BACKGROUND: Plasmids of Borrelia species are dynamic structures that contain a large number of repetitive genes, gene fragments, and gene fusions. In addition, the transposable element IS605/200 family, as well as degenerate forms of this IS element, are prevalent. In Helicobacter pylori, flanking regions of the IS605 transposase gene contain sequences that fold into identical small stem loops. These function in transposition at the single-stranded DNA level. METHODOLOGY/PRINCIPAL FINDINGS: In work reported here, bioinformatics techniques were used to scan Borrelia plasmid genomes for IS605 transposable element specific stem loop sequences. Two variant stem loop motifs are found in the left and right flanking regions of the transposase gene. Both motifs appear to have dispersed in plasmid genomes and are found "free-standing" and phylogenetically conserved without the associated IS605 transposase gene or the adjacent flanking sequence. Importantly, IS605 specific stem loop sequences are also found at the 3' ends of lipoprotein genes (PFam12 and PFam60, however the left and right sequences appear to develop their own evolutionary patterns. The lipoprotein gene-linked left stem loop sequences maintain the IS605 stem loop motif in orthologs but only at the RNA level. These show mutations whereby variants fold into phylogenetically conserved RNA-type stem loops that contain the wobble non-Watson-Crick G-U base-pairing. The right flanking sequence is associated with the family lipoprotein-1 genes. A comparison of homologs shows that the IS605 stem loop motif rapidly dissipates, but a more elaborate secondary structure appears to develop in its place. CONCLUSIONS/SIGNIFICANCE: Stem loop sequences specific to the transposable element IS605 are present in plasmid regions devoid of a transposase gene and significantly, are found linked to lipoprotein genes in Borrelia plasmids. These sequences are evolutionarily conserved and/or structurally developed in

  3. The Presence of Borrelia miyamotoi, A Relapsing Fever Spirochaete, in Questing Ixodes ricinus in Belgium and in The Netherlands.

    Science.gov (United States)

    Cochez, C; Heyman, P; Heylen, D; Fonville, M; Hengeveld, P; Takken, W; Simons, L; Sprong, H

    2015-08-01

    Borrelia miyamotoi is a tick-borne bacterium that may cause relapsing fever in humans. As this pathogen has been discovered in Europe only recently, only little is known about its local impact on human health and its spatial distribution. In this study, we show the results of PCR screenings for B. miyamotoi in flagged Ixodes ricinus from Belgium and the Netherlands. B. miyamotoi was detected in nine of thirteen, and three of five locations from the Netherlands and Belgium, respectively. These outcomes indicate that B. miyamotoi is more spread than previously thought. The mean infection rate B. miyamotoi was 1.14% for Belgium and 3.84% for the Netherlands. © 2014 Blackwell Verlag GmbH.

  4. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion.

    Science.gov (United States)

    Zhang, J R; Norris, S J

    1998-08-01

    The Lyme disease spirochete Borrelia burgdorferi possesses 15 silent vls cassettes and a vls expression site (vlsE) encoding a surface-exposed lipoprotein. Segments of the silent vls cassettes have been shown to recombine with the vlsE cassette region in the mammalian host, resulting in combinatorial antigenic variation. Despite promiscuous recombination within the vlsE cassette region, the 5' and 3' coding sequences of vlsE that flank the cassette region are not subject to sequence variation during these recombination events. The segments of the silent vls cassettes recombine in the vlsE cassette region through a unidirectional process such that the sequence and organization of the silent vls loci are not affected. As a result of recombination, the previously expressed segments are replaced by incoming segments and apparently degraded. These results provide evidence for a gene conversion mechanism in VlsE antigenic variation.

  5. Selective Assembly of Na,K-ATPase α2β2 Heterodimers in the Heart: DISTINCT FUNCTIONAL PROPERTIES AND ISOFORM-SELECTIVE INHIBITORS.

    Science.gov (United States)

    Habeck, Michael; Tokhtaeva, Elmira; Nadav, Yotam; Ben Zeev, Efrat; Ferris, Sean P; Kaufman, Randal J; Bab-Dinitz, Elizabeta; Kaplan, Jack H; Dada, Laura A; Farfel, Zvi; Tal, Daniel M; Katz, Adriana; Sachs, George; Vagin, Olga; Karlish, Steven J D

    2016-10-28

    The Na,K-ATPase α 2 subunit plays a key role in cardiac muscle contraction by regulating intracellular Ca 2+ , whereas α 1 has a more conventional role of maintaining ion homeostasis. The β subunit differentially regulates maturation, trafficking, and activity of α-β heterodimers. It is not known whether the distinct role of α 2 in the heart is related to selective assembly with a particular one of the three β isoforms. We show here by immunofluorescence and co-immunoprecipitation that α 2 is preferentially expressed with β 2 in T-tubules of cardiac myocytes, forming α 2 β 2 heterodimers. We have expressed human α 1 β 1 , α 2 β 1 , α 2 β 2 , and α 2 β 3 in Pichia pastoris, purified the complexes, and compared their functional properties. α 2 β 2 and α 2 β 3 differ significantly from both α 2 β 1 and α 1 β 1 in having a higher K 0.5 K + and lower K 0.5 Na + for activating Na,K-ATPase. These features are the result of a large reduction in binding affinity for extracellular K + and shift of the E 1 P-E 2 P conformational equilibrium toward E 1 P. A screen of perhydro-1,4-oxazepine derivatives of digoxin identified several derivatives (e.g. cyclobutyl) with strongly increased selectivity for inhibition of α 2 β 2 and α 2 β 3 over α 1 β 1 (range 22-33-fold). Molecular modeling suggests a possible basis for isoform selectivity. The preferential assembly, specific T-tubular localization, and low K + affinity of α 2 β 2 could allow an acute response to raised ambient K + concentrations in physiological conditions and explain the importance of α 2 β 2 for cardiac muscle contractility. The high sensitivity of α 2 β 2 to digoxin derivatives explains beneficial effects of cardiac glycosides for treatment of heart failure and potential of α 2 β 2 -selective digoxin derivatives for reducing cardiotoxicity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Modulation of expression of the nuclear receptor NR0B2 (small heterodimer partner 1 and its impact on proliferation of renal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Prestin K

    2016-08-01

    Full Text Available Katharina Prestin,1,* Maria Olbert,2,* Janine Hussner,1 Tamara L Isenegger,1 Daniel G Gliesche,1 Kerstin Böttcher,2 Uwe Zimmermann,3 Henriette E Meyer zu Schwabedissen1 1Department of Pharmaceutical Sciences, Biopharmacy, University of Basel, Basel, Switzerland; 2Center of Drug Absorption and Transport, Institute of Pharmacology, 3Department of Urology, University Medicine Greifswald, Greifswald, Germany *These authors contributed equally to this work Abstract: Mammalian nuclear receptors (NRs are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2 is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity. The aim of our study was to elucidate whether NR0B2 may also play a role in other tumor entities. Comparing NR0B2 expression in renal cell carcinoma and adjacent nonmalignant transformed tissue revealed significant downregulation in vivo. Additionally, the impact of heterologous expression of NR0B2 on cell cycle progression and proliferation in cells of renal origin was characterized. Monitoring fluorescence intensity of resazurin turnover in RCC-EW cells revealed no significant differences in metabolic activity in the presence of NR0B2. However, there was a significant decrease of cellular proliferation in cells overexpressing this NR, and NR0B2 was more efficient than currently used antiproliferative agents. Furthermore, flow cytometry analysis showed that heterologous overexpression of NR0B2 significantly reduced the amount of cells passing the G1 phase, while on

  7. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation.

    Science.gov (United States)

    Wang, Jingxiao; Zheng, Yuanna; Zhao, Juan; Liu, Tie; Gao, Lixia; Gu, Zhiyuan; Wu, Gang

    2012-01-01

    To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created surrounding SLA-treated titanium implants (3.1 mm in diameter, 10 mm in length) in minipig's calvaria. We administrated collagen sponges with adsorbed low-dose (30 ng/mm(3) ) BMP2/7 to treat the defects using BMP2, BMP7 or no BMP as controls.2, 3 and 6 weeks after implantation, we adopted micro-computer tomography to evaluate the micro-architectures of new bone using the following parameters: relative bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), connectivity density, and structure mode index (SMI). Bone implant contact (BIC) was also revealed histologically. Consistent with 2 and 3 weeks, after 6 weeks post-operation, BMP2/7 resulted in significantly higher BV/TV (63.033 ± 2.055%) and significantly lower SMI (-4.405 ± 0.500) than BMP2 (BV/TV: 43.133 ± 2.001%; SMI: -0.086 ± 0.041) and BMP7 (BV/TV: 41.467 ± 1.850%; SMI: -0.044 ± 0.016) respectively. Significant differences were also found in Tb.N, Tb.Th and Tb.Sp at all time points. At 2 weeks, BMP2/7 resulted in significantly higher BIC than the controls. Low-dose BMP2/7 heterodimer facilitated more rapid bone regeneration in better quality in peri-implant bone defects than BMP2 and BMP7 homodimers. © 2011 John Wiley & Sons A/S.

  8. Recurrent evolution of host and vector association in bacteria of the Borrelia burgdorferi sensu lato species complex.

    Science.gov (United States)

    Becker, Noémie S; Margos, Gabriele; Blum, Helmut; Krebs, Stefan; Graf, Alexander; Lane, Robert S; Castillo-Ramírez, Santiago; Sing, Andreas; Fingerle, Volker

    2016-09-15

    The Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations. Illumina Technology was used to obtain genome-wide sequence data for 93 strains of 14 named genospecies of the B. burgdorferi species complex and genomic data already published for 18 additional strain (including one new species) was added. Phylogenetic reconstruction based on 114 orthologous single copy genes shows that the genospecies represent clearly distinguishable taxa with recent and still ongoing speciation events apparent in Europe and Asia. The position of Borrelia species in the phylogeny is consistent with host associations constituting a major driver for speciation. Interestingly, the data also demonstrate that vector associations are an additional driver for diversification in this tick-borne species complex. This is particularly obvious in B. bavariensis, a rodent adapted species that has diverged from the bird-associated B. garinii most likely in Asia. It now consists of two populations one of which most probably invaded Europe following adaptation to a new vector (Ixodes ricinus) and currently expands its distribution range. The results imply that genotypes/species with novel properties regarding host or vector associations have evolved recurrently during the history of the species complex and may emerge at any time. We suggest that the finding of vector associations as a driver for diversification may be a general pattern for tick-borne pathogens. The core genome analysis presented here

  9. Lyme disease caused by Borrelia burgdorferi with two homeologous 16S rRNA genes: a case report

    Directory of Open Access Journals (Sweden)

    Lee SH

    2016-04-01

    Full Text Available Sin Hang Lee,1,21Pathology Department, Milford Hospital, Milford, CT, USA; 2Milford Molecular Diagnostics, Milford, CT, USA Abstract: Lyme disease (LD, the most common tick-borne disease in North America, is believed to be caused exclusively by Borrelia burgdorferi sensu stricto and is usually diagnosed by clinical evaluation and serologic assays. As reported previously in a peer-reviewed article, a 13-year-old boy living in the Northeast of the USA was initially diagnosed with LD based on evaluation of his clinical presentations and on serologic test results. The patient was treated with a course of oral doxycycline for 28 days, and the symptoms resolved. A year later, the boy developed a series of unusual symptoms and did not attend school for 1 year. A LD specialist reviewed the case and found the serologic test band patterns nondiagnostic of LD. The boy was admitted to a psychiatric hospital. After discharge from the psychiatric hospital, a polymerase chain reaction test performed in a winter month when the boy was 16 years old showed a low density of B. burgdorferi sensu lato in the blood of the patient, confirmed by partial 16S rRNA (ribosomal RNA gene sequencing. Subsequent DNA sequencing analysis presented in this report demonstrated that the spirochete isolate was a novel strain of B. burgdorferi with two homeologous 16S rRNA genes, which has never been reported in the world literature. This case report shows that direct DNA sequencing is a valuable tool for reliable molecular diagnosis of Lyme and related borrelioses, as well as for studies of the diversity of the causative agents of LD because LD patients infected by a rare or novel borrelial variant may produce an antibody pattern that can be different from the pattern characteristic of an infection caused by a typical B. burgdorferi sensu stricto strain. Keywords: Lyme disease, Borrelia burgdorferi, homeologous 16S rRNA genes, DNA sequencing

  10. The role of Ixodes scapularis, Borrelia burgdorferi and wildlife hosts in Lyme disease prevalence: A quantitative review.

    Science.gov (United States)

    Halsey, Samniqueka J; Allan, Brian F; Miller, James R

    2018-04-16

    Due to the ongoing expansion of Ixodes scapularis (blacklegged tick) throughout the northeastern and midwestern United States, there is need to identify the role wildlife hosts play in the establishment and maintenance of tick populations. To quantify and synthesize the patterns of I. scapularis and Borrelia burgdorferi sensu stricto and sensu lato prevalence relative to wildlife hosts, we reviewed the findings of independent studies conducted throughout the United States. We performed a comprehensive literature search from 1970 to 2017 using the ISS Web of Science Core Collection and the keywords "Ixodes scapularis," "Ixodes dammini" and "Borrelia burgdorferi." We identified 116 studies for inclusion in our meta-analysis, with 187,414 individual wildlife hosts captured and examined for I. scapularis and either the host or ticks collected subsequently tested for B. burgdorferi. We found that only 13% of the wildlife mammals sampled comprised species other than Odocoileus virginianus (white-tailed deer) and Peromyscus leucopus (white-footed mouse). To examine whether there were regional differences between the Northeast, Midwest and the Southeast U.S. in I. scapularis infestation rates on wildlife hosts, we used general linear models (glm), with post hoc pairwise comparisons. In most cases, detection of I. scapularis and B. burgdorferi was significantly higher in the Northeast than the Midwest. Using data on host-specific I. scapularis infestation prevalence, B. burgdorferi prevalence in feeding larvae, and host permissiveness, we developed an epizootiological model to determine the relative contributions of individual hosts to B. burgdorferi-infected nymphs. Our model provides additional evidence that wildlife hosts other than P. leucopus may contribute more to Lyme disease risk than commonly thought. To aid in understanding the ecology of Lyme disease, we propose that additional studies sample non-Peromyscus spp. hosts to obtain more detailed tick and pathogen

  11. Closely-related Borrelia burgdorferi (sensu stricto) strains exhibit similar fitness in single infections and asymmetric competition in multiple infections.

    Science.gov (United States)

    Rynkiewicz, Evelyn C; Brown, Julia; Tufts, Danielle M; Huang, Ching-I; Kampen, Helge; Bent, Stephen J; Fish, Durland; Diuk-Wasser, Maria A

    2017-02-06

    Wild hosts are commonly co-infected with complex, genetically diverse, pathogen communities. Competition is expected between genetically or ecologically similar pathogen strains which may influence patterns of coexistence. However, there is little data on how specific strains of these diverse pathogen species interact within the host and how this impacts pathogen persistence in nature. Ticks are the most common disease vector in temperate regions with Borrelia burgdorferi, the causative agent of Lyme disease, being the most common vector-borne pathogen in North America. Borrelia burgdorferi is a pathogen of high public health concern and there is significant variation in infection phenotype between strains, which influences predictions of pathogen dynamics and spread. In a laboratory experiment, we investigated whether two closely-related strains of B. burgdorferi (sensu stricto) showed similar transmission phenotypes, how the transmission of these strains changed when a host was infected with one strain, re-infected with the same strain, or co-infected with two strains. Ixodes scapularis, the black-legged tick, nymphs were used to sequentially infect laboratory-bred Peromyscus leucopus, white-footed mice, with one strain only, homologous infection with the same stain, or heterologous infection with both strains. We used the results of this laboratory experiment to simulate long-term persistence and maintenance of each strain in a simple simulation model. Strain LG734 was more competitive than BL206, showing no difference in transmission between the heterologous infection groups and single-infection controls, while strain BL206 transmission was significantly reduced when strain LG734 infected first. The results of the model show that this asymmetry in competition could lead to extinction of strain BL206 unless there was a tick-to-host transmission advantage to this less competitive strain. This asymmetric competitive interaction suggests that strain identity and

  12. Evaluation of recomBead Borrelia. Quantitative analysis using 13 antigens for IgM and IgG. Do Borrelia IgM antibodies have diagnostic use in Northern Scandinavia? - A comparison of sero-reactivity of samples from Åland and Denmark

    DEFF Research Database (Denmark)

    Dessau, Ram; Møller, Jens Kjølseth

    2012-01-01

    Evaluering af recomBead borrelia. Ny multiplex metode. Der blev præsenteret overvejelser om hvordan man skal score den den store mængde resultater for at opnå optimal diagnostisk diskriminations evne. Disse metode overvejelser er var vigtige, da det samme kit afprøves både to steder i Sverige ogs...

  13. Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas.

    Science.gov (United States)

    Ralfkiaer, E; Wollf-Sneedorff, A; Vejlsgaard, G L

    1991-11-01

    Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.

  14. Coordinated Expression of Borrelia burgdorferi Complement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle▿

    OpenAIRE

    Bykowski, Tomasz; Woodman, Michael E.; Cooley, Anne E.; Brissette, Catherine A.; Brade, Volker; Wallich, Reinhard; Kraiczy, Peter; Stevenson, Brian

    2007-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts’ alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three ...

  15. Tick-Borne Relapsing Fever Imported from West Africa: Diagnosis by Quantitative Buffy Coat Analysis and In Vitro Culture of Borrelia crocidurae

    OpenAIRE

    van Dam, Alje P.; van Gool, Tom; Wetsteyn, José C. F. M.; Dankert, Jacob

    1999-01-01

    West African tick-borne relapsing fever (TBRF) is difficult to diagnose due to the low number of spirochetes in the bloodstream of patients. Previously, the causative microorganism, Borrelia crocidurae, had never been cultured in vitro. TBRF was rapidly diagnosed for two patients returning from western Africa with fever of unknown origin by quantitative buffy coat (QBC) analysis. Diagnosis was confirmed by intraperitoneal inoculation of blood specimens from patients into laboratory mice. In v...

  16. Detection of Borrelia bissetii in the South Bohemia region of the Czech Republic: cases of single and multiple infections in humans

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Piskunova, N.; Růžek, Daniel; Grubhoffer, Libor

    2008-01-01

    Roč. 14, S7 (2008), S109-S110 ISSN 1198-743X. [ECCMID /18./. 19.04.2008-22.04.2008, Barcelona] R&D Projects: GA MŠk(CZ) LC06009; GA ČR GD524/03/H133; GA ČR(CZ) GA524/06/1479 Institutional research plan: CEZ:AV0Z60220518 Keywords : Lyme disease * Borrelia bissettii * causative agent * human samples Subject RIV: EC - Immunology

  17. Detection of Borrelia bissettii in cardiac valve tissue of a patient with endocarditis and aortic valve stenosis in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Rudenko, Natalia; Golovchenko, Maryna; Mokráček, A.; Piskunova, N.; Růžek, Daniel; Mallátová, N.; Grubhoffer, Libor

    2008-01-01

    Roč. 46, č. 10 (2008), s. 3540-3543 ISSN 0095-1137 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GD524/03/H133; GA ČR(CZ) GA524/06/1479 Institutional research plan: CEZ:AV0Z60220518 Keywords : Lyme disease * Borrelia bissettii * carditis * causative agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.945, year: 2008

  18. 北海道におけるBorrelia spp.の伝播に対する鹿の役割 [全文の要約

    OpenAIRE

    李, 景利

    2014-01-01

    The intent of this research was to describe the role of deer in the transmission of different species of Borrelia spp. Sika deer (Cervus nippon yesoensis) are the hosts of ticks of various species and stages in Hokkaido. Deer overpopulation has caused problems with forestry and agricultural production. The potential of deer involvement in zoonoses is also being watched. In this study, deer caught in the nuisance control scheme and ticks collected from deer and the field were tested to detect ...

  19. Validate or falsify: Lessons learned from a microscopy method claimed to be useful for detecting Borrelia and Babesia organisms in human blood

    Czech Academy of Sciences Publication Activity Database

    Aase, A.; Hajdušek, Ondřej; Øines, Ø.; Quarsten, H.; Wilhelmsson, P.; Herstad, T.K.; Kjelland, V.; Šíma, Radek; Jalovecká, Marie; Lindgren, P-E.; Aaberge, I.S.

    2016-01-01

    Roč. 48, č. 6 (2016), s. 411-419 ISSN 2374-4235 R&D Projects: GA ČR GP13-27630P; GA ČR GP13-12816P EU Projects: European Commission(XE) 316304 - MODBIOLIN Institutional support: RVO:60077344 Keywords : Lyme disease * Borrelia burgdorferi sensu lato * babesiosis * Babesia spp. * Lyme borreliosis * PCR * microscopy Subject RIV: EC - Immunology Impact factor: 1.119, year: 2016

  20. Exposure to hepatitis E virus, hepatitis A virus and Borrelia spp. infections in forest rangers from a single forest district in western Poland.

    Science.gov (United States)

    Bura, Maciej; Bukowska, Alicja; Michalak, Michał; Bura, Aleksandra; Nawrocki, Mariusz J; Karczewski, Marek; Mozer-Lisewska, Iwona

    2018-03-13

    Hepatitis E virus (HEV) infection is an emerging problem in developed countries. At least 2 zoonotic genotypes of the virus (HEV-3 and HEV-4) infect human beings. There are some data suggesting that forest rangers (FRs) can be at a higher risk of contact with HEV. The aim of this study was to assess the prevalence of HEV exposure markers in FRs from a single forest district in Greater Poland in relation to anti-HAV (hepatitis A virus) IgG, and anti-Borrelia spp. IgM and IgG antibodies. In total, 138 participants (48 FRs and 90 blood donors - BDs) were tested for anti-HEV IgM and IgG (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and 96 individuals (48 FRs and 48 BDs) were tested for anti-HAV IgG (ARCHITECT immunoassays, Abbott Laboratories, Wiesbaden, Germany); anti-Borrelia IgM and IgG (EUROIMMUN kits) were assessed in FRs only. Anti-HEV markers were detected in 3 participants (2.2%; IgM in 1 FR, IgG in 2 BDs), less frequently than anti-HAV (16 out of 96 individuals, about 17%; FRs 19% vs BDs 15%) or anti-Borrelia antibodies (18 out of 48 individuals, 37.5%) (p < 0.0001 for both). Older study participants (≥45 years of age) were more frequently HAV-seropositive (29% vs 4% of the younger individuals; p = 0.0012). We failed to unequivocally prove HEV exposure in FRs. The HAV seroprevalence in this study paralleled the situation in the general population. Exposure to Borrelia spp. in FRs was common.

  1. Prevalence of Borrelia burgdorferi in ticks removed from skin of people and circumstances of being bitten – research from the area of Poland, 2012–2014

    Directory of Open Access Journals (Sweden)

    Edyta Gałęziowska

    2018-03-01

    Infestation of ticks infected with Lyme disease spirochete in this study proved to be variable and depend on the season, the area of tick attack and the region in Poland. The results of the study clearly show that ticks infected with Borrelia burgdorferi inhabit all regions of Poland. The results are consistent with National Institute of Hygiene data which indicates that Lyme disease cases are recorded in all regions of Poland.

  2. Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks

    Czech Academy of Sciences Publication Activity Database

    Horká, Helena; Černá-Kýčková, Kateřina; Skallová, Anna; Kopecký, Jan

    2009-01-01

    Roč. 299, č. 5 (2009), s. 373-380 ISSN 1438-4221 R&D Projects: GA AV ČR IAA600960811; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi * Ixodes ricinus * saliva-activated transmission * real-time PCR Subject RIV: EC - Immunology Impact factor: 2.802, year: 2009

  3. Search for Borrelia sp. in ticks collected from potential reservoirs in an urban forest reserve in the State of Mato Grosso do Sul, Brazil: a short report

    Directory of Open Access Journals (Sweden)

    IP da Costa

    2002-07-01

    Full Text Available A total of 128 ticks of the genus Amblyomma were recovered from 5 marsupials (Didelphis albiventris - with 4 recaptures - and 17 rodents (16 Bolomys lasiurus and 1 Rattus norvegicus captured in an urban forest reserve in Campo Grande, State of Mato Grosso do Sul, Brazil. Of the ticks collected, 95 (78.9% were in larval form and 22 (21.1% were nymphs; the only adult (0.8% was identified as A. cajennense. Viewed under dark-field microscopy in the fourth month after seeding, 9 cultures prepared from spleens and livers of the rodents, blood of the marsupials, and macerates of Amblyomma sp. nymphs revealed spiral-shaped, spirochete-like structures resembling those of Borrelia sp. Some of them showed little motility, while others were non-motile. No such structures could be found either in positive Giemsa-stained culture smears or under electron microscopy. No PCR amplification of DNA from those cultures could be obtained by employing Leptospira sp., B. burgdorferi, and Borrelia sp. primers. These aspects suggest that the spirochete-like structures found in this study do not fit into the genera Borrelia or Leptospira, requiring instead to be isolated for proper identification.

  4. Molecular Survey on Rickettsia spp., Anaplasma phagocytophilum, Borrelia burgdorferi Sensu Lato, and Babesia spp. in Ixodes ricinus Ticks Infesting Dogs in Central Italy.

    Science.gov (United States)

    Morganti, Giulia; Gavaudan, Stefano; Canonico, Cristina; Ravagnan, Silvia; Olivieri, Emanuela; Diaferia, Manuela; Marenzoni, Maria Luisa; Antognoni, Maria Teresa; Capelli, Gioia; Silaghi, Cornelia; Veronesi, Fabrizia

    2017-11-01

    Dogs are a common feeding hosts for Ixodes ricinus and may act as reservoir hosts for zoonotic tick-borne pathogens (TBPs) and as carriers of infected ticks into human settings. The aim of this work was to evaluate the presence of several selected TBPs of significant public health concern by molecular methods in I. ricinus recovered from dogs living in urban and suburban settings in central Italy. A total of 212 I. ricinus specimens were collected from the coat of domestic dogs. DNA was extracted from each specimen individually and tested for Rickettsia spp., Borrelia burgdorferi sensu lato, Babesia spp., and Anaplasma phagocytophilum, using real-time and conventional PCR protocols, followed by sequencing. Sixty-one ticks (28.8%) tested positive for TBPs; 57 samples were infected by one pathogen, while four showed coinfections. Rickettsia spp. was detected in 39 specimens (18.4%), of which 32 were identified as Rickettsia monacensis and seven as Rickettsia helvetica. Twenty-two samples (10.4%) tested positive for A. phagocytophilum; Borrelia lusitaniae and Borrelia afzelii were detected in two specimens and one specimen, respectively. One tick (0.5%) was found to be positive for Babesia venatorum (EU1). Our findings reveal the significant exposure of dogs to TBPs of public health concern and provide data on the role of dogs in the circulation of I. ricinus-borne pathogens in central Italy.

  5. Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of “Humanized” Multiple Sclerosis-like Disease*

    Science.gov (United States)

    Kaushansky, Nathali; Eisenstein, Miriam; Boura-Halfon, Sigalit; Hansen, Bjarke Endel; Nielsen, Claus Henrik; Milo, Ron; Zeilig, Gabriel; Lassmann, Hans; Altmann, Daniel M.; Ben-Nun, Avraham

    2015-01-01

    Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new “humanized” model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142–161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142–161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142–161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142–161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142–161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS

  6. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

    Directory of Open Access Journals (Sweden)

    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

  7. Canine infection with Borrelia burgdorferi, Dirofilaria immitis, Anaplasma spp. and Ehrlichia spp. in Canada, 2013-2014.

    Science.gov (United States)

    Herrin, Brian H; Peregrine, Andrew S; Goring, Jonas; Beall, Melissa J; Little, Susan E

    2017-05-19

    Canine test results generated by veterinarians throughout Canada from 2013-2014 were evaluated to assess the geographical distribution of canine infection with Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia spp., and Anaplasma spp. The percent positive test results of 115,636 SNAP® 4Dx® Plus tests from dogs tested were collated by province and municipality to determine the distribution of these vector-borne infections in Canada. A total of 2,844/115,636 (2.5%) dogs tested positive for antibody to B. burgdorferi. In contrast, positive test results for D. immitis antigen and antibodies to Ehrlichia spp. and Anaplasma spp. were low, with less than 0.5% of dogs testing positive for any one of these three agents nationwide. Provincial seroprevalence for antibodies to B. burgdorferi ranged from 0.5% (Saskatchewan)-15.7% (Nova Scotia); the areas of highest percent positive test results were in proximity to regions in the USA considered endemic for Lyme borreliosis, including Nova Scotia (15.7%) and Eastern Ontario (5.1%). These high endemic foci, which had significantly higher percent positive test results than the rest of the nation (P Canada. Using dogs as sentinels for these pathogens can aid in recognition of the public and veterinary health threat that each pose.

  8. Polysynovitis in a horse due to [i]Borrelia burgdorferi[/i] sensu lato infection – Case study

    Directory of Open Access Journals (Sweden)

    Fabrizio Passamonti

    2015-05-01

    Full Text Available Lyme borreliosis (LB is a multi-systemic tick-borne disease affecting both humans and animals, including horses, and is caused by a group of interrelated spirochetes classified within the[i] Borrelia burgdorferi [/i]sensu lato (s.l. complex. Despite the high reported seroprevalence in the European equine population for [i]B. burgdorferi[/i] s.l., to-date no documented clinical cases have been described. A 6-year-old Paint gelding was referred with a history of three weeks of fever, intermittent lameness and digital flexor tendon sheath effusion of the right hind limb. Based on a strict diagnostic protocol, which included serological tests for infectious diseases and molecular investigations, a final diagnosis was made of polysynovitis due to [i]B. burgdorferi [/i]s.l. infection. An unreported aspect observed in this case was the absence of the pathogen DNA in two of the affected joints. To the authors’ knowledge, the case described represents the first documented clinical case of equine LB in Italy. Moreover, the absence of pathogen DNA in two of the affected joints observed in this case revealed a possible similarity with the same condition described in humans, where an immunomediated pathogenesis for arthropathy due to [i]B. burgdorferi[/i] s.l. infection is suspected. Since humans and horses share the same habitat, this report supports the role of the horse as potential sentinel for human biological risk.

  9. Leptospira spp. vaccinal antibodies do not react with Borrelia burgdorferi peptides used in the AccuPlex 4.

    Science.gov (United States)

    Caress, Amber L; Moroff, Scott; Lappin, Michael R

    2017-11-01

    We attempted to determine if Leptospira spp. antibodies induced by vaccination would cross-react with Borrelia burgdorferi antigens used in a commercial automated immunofluorescent assay (AccuPlex 4 BioCD; Antech). Staff- and student-owned dogs ( n = 31) were recruited at a veterinary teaching hospital in a B. burgdorferi nonendemic area. The dogs were randomized and administered 1 of 4 commercial Leptospira spp. vaccines that contained serovars Canicola, Grippotyphosa, Icterohaemorrhagiae, and Pomona, then booster vaccinated 3 wk later. Blood was collected on weeks 0, 3, 4, 8, and 12. After confirming that maximal Leptospira spp. titers occurred on week 4, aliquots of sera from week 4 were shipped frozen for analysis of B. burgdorferi antibodies against OspA, OspC, OspF, P39, and SLP with the AccuPlex system. Week 4 sera from all 31 dogs had a titer of 1:100 for at least 1 Leptospira spp. serovar. Titers of 1:800 or greater were detected against multiple serovars in 27 dogs. None of the samples contained antibodies against the B. burgdorferi OspA, OspC, OspF, P39, and SLP peptides used in the commercial assay. The B. burgdorferi peptides used in the AccuPlex system do not recognize naturally occurring Leptospira spp. antibodies or those induced by the commercial Leptospira spp. vaccines administered in our study.

  10. Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival.

    Science.gov (United States)

    Caine, Jennifer A; Lin, Yi-Pin; Kessler, Julie R; Sato, Hiromi; Leong, John M; Coburn, Jenifer

    2017-12-01

    Borrelia burgdorferi (Bb) is the causative agent of Lyme disease in the United States, a disease that can result in carditis, and chronic and debilitating arthritis and/or neurologic symptoms if left untreated. Bb survives in the midgut of the Ixodes scapularis tick, or within tissues of immunocompetent hosts. In the early stages of infection, the bacteria are present in the bloodstream where they must resist clearance by the innate immune system of the host. We have found a novel role for outer surface protein C (OspC) from B. burgdorferi and B. garinii in interactions with the complement component C4b and bloodstream survival in vivo. Our data show that OspC inhibits the classical and lectin complement pathways and competes with complement protein C2 for C4b binding. Resistance to complement is important for maintenance of the lifecycle of Bb, enabling survival of the pathogen within the host as well as in the midgut of a feeding tick when ospC expression is induced. © 2017 John Wiley & Sons Ltd.

  11. Minimal role of eastern fence lizards in Borrelia burgdorferi transmission in central New Jersey oak/pine woodlands

    Science.gov (United States)

    Rulison, Eric L.; Kerr, Kaetlyn T; Dyer, Megan C; Han, Seungeun; Burke, Russell L.; Tsao, Jean I.; Ginsberg, Howard S.

    2014-01-01

    The Eastern fence lizard, Sceloporus undulatus, is widely distributed in eastern and central North America, ranging through areas with high levels of Lyme disease, as well as areas where Lyme disease is rare or absent. We studied the potential role of S. undulatus in transmission dynamics of Lyme spirochetes by sampling ticks from a variety of natural hosts at field sites in central New Jersey, and by testing the reservoir competence of S. undulatus for Borrelia burgdorferi in the laboratory. The infestation rate of ticks on fence lizards was extremely low (proportion infested = 0.087, n = 23) compared to that on white footed mice and other small mammals (proportion infested = 0.53, n = 140). Of 159 nymphs that had fed as larvae on lizards that had previously been exposed to infected nymphs, none was infected with B. burgdorferi, compared with 79.9% of 209 nymphs that had fed as larvae on infected control mice. Simulations suggest that changes in the numbers of fence lizards in a natural habitat would have little effect on the infection rate of nymphal ticks with Lyme spirochetes. We conclude that in central New Jersey S. undulatus plays a minimal role in the enzootic transmission cycle of Lyme spirochetes.

  12. Managing Japanese barberry (Ranunculales: Berberidaceae) infestations reduces blacklegged tick (Acari: Ixodidae) abundance and infection prevalence with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae).

    Science.gov (United States)

    Williams, Scott C; Ward, Jeffrey S; Worthley, Thomas E; Stafford, Kirby C

    2009-08-01

    In many Connecticut forests with an overabundance of white-tailed deer (Odocoileus virginianus Zimmermann), Japanese barberry (Berberis thunbergii DC) has become the dominant understory shrub, which may provide a habitat favorable to blacklegged tick (Ixodes scapularis Say) and white-footed mouse (Peromyscus leucopus Rafinesque) survival. To determine mouse and larval tick abundances at three replicate sites over 2 yr, mice were trapped in unmanipulated dense barberry infestations, areas where barberry was controlled, and areas where barberry was absent. The number of feeding larval ticks/mouse was recorded. Adult and nymphal ticks were sampled along 200-m draglines in each treatment, retained, and were tested for Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and Brenner) presence. Total first-captured mouse counts did not differ between treatments. Mean number of feeding larval ticks per mouse was highest on mice captured in dense barberry. Adult tick densities in dense barberry were higher than in both controlled barberry and no barberry areas. Ticks sampled from full barberry infestations and controlled barberry areas had similar infection prevalence with B. burgdorferi the first year. In areas where barberry was controlled, infection prevalence was reduced to equal that of no barberry areas the second year of the study. Results indicate that managing Japanese barberry will have a positive effect on public health by reducing the number of B. burgdorferi-infected blacklegged ticks that can develop into motile life stages that commonly feed on humans.

  13. Competitive advantage of Borrelia burgdorferi with outer surface protein BBA03 during tick-mediated infection of the mammalian host.

    Science.gov (United States)

    Bestor, Aaron; Rego, Ryan O M; Tilly, Kit; Rosa, Patricia A

    2012-10-01

    Linear plasmid lp54 is one of the most highly conserved and differentially expressed elements of the segmented genome of the Lyme disease spirochete Borrelia burgdorferi. We previously reported that deletion of a 4.1-kb region of lp54 (bba01 to bba07 [bba01-bba07]) led to a slight attenuation of tick-transmitted infection in mice following challenge with a large number of infected ticks. In the current study, we reduced the number of ticks in the challenge to more closely mimic the natural dose and found a profound defect in tick-transmitted infection of the bba01-bba07 mutant relative to wild-type B. burgdorferi. We next focused on deletion of bba03 as the most likely cause of this mutant phenotype, as previous studies have shown that expression of bba03 is increased by culture conditions that simulate tick feeding. Consistent with this hypothesis, we demonstrated increased expression of bba03 by spirochetes in fed relative to unfed ticks. We also observed that a bba03 deletion mutant, although fully competent by itself, did not efficiently infect mice when transmitted by ticks that were simultaneously coinfected with wild-type B. burgdorferi. These results suggest that BBA03 provides a competitive advantage to spirochetes carrying this protein during tick transmission to a mammalian host in the natural infectious cycle.

  14. Borrelia burgdorferi in small mammal reservoirs in Kentucky, a traditionally non-endemic state for Lyme disease.

    Science.gov (United States)

    Buchholz, Matthew J; Davis, Cheryl; Rowland, Naomi S; Dick, Carl W

    2018-04-01

    The incidence of tick-borne zoonoses such as Lyme disease has steadily increased in the southeastern United States. Southeastern states accounted for 1500 of over 28,000 confirmed cases of Lyme disease reported in the United States during 2015. Borrelia burgdorferi, the etiologic agent of Lyme disease, is maintained in small mammal reservoirs and vectored to new hosts by ixodid ticks. This study examined ecological relationships of the B. burgdorferi/vector/reservoir system in order to understand the dynamics of Lyme disease risk in Kentucky. Small mammals were captured using live traps from November 2014 to October 2015. Ticks were removed and blood and tissue collected from small mammals were screened for B. burgdorferi DNA by PCR with primers specific to the OspA gene. Prevalence of B. burgdorferi (21.8%) in Kentucky small mammals was comparable to the lowest recorded prevalence in regions where Lyme disease is endemic. Moreover, infestation of small mammals by Ixodes scapularis, the primary vector of B. burgdorferi, was rare, while Dermacentor variabilis comprised the majority of ticks collected. These findings provide ecological insight into the relative paucity of Lyme disease in Kentucky.

  15. Comprehensive surveillance of the antibody response to Borrelia burgdorferi s.l. in small ruminants in China

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    Jifei Yang

    2015-05-01

    Full Text Available Borrelia burgdorferi sensu lato, the etiological agent of Lyme disease, is tick transmitted and has a wide range of mammalian reservoirs in nature, including both wild and domestic animals. To understand the seroprevalence of B. burgdorferi s.l. in small ruminants will add value to the risk analysis of Lyme disease. The current study was intended to map the potential endemic regions of Lyme disease by large-scale investigation of sera from sheep and goats. In this study, a total of 2,758 serum samples from sheep and goats in 21 provinces located in 40 different districts of China were tested for antibodies against B. burgdorferi s.l. by enzyme-linked immunosorbent assay. The results of this survey indicated that the overall prevalence of B. burgdorferi s.l. infection ranges from 5.3 to 63.5 % (mean: 26.3%, and the infection was found in all provinces investigated. Generally, the positive rate declined from the south (34.7% in south and 32.4% in southwest towards the north of China (18.4% in north, 16.5% in northeast and 17.2% in northwest. A significant difference was also observed in the infection rate between south and north (33.2% versus 17.4%, PB. burgdorferi s.l. in small ruminants in China.

  16. Pleomorphism and Viability of the Lyme Disease Pathogen Borrelia burgdorferi Exposed to Physiological Stress Conditions: A Correlative Cryo-Fluorescence and Cryo-Scanning Electron Microscopy Study

    Czech Academy of Sciences Publication Activity Database

    Vancová, Marie; Rudenko, Natalia; Vaněček, Jiří; Golovchenko, Maryna; Strnad, Martin; Rego, Ryan O. M.; Tichá, Lucie; Grubhoffer, Libor; Nebesářová, Jana

    2017-01-01

    Roč. 8, 11 April (2017), č. článku 596. ISSN 1664-302X R&D Projects: GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LM2015062 EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : cryo-fluorescence * cryo-scanning electron microscopy * Borrelia burgdorferi * Lyme disease * round body * pleomorphism * viability staining Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: 2.11 Other engineering and technologies Impact factor: 4.076, year: 2016

  17. Prevalence of Borrelia burgdorferi in ticks removed from skin of people and circumstances of being bitten - research from the area of Poland, 2012-2014.

    Science.gov (United States)

    Gałęziowska, Edyta; Rzymowska, Jolanta; Najda, Nella; Kołodziej, Przemysław; Domżał-Drzewicka, Renata; Rząca, Marcin; Muraczyńska, Bożena; Charzyńska-Gula, Marianna; Szadowska-Szlachetka, Zdzisława; Ślusarska, Barbara; Guty, Edyta

    2018-03-14

    During feeding, the tick sucks blood from the host along with the pathogens that are in the blood, simultaneously exchanging its own pathogens with the host. Humans can also be a host. It is important to understand the most typical circumstances in which people might become infected with Borrelia burgdorferi. This knowledge will help to prepare health education programmes aimed at the prevention of Lyme disease and other tick-borne diseases. The aim of the study was to determine the percentage of ticks infected with Borrelia burgdorferi sensu lato, depending on the circumstances of getting bitten. The research material consisted of ticks acquired from people who had been bitten, and questionnaires completed by these people. 510 ticks were acquired from 257 females and 253 males. Following delivery of a tick for testing, the stage of its development was determined and a molecular assay of Borrelia burgdorferi DNA performed. A positive result of the nested-PCR test was obtained in 78 ticks, which represents 15.30% of all ticks. The infected ticks were collected from male (41 ticks - 52.56%) and female subjects (37 ticks - 47.44%). The biggest number of infected ticks were collected in autumn (54 ticks - 69.23%) and from people who had been into forests (44 ticks - 56.41%). Among the people from whom the infected ticks were acquired, the dominating group included persons over 16 years of age (53 persons - 67.95%) and children aged 0-5 years (16 persons - 20.51%). One in four infected ticks were acquired from the southwestern (20 ticks - 25.64%) and eastern regions of Poland (21 ticks - 26.92%). Infestation of ticks infected with Lyme disease spirochete in this study proved to be variable and depend on the season, the area of tick attack and the region in Poland. The results of the study clearly show that ticks infected with Borrelia burgdorferi inhabit all regions of Poland. The results are consistent with National Institute of Hygiene data which indicates that Lyme

  18. Detection of Borrelia lusitaniae, Rickettsia sp. IRS3, Rickettsia monacensis, and Anaplasma phagocytophilum in Ixodes ricinus collected in Madeira Island, Portugal.

    Science.gov (United States)

    de Carvalho, Isabel Lopes; Milhano, Natacha; Santos, Ana Sofia; Almeida, Victor; Barros, Silvia C; De Sousa, Rita; Núncio, Maria Sofia

    2008-08-01

    A total of 300 Ixodes ricinus ticks were tested by polymerase chain reaction (PCR) for the presence of Borrelia spp., Rickettsia spp., and Anaplasma phagocytophilum. Sequence analysis demonstrated 8 (2.7%) ticks infected with B. lusitaniae, 60 (20%) with Rickettsia spp., and 1 (0.3%) with A. phagocytophilum. Seven (2.3%) ticks were coinfected with B. lusitaniae and Rickettsia spp., 2 (0.6%) with R. monacensis, and 5 (1.7%) with Rickettsia sp. IRS3. The results of this study suggest simultaneous transmission of multiple tick-borne agents on Madeira Island, Portugal.

  19. Exposure to ticks and seroprevalence of [i]Borrelia burgdorferi [/i]among a healthy young population living in the area of southern Podlasie, Poland

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    Anna Pańczuk

    2014-09-01

    Full Text Available [b]Objectives[/b]. The objective of the study was assessment of risk of infection with [i]Borrelia burgdorferi[/i] in the area of southern Podlasie in Poland, near the border with Belarus, by analysis of post-exposure procedure, and evaluation of asymptomatic infection in adolescents bitten by a tick, confirmed by serologic tests. [b]Material and methods[/b]. The study was conducted among 128 healthy individuals aged 16–20 who declared being bitten by a tick. The level of IgM and IgG class antibodies was determined using the immunoenzymatic test (Borrelia 14 kD + OspC IgM ELISA and Borrelia IgG + VlsE ELISA, DRG Diagnostics. Positive and doubtful results were confirmed using the Western blot method (EUROLINE-WB, EUROIMMUN. [b]Results[/b]. In the study group, the largest number of respondents (59.4% declared tick bite in the region of the lower extremities, most often in the knee pit. Among the methods for removing the tick the largest number of respondents indicated removing it with the use of tweezers, with a simple, swift steady movement (29.7%, and pulling it out with the fingers (22.7%. In the ELISA test, a positive or doubtful result in at least one class was observed in 25.0% of respondents (n=32/128: in IgM class – 23.4% (n=30/128, and in IgG class – 4.7% (n=6/128. After verification with the Western blot test, infection was confirmed in 5.5% of respondents (n=7/128: in IgM class – 1.6% (n=2/128, in IgG class – 3.9% (n=5/128. In IgM class antibodies, the Western blot test confirmed positive or doubtful results of the ELISA test in 6.7%, while in IgG class antibodies in 83.3%. [b]Conclusion[/b]. Evaluation of the actual infection with [i]Borrelia spp.[/i] using serologic tests is difficult due to a certain non-specificity of the ELISA test, especially in IgM class antibodies, and difficulties with performance of a wide scope of specific Western blot tests. The variety of methods of tick removal declared by adolescents suggests

  20. Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi.

    Science.gov (United States)

    Feng, Jie; Zhang, Shuo; Shi, Wanliang; Zubcevik, Nevena; Miklossy, Judith; Zhang, Ying

    2017-01-01

    Although the majority of patients with acute Lyme disease can be cured with the standard 2-4 week antibiotic treatment, about 10-20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi ( B. burgdorferi ) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a

  1. Using Landscape Analysis to Test Hypotheses about Drivers of Tick Abundance and Infection Prevalence with Borrelia burgdorferi.

    Science.gov (United States)

    Ferrell, A Michelle; Brinkerhoff, R Jory

    2018-04-12

    Patterns of vector-borne disease risk are changing globally in space and time and elevated disease risk of vector-borne infection can be driven by anthropogenic modification of the environment. Incidence of Lyme disease, caused by the bacterium Borrelia burgdorferi sensu stricto, has risen in a number of locations in North America and this increase may be driven by spatially or numerically expanding populations of the primary tick vector, Ixodes scapularis . We used a model selection approach to identify habitat fragmentation and land-use/land cover variables to test the hypothesis that the amount and configuration of forest cover at spatial scales relevant to deer, the primary hosts of adult ticks, would be the predominant determinants of tick abundance. We expected that land cover heterogeneity and amount of forest edge, a habitat thought to facilitate deer foraging and survival, would be the strongest driver of tick density and that larger spatial scales (5-10 km) would be more important than smaller scales (1 km). We generated metrics of deciduous and mixed forest fragmentation using Fragstats 4.4 implemented in ArcMap 10.3 and found, after adjusting for multicollinearity, that total forest edge within a 5 km buffer had a significant negative effect on tick density and that the proportion of forested land cover within a 10 km buffer was positively associated with density of I. scapularis nymphs. None of the 1 km fragmentation metrics were found to significantly improve the fit of the model. Elevation, previously associated with increased density of I. scapularis nymphs in Virginia, while significantly predictive in univariate analysis, was not an important driver of nymph density relative to fragmentation metrics. Our results suggest that amount of forest cover (i.e., lack of fragmentation) is the most important driver of I. scapularis density in our study system.

  2. The Western progression of lyme disease: infectious and Nonclonal Borrelia burgdorferi Sensu Lato populations in Grand Forks County, North Dakota.

    Science.gov (United States)

    Stone, Brandee L; Russart, Nathan M; Gaultney, Robert A; Floden, Angela M; Vaughan, Jefferson A; Brissette, Catherine A

    2015-01-01

    Scant attention has been paid to Lyme disease, Borrelia burgdorferi, Ixodes scapularis, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports of B. burgdorferi and I. scapularis in North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified as B. burgdorferi sensu lato through sequence analyses of the 16S rRNA gene, the 16S rRNA gene-ileT intergenic spacer region, flaB, ospA, ospC, and p66. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected with B. burgdorferi isolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, and B. burgdorferi M3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larval I. scapularis ticks were able to acquire B. burgdorferi M3 from infected mice; M3 was maintained in I. scapularis during the molt from larva to nymph; and further, M3 was transmitted from infected I. scapularis nymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectious B. burgdorferi populations in eastern North Dakota. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation

    Science.gov (United States)

    2013-01-01

    Background Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. “bavariensis” (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. “finlandensis” (1). Results Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases. Conclusions Intra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues. PMID:24112474

  4. Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity.

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    Tao Lin

    Full Text Available The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication. To facilitate analysis, the insertion sites of 4,479 transposon mutants were determined by sequencing. The transposon insertions were widely distributed across the entire B. burgdorferi genome, with an average of 2.68 unique insertion sites per kb DNA. The 10 linear plasmids and 9 circular plasmids had insertions in 33 to 100 percent of their predicted genes. In contrast, only 35% of genes in the 910 kb linear chromosome had incapacitating insertions; therefore, the remaining 601 chromosomal genes may represent essential gene candidates. In initial signature-tagged mutagenesis (STM analyses, 434 mutants were examined at multiple tissue sites for infectivity in mice using a semi-quantitative, Luminex-based DNA detection method. Examples of genes found to be important in mouse infectivity included those involved in motility, chemotaxis, the phosphoenolpyruvate phosphotransferase system, and other transporters, as well as putative plasmid maintenance genes. Availability of this ordered STM library and a high-throughput screening method is expected to lead to efficient assessment of the roles of B. burgdorferi genes in the infectious cycle and pathogenesis of Lyme disease.

  5. Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin.

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    Iván Bárcena-Uribarri

    Full Text Available In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be ≤1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.

  6. Induction of type I and type III interferons by Borrelia burgdorferi correlates with pathogenesis and requires linear plasmid 36.

    Directory of Open Access Journals (Sweden)

    Michelle A Krupna-Gaylord

    Full Text Available The capacity for Borrelia burgdorferi to cause disseminated infection in humans or mice is associated with the genotype of the infecting strain. The cytokine profiles elicited by B. burgdorferi clinical isolates of different genotype (ribosomal spacer type groups were assessed in a human PBMC co-incubation model. RST1 isolates, which are more frequently associated with disseminated Lyme disease in humans and mice, induced significantly higher levels of IFN-α and IFN-λ1/IL29 relative to RST3 isolates, which are less frequently associated with disseminated infection. No differences in the protein concentrations of IFN-γ, IL-1β, IL-6, IL-8, IL-10 or TNF-α were observed between isolates of differing genotype. The ability of B. burgdorferi to induce type I and type III IFNs was completely dependent on the presence of linear plasmid (lp 36. An lp36-deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and specific dendritic cell (DC subsets less efficiently than its isogenic B31 parent strain. The association defect with mDC1s and pDCs could be restored by complementation of the mutant with the complete lp36. The RST1 clinical isolates studied were found to contain a 2.5-kB region, located in the distal one-third of lp36, which was not present in any of the RST3 isolates tested. This divergent region of lp36 may encode one or more factors required for optimal spirochetal recognition and the production of type I and type III IFNs by human DCs, thus suggesting a potential role for DCs in the pathogenesis of B. burgdorferi infection.

  7. Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi

    Science.gov (United States)

    Feng, Jie; Zhang, Shuo; Shi, Wanliang; Zubcevik, Nevena; Miklossy, Judith; Zhang, Ying

    2017-01-01

    Although the majority of patients with acute Lyme disease can be cured with the standard 2–4 week antibiotic treatment, about 10–20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a

  8. Disagreement between the results from three commercial tests for the detection of Borrelia-specific serum antibodies in the Netherlands associated with antibiotic treatment for Lyme borreliosis: a retrospective study.

    NARCIS (Netherlands)

    van Gorkom, T; Kremer, K; Voet, W; Notermans, D W; Vlaminckx, B J M; Sankatsing, S U C; Thijsen, S F T

    2017-01-01

    The diagnosis of Lyme borreliosis is challenging because of the often non-specific symptoms and persisting antibodies after infection. We investigated the diagnostic characteristics of two enzyme-linked immunosorbent assays (ELISAs) and an immunoblot for the detection of Borrelia-specific serum

  9. Use of T7 RNA polymerase to direct expression of outer Surface Protein A (OspA) from the Lyme disease Spirochete, Borrelia burgdorferi

    Science.gov (United States)

    Dunn, John J.; Lade, Barbara N.

    1991-01-01

    The OspA gene from a North American strain of the Lyme disease Spirochete, Borrelia burgdorferi, was cloned under the control of transciption and translation signals from bacteriophage T7. Full-length OspA protein, a 273 amino acid (31kD) lipoprotein, is expressed poorly in Escherichia coli and is associated with the insoluble membrane fraction. In contrast, a truncated form of OspA lacking the amino-terminal signal sequence which normally would direct localization of the protein to the outer membrane is expressed at very high levels (less than or equal to 100 mg/liter) and is soluble. The truncated protein was purified to homogeneity and is being tested to see if it will be useful as an immunogen in a vaccine against Lyme disease. Circular dichroism and fluorescence spectroscopy was used to characterize the secondary structure and study conformational changes in the protein. Studies underway with other surface proteins from B burgdorferi and a related spirochete, B. hermsii, which causes relapsing fever, leads us to conclude that a strategy similar to that used to express the truncated OspA can provide a facile method for producing variations of Borrelia lipoproteins which are highly expressed in E. coli and soluble without exposure to detergents.

  10. Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Zhipu; Kelleher, Alan J.; Darwiche, Rabih; Hudspeth, Elissa M.; Shittu, Oluwatosin K.; Krishnavajhala, Aparna; Schneiter, Roger; Lopez, Job E.; Asojo, Oluwatoyin A. (Baylor); (Fribourg); (NCI)

    2017-11-10

    Tick-borne relapsing fever (RF) borreliosis is a neglected disease that is often misdiagnosed. RF species circulating in the United States include Borrelia turicatae, which is transmitted by argasid ticks. Environmental adaptation by RF Borrelia is poorly understood, however our previous studies indicated differential regulation of B. turicatae genes localized on the 150 kb linear megaplasmid during the tick-mammalian transmission cycle, including bta121. This gene is up-regulated by B. turicatae in the tick versus the mammal, and the encoded protein (BTA121) is predicted to be surface localized. The structure of BTA121 was solved by single-wavelength anomalous dispersion (SAD) using selenomethionine-derivative protein. The topology of BTA121 is unique with four helical domains organized into two helical bundles. Due to the sequence similarity of several genes on the megaplasmid, BTA121 can serve as a model for their tertiary structures. BTA121 has large interconnected tunnels and cavities that can accommodate ligands, notably long parallel helices, which have a large hydrophobic central pocket. Preliminary in-vitro studies suggest that BTA121 binds lipids, notably palmitate with a similar order of binding affinity as tablysin-15, a known palmitate-binding protein. The reported data will guide mechanistic studies to determine the role of BTA121 in the tick-mammalian transmission cycle of B. turicatae.

  11. Crimean–Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania

    Science.gov (United States)

    Sherifi, Kurtesh; Rexhepi, Agim; Berxholi, Kristaq; Mehmedi, Blerta; Gecaj, Rreze M.; Hoxha, Zamira; Joachim, Anja; Duscher, Georg G.

    2018-01-01

    Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean–Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218), Dermacentor marginatus (n = 98), and Haemaphysalis spp. (n = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma marginatum (n = 199 from Kosovo, all from Kosovo) and Rhipicephalus bursa (n = 130, 126 from Albania) could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean–Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle) from the Prishtina region (Kosovo). B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus, two I. ricinus one female and one male) from the Mitrovica region (Kosovo). Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus, but also in D. marginatus, in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established. PMID:29560357

  12. Crimean–Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania

    Directory of Open Access Journals (Sweden)

    Kurtesh Sherifi

    2018-03-01

    Full Text Available Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean–Congo hemorrhagic fever (CCHF is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE. Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218, Dermacentor marginatus (n = 98, and Haemaphysalis spp. (n = 24 were collected from the environment by flagging (all from Kosovo, while Hyalomma marginatum (n = 199 from Kosovo, all from Kosovo and Rhipicephalus bursa (n = 130, 126 from Albania could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean–Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle from the Prishtina region (Kosovo. B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus, two I. ricinus one female and one male from the Mitrovica region (Kosovo. Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus, but also in D. marginatus, in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established.

  13. Crimean-Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania.

    Science.gov (United States)

    Sherifi, Kurtesh; Rexhepi, Agim; Berxholi, Kristaq; Mehmedi, Blerta; Gecaj, Rreze M; Hoxha, Zamira; Joachim, Anja; Duscher, Georg G

    2018-01-01

    Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean-Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus ( n  = 218), Dermacentor marginatus ( n  = 98), and Haemaphysalis spp. ( n  = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma marginatum ( n  = 199 from Kosovo, all from Kosovo) and Rhipicephalus bursa ( n  = 130, 126 from Albania) could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean-Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle) from the Prishtina region (Kosovo). B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus , two I. ricinus one female and one male) from the Mitrovica region (Kosovo). Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus , but also in D. marginatus , in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established.

  14. MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Robert B Lochhead

    2014-06-01

    Full Text Available MicroRNAs have been shown to be important regulators of inflammatory and immune responses and are implicated in several immune disorders including systemic lupus erythematosus and rheumatoid arthritis, but their role in Lyme borreliosis remains unknown. We performed a microarray screen for expression of miRNAs in joint tissue from three mouse strains infected with Borrelia burgdorferi. This screen identified upregulation of miR-146a, a key negative regulator of NF-κB signaling, in all three strains, suggesting it plays an important role in the in vivo response to B. burgdorferi. Infection of B6 miR-146a-/- mice with B. burgdorferi revealed a critical nonredundant role of miR-146a in modulating Lyme arthritis without compromising host immune response or heart inflammation. The impact of miR-146a was specifically localized to the joint, and did not impact lesion development or inflammation in the heart. Furthermore, B6 miR-146a-/- mice had elevated levels of NF-κB-regulated products in joint tissue and serum late in infection. Flow cytometry analysis of various lineages isolated from infected joint tissue of mice showed that myeloid cell infiltration was significantly greater in B6 miR-146a-/- mice, compared to B6, during B. burgdorferi infection. Using bone marrow-derived macrophages, we found that TRAF6, a known target of miR-146a involved in NF-κB activation, was dysregulated in resting and B. burgdorferi-stimulated B6 miR-146a-/- macrophages, and corresponded to elevated IL-1β, IL-6 and CXCL1 production. This dysregulated protein production was also observed in macrophages treated with IL-10 prior to B. burgdorferi stimulation. Peritoneal macrophages from B6 miR-146a-/- mice also showed enhanced phagocytosis of B. burgdorferi. Together, these data show that miR-146a-mediated regulation of TRAF6 and NF-κB, and downstream targets such as IL-1β, IL-6 and CXCL1, are critical for modulation of Lyme arthritis during chronic infection with B

  15. Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.

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    Loïc Coutte

    2009-02-01

    Full Text Available Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained "template-independent" sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.

  16. Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi.

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    Tao Lin

    2009-12-01

    Full Text Available Antigenic variation plays a vital role in the pathogenesis of many infectious bacteria and protozoa including Borrelia burgdorferi, the causative agent of Lyme disease. VlsE, a 35 kDa surface-exposed lipoprotein, undergoes antigenic variation during B. burgdorferi infection of mammalian hosts, and is believed to be a critical mechanism by which the spirochetes evade immune clearance. Random, segmental recombination between the expressed vlsE gene and adjacent vls silent cassettes generates a large number of different VlsE variants within the infected host. Although the occurrence and importance of vlsE sequence variation is well established, little is known about the biological mechanism of vlsE recombination. To identify factors important in antigenic variation and vlsE recombination, we screened transposon mutants of genes known to be involved in DNA recombination and repair for their effects on infectivity and vlsE recombination. Several mutants, including those in BB0023 (ruvA, BB0022 (ruvB, BB0797 (mutS, and BB0098 (mutS-II, showed reduced infectivity in immunocompetent C3H/HeN mice. Mutants in ruvA and ruvB exhibited greatly reduced rates of vlsE recombination in C3H/HeN mice, as determined by restriction fragment polymorphism (RFLP screening and DNA sequence analysis. In severe combined immunodeficiency (C3H/scid mice, the ruvA mutant retained full infectivity; however, all recovered clones retained the 'parental' vlsE sequence, consistent with low rates of vlsE recombination. These results suggest that the reduced infectivity of ruvA and ruvB mutants is the result of ineffective vlsE recombination and underscores the important role that vlsE recombination plays in immune evasion. Based on functional studies in other organisms, the RuvAB complex of B. burgdorferi may promote branch migration of Holliday junctions during vlsE recombination. Our findings are consistent with those in the accompanying article by Dresser et al., and together

  17. Prevalence of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and assessment of entomological risk index at localities in Belgrade

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    Krstić Milena

    2016-01-01

    Full Text Available Background/Aim. The first case of human Lyme borreliosis (LB in Serbia was recorded in 1987. The number of reported LB cases has increased in the past decade. The aim of this study was to estimate the density of Ixodes ricinus (I. ricinus ticks, the prevalence of Borrelia burgdorferi sensu lato (B. burgdorferi in them, and entomological risk index (ERI at 19 Belgrade localities which were grouped into three categories (forests, parkforests, parks. The values of ERI were compared with the number of tick bites in humans. Methods. Ticks were collected monthly by using the flag hours method and the infection rate was determined by using dark field microscopy. The ERI value was calculated for each locality where the ticks were collected. The related data about tick bites was obtained from the patient protocol of the Institute of Epidemiology, Military Medical Academy, Belgrade. Results. The total number of collected ticks, the number of nymphs and the infection rates of the nymphs were significantly higher in forests (p < 0.05 than park-forests and parks. Statistically, the ERI value was significantly higher in forests than parks of Belgrade (χ2 = 7.78, p < 0.01. In March and July, the ERI value was also significantly higher in forests, than park-forests (p < 0.01 and parks (p < 0.01. May was the month with the highest ERI value in each ecological category (forests p < 0.05; park-forests p < 0.01; parks p < 0.001. However, the number of tick bites in humans did not correlate with ERI values. Conclusion. The obtained results indicate that the risk of tick bite and human exposure to B. burgdorferi sensu lato is present at all selected localities in Belgrade. For a more comprehensive Lyme disease risk assessment the method of entomological risk index assessment should be combined with other methods, taking into consideration all tick stages and the behaviour and habits of people who may get infected B. burgdorferi sensu lato.

  18. Immunization with a recombinant subunit OspA vaccine markedly impacts the rate of newly acquired Borrelia burgdorferi infections in client-owned dogs living in a coastal community in Maine, USA.

    Science.gov (United States)

    Eschner, Andrew K; Mugnai, Kristen

    2015-02-10

    In North America, Borrelia burgdorferi is the causative bacterial agent of canine Lyme borreliosis and is transmitted following prolonged attachment and feeding of vector ticks, Ixodes scapularis or Ixodes pacificus. Its prevention is predicated upon tick-avoidance, effective on-animal tick control and effective immunization strategies. The purpose of this study is to characterize dogs that are newly seropositive for Borrelia burgdorferi infection in relation to compliant use of a recombinant OspA canine Lyme borreliosis vaccine. Specifically, Preventive Fractions (PF) and Risk Ratios (RR) associated with the degree of vaccine compliancy (complete versus incomplete) are determined. 6,202 dogs were tested over a five year period in a single veterinary hospital utilizing a non-adjuvanted, recombinant OspA vaccine according to a 0, 1, 6 month (then yearly) protocol. Rates of newly acquired "Lyme-positive" antibody test results were compared between protocol compliant and poorly compliant (incompletely and/or non-vaccinated) dogs. Over the five-year span, one percent (range 0.39 - 1.3) of protocol compliant vaccinated, previously antibody negative dogs became seropositive for infection. Approximately twenty-one percent (range 16.8 - 33.3) of incompletely vaccinated dogs became positive for infection-specific antibodies. The Preventative Fraction for testing positive for antibodies specific for infection with Borrelia burgdorferi in any given year based on optimal vaccine compliance was, on average, 95.3% (range 93.29 - 98.08). The Risk Ratio for becoming infected with Borrelia burgdorferi antibodies in any given year if vaccine non-compliant was 21.41 (range 14.9 - 52.1). There was a high statistically significant relationship (p = <0.0001) in the observed data in terms of vaccination protocol compliance and the probability of Borrelia burgdorferi infection in each of the five years under study. The recombinant outer surface protein A (rOspA) vaccine for dogs is highly

  19. Tick-borne relapsing fever imported from West Africa: diagnosis by quantitative buffy coat analysis and in vitro culture of Borrelia crocidurae.

    Science.gov (United States)

    van Dam, A P; van Gool, T; Wetsteyn, J C; Dankert, J

    1999-06-01

    West African tick-borne relapsing fever (TBRF) is difficult to diagnose due to the low number of spirochetes in the bloodstream of patients. Previously, the causative microorganism, Borrelia crocidurae, had never been cultured in vitro. TBRF was rapidly diagnosed for two patients returning from western Africa with fever of unknown origin by quantitative buffy coat (QBC) analysis. Diagnosis was confirmed by intraperitoneal inoculation of blood specimens from patients into laboratory mice. In vitro experiments showed that QBC analysis may be as much as 100-fold more sensitive than thick smear. Spirochetes were also cultured from blood samples from both patients in modified Kelly's medium and were identified as B. crocidurae by partial sequencing of the PCR-amplified rrs gene.

  20. Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission.

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    Star M Dunham-Ems

    2012-02-01

    Full Text Available While the roles of rpoS(Bb and RpoS-dependent genes have been studied extensively within the mammal, the contribution of the RpoS regulon to the tick-phase of the Borrelia burgdorferi enzootic cycle has not been examined. Herein, we demonstrate that RpoS-dependent gene expression is prerequisite for the transmission of spirochetes by feeding nymphs. RpoS-deficient organisms are confined to the midgut lumen where they transform into an unusual morphotype (round bodies during the later stages of the blood meal. We show that round body formation is rapidly reversible, and in vitro appears to be attributable, in part, to reduced levels of Coenzyme A disulfide reductase, which among other functions, provides NAD+ for glycolysis. Our data suggest that spirochetes default to an RpoS-independent program for round body formation upon sensing that the energetics for transmission are unfavorable.

  1. BB0347, from the lyme disease spirochete Borrelia burgdorferi, is surface exposed and interacts with the CS1 heparin-binding domain of human fibronectin.

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    Robert A Gaultney

    Full Text Available The causative agent of Lyme disease, Borrelia burgdorferi, codes for several known fibronectin-binding proteins. Fibronectin a common the target of diverse bacterial pathogens, and has been shown to be essential in allowing for the development of certain disease states. Another borrelial protein, BB0347, has sequence similarity with these other known fibronectin-binding proteins, and may be important in Lyme disease pathogenesis. Herein, we perform an initial characterization of BB0347 via the use of molecular and biochemical techniques. We found that BB0347 is expressed, produced, and presented on the outer surface of intact B. burgdorferi. We also demonstrate that BB0347 has the potential to be important in Lyme disease progression, and have begun to characterize the nature of the interaction between human fibronectin and this bacterial protein. Further work is needed to define the role of this protein in the borrelial infection process.

  2. Complement factor H-related proteins CFHR2 and CFHR5 represent novel ligands for the infection-associated CRASP proteins of Borrelia burgdorferi.

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    Corinna Siegel

    2010-10-01

    Full Text Available One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP which interact with complement regulator factor H (CFH and factor H-like protein 1 (FHL1 or factor H-related protein 1 (CFHR1. In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi.To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins were immobilized on magnetic beads. Following incubation with human serum, bound proteins were eluted and separated by Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement regulators CFHR2 and CFHR5 were identified as novel ligands for both borrelial proteins by employing MALDI-TOF. To further assess the contributions of CRASP-3 and CRASP-5 to complement resistance, a serum-sensitive B. garinii strain G1 which lacks all CFH-binding proteins was used as a valuable model for functional analyses. Both CRASPs expressed on the B. garinii outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only miniscute amounts of CFH as demonstrated by serum adsorption assays and FACS analyses. Further functional analysis revealed that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae were killed by complement.In the absence of CFH and the presence of CFHR1, CFHR2 and CFHR5, assembly and integration of the membrane attack complex was not efficiently inhibited indicating that CFH in co-operation with CFHR1, CFHR2 and CFHR5 supports complement evasion of B. burgdorferi.

  3. Established Population of Blacklegged Ticks with High Infection Prevalence for the Lyme Disease Bacterium, Borrelia burgdorferi Sensu Lato, on Corkscrew Island, Kenora District, Ontario

    Science.gov (United States)

    Scott, John D.; Foley, Janet E.; Clark, Kerry L.; Anderson, John F.; Durden, Lance A.; Manord, Jodi M.; Smith, Morgan L.

    2016-01-01

    We document an established population of blacklegged ticks, Ixodes scapularis, on Corkscrew Island, Kenora District, Ontario, Canada. Primers of the outer surface protein A (OspA) gene, the flagellin (fla) gene, and the flagellin B (flaB) gene were used in the PCR assays to detect Borrelia burgdorferi sensu lato (s.l.), the Lyme disease bacterium. In all, 60 (73%) of 82 adult I. scapularis, were infected with B. burgdorferi s.l. As well, 6 (43%) of 14 unfed I. scapularis nymphs were positive for B. burgdorferi s.l. An I. scapularis larva was also collected from a deer mouse, and several unfed larvae were gathered by flagging leaf litter. Based on DNA sequencing of randomly selected Borrelia amplicons from six nymphal and adult I. scapularis ticks, primers for the flagellin (fla) and flagellin B (flaB) genes reveal the presence of B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. We collected all 3 host-feeding life stages of I. scapularis in a single year, and report the northernmost established population of I. scapularis in Ontario. Corkscrew Island is hyperendemic for Lyme disease and has the highest prevalence of B. burgdorferi s.l. for any established population in Canada. Because of this very high infection prevalence, this population of I. scapularis has likely been established for decades. Of epidemiological significance, cottage owners, island visitors, outdoors enthusiasts, and medical professionals must be vigilant that B. burgdorferi s.l.-infected I. scapularis on Corkscrew Island pose a serious public health risk. PMID:27877080

  4. Analysis of nanomechanical properties of Borrelia burgdorferi spirochetes under the influence of lytic factors in an in vitro model using atomic force microscopy

    Directory of Open Access Journals (Sweden)

    Małgorzata Tokarska-Rodak

    2015-11-01

    Full Text Available Background: Atomic force microscopy (AFM is an experimental technique which recently has been used in biology, microbiology, and medicine to investigate the topography of surfaces and in the evaluation of mechanical properties of cells. The aim of this study was to evaluate the influence of the complement system and specific anti-Borrelia antibodies in in vitro conditions on the modification of nanomechanical features of B. burgdorferi B31 cells. Material and methods: In order to assess the influence of the complement system and anti-Borrelia antibodies on B. burgdorferi s.s. B31 spirochetes, the bacteria were incubated together with plasma of identified status. The samples were applied on the surface of mica disks. Young’s modulus and adhesive forces were analyzed with a NanoScope V, MultiMode 8 AFM microscope (Bruker by the PeakForce QNM technique in air using NanoScope Analysis 1.40 software (Bruker.Results/Conclusion: The average value of flexibility of spirochetes’ surface expressed by Young’s modulus was 10185.32 MPa, whereas the adhesion force was 3.68 nN. AFM is a modern tool with a broad spectrum of observational and measurement abilities. Young’s modulus and the adhesion force can be treated as parameters in the evaluation of intensity and changes which take place in pathogenic microorganisms under the influence of various lytic factors. The visualization of the changes in association with nanomechanical features provides a realistic portrayal of the lytic abilities of the elements of the innate and adaptive human immune system.

  5. Efficacy of sarolaner in the prevention of Borrelia burgdorferi and Anaplasma phagocytophilum transmission from infected Ixodes scapularis to dogs.

    Science.gov (United States)

    Honsberger, Nicole A; Six, Robert H; Heinz, Thomas J; Weber, Angela; Mahabir, Sean P; Berg, Thomas C

    2016-05-30

    The efficacy of sarolaner (Simparica™, Zoetis) to prevent transmission primarily of Borrelia burgdorferi and secondarily of Anaplasma phagocytophilum from infected wild-caught Ixodes scapularis to dogs was evaluated in a placebo-controlled laboratory study. Twenty-four purpose-bred laboratory Beagles seronegative for B. burgdorferi and A. phagocytophilum antibodies were allocated randomly to one of three treatment groups: placebo administered orally on Days 0 and 7, or sarolaner at 2mg/kg administered orally on Day 0 (28 days prior to tick infestation) or on Day 7 (21 days prior to tick infestation). On Day 28, each dog was infested with approximately 25 female and 25 male wild caught adult I. scapularis that were determined to have prevalence of 57% for B. burgdorferi and 6.7% for A. phagocytophilum by PCR. In situ tick counts were conducted on Days 29 and 30. On Day 33, all ticks were counted and removed. Acaricidal efficacy was calculated based on the reduction of geometric mean live tick counts in the sarolaner-treated groups compared to the placebo-treated group for each tick count. Blood samples collected from each dog on Days 27, 49, 63, 77, 91 and 104 were tested for the presence of B. burgdorferi and A. phagocytophilum antibodies using the SNAP(®) 4Dx(®) Plus Test, and quantitatively assayed for B. burgdorferi antibodies using an ELISA test. Skin biopsies collected on Day 104 were tested for the presence of B. burgdorferi by bacterial culture and PCR. Geometric mean live tick counts for placebo-treated dogs were 14.8, 12.8, and 19.1 on Days 29, 30, and 33, respectively. The percent reductions in mean live tick counts at 1, 2, and 5 days after infestation were 86.3%, 100%, and 100% for the group treated with sarolaner 21 days prior to infestation, and 90.9%, 97.1%, and 100% for the group treated with sarolaner 28 days prior to infestation. Geometric mean live tick counts for both sarolaner-treated groups were significantly lower than those for the

  6. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  7. An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands.

    Science.gov (United States)

    van Gorkom, T; Sankatsing, S U C; Voet, W; Ismail, D M; Muilwijk, R H; Salomons, M; Vlaminckx, B J M; Bossink, A W J; Notermans, D W; Bouwman, J J M; Kremer, K; Thijsen, S F T

    2018-04-01

    Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia -specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) ( P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) ( P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis. Copyright © 2018 van Gorkom et al.

  8. Integration of a Tick-Borne Encephalitis Virus and Borrelia burgdorferi sensu lato into Mountain Ecosystems, Following a Shift in the Altitudinal Limit of Distribution of Their Vector, Ixodes ricinus (Krkonoše Mountains, Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Danielová, V.; Daniel, M.; Schwarzová, L.; Materna, J.; Rudenko, Natalia; Golovchenko, Maryna; Holubová, J.; Grubhoffer, Libor; Kilian, P.

    2010-01-01

    Roč. 10, č. 3 (2010), s. 223-230 ISSN 1530-3667 Grant - others:GA ČR(CZ) GA310/06/1546 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi genospecies * Climate * Ixodes ricinus tick * Mountain ecosystems * Tick-borne encephalitis virus Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.733, year: 2010

  9. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  10. Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FB-PEG3-Glu-RGD-BBN.

    Science.gov (United States)

    Liu, Zhaofei; Yan, Yongjun; Chin, Frederic T; Wang, Fan; Chen, Xiaoyuan

    2009-01-22

    Radiolabeled RGD and bombesin peptides have been extensively investigated for tumor integrin alpha(v)beta(3) and GRPR imaging, respectively. Due to the fact that many tumors are both integrin and GRPR positive, we designed and synthesized a heterodimeric peptide Glu-RGD-BBN, which is expected to be advantageous over the monomeric peptides for dual-receptor targeting. A PEG(3) spacer was attached to the glutamate alpha-amino group of Glu-RGD-BBN to enhance the (18)F labeling yield and to improve the in vivo kinetics. PEG(3)-Glu-RGD-BBN possesses the comparable GRPR and integrin alpha(v)beta(3) receptor-binding affinities as the corresponding monomers, respectively. The dual-receptor targeting properties of (18)F-FB-PEG(3)-Glu-RGD-BBN were observed in PC-3 tumor model. (18)F-FB-PEG(3)-Glu-RGD-BBN with high tumor contrast and favorable pharmacokinetics is a promising PET tracer for dual integrin and GRPR positive tumor imaging. This heterodimer strategy may also be an applicable method to develop other molecules with improved in vitro and in vivo characterizations for tumor diagnosis and therapy.

  11. ErpC, a member of the complement regulator-acquiring family of surface proteins from Borrelia burgdorferi, possesses an architecture previously unseen in this protein family

    International Nuclear Information System (INIS)

    Caesar, Joseph J. E.; Johnson, Steven; Kraiczy, Peter; Lea, Susan M.

    2013-01-01

    The structure of ErpC, a member of the complement regulator-acquiring surface protein family from B. burgdorferi, has been solved, providing insights into the strategies of complement evasion by this zoonotic bacterium and suggesting a common architecture for other members of this protein family. Borrelia burgdorferi is a spirochete responsible for Lyme disease, the most commonly occurring vector-borne disease in Europe and North America. The bacterium utilizes a set of proteins, termed complement regulator-acquiring surface proteins (CRASPs), to aid evasion of the human complement system by recruiting and presenting complement regulator factor H on its surface in a manner that mimics host cells. Presented here is the atomic resolution structure of a member of this protein family, ErpC. The structure provides new insights into the mechanism of recruitment of factor H and other factor H-related proteins by acting as a molecular mimic of host glycosaminoglycans. It also describes the architecture of other CRASP proteins belonging to the OspE/F-related paralogous protein family and suggests that they have evolved to bind specific complement proteins, aiding survival of the bacterium in different hosts

  12. Further structural insights into the binding of complement factor H by complement regulator-acquiring surface protein 1 (CspA) of Borrelia burgdorferi

    International Nuclear Information System (INIS)

    Caesar, Joseph J. E.; Wallich, Reinhard; Kraiczy, Peter; Zipfel, Peter F.; Lea, Susan M.

    2013-01-01

    B. burgdorferi binds complement factor H using a dimeric surface protein, CspA (BbCRASP-1). Presented here is a new structure of CspA that suggests that there is a degree of flexibility between subunits which may have implications for complement regulator binding. Borrelia burgdorferi has evolved many mechanisms of evading the different immune systems across its range of reservoir hosts, including the capture and presentation of host complement regulators factor H and factor H-like protein-1 (FHL-1). Acquisition is mediated by a family of complement regulator-acquiring surface proteins (CRASPs), of which the atomic structure of CspA (BbCRASP-1) is known and shows the formation of a homodimeric species which is required for binding. Mutagenesis studies have mapped a putative factor H binding site to a cleft between the two subunits. Presented here is a new atomic structure of CspA which shows a degree of flexibility between the subunits which may be critical for factor H scavenging by increasing access to the binding interface and allows the possibility that the assembly can clamp around the bound complement regulators

  13. Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

    Science.gov (United States)

    Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

    2006-05-01

    Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

  14. Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN-β and Requires Upregulation of Myostatin.

    Science.gov (United States)

    Paquette, Jackie K; Ma, Ying; Fisher, Colleen; Li, Jinze; Lee, Sang Beum; Zachary, James F; Kim, Yong Soo; Teuscher, Cory; Weis, Janis J

    2017-11-15

    Previously, using a forward genetic approach, we identified differential expression of type I IFN as a positional candidate for an expression quantitative trait locus underlying Borrelia burgdorferi arthritis-associated locus 1 ( Bbaa1 ). In this study, we show that mAb blockade revealed a unique role for IFN-β in Lyme arthritis development in B6.C3- Bbaa1 mice. Genetic control of IFN-β expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi , and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3- Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45 - joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-β production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi . Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Prevalence of Babesia canis, Borrelia burgdorferi sensu lato, and Anaplasma phagocytophilum in hard ticks collected from meadows of Lubelskie Voivodship (eastern Poland

    Directory of Open Access Journals (Sweden)

    Dzięgiel Beata

    2014-03-01

    Full Text Available The aim of the study was to assess the distribution of Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, and Babesia canis in adult females and males of Ixodes ricinus and Dermacentor reticulatus ticks, inhabiting meadows near large forest complexes throughout the Lubelskie Voivodship (eastern region of Poland. Ticks were collected using the flagging method. Among 720 ticks collected, 506 were identified as D. reticulatus, and 214 as I. ricinus. DNA of B. canis and B. burgdorferi s.l. was detected in 21.3% and 0.6% of D. reticulatus ticks, respectively. In I. ricinus ticks, DNA specific to B. burgdorferi s.l. and A. phagocytophilum was detected in 5.6% and 10.3%, respectively. Co-infections of B. burgdorferi s.l. and A. phagocytophilum were found in two I. ricinus ticks. These results indicate that the Lublin region is an area at risk of tick-borne diseases of humans and animals, which must be considered in clinical practice.

  16. Weak Organic Acids Decrease Borrelia burgdorferi Cytoplasmic pH, Eliciting an Acid Stress Response and Impacting RpoN- and RpoS-Dependent Gene Expression

    Directory of Open Access Journals (Sweden)

    Daniel P. Dulebohn

    2017-09-01

    Full Text Available The spirochete Borrelia burgdorferi survives in its tick vector, Ixodes scapularis, or within various hosts. To transition between and survive in these distinct niches, B. burgdorferi changes its gene expression in response to environmental cues, both biochemical and physiological. Exposure of B. burgdorferi to weak monocarboxylic organic acids, including those detected in the blood meal of fed ticks, decreased the cytoplasmic pH of B. burgdorferi in vitro. A decrease in the cytoplasmic pH induced the expression of genes encoding enzymes that have been shown to restore pH homeostasis in other bacteria. These include putative coupled proton/cation exchangers, a putative Na+/H+ antiporter, a neutralizing buffer transporter, an amino acid deaminase and a proton exporting vacuolar-type VoV1 ATPase. Data presented in this report suggested that the acid stress response triggered the expression of RpoN- and RpoS-dependent genes including important virulence factors such as outer surface protein C (OspC, BBA66, and some BosR (Borreliaoxidative stress regulator-dependent genes. Because the expression of virulence factors, like OspC, are so tightly connected by RpoS to general cellular stress responses and cell physiology, it is difficult to separate transmission-promoting conditions in what is clearly a multifactorial and complex regulatory web.

  17. Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite

    DEFF Research Database (Denmark)

    Dessau, Ram B; Fryland, Linda; Wilhelmsson, Peter

    2015-01-01

    or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay......Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays...... (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion...

  18. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  19. Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

    Science.gov (United States)

    Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

    2012-01-01

    Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

  20. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  1. Enhancement of immune response towards non-lipidized Borrelia burgdorferi recombinant OspC antigen by binding onto the surface of metallochelating nanoliposomes with entrapped lipophilic derivatives of norAbuMDP

    Czech Academy of Sciences Publication Activity Database

    Křupka, M.; Mašek, J.; Bartheldyová, E.; Turánek Knotigová, P.; Plocková, J.; Korvasová, Z.; Škrabalová, M.; Koudelka, Š.; Kulich, P.; Zachová, K.; Czerneková, L.; Strouhal, O.; Horynová, M.; Šebela, M.; Miller, A. D.; Ledvina, Miroslav; Raška, M.; Turánek, J.

    2012-01-01

    Roč. 160, č. 2 (2012), s. 374-381 ISSN 0168-3659 R&D Projects: GA ČR(CZ) GAP304/10/1951; GA TA ČR TA01011165; GA AV ČR(CZ) KAN200520703; GA AV ČR KAN200100801 Grant - others:GA UP(CZ) LF-2010-014; GA UP(CZ) LF-2011-002 Institutional research plan: CEZ:AV0Z40550506 Keywords : Borrelia burgdorferi * OspC * metallochelating liposomes * MDP Subject RIV: CC - Organic Chemistry Impact factor: 7.633, year: 2012

  2. Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer.

    Science.gov (United States)

    Korpal, Manav; Puyang, Xiaoling; Jeremy Wu, Zhenhua; Seiler, Roland; Furman, Craig; Oo, Htoo Z; Seiler, Michael; Irwin, Sean; Subramanian, Vanitha; Julie Joshi, Jaya; Wang, Chris K; Rimkunas, Victoria; Tortora, Davide; Yang, Hua; Kumar, Namita; Kuznetsov, Galina; Matijevic, Mark; Chow, Jesse; Kumar, Pavan; Zou, Jian; Feala, Jacob; Corson, Laura; Henry, Ryan; Selvaraj, Anand; Davis, Allison; Bloudoff, Kristjan; Douglas, James; Kiss, Bernhard; Roberts, Morgan; Fazli, Ladan; Black, Peter C; Fekkes, Peter; Smith, Peter G; Warmuth, Markus; Yu, Lihua; Hao, Ming-Hong; Larsen, Nicholas; Daugaard, Mads; Zhu, Ping

    2017-07-24

    Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations in RXRα at serine 427 (S427F/Y), through conformational activation of the PPARγ/RXRα heterodimer, and focal amplification/overexpression of PPARγ converge to modulate PPARγ/RXRα-dependent transcription programs. Immune cell-infiltration is controlled by activated PPARγ/RXRα that inhibits expression/secretion of inflammatory cytokines. Clinical data sets and an in vivo tumor model indicate that PPARγ High /RXRα S427F/Y impairs CD8 + T-cell infiltration and confers partial resistance to immunotherapies. Knockdown of PPARγ or RXRα and pharmacological inhibition of PPARγ significantly increase cytokine expression suggesting therapeutic approaches to reviving immunosurveillance and sensitivity to immunotherapies. Our study reveals a class of tumor cell-intrinsic "immuno-oncogenes" that modulate the immune microenvironment of cancer.Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease. Here the authors characterize diverse genetic alterations in MIBC that convergently lead to constitutive activation of PPARgamma/RXRalpha and result in immunosurveillance escape by inhibiting CD8+ T-cell recruitment.

  3. Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction

    Directory of Open Access Journals (Sweden)

    NM Coelho

    2010-06-01

    Full Text Available Considering the structural role of type IV collagen (Col IV in the assembly of the basement membrane (BM and the perspective of mimicking its organization for vascular tissue engineering purposes, we studied the adsorption pattern of this protein on model hydrophilic (clean glass and hydrophobic trichloro(octadecylsilane (ODS surfaces known to strongly affect the behavior of other matrix proteins. The amount of fluorescently labeled Col IV was quantified showing saturation of the surface for concentration of the adsorbing solution of about 50μg/ml, but with approximately twice more adsorbed protein on ODS. AFM studies revealed a fine – nearly single molecular size – network arrangement of Col IV on hydrophilic glass, which turns into a prominent and growing polygonal network consisting of molecular aggregates on hydrophobic ODS. The protein layer forms within minutes in a concentration-dependent manner. We further found that human umbilical vein endothelial cells (HUVEC attach less efficiently to the aggregated Col IV (on ODS, as judged by the significantly altered cell spreading, focal adhesions formation and the development of actin cytoskeleton. Conversely, the immunofluorescence studies for integrins revealed that the fine Col IV network formed on hydrophilic substrata is better recognized by the cells via both α1 and α2 heterodimers which support cellular interaction, apart from these on hydrophobic ODS where almost no clustering of integrins was observed.

  4. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

    Science.gov (United States)

    Weiner, Zachary P.; Crew, Rebecca M.; Brandt, Kevin S.; Ullmann, Amy J.; Schriefer, Martin E.; Molins, Claudia R.

    2015-01-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID:26376927

  5. The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades Extracellular Matrix Components by Interacting with Plasmin(ogen

    Directory of Open Access Journals (Sweden)

    Ngoc T. T. Nguyen

    2018-02-01

    Full Text Available The emerging relapsing fever spirochete Borrelia (B. miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD. More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen. Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.

  6. Seroprevalence and risk factors associated with Ehrlichia canis, Anaplasma spp., Borrelia burgdorferi sensu lato, and D. immitis in hunting dogs from southern Italy.

    Science.gov (United States)

    Piantedosi, Diego; Neola, Benedetto; D'Alessio, Nicola; Di Prisco, Francesca; Santoro, Mario; Pacifico, Laura; Sgroi, Giovanni; Auletta, Luigi; Buch, Jesse; Chandrashekar, Ramaswamy; Breitschwerdt, Edward B; Veneziano, Vincenzo

    2017-10-01

    Canine vector-borne diseases (CVBDs) are caused by a range of pathogens transmitted to dogs by arthropods. The present study investigates Ehrlichia canis, Anaplasma spp., Borrelia burgdorferi sensu lato, and Dirofilaria immitis seroprevalences in hunting dogs from southern Italy. Dogs (no. 1335) were tested using a commercial in-clinic enzyme-linked immunosorbent assay kit. Odds ratios (ORs) were calculated by logistic regression analysis to identify risk factors. Overall, 138/1335 dogs (10.3%) were seroreactive to at least one CVBD pathogen. E. canis, Anaplasma spp., B. burgdorferi s.l., and D. immitis seroprevalences were 7.6, 4.4, 0.3, and 0.2%, respectively. E. canis and Anaplasma spp. co-exposures were found in 30 dogs (2.2%), compared with Anaplasma spp. and B. burgdorferi s.l. co-exposures in 2 dogs (0.1%). Adult age was a risk factor for E. canis (OR 2.35) seroreactivity whereas hunting fur-bearing animals for E. canis (OR 4.75) and Anaplasma spp. (OR 1.87), respectively. The historical presence of tick infestation was identified as a risk factor for positivity to E. canis (OR 2.08) and Anaplasma spp. (OR 2.15). Finally, larger dog pack size was significantly associated with E. canis (OR 1.85) and Anaplasma spp. (OR 2.42) exposures. The results of the present survey indicated that hunting dog populations are at relative risk of CVBDs in southern Italy. Further studies are needed to evaluate the role of hunting dogs in the epidemiology of vector-borne organisms due to sharing common environments with wild, sympatric animal populations.

  7. Long-Term Effects of Berberis thunbergii (Ranunculales: Berberidaceae) Management on Ixodes scapularis (Acari: Ixodidae) Abundance and Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) Prevalence in Connecticut, USA.

    Science.gov (United States)

    Williams, Scott C; Linske, Megan A; Ward, Jeffrey S

    2017-12-08

    Japanese barberry (Berberis thunbergii de Candolle; Ranunculales: Berberidaceae) is an exotic invasive shrub that escaped cultivation in the United States and is now permanently established in many eastern and midwestern states. This study examined the long-term impacts of Japanese barberry management on blacklegged tick (Ixodes scapularis Say; Acari: Ixodidae) abundances and associated prevalence of Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and Brenner; Spirochaetales: Spirochaetaceae), the etiologic agent of Lyme disease. At six locations across Connecticut, adult I. scapularis were sampled for up to 10 yr. At each location, we sampled an area where barberry infestations were unmanipulated, adjacent areas where barberry was virtually nonexistent, and areas where barberry was managed utilizing a variety of techniques. Barberry management reduced B. burgdorferi-infected adult I. scapularis (BBIAIS) abundances (191/ha ± 64 SE) over 6 yr to statistically indifferent from that of no barberry areas (140/ha ± 47 SE; P = 0.080) and significantly less than intact barberry stands (458/ha ± 80 SE; P = 0.026). Over 9 yr, BBIAIS abundances in managed barberry remained lower than intact barberry stands (P = 0.037), but increased to be significantly greater than no barberry areas (P = 0.007) as cover increased over time. Longer-term data further document that Japanese barberry infestations are favorable habitat for I. scapularis. Control of Japanese barberry and other invasives should be at least on a 5-yr rotation to maintain low levels of invasive cover and eliminate humidity refugia to expose juvenile I. scapularis to more hostile environmental conditions in the interest of public health. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Disruption of bbe02 by Insertion of a Luciferase Gene Increases Transformation Efficiency of Borrelia burgdorferi and Allows Live Imaging in Lyme Disease Susceptible C3H Mice.

    Directory of Open Access Journals (Sweden)

    Kamfai Chan

    Full Text Available Lyme disease is the most prevalent tick-borne disease in North America and Europe. The causative agent, Borrelia burgdorferi persists in the white-footed mouse. Infection with B. burgdorferi can cause acute to persistent multisystemic Lyme disease in humans. Some disease manifestations are also exhibited in the mouse model of Lyme disease. Genetic manipulation of B. burgdorferi remains difficult. First, B. burgdorferi contains a large number of endogenous plasmids with unique sequences encoding unknown functions. The presence of these plasmids needs to be confirmed after each genetic manipulation. Second, the restriction modification defense systems, including that encoded by bbe02 gene lead to low transformation efficiency in B. burgdorferi. Therefore, studying the molecular basis of Lyme pathogenesis is a challenge. Furthermore, investigation of the role of a specific B. burgdorferi protein throughout infection requires a large number of mice, making it labor intensive and expensive. To overcome the problems associated with low transformation efficiency and to reduce the number of mice needed for experiments, we disrupted the bbe02 gene of a highly infectious and pathogenic B. burgdorferi strain, N40 D10/E9 through insertion of a firefly luciferase gene. The bbe02 mutant shows higher transformation efficiency and maintains luciferase activity throughout infection as detected by live imaging of mice. Infectivity and pathogenesis of this mutant were comparable to the wild-type N40 strain. This mutant will serve as an ideal parental strain to examine the roles of various B. burgdorferi proteins in Lyme pathogenesis in the mouse model in the future.

  9. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

    Science.gov (United States)

    Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

    2015-11-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Assessment of decorin-binding protein A to the infectivity of Borrelia burgdorferi in the murine models of needle and tick infection

    Directory of Open Access Journals (Sweden)

    Hagman Kayla E

    2008-05-01

    Full Text Available Abstract Background Decorin-binding proteins (Dbps A and B of Borrelia burgdorferi, the agent of Lyme disease, are surface-exposed lipoproteins that presumably bind to the extracellular matrix proteoglycan, decorin. B. burgdorferi infects various tissues including the bladder, heart, joints, skin and the central nervous system, and the ability of B. burgdorferi to bind decorin has been hypothesized to be important for this disseminatory pathogenic strategy. Results To determine the role of DbpBA in the infectious lifecycle of B. burgdorferi, we created a DbpBA-deficient mutant of B. burgdorferi strain 297 and compared the infectious phenotype of the mutant to the wild-type strain in the experimental murine model of Lyme borreliosis. The mutant strain exhibited a 4-log decrease in infectivity, relative to the wild-type strain, when needle inoculated into mice. Upon complementation of the DbpBA-mutant strain with DbpA, the wild-type level of infectivity was restored. In addition, we demonstrated that the DbpBA-deficient mutant was able to colonize Ixodes scapularis larval ticks after feeding on infected mice and persist within the ticks during the molt to the nymphal state. Moreover, surprisingly, the DbpBA-mutant strain was capable of being transmitted to naïve mice via tick bite, giving rise to infected mice. Conclusion These results suggest that DbpBA is not required for the natural tick-transmission process to mammals, despite inferences from needle-inoculation experiments implying a requirement for DbpBA during mammalian infection. The combined findings also send a cautionary note regarding how results from needle-inoculation experiments with mice should be interpreted.

  11. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  12. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-05-01

    Full Text Available Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

  13. Genetic characterization of the human relapsing fever spirochete Borrelia miyamotoi in vectors and animal reservoirs of Lyme disease spirochetes in France.

    Science.gov (United States)

    Cosson, Jean-François; Michelet, Lorraine; Chotte, Julien; Le Naour, Evelyne; Cote, Martine; Devillers, Elodie; Poulle, Marie-Lazarine; Huet, Dominique; Galan, Maxime; Geller, Julia; Moutailler, Sara; Vayssier-Taussat, Muriel

    2014-05-20

    In France as elsewhere in Europe the most prevalent TBD in humans is Lyme borreliosis, caused by different bacterial species belonging to Borrelia burgdorferi sensu lato complex and transmitted by the most important tick species in France, Ixodes ricinus. However, the diagnosis of Lyme disease is not always confirmed and unexplained syndromes occurring after tick bites have become an important issue. Recently, B. miyamotoi belonging to the relapsing fever group and transmitted by the same Ixodes species has been involved in human disease in Russia, the USA and the Netherlands. In the present study, we investigate the presence of B. miyamotoi along with other Lyme Borreliosis spirochetes, in ticks and possible animal reservoirs collected in France. We analyzed 268 ticks (Ixodes ricinus) and 72 bank voles (Myodes glareolus) collected and trapped in France for the presence of DNA from B. miyamotoi as well as from Lyme spirochetes using q-PCR and specific primers and probes. We then compared the French genotypes with those found in other European countries. We found that 3% of ticks and 5.55% of bank voles were found infected by the same B. miyamotoi genotype, while co-infection with other Lyme spirochetes (B. garinii) was identified in 12% of B. miyamotoi infected ticks. Sequencing showed that ticks and rodents carried the same genotype as those recently characterized in a sick person in the Netherlands. The genotype of B. miyamotoi circulating in ticks and bank voles in France is identical to those already described in ticks from Western Europe and to the genotype isolated from a sick person in The Netherlands. This results suggests that even though no human cases have been reported in France, surveillance has to be improved. Moreover, we showed that ticks could simultaneously carry B. miyamotoi and Lyme disease spirochetes, increasing the problem of co-infection in humans.

  14. The occurrence of Ixodes ricinus ticks and important tick-borne pathogens in areas with high tick-borne encephalitis prevalence in different altitudinal levels of the Czech Republic Part II. Ixodes ricinus ticks and genospecies of Borrelia burgdorferi sensu lato complex

    Czech Academy of Sciences Publication Activity Database

    Daniel, M.; Rudenko, Natalia; Golovchenko, Maryna; Danielová, V.; Fialová, A.; Kříž, B.; Malý, M.

    2016-01-01

    Roč. 65, č. 2 (2016), s. 182-192 ISSN 1210-7913 Institutional support: RVO:60077344 Keywords : Ixodes ricinus * Borrelia afezelii * B. garinii * B. burgdorferi s. s. * B. bavariensis * B. valaisiana * B. spielmanii * B. lusitaniae * B. bissettii * distribution * altitude * season * medical importance Subject RIV: EE - Microbiology, Virology Impact factor: 0.500, year: 2016

  15. What Is the Structure of the Naphthalene-Benzene Heterodimer Radical Cation? Binding Energy, Charge Delocalization, and Unexpected Charge-Transfer Interaction in Stacked Dimer and Trimer Radical Cations.

    Science.gov (United States)

    Attah, Isaac K; Platt, Sean P; Meot-Ner Mautner, Michael; El-Shall, M Samy; Peverati, Roberto; Head-Gordon, Martin

    2015-04-02

    The binding energy of the naphthalene(+•)(benzene) heterodimer cation has been determined to be 7.9 ± 1 kcal/mol for C10H8(+•)(C6H6) and 8.1 ± 1 kcal/mol for C10H8(+•)(C6D6) by equilibrium thermochemical measurements using the mass-selected drift cell technique. A second benzene molecule binds to the C10H8(+•)(C6D6) dimer with essentially the same energy (8.4 ± 1 kcal/mol), suggesting that the two benzene molecules are stacked on opposite sides of the naphthalene cation in the (C6D6)C10H8(+•)(C6D6) heterotrimer. The lowest-energy isomers of the C10H8(+•)(C6D6) and (C6D6)C10H8(+•)(C6D6) dimer and trimer calculated using the M11/cc-pVTZ method have parallel stacked structures with enthalpies of binding (-ΔH°) of 8.4 and 9.0 kcal/mol, respectively, in excellent agreement with the experimental values. The stacked face-to-face class of isomers is calculated to have substantial charge-transfer stabilization of about 45% of the total interaction energy despite the large difference between the ionization energies of benzene and naphthalene. Similarly, significant delocalization of the positive charge is found among all three fragments of the (C6D6)C10H8(+•)(C6D6) heterotrimer, thus leaving only 46% of the total charge on the central naphthalene moiety. This unexpectedly high charge-transfer component results in activating two benzene molecules in the naphthalene(+•)(benzene)2 heterotrimer cation to associate with a third benzene molecule at 219 K to form a benzene trimer cation and a neutral naphthalene molecule. The global minimum of the C10H8(+•)(C6H6)2 heterotrimer is found to be the one where the naphthalene cation is sandwiched between two benzene molecules. It is remarkable, and rather unusual, that the binding energy of the second benzene molecule is essentially the same as that of the first. This is attributed to the enhanced charge-transfer interaction in the stacked trimer radical cation.

  16. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  17. Genetic Alterations in Glioma

    International Nuclear Information System (INIS)

    Bralten, Linda B. C.; French, Pim J.

    2011-01-01

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  18. Altered Perspectives: Immersive Environments

    Science.gov (United States)

    Shipman, J. S.; Webley, P. W.

    2016-12-01

    Immersive environments provide an exciting experiential technology to visualize the natural world. Given the increasing accessibility of 360o cameras and virtual reality headsets we are now able to visualize artistic principles and scientific concepts in a fully immersive environment. The technology has become popular for photographers as well as designers, industry, educational groups, and museums. Here we show a sci-art perspective on the use of optics and light in the capture and manipulation of 360o images and video of geologic phenomena and cultural heritage sites in Alaska, England, and France. Additionally, we will generate intentionally altered perspectives to lend a surrealistic quality to the landscapes. Locations include the Catacombs of Paris, the Palace of Versailles, and the Northern Lights over Fairbanks, Alaska. Some 360o view cameras now use small portable dual lens technology extending beyond the 180o fish eye lens previously used, providing better coverage and image quality. Virtual reality headsets range in level of sophistication and cost, with the most affordable versions using smart phones and Google Cardboard viewers. The equipment used in this presentation includes a Ricoh Theta S spherical imaging camera. Here we will demonstrate the use of 360o imaging with attendees being able to be part of the immersive environment and experience our locations as if they were visiting themselves.

  19. Serological survey of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, and Ehrlichia canis infections in rural and urban dogs in Central Italy

    Directory of Open Access Journals (Sweden)

    Valentina Virginia Ebani

    2014-11-01

    Full Text Available [b]Introduction[i][/i][/b][i]. Borrelia burgdorferi [/i]sensu lato (s.l. and Anaplasma phagocytophilum are well known zoonotic pathogens, whereas[i] Ehrlichia canis[/i] is usually considered to be of veterinary concern, although on the basis of recent reports it also seems to be able to infect humans. [b]objective[/b]. The aim of the study was to determine the seroprevalence of [i]B. burgdorferi [/i]s.l., A. phagocytophilum and [i]E. canis[/i] in an Italian canine population, and to verify if there are differences between dogs living in urban areas and those from a rural environment. [b]materials and method.[/b] Blood sera of 1,965 dogs, 1,235 from cities and 730 from rural areas, were tested by indirect immunofluorescent assay (IFAT. [b]results[/b]. The overall seroprevalence was highest for E. canis (7.07%, followed by [i]A. phagocytophilum[/i] (4.68%, and [i]B. burgdorferi[/i] s.l. (1.47%. Rural dogs showed the highest seroprevalence to [i]B. burgdorferi[/i] s.l. and [i]A. phagocytophilum[/i]. No significant differences were observed between rural and urban [i]E. canis[/i]-positive dogs. A low percentage (1.32% of dogs with dual seropositivity was detected, and no triple positive reactions were observed. No significant differences were detected in the seroprevalence of the three agents in relationship to the age and gender of the dogs. Seroprevalence in the five years considered were not statistically different, except for the lowest rate for [i]E. canis[/i] observed in 2012. [b]conclusions[/b]. The results confirm the presence of [i]B. burgdorferi[/i] s.l., [i]A. phagocytophilum[/i] and [i]E. canis[/i] in Italian dogs in both urban and rural areas. Monitoring pet dogs, which share the same environment with their owners, is useful for identifying the presence of tick-borne disease agents of both veterinary and public health significance

  20. Eradication of Biofilm-like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-02-01

    Full Text Available Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS. Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics. Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters. However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions. In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin. Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 µM, as well as in drug combinations with doxycycline and cefuroxime. In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters. However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 days and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 day or 21 day subculture. Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture. Furthermore, we found that

  1. Nested-PCR real time as alternative molecular tool for detection of Borrelia burgdorferi compared to the classical serological diagnosis of the blood.

    Science.gov (United States)

    Sroka-Oleksiak, Agnieszka; Ufir, Krzysztof; Salamon, Dominika; Bulanda, Malgorzata; Gosiewski, Tomasz

    Lyme disease, caused by Borrelia burgdorferi, is a multisystem disease that often makes difficulties to recognize caused by their genetic heterogenity. Currently, the gold standard for the detection of Lyme disease (LD) is serologic diagnostics based mainly on tests: ELISA and Western blot (WB). These methods, however, are subject to consider- able defect, especially in the initial phase of infection due to the occurrence of so-called serological window period and low specificity. For this reason, they might be replaced by molecular methods, for example polymerase chain reaction (PCR), which should be more sensitivity and specificity. In the present study we attempt to optimize the PCR reaction conditions and enhance existing test sensitivity by applying the equivalent of real time PCR - nested PCR for detection B. burgdorferi DNA in the patient's blood. The study involved 94 blood samples of patients with suspected LD. From each sample, 1.5 ml of blood was used for the isolation of bacterial DNA and PCR real time am- plification and its equivalent, in nested version. The remaining part earmarked for serologi- cal testing. Optimization of the reaction conditions made experimentally, using gradient of the temperature and gradient of the magnesium ions concentration for reaction real time in nested-PCR and PCR version. The results show that the nested-PCR real time, has a much higher sensitivity 45 (47.8%) of positive results for the detection of B. burgdorferi compared to the single- variety, without a preceding pre-amplification 2 (2.1%). Serological methods allowed the detection of infection in 41 (43.6%) samples. These results support of the nested PCR method as a better molecular tool for the detection of B. burgdorferi infection than classical PCR real time reaction. The nested-PCR real time method may be considered as a complement to ELISA and WB mainly in the early stages of infection, when in the blood circulating B. burgdorferi cells. By contrast, the

  2. Gesundheit und Pflege im Alter

    OpenAIRE

    Pfaff, Martin

    1989-01-01

    Gesundheit und Pflege im Alter : d. Gesundheitsreformgesetz (GRG) ; Möglichkeiten, Grenzen u. weitere Vorschläge / Martin Pfaff ; Klaus Deimer. - In: Expertengespräch "Pflege in der Familie". - Augsburg, 1989. - Getr. Zählung

  3. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

    Science.gov (United States)

    Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

    2016-01-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

  4. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

    Science.gov (United States)

    Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

    2016-08-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. On the pathologically altered pulmonary pattern

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1982-01-01

    The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

  6. Epigenetic Alterations in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Johannes eGräff

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  7. Epigenetic Alterations in Alzheimer's Disease.

    Science.gov (United States)

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  8. Systemic dystrophic alterations of skeleton

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    A roentgenologic picture of dystrophic alterations of bones following hard, acute and chronic infections diseases, distinct disorders of vitanium balance, diseases of endocrine system, disorder of metabolism and diet, long-term exogenous intoxications including medicinal is given. Distinct dystrophic disorders are characterized both by quantitative and qualitative deviations in physiological change of bones

  9. Digital media and altered states

    OpenAIRE

    Ressel, James

    2014-01-01

    This article is a reflection on whether technology has altered our perception of the spaces surrounding us and those we make, how we express ourselves and how we interact with our experiences. The reflection is based on a brief examination of the history of Northampton Chronicle & Echo as a print newspaper, its digital manifestation and human creative expression in the digital world.

  10. Modelling glass alteration in an altered argillaceous environment

    International Nuclear Information System (INIS)

    Bildstein, O.; Trotignon, L.; Pozo, C.; Jullien, M.

    2007-01-01

    The long term behaviour of materials such as glass, steel and clay has been investigated in the context of deep geological disposal of radioactive wastes. The interactions between vitrified wastes, canister corrosion products (CPs) and clay are studied using a modified version of the reaction-transport code Crunch, especially looking at pH changes and possible cementation at the interface with the clayey materials. These perturbations may indeed affect the lifetime of glass matrix in deep repositories, e.g., high pH enhances the rate of glass alteration. This work focuses on the argillite of Bure. The calculations were performed at 323 K with a glass alteration rate switching from a high initial rate to a residual rate according to the sorption capacity of CPs. The time at which this sorption capacity is saturated is crucial to the system in terms of wastes package lifetime. The results show that the glass alteration imposes a high pH value at the interface with CPs and clay: up to a value of 9.2, compared to 7.3 which is the initial pH value in the argillite. Experimental data show that the rate of glass alteration is much higher in such pH conditions. For a R7T7-type glass, the rate is about five times higher at pH 9 than at pH 7. This pH perturbation migrates through the clayey domain as a result of the migration of mobile elements such as boron and sodium, and despite the existence of strong pH buffers in the argillite. The cementation of porosity at the interface between glass and clay is predicted by the model due to the massive precipitation of iron corrosion products and glass alteration products. At this point of the evolution of the system, the pH starts to decrease and the alteration rate of the glass could be significantly reduced. This porosity clogging effect is difficult to confirm by experiments especially since existing data on short term experiments tend to show a pervasive precipitation of silica in the domain instead of a localized precipitation

  11. Frequency of antibodies to Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax and Borrelia burdgorferi in cattle from the northeastern region of the state of Pará, Brazil Freqüência de anticorpos para Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax e Borrelia burgdorferi em bovinos do nordeste do Estado do Pará, Brasil

    Directory of Open Access Journals (Sweden)

    Daniel S. Guedes Junior

    2008-06-01

    Full Text Available Babesiosis, anaplasmosis, and trypanosomosis are relevant diseases, potentially causing morbidity in cattle, leading to economic losses. Borreliosis is import as a potential zoonosis. The objective of this study was to determine, by indirect enzyme-linked immunosorbent assay (ELISA, the frequency of seropositive cattle to Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax and Borrelia burgdorferi in cattle from the Northeastern region of Pará, Brazil. Sera samples from 246 female adult cattle from municipalities of Castanhal and São Miguel do Guamá were used. Crude antigens ELISAs were used to detect antibodies to all agents, except to A. marginale, to which an indirect ELISA with recombinant major surface 1a protein (MSP1a antigen was used. Overall frequencies of seropositive animals were: B. bigemina - 99.2%; B. bovis - 98.8%; A. marginale - 68.3%; T. vivax - 93.1% and B. burgdorferi - 54.9%. The frequencies of seropositive cattle to B. bovis and B. bigemina suggest a high rate of transmission of these organisms by tick in the studied region, which can be classified as enzootically stable to these hemoprotozoans. The low frequency of seropositive cattle to A. marginale may be attributed to a lower sensitivity of the recombinant antigen ELISA utilized or a distinct rate of inoculation of this rickettsia by ticks, as compared with Babesia sp. transmission. The high frequency of seropositive cattle to T. vivax indicates that this hemoprotozoan is prevalent in herds from the Northeastern region of Pará. The rate of animal that showed homologues antibodies to B. burgdorferi indicates the presence of the tickborne spirochaetal agent in the cattle population in the studied region.A babesiose, a anaplasmose e a tripanossomose são enfermidades relevantes, potencialmente causadoras de morbidade em bovinos, levando a perdas econômicas. A borreliose assume importância como zoonose potencial. O objetivo desse estudo foi determinar

  12. Chemosensory alterations and cancer therapies

    International Nuclear Information System (INIS)

    Bartoshuk, L.M.

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems

  13. Buccal alterations in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Negrato Carlos

    2010-01-01

    Full Text Available Abstract Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a increased concentration of mucin and glucose; b impaired production and/or action of many antimicrobial factors; c absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d bad taste; e oral candidiasis f increased cells exfoliation after contact, because of poor lubrication; g increased proliferation of pathogenic microorganisms; h coated tongue; i halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a tongue alterations, generally a burning mouth; b periodontal disease; c white spots due to demineralization in the teeth; d caries; e delayed healing of wounds; f greater tendency to infections; g lichen planus; h mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  14. Buccal alterations in diabetes mellitus.

    Science.gov (United States)

    Negrato, Carlos Antonio; Tarzia, Olinda

    2010-01-15

    Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a) increased concentration of mucin and glucose; b) impaired production and/or action of many antimicrobial factors; c) absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d) bad taste; e) oral candidiasis f) increased cells exfoliation after contact, because of poor lubrication; g) increased proliferation of pathogenic microorganisms; h) coated tongue; i) halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a) tongue alterations, generally a burning mouth; b) periodontal disease; c) white spots due to demineralization in the teeth; d) caries; e) delayed healing of wounds; f) greater tendency to infections; g) lichen planus; h) mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  15. Acid Sulfate Alteration on Mars

    Science.gov (United States)

    Ming, D. W.; Morris, R. V.

    2016-01-01

    A variety of mineralogical and geochemical indicators for aqueous alteration on Mars have been identified by a combination of surface and orbital robotic missions, telescopic observations, characterization of Martian meteorites, and laboratory and terrestrial analog studies. Acid sulfate alteration has been identified at all three landing sites visited by NASA rover missions (Spirit, Opportunity, and Curiosity). Spirit landed in Gusev crater in 2004 and discovered Fe-sulfates and materials that have been extensively leached by acid sulfate solutions. Opportunity landing on the plains of Meridiani Planum also in 2004 where the rover encountered large abundances of jarosite and hematite in sedimentary rocks. Curiosity landed in Gale crater in 2012 and has characterized fluvial, deltaic, and lacustrine sediments. Jarosite and hematite were discovered in some of the lacustrine sediments. The high elemental abundance of sulfur in surface materials is obvious evidence that sulfate has played a major role in aqueous processes at all landing sites on Mars. The sulfate-rich outcrop at Meridiani Planum has an SO3 content of up to 25 wt.%. The interiors of rocks and outcrops on the Columbia Hills within Gusev crater have up to 8 wt.% SO3. Soils at both sites generally have between 5 to 14 wt.% SO3, and several soils in Gusev crater contain around 30 wt.% SO3. After normalization of major element compositions to a SO3-free basis, the bulk compositions of these materials are basaltic, with a few exceptions in Gusev crater and in lacustrine mudstones in Gale crater. These observations suggest that materials encountered by the rovers were derived from basaltic precursors by acid sulfate alteration under nearly isochemical conditions (i.e., minimal leaching). There are several cases, however, where acid sulfate alteration minerals (jarosite and hematite) formed in open hydrologic systems, e.g., in Gale crater lacustrine mudstones. Several hypotheses have been suggested for the

  16. The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model

    Energy Technology Data Exchange (ETDEWEB)

    Kotsyfakis, Michalis; Horka, Helena; Salat, Jiri; Andersen, John F. (South Bohemia); (ASCR-ICP); (NIAID)

    2010-11-17

    We have previously demonstrated that two salivary cysteine protease inhibitors from the Borrelia burgdorferi (Lyme disease) vector Ixodes scapularis - namely sialostatins L and L2 - play an important role in tick biology, as demonstrated by the fact that silencing of both sialostatins in tandem results in severe feeding defects. Here we show that sialostatin L2 - but not sialostatin L - facilitates the growth of B. burgdorferi in murine skin. To examine the structural basis underlying these differential effects of the two sialostatins, we have determined the crystal structures of both sialostatin L and L2. This is the first structural analysis of cystatins from an invertebrate source. Sialostatin L2 crystallizes as a monomer with an 'unusual' conformation of the N-terminus, while sialostatin L crystallizes as a domain-swapped dimer with an N-terminal conformation similar to other cystatins. Deletion of the 'unusual' N-terminal five residues of sialostatin L2 results in marked changes in its selectivity, suggesting that this region is a particularly important determinant of the biochemical activity of sialostatin L2. Collectively, our results reveal the structure of two tick salivary components that facilitate vector blood feeding and that one of them also supports pathogen transmission to the vertebrate host.

  17. Disagreement between the results from three commercial tests for the detection of Borrelia-specific serum antibodies in the Netherlands associated with antibiotic treatment for Lyme borreliosis: a retrospective study.

    Science.gov (United States)

    van Gorkom, T; Kremer, K; Voet, W; Notermans, D W; Vlaminckx, B J M; Sankatsing, S U C; Thijsen, S F T

    2017-11-01

    The diagnosis of Lyme borreliosis is challenging because of the often non-specific symptoms and persisting antibodies after infection. We investigated the diagnostic characteristics of two enzyme-linked immunosorbent assays (ELISAs) and an immunoblot for the detection of Borrelia-specific serum antibodies using different test strategies in individuals with and without antibiotic treatment for Lyme borreliosis. This retrospective study included healthy individuals, patients with active Lyme neuroborreliosis and patients treated for Lyme neuroborreliosis. Two ELISAs were compared: the C6 ELISA and the SERION ELISA. Equivocal and positive results were confirmed by immunoblot. We included 174 healthy individuals, of whom 27 (15.5%) were treated for Lyme borreliosis in the past, 36 patients were treated for Lyme neuroborreliosis and 27 patients had active Lyme neuroborreliosis. All the active Lyme neuroborreliosis patients were reactive in both ELISAs (100% sensitivity); less reactivity was seen in the other three groups (range 17.7% to 69.4%). The concordance between the ELISA results was high in active Lyme neuroborreliosis patients (26/27; 96.3%) and healthy individuals (131/147; 89.1%), but lower in treated healthy individuals (18/27; 66.7%) and treated Lyme neuroborreliosis patients (18/36; 50.0%) (p ≤ 0.005). This study showed that antibiotic treatment against Lyme borreliosis was strongly associated with discordant ELISA and test strategy results (odds ratio: 10.52; p Lyme serology.

  18. Multiplex assay (Mikrogen recomBead) for detection of serum IgG and IgM antibodies to 13 recombinant antigens of Borrelia burgdorferi sensu lato in patients with neuroborreliosis

    DEFF Research Database (Denmark)

    Dessau, Ram Benny; Møller, Jens K.; Kolmos, Birte

    2015-01-01

    A multiplex-bead-based assay for the detection of serum antibodies to Borrelia burgdorferi sensu lato was evaluated. The assay contained 13 different antigens in both the IgG and the IgM assay; thus, a total of 26 measurement results were available from each sample. A total of 49 Danish patients......, the construction of a diagnostic score, evaluation of the scoring method using an independent dataset and an assessment of the analytical quality of the multiplex assay. The VlsE IgG had the highest diagnostic value with an AUC (area under the curve) of 96% on the receiver operating characteristic curve. The Osp......C IgM had AUCs just above 80%. All the other antigens had both low quantitative reactivity and lower contrast in the patients with LNB compared to controls. The diagnostic value of the assay may be improved by using a logistic model giving a sensitivity of 90 and 79% for the specificities at 92 and 98...

  19. The risk of exposure to Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, Babesia sp. and co-infections in Ixodes ricinus ticks on the territory of Niepołomice forest (southern Poland).

    Science.gov (United States)

    Asman, Marek; Nowak, Magdalena; Cuber, Piotr; Strzelczyk, Joanna; Szilman, Ewa; Szilman, Piotr; Trapp, Gizela; Siuda, Krzysztof; Solarz, Krzysztof; Wiczkowski, Andrzej

    2013-01-01

    Niepołomice Forest is located about 20 kilometers east of Cracow (Malopolska province, southern Poland). Its natural and touristic values, as well as wide range of hosts occurring within indicate this to be an area of high risk of exposure to Ixodes ricinus and tick-borne diseases it transfers. I. ricinus is a common species in Poland and Europe. Its seasonal activity begins in Poland in the early spring, and ends with late autumn. A total number of 129 specimens of I. ricinus was collected by flagging in Niepołomice Forest. DNA was isolated by ammonia method from 30 randomly-selected individuals. PCR was used to detect tick-borne pathogens with primers specific for Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato and Babesia sp. Molecular studies confirmed the presence of all three pathogens in I. ricinus. A. phagocytophilum was found in 76.7%, Babesia sp., 60%, B. burgdorferi s. l., in 3.3% of studied ticks. A. phagocytophilum co-infection with Babesia sp., was found in 46.7% of the specimens. A co-infection of all three tested pathogens was recorded in one case (3.3%). In Poland the problem of tick-borne diseases is a growing issue, therefore people residing in southern Polish touristic areas should be informed about the prevention and protection against ticks.

  20. Infections and mixed infections with the selected species of Borrelia burgdorferi sensu lato complex in Ixodes ricinus ticks collected in eastern Poland: a significant increase in the course of 5 years.

    Science.gov (United States)

    Wójcik-Fatla, Angelina; Zając, Violetta; Sawczyn, Anna; Sroka, Jacek; Cisak, Ewa; Dutkiewicz, Jacek

    2016-02-01

    In the years 2008-2009 and 2013-2014, 1620 and 1500 questing Ixodes ricinus ticks, respectively, were examined on the territory of the Lublin province (eastern Poland). The presence of three pathogenic species causing Lyme disease was investigated: Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii. The proportion of I. ricinus ticks infected with B. burgdorferi sensu lato showed a highly significant increase between 2008-2009 and 2013-2014, from 6.0 to 15.3%. A significant increase was noted with regard to all types of infections with individual species: single (4.7-7.8%), dual (1.2-6.6%), and triple (0.1-0.9%). When expressed as the percent of all infections, the frequency of mixed infections increased from 21.4 to 49.2%. Statistical analysis performed with two methods (by calculating of odds ratios and by Fisher's exact test) showed that the frequencies of mixed infections in most cases proved to be significantly greater than expected. The strongest associations were found between B. burgdorferi s. s. and B. afzelii, and between B. burgdorferi s. s. and B. garinii. They appeared to be highly significant (P eastern Poland, and dramatic enhancement of mixed infections with individual species, which may result in mixed infections of humans and exacerbation of the clinical course of Lyme disease cases on the studied area.

  1. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  2. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2013-01-01

    Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations.......Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

  3. Altered Insula Connectivity under MDMA.

    Science.gov (United States)

    Walpola, Ishan C; Nest, Timothy; Roseman, Leor; Erritzoe, David; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

    2017-10-01

    Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

  4. Circadian disorganization alters intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Robin M Voigt

    Full Text Available Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  5. Self-alteration in HRI

    DEFF Research Database (Denmark)

    Yamazaki, Ryuji; Nørskov, Marco

    human communications. As an example of the results, in group work activities in an elementary school, we found that Telenoid's limited capability led children to change their attitudes so that they could work together. Also, in a care facility, the elderly with dementia developed prosocial behaviors......Humanlike androids are being developed with the ambition to be immersed into our daily life and meet us on an equal level in social interaction. The possibilities and limitations of these types of robots can potentially change societies and Human-Robot Interaction might affect the very way in which...... the ways in which our subjectivity can be innerly transformed, decentred, in other words, self-altered. In our trials so far, we have been investigating the potential of teleoperated androids, which are embodied telecommunication media with humanlike appearances. By conducting pilot studies in Japan...

  6. Hematological alterations in protein malnutrition.

    Science.gov (United States)

    Santos, Ed W; Oliveira, Dalila C; Silva, Graziela B; Tsujita, Maristela; Beltran, Jackeline O; Hastreiter, Araceli; Fock, Ricardo A; Borelli, Primavera

    2017-11-01

    Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Genetic alteration with variable intron/exon organization amongst five PI-homoeologous genes in Platanus acerifolia.

    Science.gov (United States)

    Zhang, Jiaqi; Guo, Cong; Liu, Guofeng; Li, Zhineng; Li, Xiaomei; Bao, Manzhu

    2011-03-01

    Flower development has been extensively characterized in the model species Arabidopsis thaliana and Antirrhinum majus. However, there have been few studies in woody species. Here, we report the isolation and characterization of five PISTILLATA (PI) homoeologous genes (PaPI1-to-5) from the London Plane tree (Platanus acerifolia Willd). PaPI1 and PaPI2 show a similar genomic structure to other known PI homoeologs, but PaPI3/4/5 lack intron sequences. In addition, PaPI5 lacks the third, fourth and fifth exons which encode the K-domain. These altered gene copies may have originated as 'processed' retrogenes. PaPI2 appears micro-regulated by alternative splicing, displaying three splice forms (PaPI2a, PaPI2b and PaPI2c). RT-PCR analysis showed different expression profiles and transcript abundance for the five PaPI genes. PaPI transcripts encoding full-length polypeptides were expressed predominantly in male/female inflorescences and PaPI2a was the most abundant transcript (59%) indicating that PaPI2 may be the major functional PI-homoeolog in London Plane. Phenotypic characterization in a heterologous expression system demonstrated that the full-length PaPI product functions as a B class gene. By contrast the PaPI5 form, which lacks the K-domain, had no apparent effect on flower development. In vitro studies also demonstrated that the K-domain is required to form PaPI/PaAP3 heterodimers. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H.

    Science.gov (United States)

    Brangulis, Kalvis; Petrovskis, Ivars; Kazaks, Andris; Akopjana, Inara; Tars, Kaspars

    2015-05-01

    Borrelia burgdorferi is the causative agent of Lyme disease, which can be acquired after the bite of an infected Ixodes tick. As a strategy to resist the innate immunity and to successfully spread and proliferate, B. burgdorferi expresses a set of outer membrane proteins that are capable of binding complement regulator factor H (CFH), factor H-like protein 1 (CFHL-1) and factor H-related proteins (CFHR) to avoid complement-mediated killing. B. burgdorferi B31 contains three proteins that belong to the Erp (OspE/F-related) protein family and are capable of binding CFH and some CFHRs, namely ErpA, ErpC and ErpP. We have determined the crystal structure of ErpP at 2.53Å resolution and the crystal structure of ErpC at 2.15Å resolution. Recently, the crystal structure of the Erp family member OspE from B. burgdorferi N40 was determined in complex with CFH domains 19-20, revealing the residues involved in the complex formation. Despite the high sequence conservation between ErpA, ErpC, ErpP and the homologous protein OspE (78-80%), the affinity for CFH and CFHRs differs markedly among the Erp family members, suggesting that ErpC may bind only CFHRs but not CFH. A comparison of the binding site in OspE with those of ErpC and ErpP revealed that the extended loop region, which is only observed in the potential binding site of ErpC, plays an important role by preventing the binding of CFH. These results can explain the inability of ErpC to bind CFH, whereas ErpP and ErpA still possess the ability to bind CFH. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis.

    Science.gov (United States)

    Strle, Klemen; Sulka, Katherine B; Pianta, Annalisa; Crowley, Jameson T; Arvikar, Sheila L; Anselmo, Anthony; Sadreyev, Ruslan; Steere, Allen C

    2017-04-01

    Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection. Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay. Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype. Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions

  10. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  11. Summability of alterations of convergent series

    Directory of Open Access Journals (Sweden)

    T. A. Keagy

    1981-01-01

    Full Text Available The effect of splitting, rearrangement, and grouping series alterations on the summability of a convergent series by ℓ−ℓ and cs−cs matrix methods is studied. Conditions are determined that guarantee the existence of alterations that are transformed into divergent series and into series with preassigned sums.

  12. Do invasive plant species alter soil health?

    Science.gov (United States)

    Invasive species may alter soil characteristics or interact with the soil microbial community to yield a competitive advantage. Our objectives were to determine: if invasive plant species alter soil properties important to soil health; and the long-term effects of invasive plant species on soil pro...

  13. Roentgenological findings in muscular alterations of extremities

    International Nuclear Information System (INIS)

    Palvoelgyi, R.

    1978-01-01

    A survey of roentgenological findings in muscular alterations of extremities based on the author's experiences and on the literature is presented. Following a description of the normal roentgen anatomy, the alterations in different diseases of interstitial lipomatosis are demonstrated. By roentgenological examinations differt muscular lesions of the extremities can be differentiated and the clinical follow-up verified. (orig.) [de

  14. An Analysis of the Alteration Specialist Occupation.

    Science.gov (United States)

    Buerkel, Elaine; Rehling, Joseph H.

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the textile service occupation. The industry needs properly trained alteration specialists, bushelmen and dressmakers, in the repairing, remodeling, altering or renovating of garments. Their personal…

  15. Prevalence of Dirofilaria immitis, Ehrlichia canis, Borrelia burgdorferi sensu lato, Anaplasma spp. and Leishmania infantum in apparently healthy and CVBD-suspect dogs in Portugal - a national serological study

    Directory of Open Access Journals (Sweden)

    Cardoso Luís

    2012-03-01

    Full Text Available Abstract Background Canine vector-borne diseases (CVBDs are caused by a wide range of pathogens transmitted to dogs by arthropods including ticks and insects. Many CVBD-agents are of zoonotic concern, with dogs potentially serving as reservoirs and sentinels for human infections. The present study aimed at assessing the seroprevalence of infection with or exposure to Dirofilaria immitis, Ehrlichia canis, Borrelia burgdorferi sensu lato, Anaplasma spp. and Leishmania infantum in dogs in Portugal. Methods Based on 120 veterinary medical centres from all the regions of mainland and insular Portugal, 557 apparently healthy and 628 CVBD-suspect dogs were sampled. Serum, plasma or whole blood was tested for qualitative detection of D. immitis antigen and antibodies to E. canis, B. burgdorferi s. l., Anaplasma spp. and L. infantum with two commercial in-clinic enzyme-linked immunosorbent assay kits. Odds ratios (OR were calculated by logistic regression analysis to identify independent risk factors of exposure to the vector-borne agents. Results Total positivity levels to D. immitis, E. canis, B. burgdorferi, Anaplasma spp., L. infantum, one or more agents and mixed agents were 3.6%, 4.1%, 0.2%, 4.5%, 4.3%, 14.0% and 2.0% in the healthy group, and 8.9%, 16.4%, 0.5%, 9.2%, 25.2%, 46.3% and 11.6% in the clinically suspect group, respectively. Non-use of ectoparasiticides was a risk factor for positivity to one or more agents both in the apparently healthy (OR = 2.1 and CVBD-suspect (OR = 1.5 dogs. Seropositivity to L. infantum (OR = 7.6, E. canis (OR = 4.1 and D. immitis (OR = 2.4 were identified as risk factors for the presence of clinical signs compatible with CVBDs. Positivity to mixed agents was not found to be a risk factor for disease. Conclusions Dogs in Portugal are at risk of becoming infected with vector-borne pathogens, some of which are of zoonotic concern. CVBDs should be considered by practitioners and prophylactic measures must be put in

  16. rights reserved Geophysical Identification of Hydrothermally Altered

    African Journals Online (AJOL)

    ADOWIE PERE

    Geophysical Identification of Hydrothermally Altered Structures That Favour .... aircraft. Total line kilometers of 36,500 were covered in the survey. Magnetic ... tie lines occur at about 2000 metres interval in the ... visual inspection of the map.

  17. Altered States: Globalization, Sovereignty, and Governance | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    For all the opportunities that globalization promises, it raises urgent ... Has the achievement of democratic government come too late for most of the ... The message of Altered States is one of both hope and warning: globalization opens great ...

  18. Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations

    DEFF Research Database (Denmark)

    Kacso, Gergely; Ravasz, Dora; Doczi, Judit

    2016-01-01

    Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and a substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with or without methylmalonyl aciduria, in addition to result...

  19. Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    2015-10-01

    Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  20. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

    Science.gov (United States)

    Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  1. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  2. Convergent Synthesis of Two Fluorescent Ebselen-Coumarin Heterodimers

    OpenAIRE

    K?ppers, Jim; Schulz-Fincke, Anna Christina; Palus, Jerzy; Giurg, Miros?aw; Skar?ewski, Jacek; G?tschow, Michael

    2016-01-01

    The organo-seleniumdrug ebselen exhibits a wide range of pharmacological effects that are predominantly due to its interference with redox systems catalyzed by seleno enzymes, e.g., glutathione peroxidase and thioredoxin reductase. Moreover, ebselen can covalently interact with thiol groups of several enzymes. According to its pleiotropic mode of action, ebselen has been investigated in clinical trials for the prevention and treatment of different ailments. Fluorescence-labeled probes contain...

  3. Mortar alteration: experimental study and ancient analogues

    International Nuclear Information System (INIS)

    Rassineux, Francois

    1987-01-01

    As the durability of cemented matrices is a matter of great importance in numerous domains, notably for the long term reliability of surface storages of radioactive wastes, the objective of this research thesis is to define mechanisms of evolution of cemented matrices when in contact with diluted aqueous solutions. The author notably studied the influence of the lixiviation mode on the evolution of two mortars having different compositions (pH, CO 2 pressure, system containment, and cement mineralogical nature appear to be the main governing parameters), the alteration (dissolution is the prevailing process in the interaction between cemented matrices and a diluted solution such as rain water), and ancient binders (archaeological binders containing mineral phases such as hydrated calcium silicates or hydro-grossulars). The obtained results lead to the definition of alteration mechanisms in modern cements, and highlight factors governing the durability of these materials when submitted to meteoric alteration [fr

  4. Alter(n – ein vielschichtiger Begriff

    Directory of Open Access Journals (Sweden)

    Nicole Maly-Lukas

    2005-07-01

    Full Text Available Diese Veröffentlichung, die aus einer Vortragsreihe an der katholischen Fachhochschule Freiburg entstanden ist, führt die Leserinnen und Leser in die verschiedenen Sichtweisen des Alter(ns in der modernen Gesellschaft ein. Es handelt sich um eine gelungene Zusammenstellung von Beiträgen aus unterschiedlichen Disziplinen, die sich alle aus ihrer Sicht dem Thema Alter(n widmen. Die einzelnen Artikel sind zwischen 8 und 38 Seiten lang und recht schnell und einfach zu lesen. Je nach Hintergrund und Interessen werden die einzelnen Leserinnen und Leser dabei sicher unterschiedliche Beiträge favorisieren. Schade ist nur, dass durch die ungleichen Längen der Beiträge bestimmte thematische Schwerpunkte – ob gewollt oder nicht – gesetzt werden. Dies sollte die Leserinnen und Leser, die offen für unterschiedlichste Sichtweisen des Alter(ns sind, jedoch nicht davon abhalten, dieses Buch zu lesen.

  5. Alterations in physiology and anatomy during pregnancy.

    Science.gov (United States)

    Tan, Eng Kien; Tan, Eng Loy

    2013-12-01

    Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Streamflow alteration at selected sites in Kansas

    Science.gov (United States)

    Juracek, Kyle E.; Eng, Ken

    2017-06-26

    An understanding of streamflow alteration in response to various disturbances is necessary for the effective management of stream habitat for a variety of species in Kansas. Streamflow alteration can have negative ecological effects. Using a modeling approach, streamflow alteration was assessed for 129 selected U.S. Geological Survey streamgages in the State for which requisite streamflow and basin-characteristic information was available. The assessment involved a comparison of the observed condition from 1980 to 2015 with the predicted expected (least-disturbed) condition for 29 streamflow metrics. The metrics represent various characteristics of streamflow including average flow (annual, monthly) and low and high flow (frequency, duration, magnitude).Streamflow alteration in Kansas was indicated locally, regionally, and statewide. Given the absence of a pronounced trend in annual precipitation in Kansas, a precipitation-related explanation for streamflow alteration was not supported. Thus, the likely explanation for streamflow alteration was human activity. Locally, a flashier flow regime (typified by shorter lag times and more frequent and higher peak discharges) was indicated for three streamgages with urbanized basins that had higher percentages of impervious surfaces than other basins in the State. The combination of localized reservoir effects and regional groundwater pumping from the High Plains aquifer likely was responsible, in part, for diminished conditions indicated for multiple streamflow metrics in western and central Kansas. Statewide, the implementation of agricultural land-management practices to reduce runoff may have been responsible, in part, for a diminished duration and magnitude of high flows. In central and eastern Kansas, implemented agricultural land-management practices may have been partly responsible for an inflated magnitude of low flows at several sites.

  7. Bone alterations by stress in athletes

    International Nuclear Information System (INIS)

    Doege, H.

    1990-01-01

    This report describes our experiences with the bone imaging in athletes. We studied 10 athletes and 10 other patients with spondylolisthesis of the lumbar spine and 16 athletes with suspicion of alterations of extremities. An increased uptake of this radiopharmaceutical was detected in six of 10 athletes with spondylolisthesis caused probably by stress fracture. Bone scans were negative in seven of 16 athletes with suspicion of lesion of extremities. In the remaining 9 patients scans were abnormal and showed periosteal injuries, epiphyseal alteration, joint abnormalities, tibial stress fractures and couvert fracture. It was also abnormal in bone injuries not evident in radiography. (orig.) [de

  8. White matter alterations in temporal lobe epilepsy

    Science.gov (United States)

    Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

    2011-03-01

    In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

  9. Oxycodone Self-Administration Induces Alterations in Expression of Integrin, Semaphorin and Ephrin Genes in the Mouse Striatum

    Directory of Open Access Journals (Sweden)

    Vadim Yuferov

    2018-06-01

    Full Text Available Oxycodone is one a commonly used medication for pain, and is also a widely abused prescription opioid, like other short-acting MOPr agonists. Neurochemical and structural adaptations in brain following chronic MOPr-agonist administration are thought to underlie pathogenesis and persistence of opiate addiction. Many axon guidance molecules, such as integrins, semaphorins, and ephrins may contribute to oxycodone-induced neuroadaptations through alterations in axon-target connections and synaptogenesis, that may be implicated in the behaviors associated with opiate addiction. However, little is known about this important area. The aim of this study is to investigate alterations in expression of selected integrin, semaphorin, ephrins, netrin, and slit genes in the nucleus accumbens (NAc and caudate putamen (CPu of mice following extended 14-day oxycodone self-administration (SA, using RNAseq.Methods: Total RNA from the NAc and CPu were isolated from adult male C57BL/6J mice within 1 h after the last session of oxycodone in a 14-day self-administration paradigm (4h/day, 0.25 mg/kg/infusion, FR1 or from yoked saline controls. Gene expressions were examined using RNA sequencing (RNA-Seq technology. RNA-Seq libraries were prepared using Illumina's TruSeq® Stranded Total RNA LT kit. The reads were aligned to the mouse reference genome (version mm10 using STAR. DESeq2 was applied to the counts of protein coding genes to estimate the fold change between the treatment groups. False Discovery Rate (FDR q < 0.1 were used to select genes that have a significant expression change. For selection of a subset of genes related to axon guidance pathway, REACTOME was used.Results: Among 38 known genes of the integrin, semaphorin, and ephrin gene families, RNA-seq data revealed up-regulation of six genes in the NAc: heterodimer receptor, integrins Itgal, Itgb2, and Itgam, and its ligand semaphorin Sema7a, two semaphorin receptors, plexins Plxnd1 and Plxdc1. There was

  10. Altered membrane permeability in multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    The study was conducted with the objective of examining the outer membrane proteins and their involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the response of gram negative bacterial biomembrane alteration was studied using extended ...

  11. Connective tissue alteration in abdominal wall hernia

    DEFF Research Database (Denmark)

    Henriksen, N A; Yadete, D H; Sørensen, Lars Tue

    2011-01-01

    The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations in abdom...

  12. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated...

  13. Epigenetic Alterations in Alzheimer’s Disease

    Science.gov (United States)

    Sanchez-Mut, Jose V.; Gräff, Johannes

    2015-01-01

    Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  14. rights reserved Geophysical Identification of Hydrothermally Altered ...

    African Journals Online (AJOL)

    ADOWIE PERE

    the pole to the magnetic data aided in mapping of various hydrothermally altered structures that may favour gold mineralisation. The interpretation of the aero data set has enhanced a lot of ... water serves as a concentrating, transporting and depositing agent through faults (structures) to the earth's surface. Hydrothermal ...

  15. SEDAH. Data Server for hydrologic alteration evaluation

    International Nuclear Information System (INIS)

    Martinez Romero, R.; Magdaleno Mas, F.; Ortiz Rodriguez, J.; Fernandez Yuste, J. A.; Martinez Santa-Maria, C.

    2011-01-01

    Several tasks and studies have been developed from 2008 till 2010 all around the country in order to evaluate the hydrologic alteration of water bodies. In most cases this alteraction has been evaluated through IAHRIS (Martinez and Fernandez, 2006). The necessity of creating a new toll that allowed a better performance of the National Flow-Stage Stations Network data was showed up by developing these works. The output data series should match IAHRIS and IHA. SEDAH (Data Server for Evaluating Hydrologic Alteration) Helps to solve some of these problems by supplying an easy way to select flow stations, dates, flow series typology, etc. Moreover, other useful utilities are: a preliminary appraisement of quality data, calssification of altered or reference flow series and exportation of data in different file formats. The web application works with different data bases, daily, monthly and annual series belonging to, wither actual series from flow station data or completed series by statistical procedures. Through SEDAH the user has easy access to all this huge information ready for being applied in hydrologic alteration assessment, environmental fows regime, river restoration projects, etc. Furthermore, this first phase of the application constitute the basis for future powerful functionalities related to the natural flow series obtaining. (Author) 5 refs.

  16. Sulphur depletion altered somatic embryogenesis in Theobroma ...

    African Journals Online (AJOL)

    Somatic embryogenesis is a useful tool for Theobroma cacao improvement and propagation. Depending on culture medium composition, different morphogenetic structures (including somatic embryo) occur in response to alteration of genes expression patterns and biochemical changes. The effect of SO42- ion deficiency ...

  17. NEW, GOOD DOCTORS FOR AN ALTERED SOCIETY*

    African Journals Online (AJOL)

    NEW, GOOD DOCTORS FOR AN ALTERED SOCIETY*. ANrHONY BARKER ... the concept of trying to become one is just a psychological throwback? ... called all these things and many things besides, yet this ... sex (women ought to be better at it than men, but often are not) .... foundations to lay for a specialized career.

  18. Global alteration of climate - hopes and fears

    International Nuclear Information System (INIS)

    Viktorov, V.V.

    1992-01-01

    Problems concerning gaseous emission affecting the global climate alteration connected with hotbed effect are considered. Economical and social-political ways of solution of the problem of minimization of gaseous wastes are described. Role of nuclear power plants and alternative power plants in the hotbed effect are analyzed. International cooperation in environmental protection policy is discussed

  19. Rare endocrine cancers have novel genetic alterations

    Science.gov (United States)

    A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

  20. 28 CFR 36.402 - Alterations.

    Science.gov (United States)

    2010-07-01

    ... other types of disabilities (e.g., those who use crutches, those who have impaired vision or hearing, or... Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY BY PUBLIC.... (1) Any alteration to a place of public accommodation or a commercial facility, after January 26...

  1. Altered Cellular Metabolism Drives Trained Immunity.

    Science.gov (United States)

    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. 28 CFR 36.403 - Alterations: Path of travel.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Path of travel. 36.403... Alterations: Path of travel. (a) General. An alteration that affects or could affect the usability of or... the maximum extent feasible, the path of travel to the altered area and the restrooms, telephones, and...

  3. Epigenetic alteration of sedimentary rocks at hydrogenic uranium deposit

    International Nuclear Information System (INIS)

    Ding Wanlie; Shen Kefeng

    2001-01-01

    The author introduces the concept, the recognition criteria, the genesis and classification of the epigenetic alteration of sedimentary rocks in brief, and expounds the mineral-geochemical indications and characteristics of oxidation and reduction alterations in different geochemical zones in detail, and proposes the two models of ore-controlling zonation of epigenetic alteration. The authors finally introduce research methods of epigenetic alteration

  4. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  5. Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

    Science.gov (United States)

    Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

    2014-01-01

    Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

  6. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  7. Lung scan alterations in congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, R; Sanchez, J; Munoz, A; Lanaro, A E; Pico, A M

    1975-04-01

    This report analyzes the patterns in 54 lung scannings of 34 patients with altered pulmonary blood flow due to congenital heart disease. The technique and the results are presented. According to the images obtained, the patients are classified in three groups: Group I--normal distribution with more concentration of particles over the right lung and the bases. Group II--normal scannings found in left to right shunts unless there is pulmonary venous hypertension in which case the apex-base relationship was inverted. Group III--patients with right to left shunts of different types presenting various patterns according to severity, associated anomalies and palliative surgery. The hemodynamics created by cardiac defects and surgical procedures explain these alterations. This method is recommended in view of its advantages and accurate results.

  8. Smoking cessation alters subgingival microbial recolonization.

    Science.gov (United States)

    Fullmer, S C; Preshaw, P M; Heasman, P A; Kumar, P S

    2009-06-01

    Smoking cessation improves the clinical manifestations of periodontitis; however, its effect on the subgingival biofilm, the primary etiological agent of periodontitis, is unclear. The purpose of this study was to investigate, longitudinally, if smoking cessation altered the composition of the subgingival microbial community, by means of a quantitative, cultivation-independent assay for bacterial profiling. Subgingival plaque was collected at baseline, and 3, 6, and 12 months post-treatment from smokers who received root planing and smoking cessation counseling. The plaque was analyzed by terminal restriction fragment length polymorphism (t-RFLP). Microbial profiles differed significantly between smokers and quitters at 6 and 12 months following smoking cessation. The microbial community in smokers was similar to baseline, while quitters demonstrated significantly divergent profiles. Changes in bacterial levels contributed to this shift. These findings reveal a critical role for smoking cessation in altering the subgingival biofilm and suggest a mechanism for improved periodontal health associated with smoking cessation.

  9. Alteration of diaspore by thermal treatment

    Institute of Scientific and Technical Information of China (English)

    杨华明; 胡岳华; 杨武国; 敖伟琴; 邱冠周

    2004-01-01

    Diaspore (α-AlOOH) was heated at various temperatures from 300 to 1000 ℃ for 2 h. The alteration of diaspore by thermal treatment was investigated by differential thermal analysis, thermogravimetric analysis and X-ray diffraction. The mechanism of thermal decomposition of diaspore was discussed according to the Coats-Redfern equation. It is found that after thermal treatment at 500 ℃, diaspore is transformed entirely to corundum (α-Al2O3). Combined with the mass loss ratio obtained from the thermogravimetric analysis data, the activation energies for the thermal treatment of diaspore are calculated as Ea=10.4 kJ/mol below 400 ℃ and Eb=47.5 kJ/mol above 400 ℃, respectively, which is directly related to the structural alteration of diaspore during the thermal treatment. The results indicate that the thermal decomposition of diaspore is conducted primarily by means of an interfacial reaction.

  10. Viral haemorrhagic fever and vascular alterations.

    Science.gov (United States)

    Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

    2008-02-01

    Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

  11. Epigenetic alterations of sedimentary rocks at deposits

    International Nuclear Information System (INIS)

    Komarova, G.V.; Kondrat'eva, I.A.; Zelenova, O.I.

    1980-01-01

    Notions are explained, and technique for studying epigenetic alterations of sedimentary rocks at uranium deposits is described. Main types of epigenetic transformations and their mineralogic-geochemical characteristics are considered. Rock alterations, accompanying uranium mineralization, can be related to 2 types: oxidation and reduction. The main mineralogic-geochemical property of oxidation transformations is epigenetic limonitization. Stratal limonitization in primary grey-coloured terrigenic rocks and in epigenetically reduced (pyritized) rocks, as well as in rock, subjected to epigenetic gleying, are characterized. Reduction type of epigenetic transformations is subdivided into sulphidic and non-sulphidic (gley) subtypes. Sulphidic transformations in grey-coloured terrigenic rocks with organic substance of carbonic row, in rocks, containing organic substance of oil row, sulphide transformations of sedimentary rocks, as well as gley transformations, are considered

  12. Altered Sensory Feedbacks in Pianist's Dystonia: the altered auditory feedback paradigm and the glove effect

    Directory of Open Access Journals (Sweden)

    Felicia Pei-Hsin Cheng

    2013-12-01

    Full Text Available Background: This study investigates the effect of altered auditory feedback (AAF in musician's dystonia (MD and discusses whether altered auditory feedback can be considered as a sensory trick in MD. Furthermore, the effect of AAF is compared with altered tactile feedback, which can serve as a sensory trick in several other forms of focal dystonia. Methods: The method is based on scale analysis (Jabusch et al. 2004. Experiment 1 employs synchronization paradigm: 12 MD patients and 25 healthy pianists had to repeatedly play C-major scales in synchrony with a metronome on a MIDI-piano with 3 auditory feedback conditions: 1. normal feedback; 2. no feedback; 3. constant delayed feedback. Experiment 2 employs synchronization-continuation paradigm: 12 MD patients and 12 healthy pianists had to repeatedly play C-major scales in two phases: first in synchrony with a metronome, secondly continue the established tempo without the metronome. There are 4 experimental conditions, among them 3 are the same altered auditory feedback as in Experiment 1 and 1 is related to altered tactile sensory input. The coefficient of variation of inter-onset intervals of the key depressions was calculated to evaluate fine motor control. Results: In both experiments, the healthy controls and the patients behaved very similarly. There is no difference in the regularity of playing between the two groups under any condition, and neither did AAF nor did altered tactile feedback have a beneficial effect on patients’ fine motor control. Conclusions: The results of the two experiments suggest that in the context of our experimental designs, AAF and altered tactile feedback play a minor role in motor coordination in patients with musicians' dystonia. We propose that altered auditory and tactile feedback do not serve as effective sensory tricks and may not temporarily reduce the symptoms of patients suffering from MD in this experimental context.

  13. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  14. Enamel alteration following tooth bleaching and remineralization

    OpenAIRE

    Coceska, Emilija; Gjorgievska, Elizabeta; Coleman, Nichola; Gabric, Dragana; Slipper, Ian J.; Stevanovic, Marija; Nicholson, John

    2015-01-01

    The purpose of this study was to compare the effects of professional tooth whitening agents containing highly concentrated hydrogen peroxide (with and without laser activation), on the enamel surface; and the potential of four different toothpastes to remineralize any alterations.\\ud \\ud The study was performed on 50 human molars, divided in two groups: treated with Opalescence® Boost and Mirawhite® Laser Bleaching. Furthermore, each group was divided into five subgroups, a control one and 4 ...

  15. Silychristin: Skeletal Alterations and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

    2016-01-01

    Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

  16. Sulphur depletion altered somatic embryogenesis in Theobroma ...

    African Journals Online (AJOL)

    USER

    2010-08-30

    Aug 30, 2010 ... embryo) occur in response to alteration of genes expression patterns ... the proteins synthesis and the rate with which all amino ... thiamine-HCl, 1 mgml-1 nicotinic acid and 2 mgml-1 glycine), 20 gL-1 ... Amino acids and soluble sugar extraction .... 0.1% (v/v) Triton X-100, 0.1 % (w/v) dithiothreitol, and 0.2%.

  17. Marijuana exposure and pulmonary alterations in primates.

    Science.gov (United States)

    Fligiel, S E; Beals, T F; Tashkin, D P; Paule, M G; Scallet, A C; Ali, S F; Bailey, J R; Slikker, W

    1991-11-01

    As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

  18. Genetic alterations in hepatocellular carcinoma: An update

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  19. Genomic and Epigenomic Alterations in Cancer.

    Science.gov (United States)

    Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

    2016-07-01

    Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Obesogenic diets alter metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Megan R Showalter

    Full Text Available Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose, or very high fat diet (60%kcal fat/7% sucrose for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  1. [Alterations in arterial compliance of dyslipidemic patients].

    Science.gov (United States)

    Clara, Fernando Mario; Corral, Pablo; Blanco, Gustavo Hector; Scandurra, Adriana Graciela; Meschino, Gustavo Javier

    2015-01-01

    We studied the alteration on the distensibility of the arterial walls caused by dyslipidemia LDLc dependent, along the decades of life, by means of a study of the radial artery pulse wave. We made an analysis of the radial artery pulse wave records acquired by means a movement displacement sensor, placed on radial palpation area. We recruited 100 dyslipidemic men without other cardiovascular risk factors, between the 3rd and the 6th decade. We identified the reflected wave in the records and we computed the augmentation index in order to quantify its amplitude and position. This index is useful to assess the endothelial dysfunction. Besides, we defined a velocity coefficient as the ratio between the size of the individuals and the delay time between the peak of the systolic wave and the arrival of the reflected wave. Results were compared against those obtained in a group of 161 healthy volunteers. We found that dyslipidemic patients presented augmentation index values similar to controls until the fourth decade, increasing thereafter with significant differences only in the 6th decade. No significant differences were found in the velocity index in any of the ages studied. We conclude that alterations produced by dyslipidemia take decades to manifest, and they begin affecting the mechanism of vasodilation of distal arteries with highest proportion of smooth muscle, without altering the proximal conduit arteries with more elastin content. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  2. Altered Global Signal Topography in Schizophrenia.

    Science.gov (United States)

    Yang, Genevieve J; Murray, John D; Glasser, Matthew; Pearlson, Godfrey D; Krystal, John H; Schleifer, Charlie; Repovs, Grega; Anticevic, Alan

    2017-11-01

    Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems. Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain-i.e. the "global" signal (GS). It remains unknown, however, if these "global" alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients. We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS topography may underlie profound alterations in neural information flow in SCZ, informing development of pharmacotherapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Altered brain arginine metabolism in schizophrenia.

    Science.gov (United States)

    Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

    2016-08-16

    Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

  4. Obesogenic diets alter metabolism in mice.

    Science.gov (United States)

    Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

    2018-01-01

    Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  5. Chromite alteration processes within Vourinos ophiolite

    Science.gov (United States)

    Grieco, Giovanni; Merlini, Anna

    2012-09-01

    The renewed interest in chromite ore deposits is directly related to the increase in Cr price ruled by international market trends. Chromite, an accessory mineral in peridotites, is considered to be a petrogenetic indicator because its composition reflects the degree of partial melting that the mantle experienced while producing the chromium spinel-bearing rock (Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993). However, the understanding of chromite alteration and metamorphic modification is still controversial (e.g. Evans and Frost in Geochim Cosmochim Acta 39:959-972, 1975; Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993; Oze et al. in Am J Sci 304:67-101, 2004). Metamorphic alteration leads to major changes in chromite chemistry and to the growth of secondary phases such as ferritchromite and chlorite. In this study, we investigate the Vourinos complex chromitites (from the mines of Rizo, Aetoraches, Xerolivado and Potamia) with respect to textural and chemical analyses in order to highlight the most important trend of alteration related to chromite transformation. The present study has been partially funded by the Aliakmon project in collaboration between the Public Power Corporation of Greece and Institute of Geology and Mineral Exploration of Kozani.

  6. Chemistry, mineralogy and alteration intensity of hydrothermal altered Mt Unzen conduit rocks (Shimabara/Japan)

    Science.gov (United States)

    Hess, Kai-Uwe; Yilmaz, Tim; Gilg, H. Albert; Janots, Emilie; Mayer, Klaus; Nakada, Setsuya; Dingwell, Donald

    2017-04-01

    Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, C-O-isotope, hot-cathode CL and SEM analysis led to insights concerning chemistry, mineralogy, and intensity and type of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the volcanic conduit rocks was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite and kaolinite group minerals indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate and chlorite pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite as well as kaolinite group minerals, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite, R1 illite-smectite as well as kaolinite group minerals in the groundmass. Late chlorite veins crosscut precipitates of R1 illite-smectite as well as kaolinite group minerals. Carbonates in fractures and in pseudomorphs after hornblende comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration

  7. Reactive-brittle dynamics in peridotite alteration

    Science.gov (United States)

    Evans, O.; Spiegelman, M. W.; Kelemen, P. B.

    2017-12-01

    The interactions between reactive fluids and brittle solids are critical in Earth dynamics. Implications of such processes are wide-ranging: from earthquake physics to geologic carbon sequestration and the cycling of fluids and volatiles through subduction zones. Peridotite alteration is a common feature in many of these processes, which - despite its obvious importance - is relatively poorly understood from a geodynamical perspective. In particular, alteration reactions are thought to be self-limiting in nature, contradicting observations of rocks that have undergone 100% hydration/carbonation. One potential explanation of this observation is the mechanism of "reaction-driven cracking": that volume changes associated with these reactions are large enough to fracture the surrounding rock, leading to a positive feedback where new reactive surfaces are exposed and fluid pathways are created. The purpose of this study is to investigate the relative roles of reaction, elastic stresses and surface tension in alteration reactions. In this regard we derive a system of equations describing reactive fluid flow in an elastically deformable porous media, and explore them via a combination of analytic and numerical solutions. Using this model we show that the final stress state of a dry peridotite that has undergone reaction depends strongly on the rates of reaction versus fluid transport: significant fluid flow driven by pressure and/or surface tension gradients implies higher fractions of serpentinization, leaving behind a highly stressed residuum of partially reacted material. Using a model set-up that mimics a cylindrical triaxial apparatus we predict that the resulting stresses would lead to tensile failure and the generation of radially oriented cracks.

  8. Enamel alteration following tooth bleaching and remineralization.

    Science.gov (United States)

    Coceska, Emilija; Gjorgievska, Elizabeta; Coleman, Nichola J; Gabric, Dragana; Slipper, Ian J; Stevanovic, Marija; Nicholson, John W

    2016-06-01

    The purpose of this study was to compare the effects of professional tooth whitening agents containing highly concentrated hydrogen peroxide (with and without laser activation), on the enamel surface; and the potential of four different toothpastes to remineralize any alterations. The study was performed on 50 human molars, divided in two groups: treated with Opalescence(®) Boost and Mirawhite(®) Laser Bleaching. Furthermore, each group was divided into five subgroups, a control one and 4 subgroups remineralized with: Mirasensitive(®) hap+, Mirawhite(®) Gelleѐ, GC Tooth Mousse™ and Mirafluor(®) C. The samples were analysed by SEM/3D-SEM-micrographs, SEM/EDX-qualitative analysis and SEM/EDX-semiquantitative analysis. The microphotographs show that both types of bleaching cause alterations: emphasized perikymata, erosions, loss of interprizmatic substance; the laser treatment is more aggressive and loss of integrity of the enamel is determined by shearing off the enamel rods. In all samples undergoing remineralization deposits were observed, those of toothpastes based on calcium phosphate technologies seem to merge with each other and cover almost the entire surface of the enamel. Loss of integrity and minerals were detected only in the line-scans of the sample remineralized with GC Tooth Mousse™. The semiquantitative EDX analysis of individual elements in the surface layer of the enamel indicates that during tooth-bleaching with HP statistically significant loss of Na and Mg occurs, whereas the bleaching in combination with a laser leads to statistically significant loss of Ca and P. The results undoubtedly confirm that teeth whitening procedures lead to enamel alterations. In this context, it must be noted that laser bleaching is more aggressive for dental substances. However, these changes are reversible and can be repaired by application of remineralization toothpastes. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  9. Distinct genetic alterations in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Hassan Ashktorab

    Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.

  10. SON68 glass alteration enhanced by magnetite

    Energy Technology Data Exchange (ETDEWEB)

    Godon, Nicole; Gin, Stephane; Rebiscoul, Diane; Frugier, Pierre [CEA, DEN-Marcoule, F30207, Bagnols-sur-Ceze (France)

    2013-07-01

    This paper reports experimental and modeling results of SON68 glass / magnetite interactions while in contact with synthetic groundwater from a clay environment. It is shown that magnetite enhances glass alteration, first by the sorption of Si released from the glass onto magnetite surfaces, then by a second process that could be the precipitation of an iron silicate mineral or the transformation of magnetite into a more reactive phase like hematite or goethite. This study globally suggests a detrimental effect of magnetite on the long-term durability of nuclear glass in geological disposal conditions. (authors)

  11. Clerics urge ban on altering germline cells.

    Science.gov (United States)

    Norman, C

    1983-06-24

    A resolution calling for a ban on genetic engineering of human reproductive cells has been signed by leaders of almost every major church group in the United States. Some of the religious leaders, while not certain that a total moratorium should be placed on altering germline cells, signed the statement in order to stimulate public debate on the issue. Legislation has recently been introduced in Congress to set up a committee to monitor genetic engineering and its human applications, but author Jeremy Rifkin, the impetus behind the church leaders' resolution, argues that such tampering threatens the gene pool and should be banned altogether.

  12. Metabolic alterations during ascosporogenesis of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Carvalho, Sandra; Nadkarni, G.B.

    1977-01-01

    Sporulation of S. cerevisiae has been shown to alter the profiles of enzymes involved in gluconeogenesis and glycolysis. The enhancement in the levels of total cellular carbohydrates could be correlated with the enhancement in fructose 1,6-diphosphatase and trehalose-phosphate synthetase. The latter activity could account for the 15-fold increase in trehalose levels in sporulating cells. Glucose-6-phosphatase, pyruvate kinase and phosphofructokinase showed continuous decline during ascosporogenesis. The relative incorporation of radioactivity from possible precursors of gluconeogenesis indicated that acetate-2- 14 C alone could contribute to carbohydrate synthesis. (author)

  13. Phase alteration compensation in reflection digital holography

    International Nuclear Information System (INIS)

    Rincon, O; Amezquita, R; Monroy, F

    2011-01-01

    The phase maps obtained from digital holographic microscopy techniques carry information about the axial lengths of the object under study. Additionally, these phase maps have information of tilt and curvatures with origin in the off-axis geometry and the magnification lenses system, respectively. Only a complete compensation of these extra phases allows a correct interpretation of the phase information. In this article a numerical strategy to compensate for these alterations is designed, using a phase mask located in different planes. This strategy is applied in the measurement of a phase steps plate using a digital holography setup.

  14. Ethic's pedagogy: from responsibility to alterity

    Directory of Open Access Journals (Sweden)

    Eduardo S. Vila Merino

    2004-11-01

    Full Text Available Ethics, since the so-called 'linguistic turn' and the rise of the notion of discursive formations, has tended to combine the teleological and the deontological. That means that, if ethics is to be useful in understanding relationships and other social issues, or in building the common good, it ought to take a procedural position. We believe that the teaching of ethics should be based on the notions of responsibility and alterity. These two concepts are helpful in promoting mutual understanding and other-directedness.

  15. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  16. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Detailed Conceptual Diagram

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  17. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Simple Conceptual Diagram

    Science.gov (United States)

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  18. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair

    NARCIS (Netherlands)

    Y.J. Choi (Yong Jun); H. Li (Han); M.Y. Son (Mi Young); X.-H. Wang (Xiao-Hong); J.L. Fornsaglio (Jamie L.); R.W. Sobol (Robert W.); M. Lee (Moonsook); J. Vijg (Jan); S. Imholz (Sandra); M.E.T. Dollé (Martijn); H. van Steeg (Harry); E. Reiling (Erwin); P. Hasty (Paul)

    2014-01-01

    textabstractKu70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB

  19. Altered pharyngeal muscles in Parkinson disease.

    Science.gov (United States)

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

    2012-06-01

    Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

  20. Origins of altered reinforcement effects in ADHD

    Directory of Open Access Journals (Sweden)

    Tripp Gail

    2009-02-01

    Full Text Available Abstract Attention-deficit/hyperactivity disorder (ADHD, characterized by hyperactivity, impulsiveness and deficient sustained attention, is one of the most common and persistent behavioral disorders of childhood. ADHD is associated with catecholamine dysfunction. The catecholamines are important for response selection and memory formation, and dopamine in particular is important for reinforcement of successful behavior. The convergence of dopaminergic mesolimbic and glutamatergic corticostriatal synapses upon individual neostriatal neurons provides a favorable substrate for a three-factor synaptic modification rule underlying acquisition of associations between stimuli in a particular context, responses, and reinforcers. The change in associative strength as a function of delay between key stimuli or responses, and reinforcement, is known as the delay of reinforcement gradient. The gradient is altered by vicissitudes of attention, intrusions of irrelevant events, lapses of memory, and fluctuations in dopamine function. Theoretical and experimental analyses of these moderating factors will help to determine just how reinforcement processes are altered in ADHD. Such analyses can only help to improve treatment strategies for ADHD.

  1. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-01-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  2. Parental Virtue and Prenatal Genetic Alteration Research.

    Science.gov (United States)

    Tonkens, Ryan

    2015-12-01

    Although the philosophical literature on the ethics of human prenatal genetic alteration (PGA) purports to inform us about how to act, it rarely explicitly recognizes the perspective of those who will be making the PGA decision in practice. Here I approach the ethics of PGA from a distinctly virtue-based perspective, taking seriously what it means to be a good parent making this decision for one's child. From this perspective, I generate a sound verdict on the moral standing of human PGA (research): given the current state of the art, good parents have compelling reason not to consent to PGA (research) for their child, especially as part of the first wave(s) of PGA research participants and especially for non-medically oriented purposes. This is because doing otherwise is inconsistent with a plausible and defensible understanding of virtuous parenting and parental virtues, founded on a genuine concern for promoting the overall flourishing of the eventual child. In essence, given the current and foreseeable state of the art, parents who allow prenatal genetic alteration of their children are less-than-virtuous parents to those children, even in cases where they have a right to do so and even if PGA turns out to be beneficial to the eventual child.

  3. Afforestation alters community structure of soil fungi.

    Science.gov (United States)

    Carson, Jennifer K; Gleeson, Deirdre B; Clipson, Nicholas; Murphy, Daniel V

    2010-07-01

    Relatively little is known about the effect of afforestation on soil fungal communities. This study demonstrated that afforestation altered fungal community structure and that changes were correlated to pools of soil C. Pasture at three locations on the same soil type was afforested with Eucalyptus globulus or Pinus pinaster. The structure of fungal communities under the three land uses was measured after 13y using automated ribosomal intergenic spacer analysis (ARISA). Afforestation significantly altered the structure of fungal communities. The effect of location on the structure of fungal communities was limited to pasture soils; although these contained the same plant species, the relative composition of each species varied between locations. Differences in the structure of fungal communities between pasture, E. globulus and P. pinaster were significantly correlated with changes in the amount of total organic C and microbial biomass-C in soil. Afforestation of patches of agricultural land may contribute to conserving soil fungi in agricultural landscapes by supporting fungal communities with different composition to agricultural soils. Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  4. When "altering brain function" becomes "mind control".

    Science.gov (United States)

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  5. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-02-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  6. Obesity Promotes Alterations in Iron Recycling

    Directory of Open Access Journals (Sweden)

    Marta Citelli

    2015-01-01

    Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

  7. Nucleolar proteins change in altered gravity

    Science.gov (United States)

    Sobol, M. A.; Kordyum, E. L.; Gonzalez-Camacho, F.; Medina, F. J.

    Discovery of gravisensitivity of cells no specified to gravity perception focused continuous attention on an elucidation of mechanisms involved in altered gravity effects at the different levels of cellular organization A nucleolus is the nuclear domain in which the major portion of ribosome biogenesis takes place This is a basic process for cell vitality beginning with the transcription of rDNA followed by processing newly synthesized pre-rRNA molecules A wide range of nucleolar proteins plays a highly significant role in all stages of biosynthesis of ribosomes Different steps of ribosome biogenesis should respond to various external factors affecting generally the cell metabolism Nevertheless a nucleolus remains not enough studied under the influence of altered environmental conditions For this reason we studied root apices from 2-day old Lepidium sativum seedlings germinated and grown under slow horizontal clinorotation and stationary conditions in darkness The extraction of cell nuclei followed by sequential fractionation of nuclear proteins according to their solubility in buffers of increasing ionic strength was carried out This procedure gave rise to 5 distinct fractions We analyzed nuclear subproteomes of the most soluble fraction called S2 It is actually a functionally significant fraction consisting of ribonucleoproteins actively engaged in pre-rRNA synthesis and processing 2D-electrophoresis of S2 fraction proteins was carried out The gels were silver stained and stained gels were scanned and analyzed

  8. Adaptive optics without altering visual perception.

    Science.gov (United States)

    Koenig, D E; Hart, N W; Hofer, H J

    2014-04-01

    Adaptive optics combined with visual psychophysics creates the potential to study the relationship between visual function and the retina at the cellular scale. This potential is hampered, however, by visual interference from the wavefront-sensing beacon used during correction. For example, we have previously shown that even a dim, visible beacon can alter stimulus perception (Hofer et al., 2012). Here we describe a simple strategy employing a longer wavelength (980nm) beacon that, in conjunction with appropriate restriction on timing and placement, allowed us to perform psychophysics when dark adapted without altering visual perception. The method was verified by comparing detection and color appearance of foveally presented small spot stimuli with and without the wavefront beacon present in 5 subjects. As an important caution, we found that significant perceptual interference can occur even with a subliminal beacon when additional measures are not taken to limit exposure. Consequently, the lack of perceptual interference should be verified for a given system, and not assumed based on invisibility of the beacon. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Natal Host Plants Can Alter Herbivore Competition.

    Science.gov (United States)

    Pan, Huipeng; Preisser, Evan L; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Zhang, Youjun

    2016-01-01

    Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore's natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems.

  10. Thermal remediation alters soil properties - a review.

    Science.gov (United States)

    O'Brien, Peter L; DeSutter, Thomas M; Casey, Francis X M; Khan, Eakalak; Wick, Abbey F

    2018-01-15

    Contaminated soils pose a risk to human and ecological health, and thermal remediation is an efficient and reliable way to reduce soil contaminant concentration in a range of situations. A primary benefit of thermal treatment is the speed at which remediation can occur, allowing the return of treated soils to a desired land use as quickly as possible. However, this treatment also alters many soil properties that affect the capacity of the soil to function. While extensive research addresses contaminant reduction, the range and magnitude of effects to soil properties have not been explored. Understanding the effects of thermal remediation on soil properties is vital to successful reclamation, as drastic effects may preclude certain post-treatment land uses. This review highlights thermal remediation studies that have quantified alterations to soil properties, and it supplements that information with laboratory heating studies to further elucidate the effects of thermal treatment of soil. Notably, both heating temperature and heating time affect i) soil organic matter; ii) soil texture and mineralogy; iii) soil pH; iv) plant available nutrients and heavy metals; v) soil biological communities; and iv) the ability of the soil to sustain vegetation. Broadly, increasing either temperature or time results in greater contaminant reduction efficiency, but it also causes more severe impacts to soil characteristics. Thus, project managers must balance the need for contaminant reduction with the deterioration of soil function for each specific remediation project. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. [Hepatic alterations in patients with dengue].

    Science.gov (United States)

    Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

    2005-06-01

    Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

  12. 46 CFR 115.700 - Permission for repairs and alterations.

    Science.gov (United States)

    2010-10-01

    ... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2010-10-01 2010-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

  13. 28 CFR 36.405 - Alterations: Historic preservation.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Historic preservation. 36... Alterations: Historic preservation. (a) Alterations to buildings or facilities that are eligible for listing in the National Register of Historic Places under the National Historic Preservation Act (16 U.S.C...

  14. Alterations in adipokines in feline hepatic lipidosis.

    Science.gov (United States)

    Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

    2013-01-01

    Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  15. Altered brain connectivity in sagittal craniosynostosis.

    Science.gov (United States)

    Beckett, Joel S; Brooks, Eric D; Lacadie, Cheryl; Vander Wyk, Brent; Jou, Roger J; Steinbacher, Derek M; Constable, R Todd; Pelphrey, Kevin A; Persing, John A

    2014-06-01

    Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC. Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite. Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: -6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates -31, -61, 34), posterior cingulate cortex (MNI coordinates 13, -52, 18), precuneus (MNI coordinates 10, -55, 54), left and right parahippocampus (MNI coordinates -13, -52, 2 and MNI coordinates 11, -50, 2, respectively), lingual (MNI coordinates -11, -86, -10), and fusiform gyri (MNI coordinates -30, -79, -18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices

  16. Are relative depletions altered inside diffuse clouds?

    International Nuclear Information System (INIS)

    Joseph, C.L.

    1988-01-01

    The data of Jenkins, Savage, and Spitzer (1986) were used to analyze interstellar abundances and depletions of Fe, P, Mg, and Mn toward 37 stars, spanning nearly 1.0 (dex) in mean line-of-sight depletion. It was found that the depletions of these elements are linearly correlated and do not show evidence of differences in the rates of depletion or sputtering from one element to another. For a given level of overall depletion, the sightline-to-sightline rms variance in the depletion for each of these elements was less than 0.16 (dex), which is significantly smaller than is the element-to-element variance. The results suggest that, for most diffuse lines of sight, the relative abundances of these elements are set early in the lifetime of the grains and are not altered significantly thereafter. 53 references

  17. Oral complications of cancer therapies. Mucosal alterations

    International Nuclear Information System (INIS)

    Squier, C.A.

    1990-01-01

    The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections

  18. Anaerobic Digestion Alters Copper and Zinc Speciation.

    Science.gov (United States)

    Legros, Samuel; Levard, Clément; Marcato-Romain, Claire-Emmanuelle; Guiresse, Maritxu; Doelsch, Emmanuel

    2017-09-19

    Anaerobic digestion is a widely used organic waste treatment process. However, little is known on how it could alter the speciation of contaminants in organic waste. This study was focused on determining the influence of anaerobic digestion on the speciation of copper and zinc, two metals that generally occur at high concentration in organic waste. Copper and zinc speciation was investigated by X-ray absorption spectroscopy in four different raw organic wastes (predigestion) and their digested counterparts (postdigestion, i.e., digestates). The results highlighted an increase in the digestates of the proportion of amorphous or nanostructured copper sulfides as well as amorphous or nanostructured zinc sulfides and zinc phosphate as compared to raw waste. We therefore suggest that the environmental fate of these elements would be different when spreading either digestates or raw waste on cropland.

  19. Hydraulic characterization of hydrothermally altered Nopal tuff

    Energy Technology Data Exchange (ETDEWEB)

    Green, R.T.; Meyer-James, K.A. [Southwest Research Institute, San Antonio, TX (United States); Rice, G. [George Rice and Associates, San Antonio, TX (United States)

    1995-07-01

    Understanding the mechanics of variably saturated flow in fractured-porous media is of fundamental importance to evaluating the isolation performance of the proposed high-level radioactive waste repository for the Yucca Mountain site. Developing that understanding must be founded on the analysis and interpretation of laboratory and field data. This report presents an analysis of the unsaturated hydraulic properties of tuff cores from the Pena Blanca natural analog site in Mexico. The basic intent of the analysis was to examine possible trends and relationships between the hydraulic properties and the degree of hydrothermal alteration exhibited by the tuff samples. These data were used in flow simulations to evaluate the significance of a particular conceptual (composite) model and of distinct hydraulic properties on the rate and nature of water flow.

  20. Method and apparatus for altering material

    Science.gov (United States)

    Stinnett, Regan W.; Greenly, John B.

    2002-02-05

    Methods and apparatus for thermally altering the near surface characteristics of a material are described. In particular, a repetitively pulsed ion beam system comprising a high energy pulsed power source and an ion beam generator are described which are capable of producing single species high voltage ion beams (0.25-2.5 MeV) at 1-1000 kW average power and over extended operating cycles (10.sup.8). Irradiating materials with such high energy, repetitively pulsed ion beams can yield surface treatments including localized high temperature anneals to melting, both followed by rapid thermal quenching to ambient temperatures to achieve both novel and heretofore commercially unachievable physical characteristics in a near surface layer of material.