Publications

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community partnership designed to promote lyme disease prevention and engagement in citizen science.the goal of this project is to promote lyme disease prevention and to cultivate an interest in science through a citizen-science project coordinated by researchers at a public university and teachers at rural high schools. the lesson plan is designed to increase student interest in pursuing a science career through participation in an authentic research experience, utilizing a topic that has implications on the health of the surrounding community. students are introduced in the classroom to zoon ...201627047593
lyme disease in hispanics, united states, 2000-2013.hispanics comprise a growing portion of the us population and might have distinct risk factors for tickborne diseases. during 2000-2013, a total of 5,473 lyme disease cases were reported among hispanics through national surveillance. hispanics were more likely than non-hispanics to have signs of disseminated infection and onset during fall months.201626889721
evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma.localized scleroderma is an autoimmune disease primarily affecting the skin. the cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components.201626985179
molecular evidence for bacterial pathogens in ixodes ricinus ticks infesting shetland ponies.ixodes ricinus has the potential to transmit zoonotic pathogens to humans and domestic animals. the feeding i. ricinus (n = 1737) collected from 49 shetland ponies and questing ones from vegetation (n = 371) were tested for the presence and differentiation of the bacterial species. dna of i. ricinus ticks was examined with pcr and sequencing analysis to identify species of borrelia burgdorferi sensu lato (bbsl), anaplasma phagocytophilum and rickettsia spp. altogether, 24.3 % i. ricinus of the i ...201626920921
serological detection of borrelia burgdorferi among horses in korea.lyme disease is a tick-borne zoonotic infectious disease caused by borrelia burgdorferi. the present study assessed the infection status of b. burgdorferi among horses reared in korea using elisa and pcr. between 2009 and 2013, blood samples were collected from 727 horses throughout korea. data for each animal including age, gender, breed, and region of sample collection were used for epidemiological analysis. overall, 38 (5.2%; true prevalence: 5.5%) of 727 horses were seropositive by elisa. th ...201626951987
expression of the tick-associated vtp protein of borrelia hermsii in a murine model of relapsing fever.borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. this is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. another major surface protein, the variable tick protein (vtp), is expressed in the tick vector and is invariable at its genetic locus. given the limited immune systems of ticks, the finding of considerable diversity among the vtp prote ...201626918760
phosphoenolpyruvate phosphotransferase system components modulate gene transcription and virulence of borrelia burgdorferi.the phosphoenolpyruvate phosphotransferase system (pep-pts) and adenylate cyclase (ac) iv (encoded by bb0723 [cyab]) are well conserved in different species of borrelia. however, the functional roles of pep-pts and ac in the infectious cycle of borrelia have not been characterized previously. we examined 12 pep-pts transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. transposon mutants with mutations in the eiibc components (ptsg) (bb0645, ...201626712207
analysis of endothelial adherence of bartonella henselae and acinetobacter baumannii using a dynamic human ex vivo infection model.bacterial adherence determines the virulence of many human-pathogenic bacteria. experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. however, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. therefore, ex vivo infection of human organs might represent an attractive method to overcome th ...201626712205
surface proteoglycans as mediators in bacterial pathogens infections.infectious diseases remain an important global health problem. the interaction of a wide range of pathogen bacteria with host cells from many different tissues is frequently mediated by proteoglycans. these compounds are ubiquitous complex molecules which are not only involved in adherence and colonization, but can also participate in other steps of pathogenesis. to overcome the problem of microbial resistance to antibiotics new therapeutic agents could be developed based on the characteristics ...201626941735
evidence for host-genotype associations of borrelia burgdorferi sensu stricto.different genotypes of the agent of lyme disease in north america, borrelia burgdorferi sensu stricto, show varying degrees of pathogenicity in humans. this variation in pathogenicity correlates with phylogeny and we have hypothesized that the different phylogenetic lineages in north america reflect adaptation to different host species. in this study, evidence for host species associations of b. burgdorferi genotypes was investigated using 41 b. burgdorferi-positive samples from five mammal spec ...201626901761
larvae of ixodes ricinus transmit borrelia afzelii and b. miyamotoi to vertebrate hosts.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 considered to cycle from nymphs to larvae through vertebrates. larvae of ixodes ricinus are occasionally b. burgdorferi (s.l) infected, but their vector competence has never been studied.201626896940
what makes a bacterial species pathogenic?:comparative genomic analysis of the genus leptospira.leptospirosis, caused by spirochetes of the genus leptospira, is a globally widespread, neglected and emerging zoonotic disease. while whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. in ...201626890609
does an nkt-cell-based immunotherapeutic approach have a future in multiple myeloma?natural killer t (nkt) cells constitute a unique subset of innate-like t lymphocytes which differ from conventional t cells by recognizing lipid antigens presented by the non-polymorphic major histocompatibility complex (mhc) i-like molecule cd1d. despite being a relatively infrequent population of lymphocytes, nkt cells can respond rapidly upon activation with glycosphingolipids by production of cytokines which aim to polarize different axes of the immune system. due to their dual effector capa ...201626895468
cerebral toxoplasmosis in a diffuse large b cell lymphoma patient.toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. t and b cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients.201627069454
cholesteryl esters stabilize human cd1c conformations for recognition by self-reactive t cells.cluster of differentiation 1c (cd1c)-dependent self-reactive t cells are abundant in human blood, but self-antigens presented by cd1c to the t-cell receptors of these cells are poorly understood. here we present a crystal structure of cd1c determined at 2.4 å revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known cd1c structures. computational simulations exploring different occupancy states of the groove reenacted thes ...201626884207
comparative speed of kill of sarolaner (simparica) and afoxolaner (nexgard against induced infestations of ixodes scapularis on dogs.the black-legged (or deer) tick, ixodes scapularis, commonly infests dogs and cats in north america and is the main vector for the pathogen that causes lyme disease in dogs and humans. the speed of kill of a parasiticide is critical to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of tick-borne pathogen transmission. in this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (simparica), aga ...201626876891
longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute lyme disease.lyme disease is a tick-borne illness caused by the bacterium borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. to gain insights into the molecular basis of acute lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to ...201626873097
origin and evolution of rickettsial plasmids.rickettsia species are strictly intracellular bacteria that have undergone a reductive genomic evolution. despite their allopatric lifestyle, almost half of the 26 currently validated rickettsia species have plasmids. in order to study the origin, evolutionary history and putative roles of rickettsial plasmids, we investigated the evolutionary processes that have shaped 20 plasmids belonging to 11 species, using comparative genomics and phylogenetic analysis between rickettsial, microbial and no ...201626866478
inhalational alzheimer's disease: an unrecognized - and treatable - epidemic.alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. identifying subtypes of alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). here i report that type 3 alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (iad), a phenotypic ma ...201626870879
eradication of biofilm-like microcolony structures of borrelia burgdorferi by daunomycin and daptomycin but not mitomycin c in combination with doxycycline and cefuroxime.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 severa ...201626903956
evidence of in vivo existence of borrelia biofilm in borrelial lymphocytomas.lyme borreliosis, caused by the spirochete borrelia burgdorferi sensu lato, has grown into a major public health problem. we recently identified a novel morphological form of b. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. however, there is no evidence of the existence of borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of borrelia biofilm in infected human skin tissues. archived skin biopsy tissu ...201627141311
bacterial gcn5-related n-acetyltransferases: from resistance to regulation.the gcn5-related n-acetyltransferases family (gnat) is an important family of proteins that includes more than 100000 members among eukaryotes and prokaryotes. acetylation appears as a major regulatory post-translational modification and is as widespread as phosphorylation. n-acetyltransferases transfer an acetyl group from acetyl-coa to a large array of substrates, from small molecules such as aminoglycoside antibiotics to macromolecules. acetylation of proteins can occur at two different posit ...201626818562
genomic insights into the ixodes scapularis tick vector of lyme disease.ticks transmit more pathogens to humans and animals than any other arthropod. we describe the 2.1 gbp nuclear genome of the tick, ixodes scapularis (say), which vectors pathogens that cause lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. the large genome reflects accumulation of repetitive dna, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. annotation of scaffolds representing ∼57% of the ge ...201626856261
identification of novel immunogenic proteins of neisseria gonorrhoeae by phage display.neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. a lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against n. gonorrhoeae. therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems ...201626859666
identification of a novel pathogenic borrelia species causing lyme borreliosis with unusually high spirochaetaemia: a descriptive study.lyme borreliosis is the most common tick-borne disease in the northern hemisphere. it is a multisystem disease caused by borrelia burgdorferi sensu lato genospecies and characterised by tissue localisation and low spirochaetaemia. in this study we aimed to describe a novel borrelia species causing lyme borreliosis in the usa.201626856777
multiple posttranslational modifications of leptospira biflexa proteins as revealed by proteomic analysis.the saprophyte leptospira biflexa is an excellent model for studying the physiology of the medically important leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. however, relatively little is known regarding the proteome of l. biflexa, limiting its utility as a model for some studies. therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of l. biflexa during exponen ...201626655756
the position of his-tag in recombinant ospc and application of various adjuvants affects the intensity and quality of specific antibody response after immunization of experimental mice.lyme disease, borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. the immune protection is mediated by phagocytic cells and by borrelia-specific complement-activating antibodies, associated with the th1 immune response. surface antigen ospc is involved in borrelia spreading through the host body. previously we reported that recombinant histidine tagged (hi ...201626848589
genetic and transcriptomic profiles of inflammation in neurodegenerative diseases: alzheimer, parkinson, creutzfeldt-jakob and tauopathies.polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic alzheimer's disease (ad) and sporadic parkinson's disease (spd). gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in ad, spd, sporadic creutzfeldt-jakob disease (scjd) subtypes mm1 and vv2, pick's disease (pid), progressive supranucl ...201626861289
a divergent spirochete strain isolated from a resident of the southeastern united states was identified by multilocus sequence typing as borrelia bissettii.out of 20 spirochete species from borrelia burgdorferi sensu lato (s.l.) complex recognized to date some are considered to have a limited distribution, while others are worldwide dispersed. among those are borrelia burgdorferi sensu stricto (s.s.) and borrelia bissettii which are distributed both in north america and in europe. while b. burgdorferi s.s. is recognized as a cause of lyme borreliosis worldwide, involvement of b. bissettii in human lyme disease was not so definite yet.201626846867
transcriptional profiling the 150 kb linear megaplasmid of borrelia turicatae suggests a role in vector colonization and initiating mammalian infection.adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. while plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. we utilized recent advances in genome sequencing to generate the most complete vers ...201626845332
neisseria meningitidis translation elongation factor p and its active-site arginine residue are essential for cell viability.translation elongation factor p (ef-p), a ubiquitous protein over the entire range of bacterial species, rescues ribosomal stalling at consecutive prolines in proteins. in escherichia coli and salmonella enterica, the post-translational β-lysyl modification of lys34 of ef-p is important for the ef-p activity. the β-lysyl ef-p modification pathway is conserved among only 26-28% of bacteria. recently, it was found that the shewanella oneidensis and pseudomonas aeruginosa ef-p proteins, containing ...201626840407
detection of borrelia burgdorferi sensu lato and spotted fever group rickettsiae in hard ticks (acari, ixodidae) parasitizing bats in poland.a total of 491 ixodes vespertilionis and 8 ixodes ricinus collected from bats and cave walls in southern poland between 2010 and 2012 were examined by the polymerase chain reaction for tick-transmitted pathogens. pcr analysis for borrelia burgdorferi s.l., rickettsia spp., and anaplasma phagocytophilum yielded negative results for all i. vespertilionis. dna of rickettsia helvetica was detected in three specimens of i. ricinus attached to rhinolophus hipposideros or myotis myotis, while borrelia ...201626833325
antigenic variation in bacterial pathogens.antigenic variation is a strategy used by a broad diversity of microbial pathogens to persist within the mammalian host. whereas viruses make use of a minimal proofreading capacity combined with large amounts of progeny to use random mutation for variant generation, antigenically variant bacteria have evolved mechanisms which use a stable genome, which aids in protecting the fitness of the progeny. here, three well-characterized and highly antigenically variant bacterial pathogens are discussed: ...201626999387
assessment of the geographic distribution of ornithodoros turicata (argasidae): climate variation and host diversity.ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete borrelia turicatae and african swine fever virus. historic collections of o. turicata have been recorded from latin america to the southern united states. however, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit.201626829327
high prevalence of borrelia miyamotoi among adult blacklegged ticks from white-tailed deer.we compared the prevalence of borrelia miyamotoi infection in questing and deer-associated adult ixodes scapularis ticks in wisconsin, usa. prevalence among deer-associated ticks (4.5% overall, 7.1% in females) was significantly higher than among questing ticks (1.0% overall, 0.6% in females). deer may be a sylvatic reservoir for this newly recognized zoonotic pathogen.201626811985
uveitis and systemic inflammatory markers in convalescent phase of ebola virus disease.we report a case of probable zaire ebola virus-related ophthalmologic complications in a physician from the united states who contracted ebola virus disease in liberia. uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. this case highlights immune phenomena that could complicate management of ebola virus disease-related uveitis during convalescence.201626812218
using tomoauto: a protocol for high-throughput automated cryo-electron tomography.cryo-electron tomography (cryo-et) is a powerful three-dimensional (3-d) imaging technique for visualizing macromolecular complexes in their native context at a molecular level. the technique involves initially preserving the sample in its native state by rapidly freezing the specimen in vitreous ice, then collecting a series of micrographs from different angles at high magnification, and finally computationally reconstructing a 3-d density map. the frozen-hydrated specimen is extremely sensitiv ...201626863591
hypothetical protein bb0569 is essential for chemotaxis of the lyme disease spirochete borrelia burgdorferi.the lyme disease spirochete borrelia burgdorferi has five putative methyl-accepting chemotaxis proteins (mcps). in this report, we provide evidence that a hypothetical protein, bb0569, is essential for the chemotaxis of b. burgdorferi. while bb0569 lacks significant homology to the canonical mcps, it contains a conserved domain (spanning residues 110 to 170) that is often evident in membrane-bound mcps such as tar and tsr of escherichia coli. unlike tar and tsr, bb0569 lacks transmembrane region ...201626644432
genetic analysis of revertants isolated from the rod-fragile flif mutant of salmonella.flif is the protein comprising the ms-ring of the bacterial flagellar basal body, which is the base for the assembly of flagellar axial structures. from a flif mutant that easily releases the rod-hook-filament in viscous environments, more than 400 revertants that recovered their swarming ability in viscous conditions, were isolated. the second-site mutations were determined for approximately 70% of them. there were three regions where the mutations were localized: two in region i, 112 in region ...201627924254
anticardiac antibodies in patients with chronic pericardial effusion.chronic pericardial effusion may be challenging in terms of diagnosis and treatment. specific laboratory parameters predicting the frequency and severity of recurrences after initial drainage of pericardial effusion are lacking.201626941472
evolutionary steps in the emergence of life deduced from the bottom-up approach and gadv hypothesis (top-down approach).it is no doubt quite difficult to solve the riddle of the origin of life. so, firstly, i would like to point out the kinds of obstacles there are in solving this riddle and how we should tackle these difficult problems, reviewing the studies that have been conducted so far. after that, i will propose that the consecutive evolutionary steps in a timeline can be rationally deduced by using a common event as a juncture, which is obtained by two counter-directional approaches: one is the bottom-up a ...201626821048
repeated activation of lung invariant nkt cells results in chronic obstructive pulmonary disease-like symptoms.chronic obstructive pulmonary disease (copd) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness. the pathologies of copd are due to an abnormal immune response. invariant natural killer t (inkt) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including copd. we have here analyzed the role of inkt ...201626811900
update on canine and feline blood donor screening for blood-borne pathogens.an update on the 2005 american college of veterinary internal medicine (acvim) consensus statement on blood donor infectious disease screening was presented at the 2015 acvim forum in indianapolis, indiana, followed by panel and audience discussion. the updated consensus statement is presented below. the consensus statement aims to provide guidance on appropriate blood-borne pathogen testing for canine and feline blood donors in north america.201626806261
characteristic cytokine and chemokine profiles in encephalitis of infectious, immune-mediated, and unknown aetiology.encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. however, in 15-60% the cause remains unknown. this study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.201626808276
borrelia burgdorferi bbk32 inhibits the classical pathway by blocking activation of the c1 complement complex.pathogens that traffic in blood, lymphatics, or interstitial fluids must adopt strategies to evade innate immune defenses, notably the complement system. through recruitment of host regulators of complement to their surface, many pathogens are able to escape complement-mediated attack. the lyme disease spirochete, borrelia burgdorferi, produces a number of surface proteins that bind to factor h related molecules, which function as the dominant negative regulator of the alternative pathway of com ...201626808924
dna charge transport: from chemical principles to the cell.the dna double helix has captured the imagination of many, bringing it to the forefront of biological research. dna has unique features that extend our interest into areas of chemistry, physics, material science, and engineering. our laboratory has focused on studies of dna charge transport (ct), wherein charges can efficiently travel long molecular distances through the dna helix while maintaining an exquisite sensitivity to base pair π-stacking. because dna ct chemistry reports on the integrit ...201626933744
enigma of il-17 and th17 cells in rheumatoid arthritis and in autoimmune animal models of arthritis.rheumatoid arthritis (ra) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune func ...201626903711
multiple and diverse vsp and vlp sequences in borrelia miyamotoi, a hard tick-borne zoonotic pathogen.based on chromosome sequences, the human pathogen borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. but atypically for relapsing fever agents, b. miyamotoi is transmitted not by soft ticks but by hard ticks, which also are vectors of lyme disease borrelia species. to further assess the relationships of b. miyamotoi to species that cause relapsing fever, i investigated extrachromosomal sequences of a north american strain with specific attention on plasmid-born ...201626785134
measuring escherichia coli gene expression during human urinary tract infections.extraintestinal escherichia coli (e. coli) evolved by acquisition of pathogenicity islands, phage, plasmids, and dna segments by horizontal gene transfer. strains are heterogeneous but virulent uropathogenic isolates more often have specific fimbriae, toxins, and iron receptors than commensal strains. one may ask whether it is the virulence factors alone that are required to establish infection. while these virulence factors clearly contribute strongly to pathogenesis, bacteria must survive by m ...201626784237
cyclic di-gmp regulates multiple cellular functions in the symbiotic alphaproteobacterium sinorhizobium meliloti.sinorhizobium meliloti undergoes major lifestyle changes between planktonic states, biofilm formation, and symbiosis with leguminous plant hosts. in many bacteria, the second messenger 3',5'-cyclic di-gmp (c-di-gmp, or cdg) promotes a sessile lifestyle by regulating a plethora of processes involved in biofilm formation, including motility and biosynthesis of exopolysaccharides (eps). here, we systematically investigated the role of cdg in s. meliloti rm2011 encoding 22 proteins putatively associ ...201626574513
effect of landscape features on the relationship between ixodes ricinus ticks and their small mammal hosts.the consequences of land use changes are among the most cited causes of emerging infectious diseases because they can modify the ecology and transmission of pathogens. this is particularly true for vector-borne diseases which depend on abiotic (e.g. climate) and biotic conditions (i.e. hosts and vectors). in this study, we investigated how landscape features affect the abundances of small mammals and ixodes ricinus ticks, and how they influence their relationship.201626767788
autophagy-associated immune responses and cancer immunotherapy.autophagy is an evolutionarily conserved catabolic process by which cellular components are sequestered into a double-membrane vesicle and delivered to the lysosome for terminal degradation and recycling. accumulating evidence suggests that autophagy plays a critical role in cell survival, senescence and homeostasis, and its dysregulation is associated with a variety of diseases including cancer, cardiovascular disease, neurodegeneration. recent studies show that autophagy is also an important r ...201626788909
diagnostic impact of routine lyme serology in recent-onset arthritis: results from the espoir cohort.lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. the aim of this study was to determine the diagnostic impact of routine lyme serology in a french cohort of patients with recent-onset arthritis affecting at least 2 joints.201626819751
ixodes scapularis tick saliva proteins sequentially secreted every 24 h during blood feeding.ixodes scapularis is the most medically important tick species and transmits five of the 14 reportable human tick borne disease (tbd) agents in the usa. this study describes lc-ms/ms identification of 582 tick- and 83 rabbit proteins in saliva of i. scapularis ticks that fed for 24, 48, 72, 96, and 120 h, as well as engorged but not detached (bd), and spontaneously detached (sd). the 582 tick proteins include proteases (5.7%), protease inhibitors (7.4%), unknown function proteins (22%), immunity ...201626751078
structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein pur-alpha.the neuronal dna-/rna-binding protein pur-alpha is a transcription regulator and core factor for mrna localization. pur-alpha-deficient mice die after birth with pleiotropic neuronal defects. here, we report the crystal structure of the dna-/rna-binding domain of pur-alpha in complex with ssdna. it reveals base-specific recognition and offers a molecular explanation for the effect of point mutations in the 5q31.3 microdeletion syndrome. consistent with the crystal structure, biochemical and nmr ...201626744780
sod enzymes and microbial pathogens: surviving the oxidative storm of infection. 201626742105
monoclonal antibodies for the diagnosis of borrelia crocidurae.relapsing fever borreliae, produced by ectoparasite-borne borrelia species, cause mild to deadly bacteremia and miscarriage. in the perspective of developing inexpensive assays for the rapid detection of relapsing fever borreliae, we produced 12 monoclonal antibodies (mabs) against borrelia crocidurae and characterized the two exhibiting the highest titers. p3a10 mab reacts with the 35.6-kda flagellin b (flab) of b. crocidurae while p6d9 mab recognizes a 35.1-kda variable-like protein (vlp) in b ...201626598566
an immersed boundary method for two-phase fluids and gels and the swimming of caenorhabditis elegans through viscoelastic fluids.the swimming of microorganisms typically involves the undulation or rotation of thin, filamentary objects in a fluid or other medium. swimming in newtonian fluids has been examined extensively, and only recently have investigations into microorganism swimming through non-newtonian fluids and gels been explored. the equations that govern these more complex media are often nonlinear and require computational algorithms to study moderate to large amplitude motions of the swimmer. here, we develop a ...201626858520
epidemiologic studies of the human microbiome and cancer.the human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. previously detected associations of individual bacteria (e.g., helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. this short review summarises microbiome re ...201626730578
coagulase and efb of staphylococcus aureus have a common fibrinogen binding motif.coagulase (coa) and efb, secreted staphylococcus aureus proteins, are important virulence factors in staphylococcal infections. coa interacts with fibrinogen (fg) and induces the formation of fibrin(ogen) clots through activation of prothrombin. efb attracts fg to the bacterial surface and forms a shield to protect the bacteria from phagocytic clearance. this communication describes the use of an array of synthetic peptides to identify variants of a linear fg binding motif present in coa and efb ...201626733070
epigenetic segregation of microbial genomes from complex samples using restriction endonucleases hpaii and mcrb.we describe continuing work to develop restriction endonucleases as tools to enrich targeted genomes of interest from diverse populations. two approaches were developed in parallel to segregate genomic dna based on cytosine methylation. first, the methyl-sensitive endonuclease hpaii was used to bind non-cg methylated dna. second, a truncated fragment of mcrb was used to bind cpg methylated dna. enrichment levels of microbial genomes can exceed 100-fold with hpaii allowing improved genomic detect ...201626727463
intentions to receive a potentially available lyme disease vaccine in an urban sample.the only human lyme disease vaccine of lymerix was voluntarily removed from the market in the united states in 2002 for a number of reasons. a new human lyme disease vaccine is currently being developed. we would like any future approved human lyme disease vaccine to be of interest and marketable to consumers.201627551427
substance p and antagonists of the neurokinin-1 receptor in neuroinflammation associated with infectious and neurodegenerative diseases of the central nervous system.this review addresses the role that substance p (sp) and its preferred receptor neurokinin-1 (nk1r) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. the sp/nk1r complex is a key player in the interaction between the immune and nervous systems. a common effect of this interaction is inflammation. for this reason and because of the predominance in the human brain of the nk1r, its antagonists are attractive p ...201627430034
guillain-barré syndrome with hyperreflexia and bilateral papillitis in a child.guillain-barré syndrome (gbs) is an acute inflammatory polyneuropathy characterized by rapidly progressive symmetric weakness, and areflexia. areflexia is necessary for the diagnosis of gbs. however, recently there have been studies of hyperreflexia with axonal neuropathy form of gbs. we report a 14-year-old boy with gbs, who presented with hyperreflexia and bilateral papillitis. to the best of our knowledge, this is the first pediatric patient presenting with papillitis and hyperreflexia with a ...201627195040
infectious aetiology of marginal zone lymphoma and role of anti-infective therapy.marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. pathogenetic mechanisms are currently not completely understood. however, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. gastric malt lymphoma is strictly associated with helicobacter pylori infe ...201626740867
understanding luminal microorganisms and their potential effectiveness in treating intestinal inflammation.the human intestine contains 10 bacteria, which outnumber the mammalian cells 10-fold. certain other commensal or infectious agents, like helminthic parasites, become members of this microbial ecosystem, especially in populations living under less hygienic conditions. intestinal microbes, also called the microbiome or microbiota, shape the host immune reactivity to self and nonself throughout life. changes in microbiome composition may impair the maturation of immune regulatory pathways and pred ...201626457381
diversity takes shape: understanding the mechanistic and adaptive basis of bacterial morphology.the modern age of metagenomics has delivered unprecedented volumes of data describing the genetic and metabolic diversity of bacterial communities, but it has failed to provide information about coincident cellular morphologies. much like metabolic and biosynthetic capabilities, morphology comprises a critical component of bacterial fitness, molded by natural selection into the many elaborate shapes observed across the bacterial domain. in this essay, we discuss the diversity of bacterial morpho ...201627695035
genome-wide gene order distances support clustering the gram-positive bacteria.initially using 143 genomes, we developed a method for calculating the pair-wise distance between prokaryotic genomes using a monte carlo method to estimate the conservation of gene order. the method was based on repeatedly selecting five or six non-adjacent random orthologs from each of two genomes and determining if the chosen orthologs were in the same order. the raw distances were then corrected for gene order convergence using an adaptation of the jukes-cantor model, as well as using the co ...201525653643
genome-wide gene order distances support clustering the gram-positive bacteria.initially using 143 genomes, we developed a method for calculating the pair-wise distance between prokaryotic genomes using a monte carlo method to estimate the conservation of gene order. the method was based on repeatedly selecting five or six non-adjacent random orthologs from each of two genomes and determining if the chosen orthologs were in the same order. the raw distances were then corrected for gene order convergence using an adaptation of the jukes-cantor model, as well as using the co ...201525653643
dynamic structure of plasma fibronectin.fibronectin is a large vertebrate glycoprotein that is found in soluble and insoluble forms and involved in diverse processes. protomeric fibronectin is a dimer of subunits, each of which comprises 29-31 modules - 12 type i, two type ii and 15-17 type iii. plasma fibronectin is secreted by hepatocytes and circulates in a compact conformation before it binds to cell surfaces, converts to an extended conformation and is assembled into fibronectin fibrils. here we review biophysical and structural ...201527185500
dynamic structure of plasma fibronectin.fibronectin is a large vertebrate glycoprotein that is found in soluble and insoluble forms and involved in diverse processes. protomeric fibronectin is a dimer of subunits, each of which comprises 29-31 modules - 12 type i, two type ii and 15-17 type iii. plasma fibronectin is secreted by hepatocytes and circulates in a compact conformation before it binds to cell surfaces, converts to an extended conformation and is assembled into fibronectin fibrils. here we review biophysical and structural ...201527185500
treatment with doxycycline of generalized annular elastolytic giant cell granuloma associated with borrelia burgdorferi infection.this is a case of generalized annular elastolytic giant cell granuloma (aegcg) associated with borrelia infection and genes of p-30, p-31, p-39. a possible cross-mediated reaction from the t-cell type which might have induced the aegcg is discussed from the concept of "heat-shock proteins (hsps) and molecular mimicry".201526624605
treatment with doxycycline of generalized annular elastolytic giant cell granuloma associated with borrelia burgdorferi infection.this is a case of generalized annular elastolytic giant cell granuloma (aegcg) associated with borrelia infection and genes of p-30, p-31, p-39. a possible cross-mediated reaction from the t-cell type which might have induced the aegcg is discussed from the concept of "heat-shock proteins (hsps) and molecular mimicry".201526624605
expression of alzheimer-type neurofibrillary epitopes in primary rat cortical neurons following infection with enterococcus faecalis.the neurofibrillary tau pathology and amyloid deposits seen in alzheimer's disease (ad) also have been seen in bacteria-infected brains. however, few studies have examined the role of these bacteria in the generation of tau pathology. one suggested link between infection and ad is edentulism, the complete loss of teeth. edentulism can result from chronic periodontal disease due to infection by enterococcus faecalis. the current study assessed the ability to generate early alzheimer-like neurofib ...201526834627
expression of alzheimer-type neurofibrillary epitopes in primary rat cortical neurons following infection with enterococcus faecalis.the neurofibrillary tau pathology and amyloid deposits seen in alzheimer's disease (ad) also have been seen in bacteria-infected brains. however, few studies have examined the role of these bacteria in the generation of tau pathology. one suggested link between infection and ad is edentulism, the complete loss of teeth. edentulism can result from chronic periodontal disease due to infection by enterococcus faecalis. the current study assessed the ability to generate early alzheimer-like neurofib ...201526834627
new insights into the classification and integration specificity of streptococcus integrative conjugative elements through extensive genome exploration.recent genome analyses suggest that integrative and conjugative elements (ices) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. however, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. even though previous analysis showed the presence of ices in some species of streptococci, the global prevalence and diversity of ices was not analyzed in this genus. in this study, we searched fo ...201526779141
new insights into the classification and integration specificity of streptococcus integrative conjugative elements through extensive genome exploration.recent genome analyses suggest that integrative and conjugative elements (ices) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. however, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. even though previous analysis showed the presence of ices in some species of streptococci, the global prevalence and diversity of ices was not analyzed in this genus. in this study, we searched fo ...201526779141
acceptability of tick control interventions to prevent lyme disease in switzerland and canada: a mixed-method study.lyme disease control strategies may include tick control interventions in high risk areas. public authorities may be interested to assess how these types of interventions are perceived by the public which may then impact their acceptability. the aims of this paper are to compare socio-cognitive factors associated with high acceptability of tick control interventions and to describe perceived issues that may explain their low acceptability in populations living in two different regions, one being ...201526733007
acceptability of tick control interventions to prevent lyme disease in switzerland and canada: a mixed-method study.lyme disease control strategies may include tick control interventions in high risk areas. public authorities may be interested to assess how these types of interventions are perceived by the public which may then impact their acceptability. the aims of this paper are to compare socio-cognitive factors associated with high acceptability of tick control interventions and to describe perceived issues that may explain their low acceptability in populations living in two different regions, one being ...201526733007
codon usage bias and determining forces in taenia solium genome.the tapeworm taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. at present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. in this study, codon usage patterns in the t. solium genome were examined through 8,484 protein-coding genes. neutrality analysis showed that t. solium had a narrow gc distribution, and a significant correlation was observed between gc12 an ...201526797435
epitope-specific evolution of human b cell responses to borrelia burgdorferi vlse protein from early to late stages of lyme disease.most immunogenic proteins of borrelia burgdorferi, the causative agent of lyme disease, are known or expected to contain multiple b cell epitopes. however, the kinetics of the development of human b cell responses toward the various epitopes of individual proteins during the course of lyme disease has not been examined. using the highly immunogenic vlse as a model ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of earl ...201526718339
epitope-specific evolution of human b cell responses to borrelia burgdorferi vlse protein from early to late stages of lyme disease.most immunogenic proteins of borrelia burgdorferi, the causative agent of lyme disease, are known or expected to contain multiple b cell epitopes. however, the kinetics of the development of human b cell responses toward the various epitopes of individual proteins during the course of lyme disease has not been examined. using the highly immunogenic vlse as a model ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of earl ...201526718339
antagonist of the neurokinin-1 receptor curbs neuroinflammation in ex vivo and in vitro models of lyme neuroborreliosis.lyme neuroborreliosis (lnb) can affect both the peripheral (pns) and the central nervous systems (cns); it is caused by the spirochete borrelia burgdorferi. the neuropeptide substance p (sp) is an important mediator of both neuroinflammation and blood-brain barrier dysfunction, through its nk1 receptor. increased levels of sp have been shown to correlate with cell death. the present study used both ex vivo and in vitro models of experimentation to determine if the inflammatory mediator productio ...201526714480
a ribosome-inactivating protein in a drosophila defensive symbiont.vertically transmitted symbionts that protect their hosts against parasites and pathogens are well known from insects, yet the underlying mechanisms of symbiont-mediated defense are largely unclear. a striking example of an ecologically important defensive symbiosis involves the woodland fly drosophila neotestacea, which is protected by the bacterial endosymbiont spiroplasma when parasitized by the nematode howardula aoronymphium. the benefit of this defense strategy has led to the rapid spread ...201526712000
a ribosome-inactivating protein in a drosophila defensive symbiont.vertically transmitted symbionts that protect their hosts against parasites and pathogens are well known from insects, yet the underlying mechanisms of symbiont-mediated defense are largely unclear. a striking example of an ecologically important defensive symbiosis involves the woodland fly drosophila neotestacea, which is protected by the bacterial endosymbiont spiroplasma when parasitized by the nematode howardula aoronymphium. the benefit of this defense strategy has led to the rapid spread ...201526712000
rna helicase important for listeria monocytogenes hemolytic activity and virulence factor expression.rna helicases have been shown to be important for the function of rna molecules at several levels, although their putative involvement in microbial pathogenesis has remained elusive. we have previously shown that listeria monocytogenes dexd-box rna helicases are important for bacterial growth, motility, ribosomal maturation, and rrna processing. we assessed the importance of the rna helicase lmo0866 (here named csha) for expression of virulence traits. we observed a reduction in hemolytic activi ...201526483402
rna helicase important for listeria monocytogenes hemolytic activity and virulence factor expression.rna helicases have been shown to be important for the function of rna molecules at several levels, although their putative involvement in microbial pathogenesis has remained elusive. we have previously shown that listeria monocytogenes dexd-box rna helicases are important for bacterial growth, motility, ribosomal maturation, and rrna processing. we assessed the importance of the rna helicase lmo0866 (here named csha) for expression of virulence traits. we observed a reduction in hemolytic activi ...201526483402
bacterial profiling reveals novel "ca. neoehrlichia", ehrlichia, and anaplasma species in australian human-biting ticks.in australia, a conclusive aetiology of lyme disease-like illness in human patients remains elusive, despite growing numbers of people presenting with symptoms attributed to tick bites. in the present study, we surveyed the microbial communities harboured by human-biting ticks from across australia to identify bacteria that may contribute to this syndrome. universal pcr primers were used to amplify the v1-2 hyper-variable region of bacterial 16s rrna genes in dna samples from individual ixodes h ...201526709826
cronobacter sakazakii dna detection in cerebrospinal fluid of a patient with amyotrophic lateral sclerosis mimic syndrome.a 45-year-old male noticed progressive weakness of the right lower limb with gait disturbance. over the following months, motor deficits worsened, spreading to the right upper limb. electromyography showed active denervation in the upper and lower limb muscles. a diagnosis of amyotrophic lateral sclerosis (als) was made. about 2 years after symptom onset, gradual improvement occurred. cerebrospinal fluid analysis performed about 3 years after the beginning of symptoms identified cronobacter saka ...201526955334
anti-inflammatory effects of dexamethasone and meloxicam on borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system.lyme neuroborreliosis (lnb), caused by the spirochete borrelia burgdorferi (bb), could result in cognitive impairment, motor dysfunction, and radiculoneuritis. we hypothesized that inflammation is a key factor in lnb pathogenesis and recently evaluated the effects of dexamethasone, a steroidal anti-inflammatory drug, and meloxicam a non-steroidal anti-inflammatory drug (nsaid), in a rhesus monkey model of acute lnb. dexamethasone treatment significantly reduced the levels of immune mediators, an ...201526700298
melkersson-rosenthal syndrome as an early manifestation of mixed connective tissue disease.we aim to illustrate the potential viability of mctd as an underlying aetiology of melkersson-rosenthal syndrome. the case is probably the first description available in the literature of the melkersson-rosenthal as an early manifestation of mixed connective tissue disease.201526698837
phylogenetic analysis of human chlamydia pneumoniae strains reveals a distinct australian indigenous clade that predates european exploration of the continent.the obligate intracellular bacterium chlamydia pneumoniae is a common respiratory pathogen, which has been found in a range of hosts including humans, marsupials and amphibians. whole genome comparisons of human c. pneumoniae have previously highlighted a highly conserved nucleotide sequence, with minor but key polymorphisms and additional coding capacity when human and animal strains are compared.201526694618
specialized pro-resolving mediators: endogenous regulators of infection and inflammation.specialized pro-resolving mediators (spms) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation - that is, catabasis. host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. spms are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. these immuno ...201526688348
specialized pro-resolving mediators: endogenous regulators of infection and inflammation.specialized pro-resolving mediators (spms) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation - that is, catabasis. host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. spms are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. these immuno ...201526688348
intravital imaging of vascular transmigration by the lyme spirochete: requirement for the integrin binding residues of the b. burgdorferi p66 protein.vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. the lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. this pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. in this ...201526684456
multi-trophic interactions driving the transmission cycle of borrelia afzelii between ixodes ricinus and rodents: a review.the tick ixodes ricinus is the main vector of the spirochaete borrelia burgdorferi sensu lato, the causal agent of lyme borreliosis, in the western palearctic. rodents are the reservoir host of b. afzelii, which can be transmitted to i. ricinus larvae during a blood meal. the infected engorged larvae moult into infected nymphs, which can transmit the spirochaetes to rodents and humans. interestingly, even though only about 1% of the larvae develop into a borreliae-infected nymph, the enzootic bo ...201526684199
metabolic interactions in the gastrointestinal tract (git): host, commensal, probiotics, and bacteriophage influences.life on this planet has been intricately associated with bacterial activity at all levels of evolution and bacteria represent the earliest form of autonomous existence. plants such as those from the leguminosae family that form root nodules while harboring nitrogen-fixing soil bacteria are a primordial example of symbiotic existence. similarly, cooperative activities between bacteria and animals can also be observed in multiple domains, including the most inhospitable geographical regions of the ...201527682125
acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in borrelia burgdorferi.in b. burgdorferi, the rrp2-rpon-rpos signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. rrp2 (bb0763), an rpon specific response regulator, is essential to activate this regulatory pathway. previous investigations have attempted to identify the phosphate donor of rrp2, including the cognate histidine kinase, hk2 (bb0764), non-cognate histidine kinases such as hk1, che ...201526681317
the nebop score - a clinical prediction test for evaluation of children with lyme neuroborreliosis in europe.the diagnosis of lyme neuroborreliosis (lnb) in europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-borrelia antibodies in serum and csf according to guidelines. however, the decision to start antibiotic treatment on admission cannot be based on borrelia serology since results are not available at the time of lumbar puncture. therefore, an early prediction test would be useful in clinical practice. the aim of the study was to develop and evaluate a clinical pre ...201526678681
stroke as an unusual first presentation of lyme disease.introduction. lyme neuroborreliosis is a nervous system infection caused by spirochete borrelia burgdorferi with diverse neurological complications. stroke due to cerebral vasculitis is a rare consequence of neuroborreliosis and has been described in just a few case reports. case presentation. here, we report the case of a 43-year-old patient who presented with discrete left-sided hemiparesis and amnestic cognitive impairment. brain magnetic resonance imaging showed a thalamic infarct, and serol ...201526788385
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