Publications

early lymphoid lesions: conceptual, diagnostic and clinical challenges.	there are no "benign lymphomas", a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as bcl2/igh and ccnd1/igh transloca ...	2014	25176983
prostatitis, steatitis, and diarrhea in a dog following presumptive flea-borne transmission of bartonella henselae.	bartonella henselae is increasingly associated with a variety of pathological entities, which are often similar in dogs and human patients. following an acute flea infestation, a dog developed an unusual clinical presentation for canine bartonellosis. comprehensive medical, microbiological, and surgical interventions were required for diagnosis and to achieve a full recovery.	2014	24920774
comparative analysis of the infectivity rate of both borrelia burgdorferi and anaplasma phagocytophilum in humans and dogs in a new jersey community.	ticks are important vectors of disease and transmit an extensive array of bacterial, viral and protozoan diseases to both humans and dogs within a community. borrelia burgdorferi, the causative agent of lyme disease, has been extensively studied within both the human and veterinary population. anaplasma phagocytophilum, an intracellular rickettsial pathogen also transmitted by ixodid ticks, has emerged as an important zoonotic infection with significant veterinary and medical implications, and i ...	2014	25143748
gamma delta t-lymphocytes in hepatitis c and chronic liver disease.	discovered 30 years ago, gamma delta (γδ) t-lymphocytes remain an intriguing and enigmatic t-cell subset. although in humans they comprise a small fraction of the total circulating t-lymphocyte pool, they represent an important t-cell subset in tissues such as the liver, with roles bridging the innate and adaptive immune systems. the associations of γδ t-lymphocytes with chronic liver disease have been explored - however, there remain conflicting data as to whether these t-cells are pathogenic o ...	2014	25206355
structure of the periplasmic adaptor protein from a major facilitator superfamily (mfs) multidrug efflux pump.	periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. the 2.85 å resolution structure of an mfs (major facilitator superfamily) pump adaptor, aquifex aeolicus emra, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. the adaptor α-hairpin, which binds outer membrane tolc, is exceptionally long at 127 å, and the β-barrel conta ...	2014	24996185
disrupted human-pathogen co-evolution: a model for disease.	a major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. however, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. we suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into gen ...	2014	25202324
a (p)ppgpp-null mutant of haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes.	(p)ppgpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. the stringent response has been implicated in the virulence of several pathogenic bacterial species. haemophilus ducreyi, the causative agent of chancroid, has homologs of both rela and spot, which primarily synthesize and hydrolyze (p)ppgpp in escherichia coli. we constructed rela and rela spot deletion mutants to assess the contribution of (p)ppgpp to h. ducreyi pathogenesis. both ...	2014	24914217
bickerstaff's encephalitis.	bickerstaff's brainstem encephalitis is a rare syndrome defined by the triad of ophthalmoplegia, ataxia and decreased consciousness. it is considered to be a variant of miller fisher syndrome and guillain-barré syndrome but is differentiated from the two by the presence of central nervous system involvement, commonly in the form of impaired consciousness. we present an unusual case of bickerstaff's encephalitis, where the patient presented with pseudobulbar affect.	2014	25080547
inter-model comparison of the landscape determinants of vector-borne disease: implications for epidemiological and entomological risk modeling.	extrapolating landscape regression models for use in assessing vector-borne disease risk and other applications requires thoughtful evaluation of fundamental model choice issues. to examine implications of such choices, an analysis was conducted to explore the extent to which disparate landscape models agree in their epidemiological and entomological risk predictions when extrapolated to new regions. agreement between six literature-drawn landscape models was examined by comparing predicted coun ...	2014	25072884
high-throughput screening of tick-borne pathogens in europe.	due to increased travel, climatic, and environmental changes, the incidence of tick-borne disease in both humans and animals is increasing throughout europe. therefore, extended surveillance tools are desirable. to accurately screen tick-borne pathogens (tbps), a large scale epidemiological study was conducted on 7050 ixodes ricinus nymphs collected from france, denmark, and the netherlands using a powerful new high-throughput approach. this advanced methodology permitted the simultaneous detect ...	2014	25120960
the borrelia hermsii factor h binding protein fhba is not required for infectivity in mice or for resistance to human complement in vitro.	the primary causative agent of tick-borne relapsing fever in north america is borrelia hermsii. it has been hypothesized that b. hermsii evades complement-mediated destruction by binding factor h (fh), a host-derived negative regulator of complement. in vitro, b. hermsii produces a single fh binding protein designated fhba (fh binding protein a). the properties and ligand binding activity of fhba suggest that it plays multiple roles in pathogenesis. it binds plasminogen and has been identified a ...	2014	24866803
more than meets the eye: the 'pink salmon patch'.	ocular adnexal lymphomas account for 1-2% of all non-hodgkin's lymphomas. conjunctiva is the primary site of involvement in one-third of cases. we present a case of a 47-year-old hispanic woman who presented with left eye itching and irritation associated with a painless pink mass. physical examination revealed the presence of a 'pink salmon-patch' involving her left medial conjunctiva. orbital ct showed a subcentimeter left preseptal soft tissue density. biopsy revealed a dense subepithelial ly ...	2014	25168823
the heterogeneity, distribution, and environmental associations of borrelia burgdorferi sensu lato, the agent of lyme borreliosis, in scotland.	lyme borreliosis is an emerging infectious human disease caused by the borrelia burgdorferi sensu lato complex of bacteria with reported cases increasing in many areas of europe and north america. to understand the drivers of disease risk and the distribution of symptoms, which may improve mitigation and diagnostics, here we characterize the genetics, distribution, and environmental associations of b. burgdorferi s.l. genospecies across scotland. in scotland, reported lyme borreliosis cases have ...	2014	25221774
toll-like receptors and cancer: myd88 mutation and inflammation.	pattern recognition receptors (prrs) expressed on immune cells are crucial for the early detection of invading pathogens, in initiating early innate immune response and in orchestrating the adaptive immune response. prrs are activated by specific pathogen-associated molecular patterns that are present in pathogenic microbes or nucleic acids of viruses or bacteria. however, inappropriate activation of these prrs, such as the toll-like receptors (tlrs), due to genetic lesions or chronic inflammati ...	2014	25132836
evidence assessments and guideline recommendations in lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.	evidence-based guidelines for the management of patients with lyme disease were developed by the international lyme and associated diseases society (ilads). the guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of lyme disease. healthcare providers who evaluate and manage patients with lyme disease are the int ...	2014	25077519
immunity-related genes in ixodes scapularis--perspectives from genome information.	ixodes scapularis, commonly known as the deer tick, transmits a wide array of human and animal pathogens including borrelia burgdorferi. despite substantial advances in our understanding of immunity in model arthropods, including other disease vectors, precisely how i. scapularis immunity functions and influences persistence of invading pathogens remains largely unknown. this review provides a comprehensive analysis of the recently sequenced i. scapularis genome for the occurrence of immune-rela ...	2014	25202684
multivariate inference of pathway activity in host immunity and response to therapeutics.	developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. we present a computational framework, named multivariate inference of pathway activity (mipa), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. statistical significance of inferred activity is examined using multiple independent self- ...	2014	25147207
pathogen inactivation technologies for cellular blood components: an update.	nowadays patients receiving blood components are exposed to much less transfusion-transmitted infectious diseases than three decades before when among others hiv was identified as causative agent for the acquired immunodeficiency syndrome and the transmission by blood or coagulation factors became evident. since that time the implementation of measures for risk prevention and safety precaution was socially and politically accepted. currently emerging pathogens like arboviruses and the well-known ...	2014	25254027
genome sequence of borrelia garinii strain sz, isolated in china.	we announce the genome sequence of borrelia garinii strain sz, isolated from dermacentor ticks collected in northeastern china. b. garinii strain sz carries numerous plasmids, both 10 circular and 9 linear plasmids. the 902,487-bp linear chromosome (28.2% gc content) contains 820 open reading frames, 33 trnas, and 4 complete rrnas. the plasmid cp32-10 contains one clustered regularly interspaced short palindromic repeat (crispr) with four repeats.	2014	25035317
card integrates three functional modules to promote efficient transcription, antibiotic tolerance, and pathogenesis in mycobacteria.	although the basic mechanisms of prokaryotic transcription are conserved, it has become evident that some bacteria require additional factors to allow for efficient gene transcription. card is an rna polymerase (rnap)-binding protein conserved in numerous bacterial species and essential in mycobacteria. despite the importance of card, its function at transcription complexes remains unclear. we have generated a panel of mutations that individually target three independent functional modules of ca ...	2014	24962732
bb0323 and novel virulence determinant bb0238: borrelia burgdorferi proteins that interact with and stabilize each other and are critical for infectivity.	we have shown that borrelia burgdorferi gene product bb0323 is essential for cell fission and pathogen persistence in vivo. here we describe characterization of a conserved hypothetical protein annotated as bb0238, which specifically interacts with the n-terminal region of bb0323. we show that bb0238 is a subsurface protein, and similar to bb0323, exists in the periplasm and as a membrane-bound protein. deletion of bb0238 in infectious b. burgdorferi did not affect microbial growth in vitro or s ...	2014	25139020
bb0323 and novel virulence determinant bb0238: borrelia burgdorferi proteins that interact with and stabilize each other and are critical for infectivity.	we have shown that borrelia burgdorferi gene product bb0323 is essential for cell fission and pathogen persistence in vivo. here we describe characterization of a conserved hypothetical protein annotated as bb0238, which specifically interacts with the n-terminal region of bb0323. we show that bb0238 is a subsurface protein, and similar to bb0323, exists in the periplasm and as a membrane-bound protein. deletion of bb0238 in infectious b. burgdorferi did not affect microbial growth in vitro or s ...	2014	25139020
identification of a cyclic-di-gmp-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium.	we surveyed the eight putative cyclic-di-gmp-modulating response regulators (rrs) in desulfovibrio vulgaris hildenborough that are predicted to function via two-component signaling. using purified proteins, we examined cyclic-di-gmp (c-di-gmp) production or turnover in vitro of all eight proteins. the two rrs containing only ggdef domains (dvu2067, dvu0636) demonstrated c-di-gmp production activity in vitro. of the remaining proteins, three rrs with hd-gyp domains (dvu0722, dvua0086, and dvu2933 ...	2014	25120537
regulation of oxidative stress by methylation-controlled j protein controls macrophage responses to inflammatory insults.	mitochondria contribute to macrophage immune function through the generation of reactive oxygen species, a byproduct of the mitochondrial respiratory chain. mcj (also known as dnajc15) is a mitochondrial inner membrane protein identified as an endogenous inhibitor of respiratory chain complex i. here we show that mcj is essential for the production of tumor necrosis factor by macrophages in response to a variety of toll-like receptor ligands and bacteria, without affecting their phagocytic activ ...	2014	25028693
regulation of oxidative stress by methylation-controlled j protein controls macrophage responses to inflammatory insults.	mitochondria contribute to macrophage immune function through the generation of reactive oxygen species, a byproduct of the mitochondrial respiratory chain. mcj (also known as dnajc15) is a mitochondrial inner membrane protein identified as an endogenous inhibitor of respiratory chain complex i. here we show that mcj is essential for the production of tumor necrosis factor by macrophages in response to a variety of toll-like receptor ligands and bacteria, without affecting their phagocytic activ ...	2014	25028693
ticks infesting humans in italy and associated pathogens.	ticks may transmit a large variety of pathogens, which cause illnesses in animals and humans, commonly referred to as to tick-borne diseases (tbds). the incidence of human tbds in italy is underestimated because of poor surveillance and the scant amount of studies available.	2014	25023709
spotted fever rickettsia species in hyalomma and ixodes ticks infesting migratory birds in the european mediterranean area.	a few billion birds migrate annually between their breeding grounds in europe and their wintering grounds in africa. many bird species are tick-infested, and as a result of their innate migratory behavior, they contribute significantly to the geographic distribution of pathogens, including spotted fever rickettsiae. the aim of the present study was to characterize, in samples from two consecutive years, the potential role of migrant birds captured in europe as disseminators of rickettsia-infecte ...	2014	25011617
borreliabase: a phylogeny-centered browser of borrelia genomes.	the bacterial genus borrelia (phylum spirochaetes) consists of two groups of pathogens represented respectively by b. burgdorferi, the agent of lyme borreliosis, and b. hermsii, the agent of tick-borne relapsing fever. the number of publicly available borrelia genomic sequences is growing rapidly with the discovery and sequencing of borrelia strains worldwide. there is however a lack of dedicated online databases to facilitate comparative analyses of borrelia genomes.	2014	24994456
chemical and biological work-related risks across occupations in europe: a review.	work-related health inequalities are determined to some extent by an unequal exposure to chemical and biological risk factors of disease. although their potential economic burden in the european union (eu-25) might be substantial, comprehensive reviews focusing on the distribution of these risks across occupational groups are limited. thus, the main objective of this review is to provide a synopsis of the exposure to chemical and biological hazards across occupational groups. in addition, main i ...	2014	25071862
identification of lysine residues in the borrelia burgdorferi dbpa adhesin required for murine infection.	decorin-binding protein a (dbpa) of borrelia burgdorferi mediates bacterial adhesion to heparin and dermatan sulfate associated with decorin. lysines k82, k163, and k170 of dbpa are known to be important for in vitro interaction with decorin, and the dbpa structure, initially solved by nuclear magnetic resonance (nmr) spectroscopy, suggests these lysine residues colocalize in a pocket near the c terminus of the protein. in the current study, we solved the structure of dbpa from b. burgdorferi st ...	2014	24842928
simple objective detection of human lyme disease infection using immuno-pcr and a single recombinant hybrid antigen.	a serology-based tiered approach has, to date, provided the most effective means of laboratory confirmation of clinically suspected cases of lyme disease, but it lacks sensitivity in the early stages of disease and is often dependent on subjectively scored immunoblots. we recently demonstrated the use of immuno-pcr (ipcr) for detecting borrelia burgdorferi antibodies in patient serum samples that were positive for lyme disease. to better understand the performance of the lyme disease ipcr assay, ...	2014	24899074
broad-range survey of tick-borne pathogens in southern germany reveals a high prevalence of babesia microti and a diversity of other tick-borne pathogens.	abstract ticks harbor numerous pathogens of significance to human and animal health. a better understanding of the pathogens carried by ticks in a given geographic area can alert health care providers of specific health risks leading to better diagnosis and treatments. in this study, we tested 226 ixodes ricinis ticks from southern germany using a broad-range pcr and electrospray ionization mass spectrometry assay (pcr/esi-ms) designed to identify tick-borne bacterial and protozoan pathogens in ...	2014	25072989
the lone s41 family c-terminal processing protease in staphylococcus aureus is localized to the cell wall and contributes to virulence.	staphylococcus aureus is a versatile pathogen of humans and a continued public health concern due to the rise and spread of multidrug-resistant strains. as part of an ongoing investigation into the pathogenic mechanisms of this organism we previously demonstrated that an intracellular n-terminal processing protease is required for s. aureus virulence. following on from this, here we examine the role of ctpa, the lone c-terminal processing protease of s. aureus. ctpa, a member of the s41 family, ...	2014	24928312
high sensitive pcr method for detection of pathogenic leptospira spp. in paraffin-embedded tissues.	this study describes the development and application of a new pcr assay for the specific detection of pathogenic leptospires and its comparison with a previously reported pcr protocol. new primers were designed for pcr optimization and evaluation in artificially-infected paraffin-embedded tissues. pcr was then applied to post-mortem, paraffin-embedded samples, followed by amplicon sequencing. the pcr was more efficient than the reported protocol, allowing the amplification of expected dna fragme ...	2014	25229221
hematologic and serum biochemical values of 4 species of peromyscus mice and their hybrids.	deer mice (peromyscus maniculatus) and congeneric species are used in a wide variety of research applications, particularly studies of developmental, physiologic, and behavioral characteristics associated with habitat adaptation and speciation. because peromyscine mice readily adapt to colony conditions, animals with traits of interest in the field are moved easily into the laboratory where they can be studied under controlled conditions. the purpose of this study was to determine the serum chem ...	2014	25199088
novel mntr-independent mechanism of manganese homeostasis in escherichia coli by the ribosome-associated protein hflx.	manganese is a micronutrient required for activities of several important enzymes under conditions of oxidative stress and iron starvation. in escherichia coli, the manganese homeostasis network primarily constitutes a manganese importer (mnth) and an exporter (mntp), which are regulated by the mntr dual regulator. in this study, we find that deletion of e. coli hflx, which encodes a ribosome-associated gtpase with unknown function, renders extreme manganese sensitivity characterized by arrested ...	2014	24794564
effect of solid boundaries on swimming dynamics of microorganisms in a viscoelastic fluid.	we numerically study the effect of solid boundaries on the swimming behavior of a motile microorganism in viscoelastic media. understanding the swimmer-wall hydrodynamic interactions is crucial to elucidate the adhesion of bacterial cells to nearby substrates which is precursor to the formation of the microbial biofilms. the microorganism is simulated using a squirmer model that captures the major swimming mechanisms of potential, extensile, and contractile types of swimmers, while neglecting th ...	2014	26855446
unilateral epiphora in an adolescent.		2014	25883767
medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the interlymph non-hodgkin lymphoma subtypes project.	marginal zone lymphoma (mzl), comprised of nodal, extranodal, and splenic subtypes, accounts for 5%-10% of non-hodgkin lymphoma cases. a detailed evaluation of the independent effects of risk factors for mzl and its subtypes has not been conducted.	2014	25174026
medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and sézary syndrome: the interlymph non-hodgkin lymphoma subtypes project.	mycosis fungoides and sézary syndrome (mf/ss) are rare cutaneous t-cell lymphomas. their etiology is poorly understood.	2014	25174030
medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the interlymph non-hodgkin lymphoma subtypes project.	the etiology of mantle cell lymphoma (mcl), a distinctive subtype accounting for 2%-10% of all non-hodgkin lymphoma, is not known.	2014	25174028
are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with anaplasma phagocytophilum or tick-borne encephalitis virus?	lyme borreliosis (lb), tick-borne encephalitis (tbe) and human granulocytic anaplasmosis (hga) are endemic in central part of slovenia. we tested the hypothesis that patients with erythema migrans (em) from this region, who have leukopenia and/or thrombocytopenia (typical findings in hga and in the initial phase of tbe but not in patients with lb) are coinfected with anaplasma phagocytophilum and/or with tbe virus, i.e. that cytopenia is a result of concomitant hga or the initial phase of tbe. c ...	2014	25057802
maldi-tof mass spectrometry detection of pathogens in vectors: the borrelia crocidurae/ornithodoros sonrai paradigm.	in africa, relapsing fever borreliae are neglected vector-borne pathogens that cause mild to deadly septicemia and miscarriage. screening vectors for the presence of borreliae currently requires technically demanding, time- and resource-consuming molecular methods. matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof-ms) has recently emerged as a tool for the rapid identification of vectors and the identification of cultured borreliae. we investigated whether m ...	2014	25058611
exploring diversity among norwegian borrelia strains originating from ixodes ricinus ticks.	characterisation of borrelia strains from ixodes ricinus ticks is important in the epidemiological surveillance of vector-borne pathogens. multilocus sequences analysis (mlsa) is a molecular genotyping tool with high discriminatory power that has been applied in evolutionary studies and for the characterisation of borrelia genospecies. mlsa was used to study genetic variations in borrelia strains isolated from i. ricinus ticks collected from the woodlands in skodje. the results demonstrate that ...	2014	25243011
specificity of metal sensing: iron and manganese homeostasis in bacillus subtilis.	metalloregulatory proteins allow cells to sense metal ions and appropriately adjust the expression of metal uptake, storage, and efflux pathways. bacillus subtilis provides a model for the coordinate regulation of iron and manganese homeostasis that involves three key regulators: fur senses iron sufficiency, mntr senses manganese sufficiency, and perr senses the intracellular fe/mn ratio. here, i review the structural and physiological bases of selective metal perception, the effects of non-cogn ...	2014	25160631
comparison of survival patterns of northern and southern genotypes of the north american tick ixodes scapularis (acari: ixodidae) under northern and southern conditions.	several investigators have reported genetic differences between northern and southern populations of ixodes scapularis in north america, as well as differences in patterns of disease transmission. ecological and behavioral correlates of these genetic differences, which might have implications for disease transmission, have not been reported. we compared survival of northern with that of southern genotypes under both northern and southern environmental conditions in laboratory trials.	2014	25160464
strain-specific variation of the decorin-binding adhesin dbpa influences the tissue tropism of the lyme disease spirochete.	lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. for example, the three major lyme disease spirochete species, borrelia burgdorferi sensu stricto, b. garinii, and b. afzelii, are each most commonly associated with overlapping but distinct spectra of clinical manifestations. borrelia burgdorferi sensu stricto, the most common lyme spirochete in the u.s., is closely associated with arthritis. the attachment of microbial pathogens to cells or to the e ...	2014	25079227
irspi, a tick serine protease inhibitor involved in tick feeding and bartonella henselae infection.	ixodes ricinus is the most widespread and abundant tick in europe, frequently bites humans, and is the vector of several pathogens including those responsible for lyme disease, tick-borne encephalitis, anaplasmosis, babesiosis and bartonellosis. these tick-borne pathogens are transmitted to vertebrate hosts via tick saliva during blood feeding, and tick salivary gland (sg) factors are likely implicated in transmission. in order to identify such tick factors, we characterized the transcriptome of ...	2014	25057911
platelet volume and plateletcrit in dogs with presumed primary immune-mediated thrombocytopenia.	mean platelet volume (mpv) and plateletcrit (pct) are indices used in evaluating immune-mediated thrombocytopenia (imt) in humans and in dogs with congenital macrothrombocytopenia. these indices may provide clinically valuable information in acquired thrombocytopenia.	2014	25056453
de novo morphogenesis in l-forms via geometric control of cell growth.	in virtually all bacteria, the cell wall is crucial for mechanical integrity and for determining cell shape. escherichia coli's rod-like shape is maintained via the spatiotemporal patterning of cell-wall synthesis by the actin homologue mreb. here, we transiently inhibited cell-wall synthesis in e. coli to generate cell-wall-deficient, spherical l-forms, and found that they robustly reverted to a rod-like shape within several generations after inhibition cessation. the chemical composition of th ...	2014	24995493
recovery of a medieval brucella melitensis genome using shotgun metagenomics.	shotgun metagenomics provides a powerful assumption-free approach to the recovery of pathogen genomes from contemporary and historical material. we sequenced the metagenome of a calcified nodule from the skeleton of a 14th-century middle-aged male excavated from the medieval sardinian settlement of geridu. we obtained 6.5-fold coverage of a brucella melitensis genome. sequence reads from this genome showed signatures typical of ancient or aged dna. despite the relatively low coverage, we were ab ...	2014	25028426
macromolecular crowding effects on two homologs of ribosomal protein s16: protein-dependent structural changes and local interactions.	proteins function in cellular environments that are crowded with biomolecules, and in this reduced available space, their biophysical properties may differ from those observed in dilute solutions in vitro. here, we investigated the effects of a synthetic macromolecular crowding agent, dextran 20, on the folded states of hyperthermophilic (s16thermo) and mesophilic (s16meso) homologs of the ribosomal protein s16. as expected for an excluded-volume effect, the resistance of the mesophilic protein ...	2014	25028882
population and demographic structure of ixodes scapularis say in the eastern united states.	the most significant vector of tick-borne pathogens in the united states is ixodes scapularis say (the blacklegged tick). previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission.	2014	25025532
cloning and characterisation of multiple ferritin isoforms in the atlantic salmon (salmo salar).	ferritin is a highly-conserved iron-storage protein that has also been identified as an acute phase protein within the innate immune system. the iron-storage function is mediated through complementary roles played by heavy (h)-chain subunit as well as the light (l) in mammals or middle (m)-chain in teleosts, respectively. in this study, we report the identification of five ferritin subunits (h1, h2, m1, m2, m3) in the atlantic salmon that were supported by the presence of iron-regulatory regions ...	2014	25078784
borrelia burgdorferi protein bbk32 binds to soluble fibronectin via the n-terminal 70-kda region, causing fibronectin to undergo conformational extension.	bbk32 is a fibronectin (fn)-binding protein expressed on the cell surface of borrelia burgdorferi, the causative agent of lyme disease. there is conflicting information about where and how bbk32 interacts with fn. we have characterized interactions of a recombinant 86-mer polypeptide, "bbk32," comprising the unstructured fn-binding region of bbk32. competitive enzyme-linked assays utilizing various fn fragments and epitope-mapped anti-fn monoclonal antibodies showed that bbk32 binding involves b ...	2014	24962582
a 24-48 h fed amblyomma americanum tick saliva immuno-proteome.	multiple tick saliva proteins, the majority of which are unknown, confer tick resistance in repeatedly infested animals. the objective of this study was to identify the 24-48 h fed amblyomma americanum tick saliva immuno-proteome. the 24-48 h tick-feeding phase is critical to tick parasitism as it precedes important events in tick biology, blood meal feeding and disease agent transmission. fed male, 24 and 96 h fed female phage display cdna expression libraries were biopanned using rabbit antibo ...	2014	24962723
outer membrane protein p4 is not required for virulence in the human challenge model of haemophilus ducreyi infection.	bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. such lipoproteins are viable vaccine candidates. haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. one such lipoprotein, ompp4, is homologous to the outer membrane lipoprotein e (p4) of h. influenzae. in h. influenzae, e (p4) stimulates production of bactericidal and protective antibodies and contri ...	2014	24961160
the ability of an oral formulation of afoxolaner to block the transmission of babesia canis by dermacentor reticulatus ticks to dogs.	canine babesiosis due to babesia canis is an endemic disease in many european countries. a vaccine is available in some countries, but it does not prevent the infection and just helps in reducing the gravity of clinical signs. therefore, the major way to help preventing the disease is by controlling tick infestations on dogs.to assess the preventive efficacy of afoxolaner (nexgard®), a new oral anti- flea and tick product, against babesia canis infected adult dermacentor reticulatus in an experi ...	2014	24957215
identification of novel activity against borrelia burgdorferi persisters using an fda approved drug library.	although antibiotic treatment for lyme disease is effective in the majority of cases, especially during the early phase of the disease, a minority of patients suffer from post-treatment lyme disease syndrome (ptlds). it is unclear what mechanisms drive this problem, and although slow or ineffective killing of borrelia burgdorferi has been suggested as an explanation, there is a lack of evidence that viable organisms are present in ptlds. although not a clinical surrogate, insight may be gained b ...	2014	26038747
correction: in vivo expression technology identifies a novel virulence factor critical for borrelia burgdorferi persistence in mice.	analysis of the transcriptome of borrelia burgdorferi, the causative agent of lyme disease, during infection has proven difficult due to the low spirochete loads in the mammalian tissues. to overcome this challenge, we have developed an in vivo expression technology (ivet) system for identification of b. burgdorferi genes expressed during an active murine infection. spirochetes lacking linear plasmid (lp) 25 are non-infectious yet highly transformable.mouse infection can be restored to these spi ...	2014	24950221
immunopathogenesis of ocular behçet's disease.	behçet's disease (bd) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. the ocular involvement of bd, or behçet's uveitis (bu), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. although pathogenesis of bd is unclear, researches ha ...	2014	25061613
toll-like receptor polymorphisms are associated with increased neurosyphilis risk.	single-nucleotide polymorphisms (snps) in toll-like receptors (tlr) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. we investigated whether common snps in tlr1, tlr2, or tlr6 were associated with laboratory- or clinically-defined neurosyphilis.	2014	24922103
birdshot retinochoroidopathy.	birdshot retinochoroidopathy (bsrc) is an uncommon, but well-characterized chronic, bilateral posterior uveitis, which is uniquely associated with the human leukocyte antigen-a29 phenotype. the disease presents predominantly in middle-aged caucasian females who complain of blurred vision, floaters, photopsias, paracentral scotomas and nyctalopia. while autoimmune mechanisms are thought to play an important role in the pathogenesis of bsrc, its etiology remains unknown. important questions remain ...	2014	25667738
metabolic engineering of salmonella vaccine bacteria to boost human vγ2vδ2 t cell immunity.	human vγ2vδ2 t cells monitor isoprenoid metabolism by recognizing foreign (e)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (hmbpp), a metabolite in the 2-c-methyl-d-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. whereas microbial infections elicit prolonged expansion of memory vγ2vδ2 t cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-ter ...	2014	24943221
cloning, expression, purification, crystallization and preliminary x-ray diffraction analysis of glyceraldehyde-3-phosphate dehydrogenase from streptococcus agalactiae nem316.	glyceraldehyde-3-phosphate dehydrogenase (gapdh) is an essential enzyme involved in glycolysis. despite lacking the secretory signal sequence, this cytosolic enzyme has been found localized at the surface of several bacteria and fungi. as a surface protein, gapdh exhibits various adhesive functions, thereby facilitating colonization and invasion of host tissues. streptococcus agalactiae, also known as group b streptococcus (gbs), binds onto the host using its surface adhesins and causes sepsis a ...	2014	25005093
feeding by amblyomma maculatum (acari: ixodidae) enhances rickettsia parkeri (rickettsiales: rickettsiaceae) infection in the skin.	rickettsia parkeri luckman (rickettsiales: rickettsiaceae), a member of the spotted fever group of rickettsia, is the tick-borne causative agent of a newly recognized, eschar-associated rickettsiosis. because of its relatively recent designation as a pathogen, few studies have examined the pathogenesis of transmission of r. parkeri to the vertebrate host. to further elucidate the role of tick feeding in rickettsial infection of vertebrates, nymphal amblyomma maculatum koch (acari: ixodidae) were ...	2014	25118419
case for diagnosis.	idiopathic atrophoderma of pasini and pierini (iapp) is a rare, exclusively cutaneous disease. it is more frequent in females, with incidence peak in the second and third decades of life. the etiopathogenesis remains unknown. iapp most commonly affects the back, abdomen and proximal regions of the limbs. lesions may be rounded, oval or circular; single or multiple. the evolution is variable and the course is initially progressive. collagen changes such as atrophy, thinning, condensation and scle ...	2014	25054763
cloning, expression and characterization of udp-n-acetylglucosamine enolpyruvyl transferase (mura) from wolbachia endosymbiont of human lymphatic filarial parasite brugia malayi.	wolbachia, an endosymbiont of filarial nematode, is considered a promising target for treatment of lymphatic filariasis. although functional characterization of the wolbachia peptidoglycan assembly has not been fully explored, the wolbachia genome provides evidence for coding all of the genes involved in lipid ii biosynthesis, a part of peptidoglycan biosynthesis pathway. udp-n-acetylglucosamine enolpyruvyl transferase (mura) is one of the lipid ii biosynthesis pathway enzymes and it has inevita ...	2014	24941309
co-infection of blacklegged ticks with babesia microti and borrelia burgdorferi is higher than expected and acquired from small mammal hosts.	humans in the northeastern and midwestern united states are at increasing risk of acquiring tickborne diseases--not only lyme disease, but also two emerging diseases, human granulocytic anaplasmosis and human babesiosis. co-infection with two or more of these pathogens can increase the severity of health impacts. the risk of co-infection is intensified by the ecology of these three diseases because all three pathogens (borrelia burgdorferi, anaplasma phagocytophilum, and babesia microti) are tra ...	2014	24940999
reliability of nine programs of topological predictions and their application to integral membrane channel and carrier proteins.	we evaluated topological predictions for nine different programs, hmmtop, tmhmm, svmtop, das, sosui, topcons, phobius, memsat-svm (hereinafter referred to as memsat), and spoctopus. these programs were first evaluated using four large topologically well-defined families of secondary transporters, and the three best programs were further evaluated using topologically more diverse families of channels and carriers. in the initial studies, the order of accuracy was: spoctopus > memsat > hmmtop > to ...	2014	24992992
structures and metal-binding properties of helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center.	helicobacter pylori causes severe diseases, such as chronic gastritis, peptic ulcers, and stomach cancers. h. pylori neutrophil-activating protein (hp-nap) is an iron storage protein that forms a dodecameric shell, promotes the adhesion of neutrophils to endothelial cells, and induces the production of reactive oxygen radicals. hp-nap belongs to the dna-protecting proteins under starved conditions (dps) family, which has significant structural similarities to the dodecameric ferritin family. the ...	2014	24971723
targeting tlr2 for vaccine development.	novel and more effective immunization strategies against many animal diseases may profit from the current knowledge on the modulation of specific immunity through stimulation of innate immune receptors. toll-like receptor (tlr)2-targeting formulations, such as synthetic lipopeptides and antigens expressed in fusion with lipoproteins, have been shown to have built-in adjuvant properties and to be effective at inducing cellular and humoral immune mechanisms in different animal species. however, co ...	2014	25057505
opsoclonus-myoclonus syndrome attributable to west nile encephalitis: a case report.	opsoclonus-myoclonus syndrome is a very rare neurological disorder associated with some viral infections and exceptionally with the west nile virus.	2014	24968889
type ii restriction endonucleases--a historical perspective and more.	this article continues the series of surveys and summaries on restriction endonucleases (reases) begun this year in nucleic acids research. here we discuss 'type ii' reases, the kind used for dna analysis and cloning. we focus on their biochemistry: what they are, what they do, and how they do it. type ii reases are produced by prokaryotes to combat bacteriophages. with extreme accuracy, each recognizes a particular sequence in double-stranded dna and cleaves at a fixed position within or nearby ...	2014	24878924
toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver.	the ability of innate immune cells to sense and respond to impending danger varies by anatomical location. the liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. to understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. we discovered that only the tlr8 agonist ssrna ...	2014	24967632
microrna-146a provides feedback regulation of lyme arthritis but not carditis during infection with borrelia burgdorferi.	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 stra ...	2014	24967703
dna sequencing diagnosis of off-season spirochetemia with low bacterial density in borrelia burgdorferi and borrelia miyamotoi infections.	a highly conserved 357-bp segment of the 16s ribosomal rna gene (16s rdna) of borrelia burgdorferi sensu lato and the correspondent 358-bp segment of the borrelia miyamotoi gene were amplified by a single pair of nested polymerase chain reaction (pcr) primers for detection, and the amplicons were used as the templates for direct sanger dna sequencing. reliable molecular diagnosis of these borreliae was confirmed by sequence alignment analysis of the hypervariable regions of the pcr amplicon, usi ...	2014	24968274
the effectiveness of permethrin-treated deer stations for control of the lyme disease vector ixodes scapularis on cape cod and the islands: a five-year experiment.	the use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to lyme disease risk management. included among the attractive features of host-targeted approaches is the reduced need for broad-scale pesticide usage. in the eastern usa, one of the best-known of these approaches is the corn-baited "4-poster" deer feeding station, so named because of the ...	2014	24965139
beyond the chromosome: the prevalence of unique extra-chromosomal bacteriophages with integrated virulence genes in pathogenic staphylococcus aureus.	in staphylococcus aureus, the disease impact of chromosomally integrated prophages on virulence is well described. however, the existence of extra-chromosomal prophages, both plasmidial and episomal, remains obscure. despite the recent explosion in bacterial and bacteriophage genomic sequencing, studies have failed to specifically focus on extra-chromosomal elements. we selectively enriched and sequenced extra-chromosomal dna from s. aureus isolates using roche-454 technology and uncovered evide ...	2014	24963913
impairments in episodic-autobiographical memory and emotional and social information processing in cadasil during mid-adulthood.	cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) - is the most common genetic source of vascular dementia in adults, being caused by a mutation in notch3 gene. spontaneous de novo mutations may occur, but their frequency is largely unknown. ischemic strokes and cognitive impairments are the most frequent manifestations, but seizures affect up to 10% of the patients. herein, we describe a 47-year-old male scholar with a genetically confirmed dia ...	2014	25009481
survey of selected tick-borne diseases in dogs in finland.	due to climate changes during the last decades, ticks have progressively spread into higher latitudes in northern europe. although some tick borne diseases are known to be endemic in finland, to date there is limited information with regard to the prevalence of these infections in companion animals. we determined the antibody and dna prevalence of the following organisms in randomly selected client-owned and clinically healthy hunting dogs living in finland: ehrlichia canis (ec), anaplasma phago ...	2014	24957468
serological detection of anaplasma phagocytophilum, borrelia burgdorferi sensu lato and ehrlichia canis antibodies and dirofilaria immitis antigen in a countrywide survey in dogs in poland.	canine vector-borne diseases (cvbds) have increasingly become a focus of attention in the past few years. nevertheless, in many parts of europe information on their occurrence is still scarce. in a large study in poland 3,094 serum samples taken from dogs throughout all 16 polish provinces were tested using a commercial kit for the detection of circulating antibodies against anaplasma phagocytophilum, borrelia burgdorferi sensu lato and ehrlichia canis and of dirofilaria immitis antigen. a total ...	2014	24974092
bacterial tick-borne diseases caused by bartonella spp., borrelia burgdorferi sensu lato, coxiella burnetii, and rickettsia spp. among patients with cataract surgery.	clinical data have shown that tick-borne diseases caused by borrelia burgdorferi sensu lato, bartonella spp., coxiella burnetii, and rickettsia spp. can affect the central nervous system, including the eye. the aim of this study was to establish a relationship between the incidence of cataract and evidence of bacterial infections transmitted by ticks.	2014	24902636
forward genetic approaches for elucidation of novel regulators of lyme arthritis severity.	patients experiencing natural infection with borrelia burgdorferi display a spectrum of associated symptoms and severity, strongly implicating the impact of genetically determined host factors in the pathogenesis of lyme disease. herein, we provide a summary of the host genetic factors that have been demonstrated to influence the severity and chronicity of lyme arthritis symptoms, and a review of the resources available, current progress, and added value of a forward genetic approach for identif ...	2014	24926442
adult-onset still's disease presenting as myopericarditis.	a 24-year-old man presented to the emergency department with fever, maculopapular rash, myalgia and polyarthralgia, thoracic pain and dry cough, which had been present for 24 h. at the time of observation he had high fever (39°c), maculopapular rash on the torso, arms and legs proximally, axillary adenopathies and pharyngitis. laboratorial data showed elevated inflammation markers (leukocytosis, c reactive protein of 44 mg/dl, erythrocyte sedimentation rate of 120 mm), elevated transaminases, la ...	2014	24898998
people, pets, and parasites: one health surveillance in southeastern saskatchewan.	residents of remote and indigenous communities might experience higher exposure to some zoonotic parasites than the general north american population. human sero-surveillance conducted in two saulteaux communities found 113 volunteers exposed as follows: trichinella (2.7%), toxocara canis (4.4%), echinococcus (4.4%), and toxoplasma gondii (1.8%). in dogs, 41% of 51 fecal samples were positive for at least one intestinal parasite, 3% of 77 were sero-positive for borrelia burgdorferi, and 21% of 7 ...	2014	24639298
emergence of ixodes scapularis and borrelia burgdorferi, the lyme disease vector and agent, in ohio.	lyme disease, the most common vector-borne disease in the united states, is caused by a tick-borne infection with borrelia burgdorferi. currently, ohio is considered by the centers for disease control and prevention (cdc) to be non-endemic for lyme disease. the low incidence of lyme disease in this state was largely attributed to the absence of the transmitting vector, ixodes scapularis, commonly known as the blacklegged tick. however, a tick surveillance program established by ohio department o ...	2014	24926441
lyme and associated tick-borne diseases: global challenges in the context of a public health threat.		2014	24918091
preventing mosquito and tick bites: a canadian update.	the present practice point provides updated guidance on personal protective measures to safely and effectively prevent mosquito and tick bites in canada. means of avoidance as well as physical and chemical barriers are described. current information regarding insect and tick repellents and recommendations for their use are provided, along with instructions for removing ticks. guidance on using insecticide for additional chemical protection is offered.	2014	25332663
abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment.	doxycycline has been proposed for the treatment of malnourished children in developing countries, and its use has been associated with weight gain in healthy volunteers. no previous studies have assessed abnormal weight gain as a putative side effect of long-term doxycycline treatment; thus, the objective of the present study was to characterize this phenomenon. we also analyzed the role of the gut microbiota in this effect. we assessed changes in the body mass index in q fever endocarditis pati ...	2014	24687497
identification of novel small rnas and characterization of the 6s rna of coxiella burnetii.	coxiella burnetii, an obligate intracellular bacterial pathogen that causes q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (lcv) and a dormant small cell variant (scv). as such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. small rnas (srnas) have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. we hy ...	2014	24949863
crossing the interspecies barrier: opening the door to zoonotic pathogens.		2014	24945247
induction of type i and type iii interferons by borrelia burgdorferi correlates with pathogenesis and requires linear plasmid 36.	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 iso ...	2014	24945497
preliminary x-ray crystallographic analysis of an engineered glutamyl-trna synthetase from escherichia coli.	the nature of interaction between glutamyl-trna synthetase (glurs) and its trna substrate is unique in bacteria in that many bacterial glurs are capable of recognizing two trna substrates: trnaglu and trnagln. to properly understand this distinctive glurs-trna interaction it is important to pursue detailed structure-function studies; however, because of the fact that trna-glurs interaction in bacteria is also associated with phylum-specific idiosyncrasies, the structure-function correlation stud ...	2014	25005090
metagenomic analysis reveals presence of treponema denticola in a tissue biopsy of the iceman.	ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. here, we report the molecular detection of the oral spirochete treponema denticola in ancient human tissue biopsies of the iceman, a 5,300-year-old copper age natural ice mummy. initially, the metagenomic data of the iceman's genomic survey was screened for bacterial ribosomal rna (rrna) specific reads. through ranking th ...	2014	24941044
hyperinsulinemic hypoglycemia syndrome in 2 dogs with bartonellosis.		2014	24934703
intravascular persistence of anaplasma platys, ehrlichia chaffeensis, and ehrlichia ewingii dna in the blood of a dog and two family members.	anaplasmosis, caused by anaplasma phagocytophilum and anaplasma platys, and ehrlichiosis, caused by ehrlichia chaffeensis, ehrlichia ewingii, the "panola mountain ehrlichia" and ehrlichia muris-like pathogens have been identified as emerging tick borne infectious diseases in dogs and human patients. persistent intravascular infection with these bacteria is well documented in dogs, but is less well documented in human beings.	2014	24984562
borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern united states.	borrelia miyamotoi sensu lato, a relapsing fever borrelia sp., is transmitted by the same ticks that transmit b. burgdorferi (the lyme disease pathogen) and occurs in all lyme disease-endemic areas of the united states. to determine the seroprevalence of igg against b. miyamotoi sensu lato in the northeastern united states and assess whether serum from b. miyamotoi sensu lato-infected persons is reactive to b. burgdorferi antigens, we tested archived serum samples from area residents during 1991 ...	2014	24960072
massive infection of seabird ticks with bacterial species related to coxiella burnetii.	seabird ticks are known reservoirs of bacterial pathogens of medical importance; however, ticks parasitizing tropical seabirds have received less attention than their counterparts from temperate and subpolar regions. recently, rickettsia africae was described to infect seabird ticks of the western indian ocean and new caledonia, constituting the only available data on bacterial pathogens associated with tropical seabird tick species. here, we combined a pyrosequencing-based approach with a class ...	2014	24657860
lyme disease testing by large commercial laboratories in the united states.	laboratory testing is helpful when evaluating patients with suspected lyme disease (ld). a 2-tiered antibody testing approach is recommended, but single-tier and nonvalidated tests are also used. we conducted a survey of large commercial laboratories in the united states to assess laboratory practices. we used these data to estimate the cost of testing and number of infections among patients from whom specimens were submitted.	2014	24879782