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flaa proteins in leptospira interrogans are essential for motility and virulence but are not required for formation of the flagellum sheath.spirochetes have periplasmic flagella composed of a core surrounded by a sheath. the pathogen leptospira interrogans has four flab (proposed core subunit) and two flaa (proposed sheath subunit) genes. the flaa genes are organized in a locus with flaa2 immediately upstream of flaa1. in this study, flaa1 and flaa2 mutants were constructed by transposon mutagenesis. both mutants still produced periplasmic flagella. the flaa1 mutant did not produce flaa1 but continued to produce flaa2 and retained n ...201222451522
comparing the similarity of different groups of bacteria to the human proteome.numerous aspects of the relationship between bacteria and human have been investigated. one aspect that has recently received attention is sequence overlap at the proteomic level. however, there has not yet been a study that comprehensively characterizes the level of sequence overlap between bacteria and human, especially as it relates to bacterial characteristics like pathogenicity, g-c content, and proteome size. in this study, we began by performing a general characterization of the range of ...201222558081
bactquant: an enhanced broad-coverage bacterial quantitative real-time pcr assay.bacterial load quantification is a critical component of bacterial community analysis, but a culture-independent method capable of detecting and quantifying diverse bacteria is needed. based on our analysis of a diverse collection of 16 s rrna gene sequences, we designed a broad-coverage quantitative real-time pcr (qpcr) assay--bactquant--for quantifying 16 s rrna gene copy number and estimating bacterial load. we further utilized in silico evaluation to complement laboratory-based qpcr characte ...201222510143
multilocus sequence typing of total-genome-sequenced bacteria.accurate strain identification is essential for anyone working with bacteria. for many species, multilocus sequence typing (mlst) is considered the "gold standard" of typing, but it is traditionally performed in an expensive and time-consuming manner. as the costs of whole-genome sequencing (wgs) continue to decline, it becomes increasingly available to scientists and routine diagnostic laboratories. currently, the cost is below that of traditional mlst. the new challenges will be how to extract ...201222238442
involvement of multiple distinct bordetella receptor proteins in the utilization of iron liberated from transferrin by host catecholamine stress hormones.bordetella bronchiseptica is a pathogen that can acquire iron using its native alcaligin siderophore system, but can also use the catechol xenosiderophore enterobactin via the bfea outer membrane receptor. transcription of bfea is positively controlled by a regulator that requires induction by enterobactin. catecholamine hormones also induce bfea transcription and b. bronchiseptica can use the catecholamine noradrenaline for growth on transferrin. in this study, b. bronchiseptica was shown to us ...201222458330
zinc sequestration by the neutrophil protein calprotectin enhances salmonella growth in the inflamed gut.neutrophils are innate immune cells that counter pathogens by many mechanisms, including release of antimicrobial proteins such as calprotectin to inhibit bacterial growth. calprotectin sequesters essential micronutrient metals such as zinc, thereby limiting their availability to microbes, a process termed nutritional immunity. we find that while calprotectin is induced by neutrophils during infection with the gut pathogen salmonella typhimurium, calprotectin-mediated metal sequestration does no ...201222423963
pathogenetic importance and therapeutic implications of nf-κb in lymphoid malignancies.derangement of the nuclear factor κb (nf-κb) pathway initiates and/or sustains many types of human cancer. b-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the nf-κb pathway, most likely owing to the pervasive role of this pathway in normal b cells. these genetic aberrations cause tumors to be 'addicted' to nf-κb, which can be exploited therapeutically. since each subtype of lymphoid cancer utilizes differe ...201222435566
the ambiguity in immunology.in the present article, we discuss the various ambiguous aspects of the immune system that render this complex biological network so highly flexible and able to defend the host from different external invaders. this ambiguity stems mainly from the property of the immune system to be both protective and harmful. immunity cannot be fully protective without producing a certain degree of damage (immunopathology) to the host. the balance between protection and tissue damage is, therefore, critical fo ...201222566903
inherited variation in pattern recognition receptors and cancer: dangerous liaisons?the group of pattern recognition receptors includes families of toll-like receptors, nod-like receptors, c-type lectin receptors, and rig-i-like receptors. they are key sensors for a number of infectious agents, some of which are carcinogenic, and they launch an immune response against them. inherited structural variation in genes encoding these receptors and proteins of their signaling pathways may affect their function, modulating cancer risk and features of cancer progression. relevant malign ...201222427729
molecular mimicry as a mechanism of autoimmune disease.a variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. one mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. molecular mimicry has typically been characterized on an antibody or t cell level. however, structural relatedness between pathogen and self does not account for t cell activation in a number of autoimmune diseases. a proposed mechanism that could ...201222095454
elemental economy: microbial strategies for optimizing growth in the face of nutrient limitation.microorganisms play a dominant role in the biogeochemical cycling of nutrients. they are rightly praised for their facility for fixing both carbon and nitrogen into organic matter, and microbial driven processes have tangibly altered the chemical composition of the biosphere and its surrounding atmosphere. despite their prodigious capacity for molecular transformations, microorganisms are powerless in the face of the immutability of the elements. limitations for specific elements, either fleetin ...201222633059
impact of crispr immunity on the emergence and virulence of bacterial pathogens.crispr-cas systems protect prokaryotes from viruses and plasmids and function primarily as an adaptive immune system in these organisms. recent discoveries, however, revealed unexpected roles for crispr loci as barriers to horizontal gene transfer and as modulators of gene expression. we review how both of these functions of crispr-cas systems can affect the emergence and virulence of human bacterial pathogens.201324581697
impact of crispr immunity on the emergence and virulence of bacterial pathogens.crispr-cas systems protect prokaryotes from viruses and plasmids and function primarily as an adaptive immune system in these organisms. recent discoveries, however, revealed unexpected roles for crispr loci as barriers to horizontal gene transfer and as modulators of gene expression. we review how both of these functions of crispr-cas systems can affect the emergence and virulence of human bacterial pathogens.201324581697
protein selection and export via outer membrane vesicles.outer membrane vesicles (omvs) are constitutively produced by all gram-negative bacteria. omvs form when buds from the outer membrane (om) of cells encapsulate periplasmic material and pinch off from the om to form spheroid particles approximately 10 to 300nm in diameter. omvs accomplish a diversity of functional roles yet the omv's utility is ultimately determined by its unique composition. inclusion into omvs may impart a variety of benefits to the protein cargo, including: protection from pro ...201324370777
protein selection and export via outer membrane vesicles.outer membrane vesicles (omvs) are constitutively produced by all gram-negative bacteria. omvs form when buds from the outer membrane (om) of cells encapsulate periplasmic material and pinch off from the om to form spheroid particles approximately 10 to 300nm in diameter. omvs accomplish a diversity of functional roles yet the omv's utility is ultimately determined by its unique composition. inclusion into omvs may impart a variety of benefits to the protein cargo, including: protection from pro ...201324370777
feon-feoff: the helicobacter pylori fur regulator commutates iron-responsive transcription by discriminative readout of opposed dna grooves.most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of dna. here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. this mechanism accounts for the ability of the helicobacter pylori fur regulator to repress the expression of both iron-inducible and iron-repressible genes. when ...201324322295
feon-feoff: the helicobacter pylori fur regulator commutates iron-responsive transcription by discriminative readout of opposed dna grooves.most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of dna. here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. this mechanism accounts for the ability of the helicobacter pylori fur regulator to repress the expression of both iron-inducible and iron-repressible genes. when ...201324322295
communication between bacteria and their hosts.it is clear that a dialogue is occurring between microbes and their hosts and that chemical signals are the language of this interkingdom communication. microbial endocrinology shows that, through their long coexistence with animals and plants, microorganisms have evolved sensors for detecting eukaryotic hormones, which the microbe uses to determine that they are within proximity of a suitable host and to optimally time the expression of genes needed for host colonisation. it has also been shown ...201324381789
the microbiome and cancer.microbiota and host form a complex 'super-organism' in which symbiotic relationships confer benefits to the host in many key aspects of life. however, defects in the regulatory circuits of the host that control bacterial sensing and homeostasis, or alterations of the microbiome, through environmental changes (infection, diet or lifestyle), may disturb this symbiotic relationship and promote disease. increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis. in this ...201324132111
role and regulation of heme iron acquisition in gram-negative pathogens.bacteria that reside in animal tissues and/or cells must acquire iron from their host. however, almost all of the host iron is sequestered in iron-containing compounds and proteins, the majority of which is found within heme molecules. thus, likely iron sources for bacterial pathogens (and non-pathogenic symbionts) are free heme and heme-containing proteins. furthermore, the cellular location of the bacterial within the host (intra or extracellular) influences the amount and nature of the iron c ...201324116354
luxs in bacteria isolated from 25- to 40-million-year-old amber.interspecies bacterial communication is mediated by autoinducer-2, whose synthesis depends on luxs. due to the apparent universality of luxs (present in more than 40 bacterial species), it may have an ancient origin; however, no direct evidence is currently available. we amplified luxs in bacteria isolated from 25- to 40-million-year-old amber. the phylogenies and molecular clocks of luxs and the 16s rrna gene from ancient and extant bacteria were determined as well. luminescence assays using vi ...201324102660
luxs in bacteria isolated from 25- to 40-million-year-old amber.interspecies bacterial communication is mediated by autoinducer-2, whose synthesis depends on luxs. due to the apparent universality of luxs (present in more than 40 bacterial species), it may have an ancient origin; however, no direct evidence is currently available. we amplified luxs in bacteria isolated from 25- to 40-million-year-old amber. the phylogenies and molecular clocks of luxs and the 16s rrna gene from ancient and extant bacteria were determined as well. luminescence assays using vi ...201324102660
adaptive strategies and pathogenesis of clostridium difficile from in vivo transcriptomics.clostridium difficile is currently the major cause of nosocomial intestinal diseases associated with antibiotic therapy in adults. in order to improve our knowledge of c. difficile-host interactions, we analyzed the genome-wide temporal expression of c. difficile 630 genes during the first 38 h of mouse colonization to identify genes whose expression is modulated in vivo, suggesting that they may play a role in facilitating the colonization process. in the ceca of the c. difficile-monoassociated ...201323897605
multilocus sequence typing of borrelia burgdorferi suggests existence of lineages with differential pathogenic properties in humans.the clinical manifestations of lyme disease, caused by borrelia burgdorferi, vary considerably in different patients, possibly due to infection by strains with varying pathogenicity. both rrna intergenic spacer and ospc typing methods have proven to be useful tools for categorizing b. burgdorferi strains that vary in their tendency to disseminate in humans. neither method, however, is suitable for inferring intraspecific relationships among strains that are important for understanding the evolut ...201324069170
topoisomerase iv is required for partitioning of circular chromosomes but not linear chromosomes in streptomyces.filamentous bacteria of the genus streptomyces possess linear chromosomes and linear plasmids. theoretically, linear replicons may not need a decatenase for post-replicational separation of daughter molecules. yet, streptomyces contain parc and pare that encode the subunits for the decatenase topoisomerase iv. the linear replicons of streptomyces adopt a circular configuration in vivo through telomere-telomere interaction, which would require decatenation, if the circular configuration persists ...201323999094
borrelia burgdorferi oxidative stress regulator bosr directly represses lipoproteins primarily expressed in the tick during mammalian infection.differential gene expression is a key strategy adopted by the lyme disease spirochaete, borrelia burgdorferi, for adaptation and survival in the mammalian host and the tick vector. many b. burgdorferi surface lipoproteins fall into two distinct groups according to their expression patterns: one group primarily expressed in the tick and the other group primarily expressed in the mammal. here, we show that the fur homologue in this bacterium, also known as borrelia oxidative stress regulator (bosr ...201323869590
cell extract-containing medium for culture of intracellular fastidious bacteria.the culture of fastidious microorganisms is a critical step in infectious disease studies. as a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of coxiella burnetii. here, we demonstrate the exponential growth of several bacterial strains, including the c. burnetii nine mile phase i and phase ii strains, and c. burnetii isolates from humans and animals. low-oxygen-tension conditions and the presence of small ...201323740722
identification of the likely translational start of mycobacterium tuberculosis gyrb.bacterial dna gyrase is a validated target for antibacterial chemotherapy. it consists of two subunits, gyra and gyrb, which form an a₂b₂ complex in the active enzyme. sequence alignment of mycobacterium tuberculosis gyrb with other bacterial gyrbs predicts the presence of 40 potential additional amino acids at the gyrb n-terminus. there are discrepancies between the m. tuberculosis gyrb sequences retrieved from different databases, including sequences annotated with or without the additional 40 ...201323856181
iron in infection and immunity.iron is an essential nutrient for both humans and pathogenic microbes. because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and dna replication. however, the redox potential of iron also contributes to its toxicity; thus, iron concentration and distribution must be carefully controlled. given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune sy ...201323684303
life without trnaarg-adenosine deaminase tada: evolutionary consequences of decoding the four cgn codons as arginine in mycoplasmas and other mollicutes.in most bacteria, two trnas decode the four arginine cgn codons. one trna harboring a wobble inosine (trna(arg)icg) reads the cgu, cgc and cga codons, whereas a second trna harboring a wobble cytidine (trna(arg)ccg) reads the remaining cgg codon. the reduced genomes of mycoplasmas and other mollicutes lack the gene encoding trna(arg)ccg. this raises the question of how these organisms decode cgg codons. examination of 36 mollicute genomes for genes encoding trna(arg) and the tada enzyme, respons ...201323658230
viral latency locus augments b-cell response in vivo to induce chronic marginal zone enlargement, plasma cell hyperplasia, and lymphoma.kaposi sarcoma (ks) is associated with ks-associated herpesvirus (kshv). this virus also causes b-cell lymphoma and b-cell hyperplasia. there exists no in vivo model for kshv-associated b-cell malignancies or premalignant persistence in b cells. we generated a transgenic mouse that expresses multiple viral latent genes, including lana, vflip, vcyc, all viral micro rnas, and kaposin under the transcriptional control of their natural regulatory region. this promoter is b-cell specific, though it i ...201323365457
the htra protease of borrelia burgdorferi degrades outer membrane protein bmpd and chemotaxis phosphatase chex.borrelia burgdorferi, the spirochaetal agent of lyme disease, codes for a single htra protein, htrabb (bb0104) that is homologous to degp of escherichia coli (41% amino acid identity). htrabb shows physical and biochemical similarities to degp in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. recombinant htrabb exhibits proteolytic activity in vitro, while a mutant (htrabbs198a) does not. however, htrabb and degp have some important differences as ...201323565798
helicobacter pylori infection, chronic inflammation, and genomic transformations in gastric malt lymphoma.nowadays, it is believed that the main role in the development of gastric mucosa-associated lymphoid tissue (malt) lymphoma plays helicobacter pylori infection. this world-wide distributed bacteria is in charge of most cases of not only upper gastrointestinal tract disorders but also some of extragastric problems. constant stimulation of the immune system causes a b-lymphocytes proliferation, which is considered to be responsible for the neoplastic transformation. on the other hand, there are 10 ...201323606792
anti-gm2 ganglioside antibodies are a biomarker for acute canine polyradiculoneuritis.acute canine polyradiculoneuritis (acp) is considered to be the canine equivalent of the human peripheral nerve disorder guillain-barré syndrome (gbs); an aetiological relationship, however, remains to be demonstrated. in gbs, anti-glycolipid antibodies (abs) are considered as important disease mediators. to address the possibility of common ab biomarkers, the sera of 25 acp dogs, 19 non-neurological, and 15 epileptic control dogs were screened for igg abs to 10 glycolipids and their 1 : 1 heter ...201323521648
antimicrobial efflux pumps and mycobacterium tuberculosis drug tolerance: evolutionary considerations.the need for lengthy treatment to cure tuberculosis stems from phenotypic drug resistance, also known as drug tolerance, which has been previously attributed to slowed bacterial growth in vivo. we discuss recent findings that challenge this model and instead implicate macrophage-induced mycobacterial efflux pumps in antimicrobial tolerance. although mycobacterial efflux pumps may have originally served to protect against environmental toxins, in the pathogenic mycobacteria, they appear to have b ...201323242857
chagas' disease: an emergent urban zoonosis. the caracas valley (venezuela) as an epidemiological model.the unprecedented emergence of important public health and veterinary zoonoses is usually a result of exponential population growth and globalization of human activities. i characterized chagas' disease as an emergent zoonosis in the caracas valley (venezuela) due to the following findings: the presence of reservoirs (didelphis marsupialis, rattus rattus) and vectors (panstrongylus geniculatus, panstrongylus rufotuberculatus) infected with trypanosoma cruzi in urbanized or marginalized areas; th ...201425520950
impact of calcium signaling during infection of neisseria meningitidis to human brain microvascular endothelial cells.the pili and outer membrane proteins of neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. in this context expression of meningococcal pilc1 protein has been reported to play a crucial role. intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. here we employed time lapse calcium-imaging and demonstrated that pilc1 of meningococci triggered a significant increase ...201425464500
acute hemorrhagic leukoencephalitis associated with autoimmune myopathy.acute hemorrhagic leukoencephalitis is a rare acute inflammatory myelinopathy of central nervous system with high mortality. we report a case of an unusual presentation of acute hemorrhagic leukoencephalitis with autoimmune myopathy and a complete recovery with steroids and plasmapheresis.201425422709
human viruses and cancer.the first human tumor virus was discovered in the middle of the last century by anthony epstein, bert achong and yvonne barr in african pediatric patients with burkitt's lymphoma. to date, seven viruses -ebv, kshv, high-risk hpv, mcpv, hbv, hcv and htlv1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. viral oncogenic mechanisms generally include: generation of genomic instability, increase in ...201425341666
peripheral nervous system manifestations of infectious diseases.infectious causes of peripheral nervous system (pns) disease are underrecognized but potentially treatable. heightened awareness educed by advanced understanding of the presentations and management of these infections can aid diagnosis and facilitate treatment. in this review, we discuss the clinical manifestations, diagnosis, and treatment of common bacterial, viral, and parasitic infections that affect the pns. we additionally detail pns side effects of some frequently used antimicrobial agent ...201425360209
the structure and regulation of flagella in bacillus subtilis.bacterial flagellar motility is among the most extensively studied physiological systems in biology, but most research has been restricted to using the highly similar gram-negative species escherichia coli and salmonella enterica. here, we review the recent advances in the study of flagellar structure and regulation of the distantly related and genetically tractable gram-positive bacterium bacillus subtilis. b. subtilis has a thicker layer of peptidoglycan and lacks the outer membrane of the gra ...201425251856
the construction and evaluation of reference spectra for the identification of human pathogenic microorganisms by maldi-tof ms.matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) is an emerging technique for the rapid and high-throughput identification of microorganisms. there remains a dearth of studies in which a large number of pathogenic microorganisms from a particular country or region are utilized for systematic analyses. in this study, peptide mass reference spectra (pmrs) were constructed and evaluated from numerous human pathogens (a total of 1019 strains from 94 species ...201425181391
the sweet tooth of bacteria: common themes in bacterial glycoconjugates.humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. however, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. glycoconjugates are an interesting class of molecules fo ...201425184559
molecular mimicry and clonal deletion: a fresh look.in this article, i trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. if we did have complete clonal deletion, there would be major voids, the infamous "black holes", in our immune repertoire. for comprehensive, protective adaptive immunity, f ...201425172771
molecular mimicry and clonal deletion: a fresh look.in this article, i trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. if we did have complete clonal deletion, there would be major voids, the infamous "black holes", in our immune repertoire. for comprehensive, protective adaptive immunity, f ...201425172771
a quantitative prioritisation of human and domestic animal pathogens in europe.disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. previous work has shown the h-(hirsch-)index as an alternative proxy. we present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the h-index. this study established the highe ...201425136810
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.201425080547
secretion of bacterial lipoproteins: through the cytoplasmic membrane, the periplasm and beyond.bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., gram-positive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. after export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep proce ...201424780125
ge23077 binds to the rna polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic ge23077 (ge) binds directly to the bacterial rna polymerase (rnap) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. the target-based resistance spectrum for ge is unusually small, reflecting the fact that the ge binding site on rnap includes residues of the rnap active center that ...201424755292
two residues predominantly dictate functional difference in motility between shewanella oneidensis flagellins flaa and flab.nearly half of flagellated microorganisms possess a multiple-flagellin system. although a functional filament can be formed from one of multiple flagellins alone in many bacteria, it is more common that one flagellin is the major constituent and others contribute. underlying mechanisms proposed for such scenarios cover flagellin regulation of various levels, including transcription, translation, post-translational modification, secretion, and filament assembly. in shewanella oneidensis, the flag ...201424733391
molecular architecture of the bacterial flagellar motor in cells.the flagellum is one of the most sophisticated self-assembling molecular machines in bacteria. powered by the proton-motive force, the flagellum rapidly rotates in either a clockwise or counterclockwise direction, which ultimately controls bacterial motility and behavior. escherichia coli and salmonella enterica have served as important model systems for extensive genetic, biochemical, and structural analysis of the flagellum, providing unparalleled insights into its structure, function, and gen ...201424697492
superoxide dismutases and superoxide reductases. 201424684599
common infection-related conditions and risk of lymphoid malignancies in older individuals.chronic antigenic stimulation may initiate non-hodgkin (nhl) and hodgkin lymphoma (hl) development. antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited.201424691420
a case of mucosa-associated lymphoid tissue lymphoma of the sigmoid colon presenting as a semipedunculated polyp.mucosa-associated lymphoid tissue (malt) lymphomas are characterized by lymphoepithelial lesions pathologically. colonic malt lymphomas are relatively rarer than lymphomas of the stomach or small intestine. endoscopically, colonic malt lymphoma frequently appears as a nonpedunculated protruding polypoid mass and/or an ulceration in the cecum and/or rectum. we report a unique case of a colonic malt lymphoma presenting as a semipedunculated polyp. a 54-year-old man was found to have a 2-cm semiped ...201424765604
diagnostic metagenomics: potential applications to bacterial, viral and parasitic infections.the term 'shotgun metagenomics' is applied to the direct sequencing of dna extracted from a sample without culture or target-specific amplification or capture. in diagnostic metagenomics, this approach is applied to clinical samples in the hope of detecting and characterizing pathogens. here, i provide a conceptual overview, before reviewing several recent promising proof-of-principle applications of metagenomics in virus discovery, analysis of outbreaks and detection of pathogens in contemporar ...201424576467
a potential link between environmental triggers and autoimmunity.autoimmune diseases have registered an alarming rise worldwide in recent years. accumulated evidence indicates that the immune system's ability to distinguish self from nonself is negatively impacted by genetic factors and environmental triggers. genetics is certainly a factor, but since it normally takes a very long time for the human genetic pattern to change enough to register on a worldwide scale, increasingly the attention of studies has been focused on the environmental factors of a rapidl ...201424688790
catabolism of host-derived compounds during extracellular bacterial infections.efficient catabolism of host-derived compounds is essential for bacterial survival and virulence. while these links in intracellular bacteria are well studied, such studies in extracellular bacteria lag behind, mostly for technical reasons. the field has identified important metabolic pathways, but the mechanisms by which they impact infection and in particular, establishing the importance of a compound's catabolism versus alternate metabolic roles has been difficult. in this review we will exam ...201424038340
transition metal ions at the crossroads of mucosal immunity and microbial pathogenesis.transition metal ions are essential micronutrients for all living organisms. in mammals, these ions are often protein-bound and sequestered within cells, limiting their availability to microbes. moreover, in response to infection, mammalian hosts further reduce the availability of metal nutrients by activating epithelial cells and recruiting neutrophils, both of which release metal-binding proteins with antimicrobial function. microorganisms, in turn, have evolved sophisticated systems to overco ...201424478990
nitrate and periplasmic nitrate reductases.the nitrate anion is a simple, abundant and relatively stable species, yet plays a significant role in global cycling of nitrogen, global climate change, and human health. although it has been known for quite some time that nitrate is an important species environmentally, recent studies have identified potential medical applications. in this respect the nitrate anion remains an enigmatic species that promises to offer exciting science in years to come. many bacteria readily reduce nitrate to nit ...201424141308
incidence of marginal zone lymphoma in the united states, 2001-2009 with a focus on primary anatomic site.the aetiology of marginal zone lymphoma (mzl) is purported to differ by anatomic site. while this is supported by clinical series of single mzl sites, no population-based study has comprehensively assessed incidence patterns across sites. to gain insight into disease aetiology, we assessed mzl incidence by site using data from 18 u.s. surveillance, epidemiology and end results (seer) program population-based registries. we calculated age-adjusted incidence rates (irs) by sex, race, and calendar ...201424417667
fulminant guillain-barré syndrome with myocarditis.guillain-barré syndrome (gbs) represents a diverse spectrum of diseases, with variable pathophysiological mechanisms, clinical manifestation, presentation pattern, and degree of severity. we report a rare case of fatal fulminant gbs complicated with myocarditis during the course of illness.201424791246
contribution of six flagellin genes to the flagellum biogenesis of vibrio vulnificus and in vivo invasion.vibrio vulnificus is a halophilic pathogenic bacterium that is motile due to the presence of a single polar flagellum. v. vulnificus possesses a total of six flagellin genes organized into two loci (flafba and flacde). we proved that all six of the flagellin genes were transcribed, whereas only five (flaa, -b, -c, -d, and -f) of the six flagellin proteins were detected. to understand roles of the six v. vulnificus flagellins in motility and virulence, mutants with single and multiple flagellin d ...201424101693
humans and cattle: a review of bovine zoonoses.infectious disease prevention and control has been among the top public health objectives during the last century. however, controlling disease due to pathogens that move between animals and humans has been challenging. such zoonotic pathogens have been responsible for the majority of new human disease threats and a number of recent international epidemics. currently, our surveillance systems often lack the ability to monitor the human-animal interface for emergent pathogens. identifying and ult ...201424341911
peripheral neuropathy: clinical and electrophysiological considerations.this article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. magnetic resonance neurography has utility in the diagnosis of many focal peripheral nerve lesions. when combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field magnetic resonance neurography may play an increasingly important role in the evaluation of patients with peripheral neuropathy.201424210312
peripheral neuropathy: clinical and electrophysiological considerations.this article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. magnetic resonance neurography has utility in the diagnosis of many focal peripheral nerve lesions. when combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field magnetic resonance neurography may play an increasingly important role in the evaluation of patients with peripheral neuropathy.201424210312
outer membrane vesicles as platform vaccine technology.outer membrane vesicles (omvs) are released spontaneously during growth by many gram-negative bacteria. they present a range of surface antigens in a native conformation and have natural properties like immunogenicity, self-adjuvation and uptake by immune cells which make them attractive for application as vaccines against pathogenic bacteria. in particular with neisseria meningitidis, they have been investigated extensively and an omv-containing meningococcal vaccine has recently been approved ...201526912077
membrane topology and biochemical characterization of the escherichia coli baca undecaprenyl-pyrophosphate phosphatase.several integral membrane proteins exhibiting undecaprenyl-pyrophosphate (c55-pp) phosphatase activity were previously identified in escherichia coli that belonged to two distinct protein families: the baca protein, which accounts for 75% of the c55-pp phosphatase activity detected in e. coli cell membranes, and three members of the pap2 phosphatidic acid phosphatase family, namely pgpb, ybjg and lpxt. this dephosphorylation step is required to provide the c55-p carrier lipid which plays a centr ...201526560897
pathogenesis of myeloproliferative neoplasms: role and mechanisms of chronic inflammation.myeloproliferative neoplasms (mpns) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. recent advances in the biology of mpns have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the jak2, mpl, or calr genes. yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of mpns are not fully eluci ...201526538820
development of real-time pcr assays for the detection of moraxella macacae associated with bloody nose syndrome in rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques.moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. the aim of this study was to develop specific molecular diagnostic assays for m. macacae and to determine their performance characteristics.201526365904
opposite and coordinated rotation of amphitrichous flagella governs oriented swimming and reversals in a magnetotactic spirillum.current knowledge regarding the mechanism that governs flagellar motor rotation in response to environmental stimuli stems mainly from the study of monotrichous and peritrichous bacteria. little is known about how two polar flagella, one at each cell pole of the so-called amphitrichous bacterium, are coordinated to steer the swimming. here we fluorescently labeled the flagella of magnetospirillum magneticum amb-1 cells and took advantage of the magnetically controllable swimming of this bacteriu ...201526240070
lessons in fundamental mechanisms and diverse adaptations from the 2015 bacterial locomotion and signal transduction meeting.in response to rapid changes in their environment, bacteria control a number of processes, including motility, cell division, biofilm formation, and virulence. research presented in january 2015 at the biennial bacterial locomotion and signal transduction (blast) meeting in tucson, az, illustrates the elegant complexity of the nanoarrays, nanomachines, and networks of interacting proteins that mediate such processes. studies employing an array of biophysical, genetic, cell biology, and mathemati ...201526195592
ileal mucosa-associated lymphoid tissue lymphoma presenting with small bowel obstruction: a case report.extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (malt lymphoma) of the gastrointestinal tract commonly involves the stomach in the setting of concurrent helicobacter pylori (h. pylori) infection. primary ileal malt lymphoma is rare, and has not been associated with a specific infectious disease. we report a case of a 58-year-old man who presented to the emergency department with constipation and abdominal distension, and signs of an obstructing mass on computed tomography ...201526178711
acylation of biomolecules in prokaryotes: a widespread strategy for the control of biological function and metabolic stress.acylation of biomolecules (e.g., proteins and small molecules) is a process that occurs in cells of all domains of life and has emerged as a critical mechanism for the control of many aspects of cellular physiology, including chromatin maintenance, transcriptional regulation, primary metabolism, cell structure, and likely other cellular processes. although this review focuses on the use of acetyl moieties to modify a protein or small molecule, it is clear that cells can use many weak organic aci ...201526179745
investigating reports of complex regional pain syndrome: an analysis of hpv-16/18-adjuvanted vaccine post-licensure data.complex regional pain syndrome (crps) is a chronic pain disorder that typically follows trauma or surgery. suspected crps reported after vaccination with human papillomavirus (hpv) vaccines led to temporary suspension of proactive recommendation of hpv vaccination in japan. we investigated the potential crps signal in relation to hpv-16/18-adjuvanted vaccine (cervarix®) by database review of crps cases with independent expert confirmation; a disproportionality analysis and analyses of temporalit ...201526501109
mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator.ferric uptake regulator (fur) plays a key role in the iron homeostasis of prokaryotes, such as bacterial pathogens, but the molecular mechanisms and structural basis of fur-dna binding remain incompletely understood. here, we report high-resolution structures of magnetospirillum gryphiswaldense msr-1 fur in four different states: apo-fur, holo-fur, the fur-feoab1 operator complex and the fur-pseudomonas aeruginosa fur box complex. apo-fur is a transition metal ion-independent dimer whose binding ...201526134419
architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies.recent years have seen major advances in the structural understanding of the different components of tripartite efflux assemblies, which encompass the multidrug efflux (mdr) pumps and type i secretion systems. the majority of these investigations have focused on the role played by the inner membrane transporters and the outer membrane factor (omf), leaving the third component of the system - the periplasmic adaptor proteins (paps) - relatively understudied. here we review the current state of knowle ...201526074901
extensive infectious myelitis post bariatric surgery.inflammatory myelopathy is an inflammatory neurological disorder of the spinal cord (myelopathy). it occurs in 1 (severe) to 8 (mild) cases/million per year. it is often referred to in the literature as "transverse myelitis" or "acute transverse myelitis". myelopathy and by extension myelitis, can present as pyramidal (motor), sensory, and/or autonomic dysfunction to varying degrees. symptoms typically develop over hours to days and worsen over days to weeks. sensory symptoms usually present as ...201525879204
presence of zoonotic agents in engorged ticks and hedgehog faeces from erinaceus europaeus in (sub) urban areas.european hedgehogs (erinaceus europaeus) are hosts for ixodes hexagonus and i. ricinus ticks, which are vectors for zoonotic microorganisms. in addition, hedgehogs may carry several enteric zoonoses as well. it is unclear to what extent a presence of pathogens in hedgehogs poses a risk to public health, as information on the presence of zoonotic agents in hedgehogs in urban areas is relatively scarce.201525885888
genome-wide dna methylation analysis of haloferax volcanii h26 and identification of dna methyltransferase related pd-(d/e)xk nuclease family protein hvo_a0006.restriction-modification (rm) systems have evolved to protect the cell from invading dnas and are composed of two enzymes: a dna methyltransferase and a restriction endonuclease. although rm systems are present in both archaeal and bacterial genomes, dna methylation in archaea has not been well defined. in order to characterize the function of rm systems in archaeal species, we have made use of the model haloarchaeon haloferax volcanii. a genomic dna methylation analysis of h. volcanii strain h2 ...201525904898
molecular pathogenesis of malt lymphoma.approximately 8% of all non-hodgkin lymphomas are extranodal marginal zone b cell lymphoma of mucosa associated lymphoid tissue (malt), also known as malt lymphoma, which was first described in 1983 by isaacson and wright. malt lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. interestingly, at least 3 different, apparently site-specific, chromos ...201525922601
regulation of bacterial virulence by csr (rsm) systems.most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. this ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. it is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. studies over the past 2 decades have established that the csra/rsma proteins, global regulators of posttranscriptional ge ...201525833324
the challenge of efflux-mediated antibiotic resistance in gram-negative bacteria.the global emergence of multidrug-resistant gram-negative bacteria is a growing threat to antibiotic therapy. the chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. multidrug pumps, particularly those represented by the clinically relevant acrab-tolc and mex pumps of the resistance-nodulation-division (rnd) superfamily, not only mediate intrinsic and acquired mult ...201525788514
a new player at the flagellar motor: flil controls both motor output and bias.the bacterial flagellum is driven by a bidirectional rotary motor, which propels bacteria to swim through liquids or swarm over surfaces. while the functions of the major structural and regulatory components of the flagellum are known, the function of the well-conserved flil protein is not. in salmonella and escherichia coli, the absence of flil leads to a small defect in swimming but complete elimination of swarming. here, we tracked single motors of these bacteria and found that absence of fli ...201525714720
proteomic profiling of the outer membrane fraction of the obligate intracellular bacterial pathogen ehrlichia ruminantium.the outer membrane proteins (omps) of gram-negative bacteria play a crucial role in virulence and pathogenesis. identification of these proteins represents an important goal for bacterial proteomics, because it aids in vaccine development. here, we have developed such an approach for ehrlichia ruminantium, the obligate intracellular bacterium that causes heartwater. a preliminary whole proteome analysis of elementary bodies, the extracellular infectious form of the bacterium, had been performed ...201525710494
exploring the existence of lipid rafts in bacteria.an interesting concept in the organization of cellular membranes is the proposed existence of lipid rafts. membranes of eukaryotic cells organize signal transduction proteins into membrane rafts or lipid rafts that are enriched in particular lipids such as cholesterol and are important for the correct functionality of diverse cellular processes. the assembly of lipid rafts in eukaryotes has been considered a fundamental step during the evolution of cellular complexity, suggesting that bacteria a ...201525652542
extranodal marginal zone lymphoma of the lung: evolution from an underlying reactive lymphoproliferative disorder.extranodal marginal zone lymphoma (enmzl) of mucosa-associated lymphoid tissue (malt) is a problematic and sometimes controversial diagnosis. while commonly seen in the stomach in the setting of chronic helicobacter pylori infection, other extranodal sites, such as the lung, may also present with disease. enmzl is clinically and morphologically heterogeneous; however, regardless of presentation, the etiology lies in the accumulation of lymphoid tissue in non-traditional sites. this phenomenon is ...201526457231
a case of a laryngeal malt lymphoma in a patient with a history of gastric malt.we are reporting a case of a 62-year-old african american woman with a history of gastric malt lymphoma successfully treated with radiation who presented with a laryngeal malt lymphoma 4 years after her original diagnosis. she received definitive radiation with a complete response. the case presented is unique for the rare presentation of a malt lymphoma in the larynx, especially in light of the patient's previously treated gastric malt lymphoma years ago.201525664189
current and past strategies for bacterial culture in clinical microbiology.a pure bacterial culture remains essential for the study of its virulence, its antibiotic susceptibility, and its genome sequence in order to facilitate the understanding and treatment of caused diseases. the first culture conditions empirically varied incubation time, nutrients, atmosphere, and temperature; culture was then gradually abandoned in favor of molecular methods. the rebirth of culture in clinical microbiology was prompted by microbiologists specializing in intracellular bacteria. th ...201525567228
inositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy.recently, we described a novel autoantibody, anti-sj/itpr1-igg, that targets the inositol 1,4,5-trisphosphate receptor type 1 (itpr1) in patients with cerebellar ataxia. however, itpr1 is expressed not only by purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to itpr1 may be broader th ...201627776522
primary b-cell mucosa-associated lymphoid tissue lymphoma of the hard palate and parotid gland: report of one case and review of the literature.a 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. incisional biopsy from the hard palate revealed an extranodal marginal zone b-cell lymphoma, also called mucosa-associated lymphoid tissue (malt) lymphoma. final diagnosis was malt lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. to our knowledge, this report illustrates the first case of malt lymphoma of th ...201627738485
transition metals and virulence in bacteria.transition metals are required trace elements for all forms of life. due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. in bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies. host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment o ...201627617971
how rheumatoid arthritis can result from provocation of the immune system by microorganisms and viruses.the pathogenesis of rheumatoid arthritis (ra), similar to development of a majority of inflammatory and autoimmune disorders, is largely due to an inappropriate or inadequate immune response to environmental challenges. among these challenges, infectious agents are the undisputed leaders. since the 1870s, an impressive list of microorganisms suspected of provoking ra has formed, and the list is still growing. although a definite causative link between a specific infectious agent and the disease ...201627582741
mucosa-associated lymphoid tissue lymphoma of the sigmoid colon discovered on routine screening colonoscopy in patient with hepatitis c and helicobacter pylori infection.mucosa-associated lymphoid tissue (malt) lymphoma is predominantly found in the stomach. rarely, it is found in the proximal colon and even less so in the sigmoid colon. we present a rare case of primary sigmoid colon malt lymphoma in a patient with concomitant helicobacter pylori and hepatitis c infection. we also review current imaging, staging, and therapeutic modalities. to our knowledge, this is the first sigmoid colon malt lymphoma reported in the united states.201627807552
evaluation of a protective effect of in ovo delivered campylobacter jejuni omvs.campylobacter jejuni is the most prevalent cause of a food-borne gastroenteritis in the developed world, with poultry being the main source of infection. campylobacter jejuni, like other gram-negative bacteria, constitutively releases outer membrane vesicles (omvs). omvs are highly immunogenic, can be taken up by mammalian cells, and are easily modifiable by recombinant engineering. we have tested their usefulness for an oral (in ovo) vaccination of chickens. four groups of 18-day-old chicken em ...201627383607
calcium binding protects e-cadherin from cleavage by helicobacter pylori htra.the cell adhesion and tumor suppressor protein e-cadherin is an important factor in the establishment and maintenance of epithelial integrity. e-cadherin is a single transmembrane protein, which consists of an intracellular domain (ic), a transmembrane domain (td), and five extracellular domains (ec). ec domains form homophilic interactions in cis and trans that require calcium binding to the linker region between the ec domains. in our previous studies, we identified the serine protease high te ...201627274359
challenges with using names to link digital biodiversity information. 201627346955
exploring the secretomes of microbes and microbial communities using filamentous phage display.microbial surface and secreted proteins (the secretome) contain a large number of proteins that interact with other microbes, host and/or environment. these proteins are exported by the coordinated activities of the protein secretion machinery present in the cell. a group of bacteriophage, called filamentous phage, have the ability to hijack bacterial protein secretion machinery in order to amplify and assemble via a secretion-like process. this ability has been harnessed in the use of filamento ...201627092113
the interplay between the microbiome and the adaptive immune response in cancer development.the data from different studies suggest a bacterial role in cancer genesis/progression, often modulating the local immune response. this is particularly so at the mucosal level where the bacterial presence is strong and the immune system is highly reactive. the epithelial surfaces of the body, such as the skin and mucosa, are colonized by a vast number of microorganisms, which represent the so-called normal microbiome. normally the microbiome does not cause a proinflammatory response because the ...201627366226
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
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
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