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in trans t cell tolerance exacerbates experimental allergic encephalomyelitis by interfering with protective antibody responses.f1 (sjl/j×c57bl/6) mice with mog35-55-induced eae recover from disease when treated with ig-mog carrying mog35-55 peptide. however, ig-plp1, carrying plp139-151, induced reduction of anti-mog antibodies and exacerbated eae. herein, we show that ig-plp1 specifically reduces the frequency of b cells producing protective igg2a/b anti-mog antibodies. surprisingly, these cells were marginal zone (mz), rather than follicular (fo) or newly formed (nf), b cells and transfer of mz b cells into sick mice ...201324196276
in trans t cell tolerance exacerbates experimental allergic encephalomyelitis by interfering with protective antibody responses.f1 (sjl/j×c57bl/6) mice with mog35-55-induced eae recover from disease when treated with ig-mog carrying mog35-55 peptide. however, ig-plp1, carrying plp139-151, induced reduction of anti-mog antibodies and exacerbated eae. herein, we show that ig-plp1 specifically reduces the frequency of b cells producing protective igg2a/b anti-mog antibodies. surprisingly, these cells were marginal zone (mz), rather than follicular (fo) or newly formed (nf), b cells and transfer of mz b cells into sick mice ...201324196276
prospective evaluation for respiratory pathogens in children with sickle cell disease and acute respiratory illness.human rhinovirus (hrv), human coronavirus (hcov), human bocavirus (hbov), and human metapneumovirus (hmpv) infections in children with sickle cell disease have not been well studied.201324123899
prospective evaluation for respiratory pathogens in children with sickle cell disease and acute respiratory illness.human rhinovirus (hrv), human coronavirus (hcov), human bocavirus (hbov), and human metapneumovirus (hmpv) infections in children with sickle cell disease have not been well studied.201324123899
genetic analysis of bordetella pertussis isolates from the 2008-2010 pertussis epidemic in japan.a large pertussis epidemic occurred between 2008 and 2010 in japan. to investigate epidemic strains, we analyzed 33 bordetella pertussis isolates from the epidemic period by sequencing virulence-associated genes (fim3, ptxp, ptxa, and prn) and performing multilocus variable-number tandem repeat analysis (mlva), and compared these results with those of 101 isolates from non-epidemic, earlier and later time periods. dna sequencing of the fim3 allele revealed that the frequency of fim3b was 4.3%, 1 ...201324124606
effect of basti (oil enema) therapy for the management of cough in pertussis.bordetella pertussis continues to circulate even in countries with good childhood vaccination coverage. sporadic cases are still observed either due to no vaccination, incomplete vaccination or as a result of failure of vaccination. though acute in nature it has a longer disease span with multiple life-threatening complications despite adequate management. this study was undertaken to study the effect of sneha basti (oil enema) in pertussis in relation to reduction in intensity of cough and comp ...201324696577
appearance of macrolide-resistant bordetella pertussis strains in china. 201323877687
eliminating a set of four penicillin binding proteins triggers the rcs phosphorelay and cpx stress responses in escherichia coli.penicillin binding proteins (pbps) are responsible for synthesizing and modifying the bacterial cell wall, and in escherichia coli the loss of several nonessential low-molecular-weight pbps gives rise to abnormalities in cell shape and division. to determine whether these proteins help connect the flagellar basal body to the peptidoglycan wall, we surveyed a set of pbp mutants and found that motility in an agar migration assay was compromised by the simultaneous absence of four enzymes: pbp4, pb ...201323893115
posttranslational maturation of the invasion acyl carrier protein of salmonella enterica serovar typhimurium requires an essential phosphopantetheinyl transferase of the fatty acid biosynthesis pathway.salmonella pathogenicity island 1 (spi-1) carries genes required for the formation of a type 3 secretion system, which is necessary for the invasion process of salmonella. among the proteins encoded by spi-1 is iacp, a homolog of acyl carrier proteins. acyl carrier proteins are mainly involved in fatty acid biosynthesis, and they require posttranslational maturation by addition of a 4'-phosphopantetheine prosthetic group to be functional. in this study, we analyzed iacp maturation in vivo. by pe ...201323893113
randomized, controlled, multicenter study of the immunogenicity and safety of a fully liquid combination diphtheria-tetanus toxoid-five-component acellular pertussis (dtap5), inactivated poliovirus (ipv), and haemophilus influenzae type b (hib) vaccine compared with a dtap3-ipv/hib vaccine administered at 3, 5, and 12 months of age.this study compared the levels of immunogenicity and safety of diphtheria-tetanus toxoid-five-component acellular pertussis (dtap(5)), inactivated poliovirus (ipv), and haemophilus influenzae type b (hib) (dtap(5)-ipv-hib) and dtap(3)-ipv/hib vaccines for study participants 3, 5, and 12 months of age. post-dose 3 noninferiority criteria comparing dtap(5)-ipv-hib to dtap(3)-ipv/hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for pol ...201323966556
persistent cough in children. 201324152457
predicting functionally informative mutations in escherichia coli bama using evolutionary covariance analysis.the essential outer membrane β-barrel protein bama forms a complex with four lipoprotein partners bambcde that assembles β-barrel proteins into the outer membrane of escherichia coli. detailed genetic studies have shown that bama cycles through multiple conformations during substrate assembly, suggesting that a complex network of residues may be involved in coordinating conformational changes and lipoprotein partner function. while genetic analysis of bama has been informative, it has also been ...201323934888
defective sphingosine 1-phosphate receptor 1 (s1p1) phosphorylation exacerbates th17-mediated autoimmune neuroinflammation.sphingosine 1-phosphate (s1p) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. the sphingosine phosphate receptor 1 (s1p1) agonist fty-720 (gilenya) arrests immune trafficking and prevents multiple sclerosis (ms) relapses. however, alternative mechanisms of s1p-s1p1 signaling have been reported. phosphoproteomic analysis of ms brain lesions revealed s1p1 phosphorylation on s351, a residue crucial for receptor internalization. mutant mice harboring an s1pr1 ge ...201324076635
characterization of a membrane-active peptide from the bordetella pertussis cyaa toxin.bordetella pertussis, the pathogenic bacteria responsible for whooping cough, secretes several virulence factors, among which is the adenylate cyclase toxin (cyaa) that plays a crucial role in the early stages of human respiratory tract colonization. cyaa invades target cells by translocating its catalytic domain directly across the plasma membrane and overproduces camp, leading to cell death. the molecular process leading to the translocation of the catalytic domain remains largely unknown. we ...201324064217
stat3 regulates proliferation and survival of cd8+ t cells: enhances effector responses to hsv-1 infection, and inhibits il-10+ regulatory cd8+ t cells in autoimmune uveitis.stat3 regulates cd4+ t cell survival and differentiation. however, its effects on cd8+ t cells are not well understood. here, we show that in comparison to wt cd8+ t cells, stat3-deficient cd8+ t cells exhibit a preactivated memory-like phenotype, produce more il-2, proliferate faster, and are more sensitive to activation-induced cell death (aicd). the enhanced proliferation and sensitivity to aicd correlated with downregulation of class-o forkhead transcription factors (foxo1, foxo3a), p21(waf1 ...201324204098
signaling cascades of pasteurella multocida toxin in immune evasion.pasteurella multocida toxin (pmt) is a protein toxin found in toxigenic strains of pasteurella multocida. pmt is the causative agent for atrophic rhinitis in pigs, a disease characterized by loss of nasal turbinate bones due to an inhibition of osteoblast function and an increase in osteoclast activity and numbers. apart from this, pmt acts as a strong mitogen, protects from apoptosis and has an impact on the differentiation and function of immune cells. many signaling pathways have been elucida ...201324064721
characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis.autoimmunity to neuronal proteins occurs in several neurological syndromes, where cellular and humoral responses are directed to surface as well as intracellular antigens. similar to myelin autoimmunity, pathogenic immune response to neuroaxonal components such as neurofilaments may contribute to neurodegeneration in multiple sclerosis.201324053384
suppression of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells.neural stem/progenitor cells (nspcs) have the ability to migrate into the central nervous system (cns) to replace damaged cells. in inflammatory cns disease, cytokine transduced neural stem cells may be used as vehicles to specifically reduce inflammation and promote cell replacement. in this study, we used nspcs overexpressing il-10, an immunomodulatory cytokine, in an animal model for cns inflammation and multiple sclerosis (ms). intravenous injection of il-10 transduced neural stem/progenitor ...201324053338
the hierarchical process of differentiation of long-lived antibody-secreting cells is dependent on integrated signals derived from antigen and il-17a.switched cd19-positive memory b cells purified from mice with chronic immune response against thalassophrynenattereri venom proteins were cultured with venom or cytokines. our results confirm the existence of a hierarchic process of differentiation: activated memory b cells progressively acquire increasing levels of cd138 and decreasing levels of cd45r/b220 to finally arrive at asc with b220(neg) phenotype, which are igg1-secreting cells. only bmem from peritoneal cavity or bone marrow of vtn im ...201324058589
violet light down-regulates the expression of specific differentiation markers through rhodopsin in normal human epidermal keratinocytes.several recent reports have demonstrated that photoreceptors are expressed in human skin. the rod and cone photoreceptor-like proteins are expressed in human skin and rhodopsin, long wavelength-opsin, and short wavelength-opsin are also present in cultured murine melanocytes. furthermore, the photopigment rhodopsin is expressed in human melanocytes and is involved in ultraviolet a phototransduction which induces early melanin synthesis. in this study, we investigated whether rhodopsin is express ...201324069221
ca2+ influx and tyrosine kinases trigger bordetella adenylate cyclase toxin (act) endocytosis. cell physiology and expression of the cd11b/cd18 integrin major determinants of the entry route.humans infected with bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. this pathogenic bacterium produces a unique adenylate cyclase toxin (act) which enters human phagocytes and catalyzes the unregulated formation of camp, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. additionally, act permeabilizes cells through pore formation in the target cell membrane. recently, we d ...201324058533
seroprevalence of pertussis in china: need to improve vaccination strategies.pertussis remains an important cause of infant death worldwide and is an ongoing public health concern even in countries with high vaccination coverage. a cross-sectional seroepidemiological study was undertaken to estimate true incidence rates and gain further insight into the epidemiology and burden of pertussis in china. during 2011, a total of 1080 blood samples were obtained from healthy individuals between 0 and 86 y of age in zhengzhou, central china. serum igg antibodies against pertussi ...201324018405
seroprevalence of pertussis in china: need to improve vaccination strategies.pertussis remains an important cause of infant death worldwide and is an ongoing public health concern even in countries with high vaccination coverage. a cross-sectional seroepidemiological study was undertaken to estimate true incidence rates and gain further insight into the epidemiology and burden of pertussis in china. during 2011, a total of 1080 blood samples were obtained from healthy individuals between 0 and 86 y of age in zhengzhou, central china. serum igg antibodies against pertussi ...201324018405
combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis b-inactivated poliovirus-haemophilus influenzae type b vaccine; infanrix™ hexa: twelve years of experience in italy.infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11-12 mo of age was pioneered in italy. the 3-5-11 schedule is now used in a growing number of european countries. infanrix™ hexa (dtpa-hbv-ipv/hib, glaxosmithkline vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. we reviewed available clinical trial data describing the immunogenicity of dtpa-hbv-ipv/hib when administered at 3, 5, and 11 mo of age, a ...201324004825
combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis b-inactivated poliovirus-haemophilus influenzae type b vaccine; infanrix™ hexa: twelve years of experience in italy.infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11-12 mo of age was pioneered in italy. the 3-5-11 schedule is now used in a growing number of european countries. infanrix™ hexa (dtpa-hbv-ipv/hib, glaxosmithkline vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. we reviewed available clinical trial data describing the immunogenicity of dtpa-hbv-ipv/hib when administered at 3, 5, and 11 mo of age, a ...201324004825
seven transmembrane g protein-coupled receptor repertoire of gastric ghrelin cells.the molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. based on qpcr analysis of facs-purified gastric ghrelin cells, highly expressed and enriched 7tm receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. five gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the gip and the secretin receptors but surprisingly also the composite re ...201324327954
pseudomonas aeruginosa exotoxin y-mediated tau hyperphosphorylation impairs microtubule assembly in pulmonary microvascular endothelial cells.pseudomonas aeruginosa uses a type iii secretion system to introduce the adenylyl and guanylyl cyclase exotoxin y (exoy) into the cytoplasm of endothelial cells. exoy induces tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. here we investigated both microtubule behavior and centrosome activity to test the hypothesis that exoy disrupts microtubule dynamics. fluo ...201324023939
transcriptome profiling reveals th17-like immune responses induced in zebrafish bath-vaccinated with a live attenuated vibrio anguillarum.a candidate vaccine, live attenuated vibrio anguillarum developed in our laboratory could prevent vibriosis of fish resulted from v. anguillarum and v. alginolyticus. to elucidate the molecular mechanisms underlying the vaccine protection, we used microarray technology to compare the spleen transcriptomes of bath-vaccinated and unvaccinated zebrafish at 28 days post vaccination.201324023910
mesenchymal stem cells in tissue repair.the advent of mesenchymal stem cell (msc)-based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage, and subsequent regeneration and repair. application-based ability to measure msc potency and fate of the cells post-msc therapy are the variables that confound the use of mscs therapeutics in human diseases. an evaluation of msc function and applications with attention to detail in the p ...201324027567
pertussis toxin b-pentamer mediates intercellular transfer of membrane proteins and lipids.pertussis toxin (ptx) is the major virulence factor of bordetella pertussis. the enzymatic or active (a) subunit inactivates host g protein coupled receptor (gpcr) signaling pathways. the non-enzymatic binding (b) subunit also mediates biological effects due to lectin-like binding characteristics, including the induction of t cell receptor (tcr) signaling and subsequent down-regulation of chemokine receptor expression. here we report another activity attributable to ptxb, facilitating transfer o ...201324019885
differential t- and b-cell responses to pertussis in acellular vaccine-primed versus whole-cell vaccine-primed children 2 years after preschool acellular booster vaccination.this study investigated long-term cellular and humoral immunity against pertussis after booster vaccination of 4-year-old children who had been vaccinated at 2, 3, 4, and 11 months of age with either whole-cell pertussis (wp) or acellular pertussis (ap) vaccine. immune responses were evaluated until 2 years after the preschool booster ap vaccination. in a cross-sectional study (registered trial no. isrctn65428640), blood samples were taken from wp- and ap-primed children prebooster and 1 month a ...201323825195
rapid multiplex pcr assay to identify respiratory viral pathogens: moving forward diagnosing the common cold.upper respiratory tract infections (uris) can be a serious burden to the healthcare system. the majority of uris are viral in etiology, but definitive diagnosis can prove difficult due to frequently overlapping clinical presentations of viral and bacterial infections, and the variable sensitivity, and lengthy turn-around time of viral culture. we tested new automated nested multiplex pcr technology, the filmarray(®) system, in the tamc department of clinical investigations, to determine the feas ...201324052914
the synechocystis pcc6803 mera-like enzyme operates in the reduction of both mercury and uranium under the control of the glutaredoxin 1 enzyme.in a continuing effort to analyze the selectivity/redundancy of the three glutaredoxin (grx) enzymes of the model cyanobacterium synechocystis pcc6803, we have characterized an enzyme system that plays a crucial role in protection against two toxic metal pollutants, mercury and uranium. the present data show that grx1 (slr1562 in cyanobase) selectively interacts with the presumptive mercuric reductase protein (slr1849). this mera enzyme plays a crucial role in cell defense against both mercuric ...201323852862
comparison of the filmarray rp, verigene rv+, and prodesse proflu+/fast+ multiplex platforms for detection of influenza viruses in clinical samples from the 2011-2012 influenza season in belgium.respiratory tract infections (rtis) are caused by a plethora of viral and bacterial pathogens. in particular, lower rtis are a leading cause of hospitalization and mortality. timely detection of the infecting respiratory pathogens is crucial to optimize treatment and care. in this study, three u.s. food and drug administration-approved molecular multiplex platforms (prodesse proflu+/fast+, filmarray rp, and verigene rv+) were evaluated for influenza virus detection in 171 clinical samples collec ...201323824777
the complement anaphylatoxin receptors are not required for the development of experimental autoimmune uveitis.to determine if complement anaphylatoxin-mediated inflammation contributes to the development and progression of experimental autoimmune uveitis (eau), we induced disease in wild type and complement anaphylatoxin receptor-deficient mice (c3a receptor(-/-), c5a receptor(-/-) and c3ar(-/-)/c5ar(-/-)) and evaluated the eyes three weeks post-induction. no differences in disease severity or in disease incidence were seen between wild type controls and anaphylatoxin receptor-deficient mice. our data i ...201324035596
artemisinin analogue sm934 ameliorates murine experimental autoimmune encephalomyelitis through enhancing the expansion and functions of regulatory t cell.artemisinin analogue sm934 was previously reported to possess immunosuppressive properties. the aim of this study was to determine the effects and the underlying mechanisms of sm934 in murine experimental autoimmune encephalomyelitis (eae).201324009768
genome and transcriptome adaptation accompanying emergence of the definitive type 2 host-restricted salmonella enterica serovar typhimurium pathovar.salmonella enterica serovar typhimurium definitive type 2 (dt2) is host restricted to columba livia (rock or feral pigeon) but is also closely related to s. typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. dt2 isolates formed a distinct phylogenetic cluster within s. typhimurium based on whole-genome-sequence polymorphisms. comparative genome analysis of dt2 94-213 and s. typhimurium sl1344, dt104, and d23580 identified few differe ...201323982073
immune boosting explains regime-shifts in prevaccine-era pertussis dynamics.understanding the biological mechanisms underlying episodic outbreaks of infectious diseases is one of mathematical epidemiology's major goals. historic records are an invaluable source of information in this enterprise. pertussis (whooping cough) is a re-emerging infection whose intermittent bouts of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. it has been suggested that recent increases in pertussis incidence and shifts in the age-distr ...201323991047
highly polarized th17 cells induce eae via a t-bet independent mechanism.in the mog35-55 induced eae model, autoreactive th17 cells that accumulate in the central nervous system acquire th1 characteristics via a t-bet dependent mechanism. it remains to be determined whether th17 plasticity and encephalitogenicity are causally related to each other. here, we show that il-23 polarized t-bet(-/-) th17 cells are unimpaired in either activation or proliferation, and induce higher quantities of the chemokines rantes and cxcl2 than wt th17 cells. unlike their wt counterpart ...201323878008
human vaccines & immunotherapeutics: news.vaccinating boys against hpv to reduce cancer rates across the sexes: new melanoma vaccine contains natural product from marine sponges: impact of hib conjugate vaccines in developing countries: electronic health records to keep track of immunization status: pregnant women urged to get whooping cough vaccination: new nano-coating developed to preserve vaccines: alternative approach to creating a universal flu vaccine: new modular vaccine design: maps technology.201324051387
the roles of micrornas on tuberculosis infection: meaning or myth?the central proteins for protection against tuberculosis are attributed to interferon-γ, tumor necrosis factor-α, interleukin (il)-6 and il-1β, while il-10 primarily suppresses anti-mycobacterial responses. several studies found alteration of expression profile of genes involved in anti-mycobacterial responses in macrophages and natural killer (nk) cells from active and latent tuberculosis and from tuberculosis and healthy controls. this alteration of cellular composition might be regulated by m ...201324025365
plasma cell homeostasis: the effects of chronic antigen stimulation and inflammation.long-lived plasma cells (llpcs) that maintain humoral immunity to previously encountered ags occupy a compartment in the bone marrow (bm). the rules and mechanisms by which cells enter (and leave) this compartment are poorly understood. we looked at what happens to the llpc compartment and to plasma cell lifespan in general, in situations in which ag stimulation and/or inflammation persist. we find that chronic ag supply causes the generation of short-lived plasma cells in the local lymphoid org ...201323935195
structural basis of subtilase cytotoxin subab assembly.pathogenic strains of escherichia coli produce a number of toxins that belong to the ab5 toxin family, which comprise a catalytic a-subunit that induces cellular dysfunction and a b-pentamer that recognizes host glycans. although the molecular actions of many of the individual subunits of ab5 toxins are well understood, how they self-associate and the effect of this association on cytotoxicity are poorly understood. here we have solved the structure of the holo-subab toxin that, in contrast to o ...201323921389
overview of models, methods, and reagents developed for translational autoimmunity research in the common marmoset (callithrix jacchus).the common marmoset (callithrix jacchus) is a small-bodied neotropical primate and a useful preclinical animal model for translational research into autoimmune-mediated inflammatory diseases (aimid), such as rheumatoid arthritis (ra) and multiple sclerosis (ms). the animal model for ms established in marmosets has proven their value for exploratory research into (etio) pathogenic mechanisms and for the evaluation of new therapies that cannot be tested in lower species because of their specificit ...201323903050
asthma and risk of selective iga deficiency or common variable immunodeficiency: a population-based case-control study.to determine the association between a history of asthma and a diagnosis of selective iga deficiency (sigad)/common variable immunodeficiency (cvid).201323910409
the feoc protein leads to high cellular levels of the fe(ii) transporter feob by preventing ftsh protease regulation of feob in salmonella enterica.in the gammaproteobacteria, the feoa, feob, and feoc proteins constitute the feo system, which mediates ferrous iron [fe(ii)] import. of these feo proteins, feob is an inner membrane fe(ii) transporter that is aided by the small protein feoa. however, the role of another small protein, feoc, has remained unknown. here we report that the feoc protein is necessary for feob protein-mediated fe(ii) uptake in salmonella experiencing low levels of oxygen and iron. the feoc protein was found to directl ...201323708131
nucleotidyl cyclase activity of particulate guanylyl cyclase a: comparison with particulate guanylyl cyclases e and f, soluble guanylyl cyclase and bacterial adenylyl cyclases cyaa and edema factor.guanylyl cyclases (gcs) regulate many physiological processes by catalyzing the synthesis of the second messenger cgmp. the gc family consists of seven particulate gcs (pgcs) and a nitric oxide-activated soluble gc (sgc). rat sgc α1β1 possesses much broader substrate specificity than previously assumed. moreover, the exotoxins cyaa from bordetella pertussis and edema factor (ef) from bacillus anthracis possess nucleotidyl cyclase (nc) activity. pgc-a is a natriuretic peptide-activated homodimer ...201323922959
when is acute persistent cough in school-age children and adults whooping cough? a prospective case series study.pertussis is a vaccine modified disease in most age groups and hence subtle in its presentation. current diagnostic approaches require relatively invasive sampling.201323972198
pertussis: challenges today and for the future. 201323935481
acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study.newborns in need of extracorporeal membrane oxygenation (ecmo) support are at high risk of developing acute kidney injury (aki). aki may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. aki necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. we aimed to define systematically the incidence and clinical course of aki in critically ill neonates receiving ecmo support.201323883698
receptor polymorphism restricts contact-dependent growth inhibition to members of the same species.bacteria that express contact-dependent growth inhibition (cdi) systems outcompete siblings that lack immunity, suggesting that cdi mediates intercellular competition. to further explore the role of cdi in competition, we determined the target cell range of the cdiec93 system from escherichia coli ec93. the cdiaec93 effector protein recognizes the widely conserved bama protein as a receptor, yet e. coli ec93 does not inhibit other enterobacterial species. the predicted membrane topology of bama ...201323882017
histamine h(3) receptor integrates peripheral inflammatory signals in the neurogenic control of immune responses and autoimmune disease susceptibility.histamine h(3) receptor (hrh3/h(3)r) is primarily expressed by neurons in the central nervous system (cns) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor. previously, we identified an h(3)r-mediated central component in susceptibility to experimental allergic encephalomyelitis (eae), the principal autoimmune model of multiple sclerosis (ms), related to neurogenic control of blood brain barrier permeability and peripheral t cell effector responses. furthermore, we ...201323894272
the intracellular citrus huanglongbing bacterium, 'candidatus liberibacter asiaticus' encodes two novel autotransporters.proteins secreted by the type v secretion system (t5ss), known as autotransporters, are large extracellular virulence proteins localized to the bacterial poles. in this study, we characterized two novel autotransporter proteins of 'candidatus liberibacter asiaticus' (las), and redesignated them as lasai and lasaii in lieu of the previous names hyvi and hyvii. as a phloem-limited, intracellular bacterial pathogen, las has a significantly reduced genome and causes huanglongbing (hlb), a devastatin ...201323874813
the obstructive siblings: relapsing polychondritis without chondritis?progressive narrowing of the central airways due to diffuse inflammation is a potential life-threatening condition. a number of diseases have been described as possible causes. we present two siblings with severe central airway obstruction. despite considerable efforts we have not been able to match the clinical appearance of our patients with the diagnostic criteria of any of the disease entities known to cause this condition.201326029500
a comprehensive, model-based review of vaccine and repeat infection trials for filariasis.summary filarial worms cause highly morbid diseases such as elephantiasis and river blindness. since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. in this review, we have organized, to the be ...201323824365
identification of regions important for resistance and signalling within the antimicrobial peptide transporter bceab of bacillus subtilis.in the low-g+c-content gram-positive bacteria, resistance to antimicrobial peptides is often mediated by so-called resistance modules. these consist of a two-component system and an atp-binding cassette transporter and are characterized by an unusual mode of signal transduction where the transporter acts as a sensor of antimicrobial peptides, because the histidine kinase alone cannot detect the substrates directly. thus, the transporters fulfill a dual function as sensors and detoxification syst ...201323687272
garvicin a, a novel class iid bacteriocin from lactococcus garvieae that inhibits septum formation in l. garvieae strains.lactococcus garvieae 21881, isolated in a human clinical case, produces a novel class iid bacteriocin, garvicin a (gara), which is specifically active against other l. garvieae strains, including fish- and bovine-pathogenic isolates. purification from active supernatants, sequence analyses, and plasmid-curing experiments identified pgl5, one of the five plasmids found in l. garvieae [m. aguado-urda et al., plos one 7(6):e40119, 2012], as the coding plasmid for the structural gene of gara (lgna), ...201323666326
immunomodulatory activity of polysaccharides isolated from clerodendrum splendens: beneficial effects in experimental autoimmune encephalomyelitis.extracts of leaves from clerodendrum have been used for centuries to treat a variety of medicinal problems in tropical africa. however, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts.201323806004
perceptions of tetanus-diphteria-acellular pertussis (tdap) vaccination among korean women of childbearing age.the number of cases of pertussis reported has increased gradually in the last decade. pertussis vaccination is the most effective strategy for the prevention of infection. despite the fact that young infants are at the highest risk for pertussis, the rate of tetanus-diphtheria-acellular pertussis (tdap) vaccination is presumed to be very low among women of childbearing age in korea. the purpose of this study was to investigate the perceptions of women of childbearing age regarding tdap vaccinati ...201324265970
persistent inflammation in the cns during chronic eae despite local absence of il-17 production.experimental autoimmune encephalomyelitis (eae) is an artificially induced demyelination of the central nervous system (cns) that resembles multiple sclerosis in its clinical, histopathological, and immunological features. activated th1 and th17 cells are thought to be the main immunological players during eae development. this study was designed to evaluate peripheral and local contribution of il-17 to acute and chronic eae stages. c57bl/6 mice were immunized with mog plus complete freund's adj ...201323970813
calpain-mediated processing of adenylate cyclase toxin generates a cytosolic soluble catalytically active n-terminal domain.bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (act) is essential for establishment of the disease in the respiratory tract. act weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. up to now, it was believed that cell intoxication by act was a consequence of the accumulation of abnormally high levels of camp, generated exclusively beneath the host plasma membrane by the toxin n- ...201323840759
pkcβ phosphorylates pi3kγ to activate it and release it from gpcr control.all class i phosphoinositide 3-kinases (pi3ks) associate tightly with regulatory subunits through interactions that have been thought to be constitutive. pi3kγ is key to the regulation of immune cell responses activated by g protein-coupled receptors (gpcrs). remarkably we find that pkcβ phosphorylates ser582 in the helical domain of the pi3kγ catalytic subunit p110γ in response to clustering of the high-affinity ige receptor (fcεri) and/or store-operated ca²⁺- influx in mast cells. phosphorylat ...201323824069
seroprevalence of antibodies against measles, rubella, mumps, varicella-zoster, and b. pertussis in young adults of madrid, spain.in recent years, there has been an increase in the number of cases of certain immunopreventable diseases in our country. a high proportion of these have been recorded among the young adult population. the aim of this study was to determine the seroprevalence of antibodies against immunopreventable diseases with the greatest health impacts on the young adult population (19-39 y of age) in madrid. we collected a total of 1,153 serum samples from healthy volunteers undergoing routine medical visits ...201323793571
cd8(+) t cells are required for glatiramer acetate therapy in autoimmune demyelinating disease.the exact mechanism of glatiramer acetate (ga, copaxone®), an fda-approved immunomodulatory therapy for multiple sclerosis (ms), remains unclear after decades of research. previously, we have shown that ga therapy of ms induces cd8(+) t cell responses that can potentially suppress pathogenic cd4(+) t cell responses. using a murine model of ms, experimental autoimmune encephalomyelitis (eae), we now demonstrate that cd8(+) t cells are necessary in mediating the therapeutic effects of ga. further, ...201323805274
lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia.streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. given the critical role of dendritic cells (dcs) in regulating and modulating the immune response to pathogens, we investigated here the role of dcs in s. pneumoniae lung infections. using a well-established transgenic mouse line which allows the conditional transient depletion of dcs, we showed that ablation of dcs resulted in enhanced resistance to intranasal challenge with s. pneumoniae. dcs-depleted mice exhibited ...201323802100
persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy.respiratory syncytial virus (rsv) infection in infancy is associated with subsequent recurrent wheezing.201323782528
the composition of microbiome in larynx and the throat biodiversity between laryngeal squamous cell carcinoma patients and control population.the throat is an ecological assemblage involved human cells and microbiota, and the colonizing bacteria are important factors in balancing this environment. however, this bacterial community profile has thus been poorly investigated. the purpose of this study was to investigate the microbial biology of the larynx and to analyze the throat biodiversity in laryngeal carcinoma patients compared to a control population in a case-control study. barcoded pyrosequencing analysis of the 16s rrna gene wa ...201323824228
functional selectivity of 6'-guanidinonaltrindole (6'-gnti) at κ-opioid receptors in striatal neurons.there is considerable evidence to suggest that drug actions at the κ-opioid receptor (kor) may represent a means to control pain perception and modulate reward thresholds. as a g protein-coupled receptor (gpcr), the activation of kor promotes gαi/o protein coupling and the recruitment of β-arrestins. it has become increasingly evident that gpcrs can transduce signals that originate independently via g protein pathways and β-arrestin pathways; the ligand-dependent bifurcation of such signaling is ...201323775075
increased camp in monocytes augments notch signaling mechanisms by elevating rbp-j and transducin-like enhancer of split (tle).in cells of the innate immune system, pathological increases in intracellular camp attenuate immune responses and contribute to infections by bacteria such as bacillus anthracis. in this work, camp from b. anthracis edema toxin (et) is found to activate the notch signaling pathway in both mouse macrophages and human monocytes. et as well as a cell-permeable activator of pka induce notch target genes (hes1, hey1, il2ra, and il7r) and are able to significantly enhance the induction of these notch ...201323775085
rhabdomyolysis associated with parainfluenza virus.influenza virus is the most frequently reported viral cause of rhabdomyolysis. a 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.201323840985
genome-wide gene expression analysis of bordetella pertussis isolates associated with a resurgence in pertussis: elucidation of factors involved in the increased fitness of epidemic strains.bordetella pertussis (b. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. a recent resurgence pertussis is associated with the expansion of b. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxp3 in place of resident ptxp1 strains. the recent expansion of ptxp3 strains s ...201323776625
staphylococcus aureus lukab cytotoxin kills human neutrophils by targeting the cd11b subunit of the integrin mac-1.staphylococcus aureus causes diseases ranging from superficial wound infections to more invasive manifestations like osteomyelitis and endocarditis. the evasion of host phagocytes recruited to the site of infection is essential to the success of s. aureus as a pathogen. a single s. aureus strain can produce up to five different bicomponent pore-forming leukotoxins that lyse immune cells by forming pores in the cellular plasma membrane. although these leukotoxins have been considered redundant du ...201323754403
stat3 activates mir-155 in th17 cells and acts in concert to promote experimental autoimmune uveitis.microrna-155 (mir-155) and stat3 are implicated in uveitis and pathogenic mechanisms of cns autoimmune diseases. in our study, we used mir-155(-/-) mice and mice with targeted stat3 deletion in t cells (cd4-stat3ko) to investigate roles of mir-155 and stat3 in the development of experimental autoimmune uveitis (eau), a mouse model of human uveitis.201323674757
kinetics of extracellular atp in mastoparan 7-activated human erythrocytes.the peptide mastoparan 7 (mst7) stimulated atp release in human erythrocytes. we explored intra- and extracellular processes governing the time-dependent accumulation of extracellular atp (i.e., atpe kinetics).201323742824
spontaneous regression of metastatic melanoma after inoculation with tetanus-diphtheria-pertussis vaccine.spontaneous regression of metastatic melanoma is an exceedingly rare event, with only 76 well-documented cases in the literature since 1866. here, we present the case of a patient who developed metastatic melanoma despite interferon therapy and who then achieved spontaneous regression shortly after a reaction to tetanus-diphtheria-pertussis vaccination. a common theme among these cases is the development of febrile illness before remission of the malignant disease. a brief overview of proposed m ...201323737697
rip1-driven autoinflammation targets il-1α independently of inflammasomes and rip3.the protein-tyrosine phosphatase shp-1 has critical roles in immune signalling, but how mutations in shp-1 cause inflammatory disease in humans remains poorly defined. mice homozygous for the tyr208asn amino acid substitution in the carboxy terminus of shp-1 (referred to as ptpn6(spin) mice) spontaneously develop a severe inflammatory syndrome that resembles neutrophilic dermatosis in humans and is characterized by persistent footpad swelling and suppurative inflammation. here we report that rec ...201323708968
staphylococcus aureus-induced g2/m phase transition delay in host epithelial cells increases bacterial infective efficiency.staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. the epithelial surface is its principal site of colonization and infection. in this work, we investigated the cytopathic effect of s. aureus strains from human and animal origins and their ability to affect the host cell cycle in human hela and bovine mac-t epithelial cell lines. s. aureus invasion slowed down cell proliferation and induc ...201323717407
bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence.serine proteases exist in eukaryotic and prokaryotic organisms and have emerged during evolution as the most abundant and functionally diverse group. in gram-negative bacteria, there is a growing family of high molecular weight serine proteases secreted to the external milieu by a fascinating and widely employed bacterial secretion mechanism, known as the autotransporter pathway. they were initially found in neisseria, shigella, and pathogenic escherichia coli, but have now also been identified ...201323689588
bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence.serine proteases exist in eukaryotic and prokaryotic organisms and have emerged during evolution as the most abundant and functionally diverse group. in gram-negative bacteria, there is a growing family of high molecular weight serine proteases secreted to the external milieu by a fascinating and widely employed bacterial secretion mechanism, known as the autotransporter pathway. they were initially found in neisseria, shigella, and pathogenic escherichia coli, but have now also been identified ...201323689588
deciphering the impacts of vaccination and immunity on pertussis epidemiology in thailand.pertussis is a highly infectious respiratory disease that is currently responsible for nearly 300,000 annual deaths worldwide, primarily in infants in developing countries. despite sustained high vaccine uptake, a resurgence in pertussis incidence has been reported in a number of countries. this resurgence has led to critical questions regarding the transmission impacts of vaccination and pertussis immunology. we analyzed pertussis incidence in thailand--both age-stratified and longitudinal aggr ...201323690587
antigen-specific effector cd4 t lymphocytes school lamina propria dendritic cells to transfer innate tolerance.dendritic cells (dcs) have been shown to play a major role in oral tolerance, and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive regulatory t cells. in this study, we demonstrate that upon oral administration of ag, lamina propia (lp) dcs engage specific t cells and acquire a novel mechanism by which they transfer tolerance against diverse t cell specificities. indeed, when ig-myelin oligodendrocyte glycoprotein (mog) carryin ...201323686493
membrane association and destabilization by aggregatibacter actinomycetemcomitans leukotoxin requires changes in secondary structures.aggregatibacter actinomycetemcomitans is a common inhabitant of the upper aerodigestive tract of humans and non-human primates and is associated with disseminated infections, including lung and brain abscesses, pediatric infective endocarditis, and localized aggressive periodontitis. aggregatibacter actinomycetemcomitans secretes a repeats-in-toxin protein, leukotoxin, which exclusively kills lymphocyte function-associated antigen-1-bearing cells. the toxin's pathological mechanism is not fully ...201323678967
t helper 17-associated cytokines are produced during antigen-specific inflammation in the mammary gland.infectious mastitis cuts down milk production profitability and is a major animal welfare problem. bacteria-induced inflammation in the mammary gland (mg) is driven by innate immunity, but adaptive immunity can modulate the innate response. several studies have shown that it is possible to elicit inflammation in the mg by sensitization to an antigen subsequently infused into the lumen of the gland. the objective of our study was to characterize the inflammation triggered in the mg of cows sensit ...201323696826
notch ligand delta-like 4-pretreated dendritic cells alleviate allergic airway responses by enhancing il-10 production.the notch pathway plays a role in the processes of cell proliferation, differentiation, and apoptosis, which affect the development and function of various organs. dendritic cells (dcs), as professional antigen-presenting cells (apcs), induce t cell activation and promote t cell differentiation by antigen stimulation. research has shown that notch ligand delta-like 4 (dll4) in apcs is associated with stimulation of a th1-type response. however, the regulatory roles of dll4 in the activation and ...201323696838
th17 cell based vaccines in mucosal immunity.vaccination is proven to be effective in controlling many infections including small pox, influenza and hepatitis, but strain-specific factors may limit vaccine efficacy. all of these vaccines work through the generation of neutralizing antibodies but for some pathogens there may be roles for serotype-independent immunity. recently several groups using murine vaccine models have shown that induced t helper cell responses including th17 responses have shown the potential for cd4+ t-cell dependent ...201323669353
detection of bordetella pertussis from clinical samples by culture and end-point pcr in malaysian patients.pertussis or whooping cough is a highly infectious respiratory disease caused by bordetella pertussis. in vaccinating countries, infants, adolescents, and adults are relevant patients groups. a total of 707 clinical specimens were received from major hospitals in malaysia in year 2011. these specimens were cultured on regan-lowe charcoal agar and subjected to end-point pcr, which amplified the repetitive insertion sequence is481 and pertussis toxin promoter gene. out of these specimens, 275 were ...201326904725
recombinant outer membrane vesicles carrying chlamydia muridarum htra induce antibodies that neutralize chlamydial infection in vitro.outer membrane vesicles (omvs) are spheroid particles released by all gram-negative bacteria as a result of the budding out of the outer membrane. since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, omvs are being utilized as vaccines, some of which commercially available. recently, methods for manipulating the protein content of omvs have been proposed, thus making omvs a promising platform for recombinant, multivalent vaccines develop ...201324009891
critical pertussis in a young infant requiring mechanical ventilation.pertussis may likely be misdiagnosed in its initial or catarrhal phase as a common respiratory infection. the earlier diagnosis of pertussis really depends on the capability of the medical professional especially in the first line public health services. the lack of awareness in diagnosis of severe pertussis as one of the causes of severe respiratory problems may likely misdiagnose pertussis as respiratory failure or even septic shock. in fact, pertussis may manifest as a critical pertussis whic ...201323738154
critical pertussis illness in children: a multicenter prospective cohort study.pertussis persists in the united states despite high immunization rates. this report characterizes the presentation and acute course of critical pertussis by quantifying demographic data, laboratory findings, clinical complications, and critical care therapies among children requiring admission to the picu.201323548960
quantification of the adenylate cyclase toxin of bordetella pertussis in vitro and during respiratory infection.whooping cough results from infection of the respiratory tract with bordetella pertussis, and the secreted adenylate cyclase toxin (act) is essential for the bacterium to establish infection. despite extensive study of the mechanism of act cytotoxicity and its effects over a range of concentrations in vitro, act has not been observed or quantified in vivo, and thus the concentration of act at the site of infection is unknown. the recently developed baboon model of infection mimics the prolonged ...201323429530
comparison of the biofire filmarray rp, genmark esensor rvp, luminex xtag rvpv1, and luminex xtag rvp fast multiplex assays for detection of respiratory viruses.there are several u.s. fda-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. this study compares four multiplex panels, the biofire diagnostics filmarray rp (respiratory panel), the genmark dx esensor rvp (respiratory viral panel), the luminex xtag rvpv1, and the luminex xtag rvp fast. three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. the overall sensitiv ...201323486707
innate immunity and its regulation by mast cells.mast cells (mcs), which are granulated tissue-resident cells of hematopoietic lineage, constitute a major sensory arm of the innate immune system. in this review we discuss the evidence supporting the dual role of mcs, both as sentinels for invading pathogens and as regulatory cells throughout the course of acute inflammation, from its initiation to resolution. this versatility is dependent on the ability of mcs to detect pathogens and danger signals and release a unique panel of mediators to pr ...201323606723
epithelial cell proliferation arrest induced by lactate and acetate from lactobacillus casei and bifidobacterium breve.in an attempt to identify and characterize how symbiotic bacteria of the gut microbiota affect the molecular and cellular mechanisms of epithelial homeostasis, intestinal epithelial cells were co-cultured with either lactobacillus or bifidobacterium as bona fide symbionts to examine potential gene modulations. in addition to genes involved in the innate immune response, genes encoding check-point molecules controlling the cell cycle were among the most modulated in the course of these interactio ...201323646174
genomics and outbreak investigation: from sequence to consequence.outbreaks of infection can be devastating for individuals and societies. in this review, we examine the applications of new high-throughput sequencing approaches to the identification and characterization of outbreaks, focusing on the application of whole-genome sequencing (wgs) to outbreaks of bacterial infection. we describe traditional epidemiological analysis and show how wgs can be informative at multiple steps in outbreak investigation, as evidenced by many recent studies. we conclude that ...201323673226
gene therapy of multiple sclerosis using interferon β-secreting human bone marrow mesenchymal stem cells.interferon-beta (ifn- β ), a well-established standard treatment for multiple sclerosis (ms), has proved to exhibit clinical efficacy. in this study, we first evaluated the therapeutic effects for ms using human bone marrow-derived mesenchymal stem cells (hbm-mscs) as delivery vehicles with lesion-targeting capability and ifn- β as therapeutic gene. we also engineered hbm-mscs to secret ifn- β (mscs-ifn β ) via adenoviral transduction and confirmed the secretory capacity of mscs-ifn β by an elis ...201323710456
unchanged distribution density of anionic sites on the glomerular wall in rats with active heymann nephritis.in various kinds of glomerulonephritis, alteration of anionic charge on the glomerular basement membrane (gbm) and podocytes has been controversial for more than decade. to elucidate the relation between glomerular protein leakage and anionic sites on the glomerular wall, we examined the distribution of anionic sites on the gbm and podocytes of rats with active heymann nephritis (ahn). urinalysis for protein levels was conducted, and the kidneys were examined using electron microscopic cytochemi ...201323723563
mathematical model approach to describe tumour response in mice after vaccine administration and its applicability to immune-stimulatory cytokine-based strategies.immunotherapy is a growing therapeutic strategy in oncology based on the stimulation of innate and adaptive immune systems to induce the death of tumour cells. in this paper, we have developed a population semi-mechanistic model able to characterize the mechanisms implied in tumour growth dynamic after the administration of cyaa-e7, a vaccine able to target antigen to dendritic cells, thus triggering a potent immune response. the mathematical model developed presented the following main componen ...201323605806
the actinobacterial transcription factor rbpa binds to the principal sigma subunit of rna polymerase.rbpa is a small non-dna-binding transcription factor that associates with rna polymerase holoenzyme and stimulates transcription in actinobacteria, including streptomyces coelicolor and mycobacterium tuberculosis. rbpa seems to show specificity for the vegetative form of rna polymerase as opposed to alternative forms of the enzyme. here, we explain the basis of this specificity by showing that rbpa binds directly to the principal σ subunit in these organisms, but not to more diverged alternative ...201323605043
virus-induced cd8+ t cells accelerate the onset of experimental autoimmune encephalomyelitis: implications for how viral infections might trigger multiple sclerosis exacerbations.viral infections can exacerbate multiple sclerosis (ms) through poorly defined mechanisms. we developed an experimental system whereby infection with an asymptomatic neurotropic alphavirus caused a transient acceleration of experimental autoimmune encephalomyelitis (eae) without altering the expansion or differentiation of autoreactive cd4+ t cells. instead, this effect on the clinical course of eae depended on cd8+ t cells that neither participate in viral clearance nor induce neuropathology in ...201323602715
a novel adenovirus species associated with an acute respiratory outbreak in a baboon colony and evidence of coincident human infection.adenoviruses (advs) are dna viruses that infect many vertebrate hosts, including humans and nonhuman primates. here we identify a novel adv species, provisionally named "simian adenovirus c (sadv-c)," associated with a 1997 outbreak of acute respiratory illness in captive baboons (4 of 9) at a primate research facility in texas. none of the six advs recovered from baboons (baadvs) during the outbreak, including the two baboons who died from pneumonia, were typeable. since clinical samples from t ...201323592261
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