Publications

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intracellular disassembly and activity of pertussis toxin require interaction with atp.the active subunit (s1) of pertussis toxin (pt), a major virulence factor of bordetella pertussis, adp-ribosylates gi proteins in the mammalian cell cytosol to inhibit gpcr signaling. the intracellular pathway of pt includes endocytosis and retrograde transport to the trans-golgi network (tgn) and endoplasmic reticulum (er). subsequent translocation of s1 to the cytosol is presumably preceded by dissociation from the holotoxin. in vitro, such dissociation is stimulated by interaction of pt with ...201627369899
burden and outcomes of severe pertussis infection in critically ill infants.despite world health organization endorsed immunization schedules, bordetella pertussis continues to cause severe infections, predominantly in infants. there is a lack of data on the frequency and outcome of severe pertussis infections in infants requiring icu admission. we aimed to describe admission rates, severity, mortality, and costs of pertussis infections in critically ill infants.201627362854
pertussis: where did we go wrong and what can we do about it?pertussis or whooping cough, mainly caused by the gram-negative coccobacillus bordetella pertussis, is a severe respiratory disease that can by life-threatening especially in young infants. it has recently made a spectacular come-back in high vaccination-coverage countries, such as the us, australia and many european countries. although a trend towards increased pertussis incidence was already visible before the switch from whole-cell to acellular vaccines, it was really since the introduction o ...201627161992
characterization of the immune response induced by pertussis omvs-based vaccine.for the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wp) or after infection should be used as a reference point. we have recently identified a vaccine candidate based on outer membrane vesicles (omvs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. here we characterized omvs-mediated immun ...201627151884
direct molecular typing of bordetella pertussis from nasopharyngeal specimens in china in 2012-2013.data on the molecular epidemiology of bordetella pertussis are limited in developing countries where whole-cell pertussis vaccines (wcvs) have been used. the aim of this study was to determine the genotypes of circulating b. pertussis in china by direct molecular typing of clinical specimens. dna extracts of 122 nasopharyngeal swabs (nps) positive for b. pertussis by polymerase chain reaction (pcr) (targeting is481 and ptx-pr) from 2012 to 2013 were used for typing using the multiple-locus varia ...201627146879
purification design and practice for pertactin, the third component of acellular pertussis vaccine, from bordetella pertussis.development of acellular pertussis vaccine (apv) requires purification of several components from bordetella pertussis. while the components pertussis toxin (pt) and filamentous hemagglutinin (fha) have been successfully purified, the third component, pertactin, proves to be a difficult target due to its very low concentration. in order to solve its purification problem, we performed the surface potential analysis with grasp2 program. the results demonstrated that there are two major charge patc ...201627302339
calcium-driven folding of rtx domain β-rolls ratchets translocation of rtx proteins through type i secretion ducts.calcium-binding rtx proteins are equipped with c-terminal secretion signals and translocate from the ca(2+)-depleted cytosol of gram-negative bacteria directly into the ca(2+)-rich external milieu, passing through the "channel-tunnel" ducts of type i secretion systems (t1sss). using bordetella pertussis adenylate cyclase toxin, we solved the structure of an essential c-terminal assembly that caps the rtx domains of rtx family leukotoxins. this is shown to scaffold directional ca(2+)-dependent fo ...201627058787
pertussis: microbiology, disease, treatment, and prevention.pertussis is a severe respiratory infection caused by bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of b. pertussis strains. during the past 20 years, the scientific community has recognized pertussis ...201627029594
epidemiological and economic effects of priming with the whole-cell bordetella pertussis vaccine.current acellular pertussis vaccines may not protect against transmission of bordetella pertussis.201627018830
a novel igm-capture enzyme-linked immunosorbent assay using recombinant vag8 fusion protein for the accurate and early diagnosis of bordetella pertussis infection.an elisa that measures anti-pt igg antibody has been used widely for the serodiagnosis of pertussis; however, the igg-based elisa is inadequate for patients during the acute phase of the disease because of the slow response of anti-pt igg antibodies. to solve this problem, we developed a novel igm-capture elisa that measures serum anti-bordetella pertussis vag8 igm levels for the accurate and early diagnosis of pertussis. first, we confirmed that vag8 was highly expressed in all b. pertussis iso ...201626996337
effect of different detoxification procedures on the residual pertussis toxin activities in vaccines.pertussis toxin (ptx) is a major virulence factor produced by bordetella pertussis and its detoxified form is one of the major protective antigens in vaccines against whooping cough. ideally, ptx in the vaccine should be completely detoxified while still preserving immunogenicity. however, this may not always be the case. due to multilevel reaction mechanisms of chemical detoxification that act on different molecular sites and with different production processes, it is difficult to define a mole ...201626973066
complete genome sequences of four bordetella pertussis vaccine reference strains from serum institute of india.serum institute of india is among the world's largest vaccine producers. here, we report the complete genome sequences for four bordetella pertussis strains used by serum institute of india in the production of whole-cell pertussis vaccines.201628007855
impact and influence of the natural vibrio-squid symbiosis in understanding bacterial-animal interactions.animals are colonized by bacteria, and in many cases partners have co-evolved to perform mutually beneficial functions. an exciting and ongoing legacy of the past decade has been an expansion of technology to enable study of natural associations in situ/in vivo. as a result, more symbioses are being examined, and additional details are being revealed for well-studied systems with a focus on the interactions between partners in the native context. with this framing, we review recent literature fr ...201628018314
interaction with adenylate cyclase toxin from bordetella pertussis affects the metal binding properties of calmodulin.adenylate cyclase toxin domain (cyaa-acd) is a calmodulin (cam)-dependent adenylate cyclase involved in bordetella pertussis pathogenesis. calcium (ca(2+)) and magnesium (mg(2+)) concentrations impact cam-dependent cyaa-acd activation, but the structural mechanisms remain unclear. in this study, nmr, dynamic light scattering, and native page were used to probe mg(2+)-induced transitions in cam's conformation in the presence of cyaa-acd. mg(2+) binding was localized to sites i and ii, while sites ...201628097085
interaction with adenylate cyclase toxin from bordetella pertussis affects the metal binding properties of calmodulin.adenylate cyclase toxin domain (cyaa-acd) is a calmodulin (cam)-dependent adenylate cyclase involved in bordetella pertussis pathogenesis. calcium (ca(2+)) and magnesium (mg(2+)) concentrations impact cam-dependent cyaa-acd activation, but the structural mechanisms remain unclear. in this study, nmr, dynamic light scattering, and native page were used to probe mg(2+)-induced transitions in cam's conformation in the presence of cyaa-acd. mg(2+) binding was localized to sites i and ii, while sites ...201628097085
epidemiology of pertussis among young pakistani infants: a community-based prospective surveillance study.pertussis remains a cause of morbidity and mortality among young infants. there are limited data on the pertussis disease burden in this age group from low- and lower-middle-income countries, including in south asia.201627838667
forecasting epidemiological consequences of maternal immunization.the increase in the incidence of whooping cough (pertussis) in many countries with high vaccination coverage is alarming. maternal pertussis immunization has been proposed as an effective means of protecting newborns during the interval between birth and the first routine dose. however, there are concerns regarding potential interference between maternal antibodies and the immune response elicited by the routine schedule, with possible long-term population-level effects.201627838674
cysteine-mediated gene expression and characterization of the cmbr regulon in streptococcus pneumoniae.in this study, we investigated the transcriptomic response of streptococcus pneumoniae d39 to cysteine. transcriptome comparison of the d39 wild-type grown at a restricted concentration of cysteine (0.03 mm) to one grown at a high concentration of cysteine (50 mm) in chemically-defined medium (cdm) revealed elevated expression of various genes/operons, i.e., spd-0150, metq, spd-0431, metef, gsht, spd-0618, fhs, tcyb, metb-csd, meta, spd-1898, yvde, and cysk, likely to be involved in the transpor ...201627990139
fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (aps) triggered by respiratory syncytial virus (rsv) infection: a case report and review of the literature.we present a unique and informative instance of respiratory syncytial virus (rsv) infection associated with antiphospholipid syndrome (aps), and discuss this case in the context of the literature addressing the immunopathogenesis of aps associated with diverse infections. we describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. punch biopsy of th ...201627920986
fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (aps) triggered by respiratory syncytial virus (rsv) infection: a case report and review of the literature.we present a unique and informative instance of respiratory syncytial virus (rsv) infection associated with antiphospholipid syndrome (aps), and discuss this case in the context of the literature addressing the immunopathogenesis of aps associated with diverse infections. we describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. punch biopsy of th ...201627920986
a parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of type 1 diabetes and multiple sclerosis.helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. fhhdm-1, a 68-mer peptide secreted by the helminth parasite fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. unexpectedly, fhhdm-1 treatment did not affect the proliferation of auto-antigen specific t cells or t ...201627883079
pertussis in young infants throughout the world.in typical pertussis in young infants, the child will appear deceptively well; he or she will have coryza, sneezing, and a mild cough. there is no fever. this progresses to gagging, gasping, eye bulging, bradycardia, cyanosis, and vomiting. there is leukocytosis with lymphocytosis and apneic episodes. deaths relate to leukocytosis, pulmonary hypertension, and pneumonia. the source of pertussis in young infants is most often a family member with cough illness that is not recognized as pertussis. ...201627838663
pertussis-associated pneumonia in infants and children from low- and middle-income countries participating in the perch study.few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.201627838672
the burden of pertussis hospitalization in hiv-exposed and hiv-unexposed south african infants.there are limited data on pertussis in african children, including among human immunodeficiency virus (hiv)-exposed infants. we conducted population-based hospital surveillance to determine the incidence and clinical presentation of bordetella pertussis-associated hospitalization in perinatal hiv-exposed and -unexposed infants.201627838669
concentrations of immunoglobulin g antibodies against pertussis toxin does not decrease over a long period of time in japan.objective adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. while a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (elisa) with the pertussis toxin antigen. various cut-off values for the anti-pertussis toxin igg (pt-igg) ...201627853066
factors influencing the spread of pertussis in households: a prospective study, catalonia and navarre, spain, 2012 to 2013.we aimed to investigate transmission rates of pertussis in household contacts of cases and factors associated with transmission. a prospective epidemiological study was conducted in 2012 and 2013 to determine the incidence of pertussis among household contacts of reported cases in catalonia and navarre, spain. an epidemiological survey was completed for each case and contact, who were followed for 28 days to determine the source of infection (primary case) and detect the occurrence of secondary ...201627918260
gm-csf-producing th cells in rats sensitive and resistant to experimental autoimmune encephalomyelitis.given that granulocyte macrophage colony-stimulating factor (gm-csf) is identified as the key factor to endow auto-reactive th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (eae) models, the frequency and phenotype of gm-csf-producing (gm-csf+) th cells in draining lymph nodes (dlns) and spinal cord (sc) of albino oxford (ao) and dark agouti (da) rats immunized for eae were examined. the generation of neuroantigen-specific gm-csf+ th lymphocyte ...201627832210
perspectives for therapeutic hpv vaccine development.human papillomavirus (hpv) infections and associated diseases remain a serious burden worldwide. it is now clear that hpv serves as the etiological factor and biologic carcinogen for hpv-associated lesions and cancers. although preventative hpv vaccines are available, these vaccines do not induce strong therapeutic effects against established hpv infections and lesions. these concerns create a critical need for the development of therapeutic strategies, such as vaccines, to treat these existing ...201627809842
draft genome sequence of a novel luteimonas sp. strain from coral mucus, hawai'i.luteimonas sp. strain jm171 was cultivated from mucus collected around the coral porites lobata the jm171 draft genome of 2,992,353 bp contains 2,672 protein-coding open reading frames, 45 trna coding regions, and encodes a putative globin-coupled diguanylate cyclase, jmgreg.201627811107
identification of a two-component class iib bacteriocin in streptococcus pyogenes by recombinase-based in vivo expression technology.streptococcus pyogenes is a globally prominent bacterial pathogen that exhibits strict tropism for the human host, yet bacterial factors responsible for the ability of s. pyogenes to compete within this limited biological niche are not well understood. using an engineered recombinase-based in vivo expression technology (rivet) system, we identified an in vivo-induced promoter region upstream of a predicted class iib bacteriocin system in the m18 serotype s. pyogenes strain mgas8232. this promote ...201627808235
tolerance checkpoint bypass permits emergence of pathogenic t cells to neuromyelitis optica autoantigen aquaporin-4.aquaporin-4 (aqp4)-specific t cells are expanded in neuromyelitis optica (nmo) patients and exhibit th17 polarization. however, their pathogenic role in cns autoimmune inflammatory disease is unclear. although multiple aqp4 t-cell epitopes have been identified in wt c57bl/6 mice, we observed that neither immunization with those determinants nor transfer of donor t cells targeting them caused cns autoimmune disease in recipient mice. in contrast, robust proliferation was observed following immuni ...201627940915
actin activates pseudomonas aeruginosa exoy nucleotidyl cyclase toxin and exoy-like effector domains from martx toxins.the nucleotidyl cyclase toxin exoy is one of the virulence factors injected by the pseudomonas aeruginosa type iii secretion system into host cells. inside cells, it is activated by an unknown eukaryotic cofactor to synthesize various cyclic nucleotide monophosphates. exoy-like adenylate cyclases are also found in multifunctional-autoprocessing repeats-in-toxin (martx) toxins produced by various gram-negative pathogens. here we demonstrate that filamentous actin (f-actin) is the hitherto unknown ...201627917880
seroprevalence of bordetella pertussis specific immunoglobulin g antibody levels among asymptomatic individuals aged 4 to 24 years: a descriptive cross sectional study from sri lanka.in sri lanka pertussis continues to circulate in the community and cases among adolescents and adults have been reported despite 95% coverage of the four dose pertussis vaccination during early childhood. waning of immunity following natural infection or immunization may contribute to the persistent circulation. an adolescent booster dose is not included in the national immunization schedule of sri lanka, although this is routine practice in many countries. therefore information on immunity to p ...201627905894
influence of population demography and immunization history on the impact of an antenatal pertussis program.antenatal pertussis vaccination is being considered as a means to reduce the burden of infant pertussis in low- and middle-income countries (lmics), but its likely impact in such settings is yet to be quantified.201627838675
pertussis incidence by time, province and age group in iran, 2006-2011. 201628028509
chronic cough in korean adults: a literature review on common comorbidity.chronic cough is a significant medical condition with high prevalence and a strong negative impact on the quality of life. cough hypersensitivity is thought to underlie chronic cough, with several environmental and host factors interacting to cause neuronal sensitization and chronicity. comorbid conditions affecting cough reflex pathways, such as upper airway diseases, asthma, and gastroesophageal reflux, play important roles in chronic cough. however, their prevalence may vary in patients livin ...201627803879
noninvasive recognition and biomarkers of early allergic asthma in cats using multivariate statistical analysis of nmr spectra of exhaled breath condensate.asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. we sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using nmr spectra of exhaled breath condensate (ebc). statistical pattern recognition was improved considerably by preprocessing the spectra with probabilistic quotient normalization and glog transformation. classification of the 106 preprocessed spectra by principal component analysis and partial ...201627764146
induction of gut regulatory cd39(+) t cells by teriflunomide protects against eae.to determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (galt) immune responses functionally.201627766282
epidemiology of pertussis in two ibero-american countries with different vaccination policies: lessons derived from different surveillance systems.pertussis is a re-emerging disease worldwide despite its high vaccination coverage. european and latin-american countries have used different surveillance and vaccination policies against pertussis. we compared the epidemiology of this disease in two ibero-american countries with different vaccination and surveillance policies.201627876021
an anti-tnf-α antibody mimetic to treat ocular inflammation.infliximab is an antibody that neutralizes tnf-α and is used principally by systemic administration to treat many inflammatory disorders. we prepared the antibody mimetic fab-peg-fab (fpfinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. fpfinfliximab was designed to address side effects caused by antibody degradation and the presence of the fc region. surface plasmon resonance analysis indicated that i ...201627874029
in vitro activity of solithromycin against bordetella pertussis, an emerging respiratory pathogen.there has been an increase in the number of pertussis cases reported since the introduction of the acellular pertussis vaccine. while children that present with pertussis have a characteristic whooping cough, adults can simply have a persistent, nonspecific cough and remain undiagnosed. macrolide antibiotics, such as azithromycin, are the currently recommended treatment for pertussis. solithromycin is a new macrolide and the first fluoroketolide with broad activity against a wide spectrum of bac ...201627620481
complete genome sequences of four different bordetella sp. isolates causing human respiratory infections.species of the genus bordetella associate with various animal hosts, frequently causing respiratory disease. bordetella pertussis is the primary agent of whooping cough and other bordetella species can cause similar cough illness. here, we report four complete genome sequences from isolates of different bordetella species recovered from human respiratory infections.201627795250
immunological signatures after bordetella pertussis infection demonstrate importance of pulmonary innate immune cells.effective immunity against bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. we applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotect ...201627711188
bordetella pertussis infection in south african hiv-infected and hiv-uninfected mother-infant dyads: a longitudinal cohort study.there is a paucity of data regarding the burden of bordetella pertussis in african women and young infants, and particularly the impact of maternal human immunodeficiency virus (hiv) infection thereon. we performed a retrospective analysis of respiratory illness samples from longitudinal cohorts of hiv-uninfected and hiv-infected women and their infants to evaluate the burden of pertussis illness in a black-african community.201627838670
the importance of persistence. 201627838662
a new socioeconomic status measure for vaccine research in children using individual housing data: a population-based case-control study.we recently developed houses, an individual housing-based socioeconomic status (ses) measurement for health disparities research. we assessed whether houses was associated with risk of pertussis and pertussis vaccine up-to-date status in children.201627655468
complete genome sequences of bordetella pertussis vaccine reference strains 134 and 10536.vaccine formulations and vaccination programs against whooping cough (pertussis) vary worldwide. here, we report the complete genome sequences of two divergent bordetella pertussis reference strains used in the production of pertussis vaccines.201627635001
complete genome sequence of bordetella pertussis strain va-190 isolated from a vaccinated 10-year-old patient with whooping cough.the number of cases of pertussis has increased in the united states despite vaccination. we present the genome of an isolate of bordetella pertussis from a vaccinated patient from virginia. the genome was sequenced by long-read methodology and compared to that of a clinical isolate used for laboratory studies, d420.201627634997
a novel high-throughput assay to quantify the vaccine-induced inhibition of bordetella pertussis adhesion to airway epithelia.pertussis or whooping cough is an acute respiratory illness caused by the gram-negative pathogen bordetella pertussis. despite high vaccination coverage whooping cough is currently re-emerging in many developed countries. although the causes of pertussis resurgence are matter of debate, emerging evidences suggest that acellular vaccines efficiently protect against the hallmark symptoms of pertussis disease but fail to prevent colonization. this presumably impacts on increased risk of bacterial t ...201627633511
specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone.there are various autoimmunogenic antigens (ais) in testicular germ cells (tgcs) recognized as foreign by the body's immune system. however, there is little information of tgc-specific ais being available. the aim of this study is to identify tgc-specific ais. we have previously established that immunization using viable syngeneic tgc can also induce murine experimental autoimmune orchitis (eao) without using any adjuvant. this study is to identify tgc-specific ais by tgc liquid chromatography-t ...201627752123
hospital admissions for lower respiratory tract infections among infants in the canadian arctic: a cohort study.it is unknown whether this burden of disease of lower respiratory tract infections is comparable across the canadian arctic. the objectives of this surveillance study were to compare the rates of hospital admission for lower respiratory tract infection and the severity of infection across arctic canada, and to describe the responsible viruses.201628018874
pertussis toxin exploits host cell signaling pathways induced by meningitis-causing e. coli k1-rs218 and enhances adherence of monocytic thp-1 cells to human cerebral endothelial cells.pertussis toxin (ptx), the major virulence factor of the whooping cough-causing bacterial pathogen bordetella pertussis, permeabilizes the blood-brain barrier (bbb) in vitro and in vivo. breaking barriers might promote translocation of meningitis-causing bacteria across the bbb, thereby facilitating infection. ptx activates several host cell signaling pathways exploited by the neonatal meningitis-causing escherichia coli k1-rs218 for invasion and translocation across the bbb. here, we investigat ...201627754355
non-specific immunological effects of selected routine childhood immunisations: systematic review.to identify and characterise non-specific immunological effects after routine childhood vaccines against bcg, measles, diphtheria, pertussis, and tetanus.201627737830
assessing the evidence for maternal pertussis immunization: a report from the bill & melinda gates foundation symposium on pertussis infant disease burden in low- and lower-middle-income countries.implementation of effective interventions has halved maternal and child mortality over the past 2 decades, but less progress has been made in reducing neonatal mortality. almost 45% of under-5 global mortality now occurs in infants <1 month of age, with approximately 86% of neonatal deaths occurring in low- and lower-middle-income countries (lmics). as an estimated 23% of neonatal deaths globally are due to infectious causes, maternal immunization (mi) is one intervention that may reduce mortali ...201627838664
global childhood deaths from pertussis: a historical review.impact of pertussis vaccines on mortality is a key world health organization indicator, and trends in mortality rates and age distribution can inform maternal immunization strategies. we systematically reviewed studies reporting pertussis mortality rates (pmrs) per million population, identifying 19 eligible studies. during a prevaccine observation period of ≥50 years in high-income countries (hics), pmrs reduced in both infants and 1- to 4-year-olds by >80%, along with improvements in living co ...201627838665
b cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation.studies in experimental autoimmune encephalomyelitis (eae), a murine model of multiple sclerosis (ms), have shown that regulatory b cells modulate the course of the disease via the production of suppressive cytokines. while data indicate a role for transforming growth factor (tgf)-β1 expression in regulatory b cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. transgenic mice deficient for tgf-β1 expression in b cells (b-tgf-β1(-/-)) were tested in eae induce ...201627708418
moringin activates wnt canonical pathway by inhibiting gsk3β in a mouse model of experimental autoimmune encephalomyelitis.aberrant canonical wnt-β-catenin signaling has been reported in multiple sclerosis (ms), although the results are controversial. the present study aimed to examine the role of the wnt-β-catenin pathway in experimental ms and also to test moringin (4-[α-l-rhamnopyranosyloxy]-benzyl isothiocyanate), resulting from exogenous myrosinase hydrolysis of the natural phytochemical glucomoringin 4(α-l-rhamnosyloxy)-benzyl glucosinolate as a modulator of neuroinflammation via the β-catenin-pparγ axis. expe ...201627784989
structure and specificity of the type vi secretion system clpv-tssc interaction in enteroaggregative escherichia coli.the type vi secretion system (t6ss) is a versatile machine that delivers toxins into either eukaryotic or bacterial cells. it thus represents a key player in bacterial pathogenesis and inter-bacterial competition. schematically, the t6ss can be viewed as a contractile tail structure anchored to the cell envelope. the contraction of the tail sheath propels the inner tube loaded with effectors towards the target cell. the components of the contracted tail sheath are then recycled by the clpv aaa(+ ...201627698444
consensus recommendation for india and bangladesh for the use of pneumococcal vaccine in mass gatherings with special reference to hajj pilgrims.respiratory tract infections are prevalent among hajj pilgrims with pneumonia being a leading cause of hospitalization. streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during hajj. there is a significant burden of pneumococcal disease in india, which can be prevented. guidelines for preventive measures and adult immunization have been published in india, but the implementation of the guidelines is low. data from bangladesh are ...201627942192
the impact of healthcare visit timing on reported pertussis cough duration: selection bias and disease pattern from reported cases in michigan, usa, 2000-2010.pertussis is a potentially serious respiratory illness characterized by cough of exceptionally long duration of up to approximately100 days. while macrolide antibiotics are an effective treatment, there is an ongoing debate whether they also shorten the length of cough symptoms. we investigated whether public health surveillance data for pertussis, in which cases are identified at diagnosis, are potentially affected by selection bias and the possible consequences for reported cough duration.201627682251
effectiveness of pertussis vaccination and duration of immunity.a resurgence of pertussis cases among both vaccinated and unvaccinated people raises questions about vaccine effectiveness over time. our objective was to study the effectiveness of the pertussis vaccine and characterize the effect of waning immunity and whole-cell vaccine priming.201627672225
apparent life-threatening event in infancy.an apparent life-threatening event (alte) is defined as the combination of clinical presentations such as apnea, marked change in skin and muscle tone, gagging, or choking. it is a frightening event, and it predominantly occurs during infancy at a mean age of 1-3 months. the causes of alte are categorized into problems that are: gastrointestinal (50%), neurological (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (2%-5%), or others such as child abuse. up to 50% of altes ar ...201627721838
the regulator of g-protein signaling rgs16 promotes insulin secretion and β-cell proliferation in rodent and human islets.g protein-coupled receptor (gpcr) signaling regulates insulin secretion and pancreatic β cell-proliferation. while much knowledge has been gained regarding how gpcrs are activated in β cells, less is known about the mechanisms controlling their deactivation. in many cell types, termination of gpcr signaling is controlled by the family of regulators of g-protein signaling (rgs). rgs proteins are expressed in most eukaryotic cells and ensure a timely return to the gpcr inactive state upon removal ...201627689011
time series analysis of temporal trends in the pertussis incidence in mainland china from 2005 to 2016.short-term forecast of pertussis incidence is helpful for advanced warning and planning resource needs for future epidemics. by utilizing the auto-regressive integrated moving average (arima) model and exponential smoothing (ets) model as alterative models with r software, this paper analyzed data from chinese center for disease control and prevention (china cdc) between january 2005 and june 2016. the arima (0,1,0)(1,1,1)12 model (aicc = 1342.2 bic = 1350.3) was selected as the best performing ...201627577101
epigenetic regulation of kcna3-encoding kv1.3 potassium channel by cereblon contributes to regulation of cd4+ t-cell activation.the role of cereblon (crbn) in t cells is not well understood. we generated mice with a deletion in crbn and found cereblon to be an important antagonist of t-cell activation. in mice lacking crbn, cd4(+) t cells show increased activation and il-2 production on t-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. crbn restricts t-cell activation via epigenetic modification of kcna3, which encodes the kv1.3 potassium channel required for ro ...201627439875
rickettsiologist pavel f. zdrodovskii: larger than life, and not just for his famous book.this article highlights the biography and scientific accomplishments of pavel f. zdrodovskii and his contributions to understanding the biology, pathogenesis, treatment, prevention and epidemiology of brucellosis, rickettsioses and many other infectious diseases.201627551431
vaccine-mediated activation of human tlr4 is affected by modulation of culture conditions during whole-cell pertussis vaccine preparation.the potency of whole-cell pertussis (wp) vaccines is still determined by an intracerebral mouse protection test. to allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. to this end, a panel of experimental wp vaccines of varying quality was prepared by sulfate-mediated suppression of the bvgasr master virulence regulatory system of bordetella pertussis during cultivation. this system regulat ...201627548265
linking susceptibility to infectious diseases to immune system abnormalities among hiv-exposed uninfected infants.hiv-exposed uninfected (heu) infants experience increased overall mortality from infectious causes when compared to hiv-unexposed uninfected (hu) infants. this is the case in both the resource-rich and resource-limited settings. here, we explore the concept that specific types of infectious diseases that are more common among heu infants could provide clues as to the potential underlying immunological abnormalities. the most commonly reported infections in heu vs. hu infants are caused by encaps ...201627594857
a simple luminescent adenylate-cyclase functional assay for evaluation of bacillus anthracis edema factor activity.edema factor (ef), the toxic sub-unit of the bacillus anthracis edema toxin (et) is a calmodulin-dependent adenylate cyclase whose detrimental activity in the infected host results in severe edema. ef is therefore a major virulence factor of b. anthracis. we describe a simple, rapid and reliable functional adenylate-cyclase assay based on inhibition of a luciferase-mediated luminescence reaction. the assay exploits the efficient adenylate cyclase-mediated depletion of adenosine tri-phosphate (at ...201627548219
degp chaperone suppresses toxic inner membrane translocation intermediates.the periplasm of gram-negative bacteria includes a variety of molecular chaperones that shepherd the folding and targeting of secreted proteins. a central player of this quality control network is degp, a protease also suggested to have a chaperone function. we serendipitously discovered that production of the bordetella pertussis autotransporter virulence protein pertactin is lethal in escherichia coli δdegp strains. we investigated specific contributions of degp to secretion of pertactin as a ...201627626276
mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis.neuroinflammation can cause major neurological dysfunction, without demyelination, in both multiple sclerosis (ms) and a mouse model of the disease (experimental autoimmune encephalomyelitis; eae), but the mechanisms remain obscure. confocal in vivo imaging of the mouse eae spinal cord reveals that impaired neurological function correlates with the depolarisation of both the axonal mitochondria and the axons themselves. indeed, the depolarisation parallels the expression of neurological deficit ...201627624721
in vivo quantification of the secretion rates of the hemolysin a type i secretion system.type 1 secretion systems (t1ss) of gram-negative bacteria secrete a broad range of substrates into the extracellular space. common to all substrates is a c-terminal secretion sequence and nonapeptide repeats in the c-terminal part that bind ca(2+) in the extracellular space, to trigger protein folding. like all t1ss, the hemolysin a (hlya) t1ss of escherichia coli consists of an abc transporter, a membrane fusion protein and an outer membrane protein allowing the one step translocation of the su ...201627616645
epidemiology of pertussis in denmark, 1995 to 2013.we describe incidence and age distribution of laboratory-confirmed pertussis in denmark from 1995 to 2013. notification has been mandatory since 2007. since 1997, an acellular monocomponent vaccine has been used. the latest epidemic occurred in 2002 with an incidence of 36 per 100,000; since 1995, only six infant deaths have been recorded. the inter-epidemic incidence lies below 10 per 100,000. in 1995, the mean age of confirmed cases was 9.2 years (95% confidence interval (ci): 7.9-10.5; median ...201627632433
skin barrier recovery by protease-activated receptor-2 antagonist lobaric acid.atopic dermatitis (ad) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. protease-activated receptor 2 (par2) belongs to a family of g-protein coupled receptors and is expressed in suprabasal layers of the epidermis. par2 is activated by both trypsin and a specific agonist peptide, sligkv-nh₂ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. in this study, we investig ...201627169822
a cough-based algorithm for automatic diagnosis of pertussis.pertussis is a contagious respiratory disease which mainly affects young children and can be fatal if left untreated. the world health organization estimates 16 million pertussis cases annually worldwide resulting in over 200,000 deaths. it is prevalent mainly in developing countries where it is difficult to diagnose due to the lack of healthcare facilities and medical professionals. hence, a low-cost, quick and easily accessible solution is needed to provide pertussis diagnosis in such areas to ...201627583523
negatively charged residues of the segment linking the enzyme and cytolysin moieties restrict the membrane-permeabilizing capacity of adenylate cyclase toxin.the whooping cough agent, bordetella pertussis, secretes an adenylate cyclase toxin-hemolysin (cyaa) that plays a crucial role in host respiratory tract colonization. cyaa targets cr3-expressing cells and disrupts their bactericidal functions by delivering into their cytosol an adenylate cyclase enzyme that converts intracellular atp to camp. in parallel, the hydrophobic domain of cyaa forms cation-selective pores that permeabilize cell membrane. the invasive ac and pore-forming domains of cyaa ...201627581058
effects of sphingosine-1-phosphate receptor 1 phosphorylation in response to fty720 during neuroinflammation.fingolimod (fty720, gilenya), a sphingosine-1-phosphate receptor (s1pr) modulator, is one of the first-line immunomodulatory therapies for treatment of relapsing-remitting multiple sclerosis (ms). human s1pr1 variants have been reported to have functional heterogeneity in vitro, suggesting that s1pr1 function may influence fty720 efficacy. in this study, we examined the influence of s1pr1 phosphorylation on response to fty720 in neuroinflammation. we found that mice carrying a phosphorylation-de ...201627699272
predicted coverage and immuno-safety of a recombinant c-repeat region based streptococcus pyogenes vaccine candidate.the c-terminal region of the m-protein of streptococcus pyogenes is a major target for vaccine development. the major feature is the c-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. sv1 is a s. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called j14i variants) from differing c-repeat units in a single recombinant construct. here we show that the j14i variants chosen for inclusion in sv1 are the most common v ...201627310707
etiologic framework for the study of neurodegenerative disorders as well as vascular and metabolic comorbidities on the grounds of shared epidemiologic and biologic features.during the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. this article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (ndds), and their vascular- and metabolic-associated ailments.201627378910
respiratory virus detection and clinical diagnosis in children attending day care.respiratory viruses often have been studied in children with respiratory tract infection (rti), but less knowledge exists about viruses in asymptomatic children. we have studied the occurrence of a broad panel of respiratory viruses in apparently healthy children attending day care, taking into account the influence of possible confounding factors, such as age, clinical signs of respiratory tract infection (rti), location (day-care section) and season.201627433803
influenza c infections in western australia and victoria from 2008 to 2014.influenza c is usually considered a minor cause of respiratory illness in humans with many infections being asymptomatic or clinically mild. large outbreaks can occur periodically resulting in significant morbidity.201627373693
control of clostridium difficile physiopathology in response to cysteine availability.the pathogenicity of clostridium difficile is linked to its ability to produce two toxins: tcda and tcdb. the level of toxin synthesis is influenced by environmental signals, such as phosphotransferase system (pts) sugars, biotin, and amino acids, especially cysteine. to understand the molecular mechanisms of cysteine-dependent repression of toxin production, we reconstructed the sulfur metabolism pathways of c. difficile strain 630 in silico and validated some of them by testing c. difficile gr ...201627297391
role of iron uptake systems in pseudomonas aeruginosa virulence and airway infection.pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. iron is essential for bacterial growth, and p. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation. p. aeruginosa fe(3+) uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the tonb energy transducer. p. aeruginosa also has the feob tr ...201627271740
memhdx: an interactive tool to expedite the statistical validation and visualization of large hdx-ms datasets.with the continued improvement of requisite mass spectrometers and uhplc systems, hydrogen/deuterium exchange mass spectrometry (hdx-ms) workflows are rapidly evolving towards the investigation of more challenging biological systems, including large protein complexes and membrane proteins. the analysis of such extensive systems results in very large hdx-ms datasets for which specific analysis tools are required to speed up data validation and interpretation.201627412089
study on toxicity reduction and potency induction in whole-cell pertussis vaccine by developing a new optimal inactivation condition processed on bordetella pertussis.whooping cough is caused by bordetella pertussis, and it remains a public health concern. whole-cell pertussis vaccines have been commonly employed for expanded immunization. there is no doubt of the efficacy of whole cell pertussis vaccine, but it is necessary to improve the vaccine to decrease its toxicity.201627679704
a prospective view of animal and human fasciolosis.fasciolosis, a food-borne trematodiasis, results following infection with the parasites, fasciola hepatica and fasciola gigantica. these trematodes greatly affect the global agricultural community, infecting millions of ruminants worldwide and causing annual economic losses in excess of us $3 billion. fasciolosis, an important zoonosis, is classified by who as a neglected tropical disease with an estimated 17 million people infected and a further 180 million people at risk of infection. the sign ...201627314903
evaluation of outbreak response immunization in the control of pertussis using agent-based modeling.pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. multiple outbreaks have been reported in different ages worldwide. for certain outbreaks, public health authorities can launch an outbreak response immunization (ori) campaign to control pertussis spread. we investigated effects of an outbreak response immunization targeting young adolescents in averting pertussis cases.201627602299
increase in pertussis cases along with high prevalence of two emerging genotypes of bordetella pertussis in perú, 2012.as has occurred in many regions worldwide, in 2012 the incidence of pertussis increased in perú. this epidemiologic situation has been associated with a waning vaccine-induced immunity and the adaptation of bordetella pertussis to vaccine-induced immunity along with improved diagnostic methods.201627530444
respiratory presentation of pediatric patients in the 2014 enterovirus d68 outbreak.background. in the fall of 2014, a north american outbreak of enterovirus d68 resulted in a significant number of pediatric hospital admissions for respiratory illness throughout north america. this study characterized the clinical presentation and risk factors for a severe clinical course in children admitted to british columbia children's hospital during the 2014 outbreak. methods. retrospective chart review of patients with confirmed ev-d68 infection admitted to bcch with respiratory symptoms ...201627610028
capture-recapture estimators in epidemiology with applications to pertussis and pneumococcal invasive disease surveillance.surveillance networks are often not exhaustive nor completely complementary. in such situations, capture-recapture methods can be used for incidence estimation. the choice of estimator and their robustness with respect to the homogeneity and independence assumptions are however not well documented.201627529167
lncrnas bcyrn1 promoted the proliferation and migration of rat airway smooth muscle cells in asthma via upregulating the expression of transient receptor potential 1.long noncoding rnas (lncrnas) played important roles in several biological processes through regulating the expression of protein. however, the function of lncrna bcyrn1 in airway smooth muscle cells (asmcs) has not been reported.201627648131
pertussis in infants: an underestimated disease.the clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. many cases are often misclassified and underdiagnosed. we conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of bordetella pertussis infections.201627528377
subdomain 2 of the autotransporter pet is the ligand site for recognizing the pet receptor on the epithelial cell surface.most autotransporter passenger domains, regardless of their diversity in function, fold or are predicted to fold as right-handed β-helices carrying various loops that are presumed to confer functionality. our goal here was to identify the subdomain (loop) or amino acid sequence of the pet passenger domain involved in the receptor binding site on the host cell for pet endocytosis. here, we show that d1 and d2 subdomains, as well as the amino acid sequence linking the subdomain d2 and the adjacent ...201627113356
overcoming the constraints of anti-hiv/cd89 bispecific antibodies that limit viral inhibition.innovative strategies are necessary to maximize the clinical application of hiv neutralizing antibodies. to this end, bispecific constructs of human antibody f240, reactive with well-conserved gp41 epitope and antibody 14a8, reactive with the iga receptor (cd89) on effector cells, were constructed. a f240 × 14a8 bispecific single chain variable region (scfv) molecule was constructed by linking two scfvs using a conventional ggggs linker. despite immunoreactivity with hiv gp41 and neutrophils, th ...201627419146
a diguanylate cyclase acts as a cell division inhibitor in a two-step response to reductive and envelope stresses.cell division arrest is a universal checkpoint in response to environmental assaults that generate cellular stress. in bacteria, the cyclic di-gmp (c-di-gmp) signaling network is one of several signal transduction systems that regulate key processes in response to extra-/intracellular stimuli. here, we find that the diguanylate cyclase yfin acts as a bifunctional protein that produces c-di-gmp in response to reductive stress and then dynamically relocates to the division site to arrest cell divi ...201627507823
enterovirus d68 infection in children with acute flaccid myelitis, colorado, usa, 2014.during august 8, 2014-october 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near denver, colorado, usa. a respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus d68 (ev-d68) for 4. to determine whether an association exists between ev-d68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient contro ...201627434186
a bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation.in this study, a formulation of bordetella pertussis proteoliposome (plbp), diphtheria, and tetanus toxoids and alum (dt-plbp) was evaluated as a trivalent vaccine candidate in balb/c mice. vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. both, diphtheria-tetanus-whole cell pertussis (dtp) and diphtheria-tetanus vaccines (dt) were used as controls. animals immun ...201627489808
vaccination strategies in patients with solid organ transplant: evidences and future perspectives.solid organ transplant recipients need emphases on immunization that result in certainly decrease the risk of vaccine preventable diseases. organ transplant candidate should complete the recommended full vaccination schedule as early as possible during the courses of underlying disease because the patients with end stage liver or renal disease have reduced immune response to vaccine. furthermore, live attenuated vaccines are generally contraindicated after transplantation. this review summarizes ...201627489802
pyrin inflammasome activation and rhoa signaling in the autoinflammatory diseases fmf and hids.mutations in the genes encoding pyrin and mevalonate kinase (mvk) cause distinct interleukin-1β (il-1β)-mediated autoinflammatory diseases: familial mediterranean fever (fmf) and hyperimmunoglobulinemia d syndrome (hids). pyrin forms an inflammasome when mutant or in response to bacterial modification of the gtpase rhoa. we found that rhoa activated the serine-threonine kinases pkn1 and pkn2 that bind and phosphorylate pyrin. phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins tha ...201627270401
carbon nanospheres mediated delivery of nuclear matrix protein smar1 to direct experimental autoimmune encephalomyelitis in mice.owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. here, we demonstrate a novel carbon nanosphere (cnp) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein smar1. a truncated part of smar1 ie, the dna binding domain was conjugated with hydrothermally synthesized cnps. when administered intravenously, the conjugate s ...201627274234
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