Publications

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the importance of persistence. 201627838662
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
using combined diagnostic test results to hindcast trends of infection from cross-sectional data.infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. it is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. however, there is often a lack of situational awareness that may lead to over- or under-reaction. there is a widening range of tes ...201627384712
genetic ablation of ip3 receptor 2 increases cytokines and decreases survival of sod1g93a mice.amyotrophic lateral sclerosis (als) is a devastating progressive neurodegenerative disease characterized by the selective death of motor neurons. disease pathophysiology is complex and not yet fully understood. higher gene expression of the inositol 1,4,5-trisphosphate receptor 2 gene (itpr2), encoding the ip3 receptor 2 (ip3r2), was detected in sporadic als patients. here, we demonstrate that ip3r2 gene expression was also increased in spinal cords of als mice. moreover, an increase of ip3r2 ex ...201627378687
lack of association between viral load and severity of acute bronchiolitis in infants.to investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes.201627832233
novel role of cortactin in g protein-coupled receptor agonist-induced nuclear export and degradation of p21cip1.monocyte chemotactic protein 1 (mcp1) stimulates phosphorylation of cortactin on y421 and y446 residues in a time-dependent manner and phosphorylation at y446 but not y421 residue is required for mcp1-induced cdk-interacting protein 1 (p21cip1) nuclear export and degradation in facilitating human aortic smooth muscle cell (hasmc) proliferation. in addition, mcp1-induced cortactin tyrosine phosphorylation, p21cip1 degradation and hasmc proliferation are dependent on fyn activation. upstream to fy ...201627363897
comparative effects of human neural stem cells and oligodendrocyte progenitor cells on the neurobehavioral disorders of experimental autoimmune encephalomyelitis mice.since multiple sclerosis (ms) is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of f3.olig2 progenitors, established by transducing human neural stem cells (f3 nscs) with olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (mog-) induced experimental autoimmune encephalomyelitis (eae) model mice. six days after eae induction, f3 or f3.olig2 cells (1 × 10(6)/mouse) were intravenously transplanted. mog-injected mice displa ...201627429621
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
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
tssa forms a gp6-like ring attached to the type vi secretion sheath.the type vi secretion system (t6ss) is a supra-molecular bacterial complex that resembles phage tails. it is a killing machine which fires toxins into target cells upon contraction of its tssbc sheath. here, we show that tssa1 is a t6ss component forming dodecameric ring structures whose dimensions match those of the tssbc sheath and which can accommodate the inner hcp tube. the tssa1 ring complex binds the t6ss sheath and impacts its behaviour in vivo in the phage, the first disc of the gp18 sh ...201627288401
the role of neutrophils in the induction of specific th1 and th17 during vaccination against tuberculosis.mycobacterium tuberculosis causes tuberculosis (tb), a disease that killed more than 1.5 million people worldwide in 2014, and the bacillus calmette guérin (bcg) vaccine is the only currently available vaccine against tb. however, it does not protect adults. th1 and th17 cells are crucial for tb control, as well as the neutrophils that are directly involved in dc trafficking to the draining lymph nodes and the activation of t lymphocytes during infection. although several studies have shown the ...201627375607
use of vaca as a vaccine antigen.one of the major toxins secreted by h. pylori is the vacuolating cytotoxin a (vaca) named after its ability to induce the formation of "vacuole"-like membrane vesicles in the cytoplasm of gastric cells. vaca has been associated with the disruption of mitochondrial functions, stimulation of apoptosis, blockade of t cell proliferation and promotion of regulatory t cells, thereby making it a promising vaccine target. immunity to bacterial virulence factors is well known to protect humans against ba ...201627338474
"rules of engagement" of protein-glycoconjugate interactions: a molecular view achievable by using nmr spectroscopy and molecular modeling.understanding the dynamics of protein-ligand interactions, which lie at the heart of host-pathogen recognition, represents a crucial step to clarify the molecular determinants implicated in binding events, as well as to optimize the design of new molecules with therapeutic aims. over the last decade, advances in complementary biophysical and spectroscopic methods permitted us to deeply dissect the fine structural details of biologically relevant molecular recognition processes with high resoluti ...201627547635
dismantling the taboo against vaccines in pregnancy.vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. prejudice in health professionals add to fears of women and their families. both these feelings are not supported by even the smallest scientific data. harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human pa ...201627338346
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
comparative epidemiologic characteristics of pertussis in 10 central and eastern european countries, 2000-2013.we undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten central and eastern european countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. the annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. we reviewed the changes in the pertussis i ...201627257822
phytochemical profiles and inhibitory effects of tiger milk mushroom (lignosus rhinocerus) extract on ovalbumin-induced airway inflammation in a rodent model of asthma.lignosus rhinocerus (l. rhinocerus), which is known locally as tiger milk mushroom, is traditionally used in the treatment of asthma by indigenous communities in malaysia. however, to date, its efficacy on asthma has not been confirmed by scientific studies and there is also sparse information available on its active constituents. in this study, the volatile constituent of l. rhinocerus hot water extract was investigated using gas chromatography mass spectrometry (gc-ms). the potential effects o ...201627255587
the respiratory protection effectiveness clinical trial (respect): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.although n95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. a lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and exper ...201627255755
nonmuscle invasive bladder cancer: a primer on immunotherapy.intravesical bacillus calmette-guérin (bcg) has long been the gold standard treatment of nonmuscle invasive bladder cancer. recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. these agents aim to augment, modify, or enhance the immune response. such strategies include recombinant bcg, monoclonal antibodies, vaccines, gene therapy, and adoptive t-cell therapy. here, we review the emerging immunotherapeuti ...201627458527
uropathogenic escherichia coli-associated exotoxins.escherichia coli are a common cause of infectious disease outside of the gastrointestinal tract. several independently evolved e. coli clades are common causes of urinary tract and bloodstream infections. there is ample epidemiological and in vitro evidence that several different protein toxins common to many, but not all, of these strains are likely to aid the colonization and immune-evasion ability of these bacteria. this review discusses our current knowledge and areas of ignorance concerning ...201627337488
elevated pertussis reporting in response to 2011-2012 outbreak, new york city, new york, usa. 201627191867
estimated incidence of pertussis in people aged <50 years in the united states.the introduction of pertussis vaccination in the united states (us) in the 1940s has greatly reduced its burden. however, the incidence of pertussis is difficult to quantify, as many cases are not laboratory-confirmed or reported, particularly in adults. this study estimated pertussis incidence in a commercially insured us population aged <50 years. data were extracted from ims' pharmetrics plus claims database for patients with a diagnosis of pertussis or cough illness using international class ...201627246119
serum-derived exosomes from non-viremic animals previously exposed to the porcine respiratory and reproductive virus contain antigenic viral proteins.prrsv is the etiological agent of one of the most important swine diseases with a significant economic burden worldwide and limitations in vaccinology. exosomes are 30-100 nm vesicles of endocytic origin. remarkably, immunizations with exosomes containing antigens from tumors or pathogens are capable of eliciting protective immune responses, albeit variably, in cancer and infectious diseases. here we describe the isolation, molecular composition and immunogenicity of serum-derived exosomes from ...201627246926
the ysrs paralog dygs has the capacity to activate expression of the yersinia enterocolitica ysa type iii secretion system.the yersinia enterocolitica ysa type iii secretion system (t3ss) is associated with intracellular survival, and, like other characterized t3sss, it is tightly controlled. expression of the ysa genes is only detected following growth at low temperatures (26°c) and in high concentrations of sodium chloride (290 mm) in the medium. the ysrstr phosphorelay (pr) system is required for ysa expression and likely responds to nacl. during our investigations into the ysr pr system, we discovered that genes ...201627044629
is pertussis infection neglected in china? evidence from a seroepidemiology survey in zhejiang, an eastern province of china.the resurgence of pertussis has occurred in many countries. however, the epidemiological profiles of pertussis cannot be well understood by the current surveillance system in china. this study was designed to investigate the age specific serologic evidence of antibodies against pertussis, and to offer information regarding the existence of pertussis infection in zhejiang province, china.201627223467
performance characteristics of filmarray respiratory panel v1.7 for detection of adenovirus in a large cohort of pediatric nasopharyngeal samples: one test may not fit all.the filmarray respiratory panel (rp) v1.7 assay has improved sensitivity for detection of human adenovirus (hadv), compared to an earlier version (rp v1.6). rp v1.7 was designed for detection of species b, c, and e but may show variable detection of species a, d, and f. we sought to evaluate the clinical and analytical performance of rp v1.7 for detection of hadv in a large pediatric cohort. respiratory specimens obtained from a tertiary care children's hospital between february 2014 and februar ...201627008875
modulation of chemokine responses: synergy and cooperativity.chemokine biology is mediated by more complex interactions than simple monomolecular ligand-receptor interactions, as chemokines can form higher order quaternary structures, which can also be formed after binding to glycosaminoglycans (gags) on endothelial cells, and their receptors are found as dimers and/or oligomers at the cell surface. due to the complexity of the chemokine binding and signaling system, several mechanisms have been proposed to provide an explanation for the synergy observed ...201627242790
experimental priming of encephalitogenic th1/th17 cells requires pertussis toxin-driven il-1β production by myeloid cells.cd4(+) th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (eae). here we demonstrate that experimental priming of encephalitogenic th cells expressing rorγt and t-bet and producing il-17a, ifn-γ and gm-csf but not il-10 (th1/th17), is dependent on the presence of pertussis toxin (ptx) at the time of immunization. ptx induces early production of il-1β by cd11b(+)ccr2(+)gr1(+) myeloid cells, which a ...201627189410
the regulatory networks that control clostridium difficile toxin synthesis.the pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. among the enterotoxic clostridia, clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. the symptoms of c. difficile infection are essentially caused by the production of two exotoxins: tcda and tcdb. moreover, for severe forms of disease, the spectr ...201627187475
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
cytokine profiles in human metapneumovirus infected children: identification of genes involved in the antiviral response and pathogenesis.human metapneumovirus (hmpv) causes severe airway infection in children that may be caused by an unfavorable immune response. the nature of the innate immune response to hmpv in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. we examined nasopharynx aspirates and blood samples from hmpv-infected children without detectable co-infections. the expression of inflammatory and antiviral genes were m ...201627171557
genome structural diversity among 31 bordetella pertussis isolates from two recent u.s. whooping cough statewide epidemics.during 2010 and 2012, california and vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. to overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. through the use of combined next-generation sequen ...201627303739
identification and characterization of putative translocated effector proteins of the edwardsiella ictaluri type iii secretion system.edwardsiella ictaluri, a major pathogen in channel catfish aquaculture, encodes a type iii secretion system (t3ss) that is essential for intracellular replication and virulence. previous work identified three putative t3ss effectors in e. ictaluri, and in silico analysis of the e. ictaluri genome identified six additional putative effectors, all located on the chromosome outside the t3ss pathogenicity island. to establish active translocation by the t3ss, we constructed translational fusions of ...201627303737
the role of interleukin-22 and its receptor in the development and pathogenesis of experimental autoimmune uveitis.il-22 is a pro- and anti-inflammatory cytokine that is mainly produced by t cells and nk cells. recent studies have reported the increased number of il-22 producing t cells in patients with autoimmune noninfectious uveitis; however, the correlation between il-22 and uveitis remains unclear. in this study, we aimed to determine the specific role of il-22 and its receptor in the pathogenesis of uveitis. serum concentration of il-22 was significantly increased in uveitis patients. il-22rα was expre ...201627166675
a belgian serosurveillance/seroprevalence study of diphtheria, tetanus and pertussis using a luminex xmap technology-based pentaplex.serosurveillance and seroprevalence studies are an essential tool to monitor vaccine-preventable diseases. we have developed a magnetic bead-based pentaplex immunoassay (mia) for the simultaneous detection of igg antibodies against diphtheria toxin (dt), tetanus toxin (tt), pertussis toxin (pt), filamentous hemagglutinin (fha) and pertactin (prn). the in-house pentaplex mia showed a good correlation with commercial elisas with correlation coefficients between 0.89 for pt and 0.98 for tt. intra- ...201627171114
a large family of anti-activators accompanying xyls/arac family regulatory proteins.arac negative regulators (anr) suppress virulence genes by directly down-regulating arac/xyls members in gram-negative bacteria. in this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for anrs among different bacterial pathogens. we identified more than 200 anrs distributed in diverse clinically important gram negative pathogens, including vibrio spp., salmonella spp., shigella spp., yersinia spp., citrobacter spp., enterotoxigenic (etec) and ent ...201627038276
molecular cloning, phylogenetic analysis and heat shock response of babesia gibsoni heat shock protein 90.the babesia gibsoni heat shock protein 90 (bghsp90) gene was cloned and sequenced. the length of the gene was 2,610 bp with two introns. this gene was amplified from cdna corresponding to full length coding sequence (cds) with an open reading frame of 2,148 bp. a phylogenetic analysis of the cds of hsp90 gene showed that b. gibsoni was most closely related to b. bovis and babesia sp. bq1/lintan and lies within a phylogenetic cluster of protozoa. moreover, mrna transcription profile for bghsp90 e ...201627149891
factors associated with time to appropriate treatment in pertussis cases in georgia, 2009 to 2013.pertussis is endemic in the united states, with periodic epidemics that continue to highlight its importance as a public health issue. the clinical presentation of pertussis can vary by age and vaccination status. however, little is known about the factors that affect time to antibiotic treatment of pertussis cases. we analyzed 5 years of data from the georgia department of public health to understand how factors such as age, symptoms, and vaccination status can alter the clinical picture of per ...201626953196
new cysteine-rich ice-binding protein secreted from antarctic microalga, chloromonas sp.many microorganisms in antarctica survive in the cold environment there by producing ice-binding proteins (ibps) to control the growth of ice around them. an ibp from the antarctic freshwater microalga, chloromonas sp., was identified and characterized. the length of the chloromonas sp. ibp (chloroibp) gene was 3.2 kb with 12 exons, and the molecular weight of the protein deduced from the chloroibp cdna was 34.0 kda. expression of the chloroibp gene was up- and down-regulated by freezing and war ...201627097164
adaptation by deletogenic replication slippage in a nascent symbiont.as a consequence of population level constraints in the obligate, host-associated lifestyle, intracellular symbiotic bacteria typically exhibit high rates of molecular sequence evolution and extensive genome degeneration over the course of their host association. while the rationale for genome degeneration is well understood, little is known about the molecular mechanisms driving this change. to understand these mechanisms we compared the genome of sodalis praecaptivus, a nonhost associated bact ...201627189544
drivers: a biologically contextualized, cross-inferential view of the epidemiology of neurodegenerative disorders.sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (ndds), there was a need to identify specific "drivers", i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities.201626923014
a compendium for mycoplasma pneumoniae.historically, atypical pneumonia was a term used to describe an unusual presentation of pneumonia. currently, it is used to describe the multitude of symptoms juxtaposing the classic symptoms found in cases of pneumococcal pneumonia. specifically, atypical pneumonia is a syndrome resulting from a relatively common group of pathogens including chlamydophila sp., and mycoplasma pneumoniae. the incidence of m. pneumoniae pneumonia in adults is less than the burden experienced by children. transmiss ...201627148202
myelin-specific th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in c57bl/6 mice.optic neuritis affects most patients with multiple sclerosis (ms), and current treatments are unreliable. the purpose of this study was to characterize the contribution of th1 and th17 cells to the development of optic neuritis.201627122964
impact of infection prevention and control initiatives on acute respiratory infections in a pediatric long-term care facility.we evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (aris) in a pediatric long-term care facility. aris did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. influenza rates decreased significantly. infect control hosp epidemiol 2016;37:859-862.201627053088
epidemiology of pertussis-related paediatric intensive care unit (icu) admissions in australia, 1997-2013: an observational study.to review the epidemiology of pertussis-related intensive care unit (icu) admissions across australia, over a 17-year period.201627053270
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