bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Recombinant Attenuated
Salmonella enterica
Serovar Typhimurium Vaccine Encoding
Eimeria acervulina
Antigen Offers Protection against
E. acervulina
Challenge
Authors: Konjufca Vjollca , Wanda Soo-Young , Jenkins Mark C. , Curtiss Roy 
Published: November 2006

ABSTRACT

Coccidiosis is a ubiquitous disease caused by intestinal protozoan parasites belonging to several distinct species of the genus
Eimeria
. Cell-mediated immunity (CMI) is critically important for protection against
Eimeria
; thus, our approach utilizes the bacterial type III secretion system (TTSS) to deliver an antigen directly into the cell cytoplasm of the immunized host and into the major histocompatibility complex class I antigen-processing pathway for induction of CMI and antigen-specific cytotoxic T-lymphocyte responses in particular. To accomplish this goal,
Eimeria
genes encoding the sporozoite antigen EASZ240 and the merozoite antigen EAMZ250 were fused to the
Salmonella enterica
serovar Typhimurium effector protein gene
sptP
in the parental pYA3653 vector, yielding pYA3657 and pYA3658, respectively. SptP protein is secreted by the TTSS of
Salmonella
and translocated into the cytoplasm of immunized host cells. The host strain chromosomal copy of the
sptP
gene was deleted and replaced by a reporter gene,
xylE
. The newly constructed vectors pYA3657 and pYA3658 were introduced into host strain χ8879 (Δ
phoP233
Δ
sptP1033
::
xylE
Δ
asdA16
). This strain is an attenuated derivative of the highly virulent strain UK-1. When strain χ8879(pYA3653) as the vector control and strain χ8879 harboring pYA3657 or pYA3658 were used to orally immunize day-of-hatch chicks, colonization of the bursa, spleen, and liver was observed, with peak titers 6 to 9 days postimmunization. In vitro experiments show that the EASZ240 antigen is secreted into the culture supernatant via the TTSS and that it is delivered into the cytoplasm of Int-407 cells by the TTSS. In vivo experiments indicate that both humoral and cell-mediated immune responses are induced in chickens vaccinated with a recombinant attenuated
Salmonella
serovar Typhimurium vaccine, which leads to significant protection against
Eimeria
challenge.
The Frequency of BDCA3-Positive Dendritic Cells Is Increased in the Peripheral Circulation of Kenyan Children with Severe Malaria
Authors: Urban Britta C. , Cordery Damien , Shafi Mohammed J. , Bull Peter C. , Newbold Christopher I. , Williams Thomas N. , Marsh Kevin 
Published: November 2006

ABSTRACT

The ability of
Plasmodium falciparum
-infected erythrocytes to adhere to host endothelial cells via receptor molecules such as ICAM-1 and CD36 is considered a hallmark for the development of severe malaria syndromes. These molecules are also expressed on leukocytes such as dendritic cells. Dendritic cells are antigen-presenting cells that are crucial for the initiation of adaptive immune responses. In many human diseases, their frequency and function is perturbed. We analyzed the frequency of peripheral blood dendritic cell subsets and the plasma concentrations of interleukin-10 (IL-10) and IL-12 in Kenyan children with severe malaria and during convalescence and related these parameters to the adhesion phenotype of the acute parasite isolates. The frequency of CD1c
+
dendritic cells in children with acute malaria was comparable to that in healthy controls, but the frequency of BDCA3
+
dendritic cells was significantly increased. Analysis of the adhesion phenotypes of parasite isolates revealed that adhesion to ICAM-1 was associated with the frequency of peripheral blood CD1c
+
dendritic cells, whereas the adhesion of infected erythrocytes to CD36 correlated with high concentrations of IL-10 and low concentrations of IL-12 in plasma.
Neutrophil Elastase, an Innate Immunity Effector Molecule, Represses Flagellin Transcription in
Pseudomonas aeruginosa
Authors: Sonawane Avinash , Jyot Jeevan , During Russell , Ramphal Reuben 
Published: November 2006

ABSTRACT

Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors triggers an innate immune response to colonizing or invading bacteria. Conversely, many bacteria have evolved mechanisms to dampen this response by downregulating the synthesis of such PAMPs. We have previously demonstrated that
Pseudomonas aeruginosa
growing in mucopurulent human respiratory mucus from cystic fibrosis patients represses the expression of its flagellin, a potent stimulant of the innate immune response. Here we demonstrate that this phenomenon occurs in response to the presence of neutrophil elastase in such mucus. Nonpurulent mucus from animals had no such repressive effect. Furthermore, lysed neutrophils from human blood reproduced the flagellin-repressive effect ex mucus and, significantly, had no effect on the viability of this organism. Neutrophil elastase, a component of the innate host defense system, has been described to be bactericidal for gram-negative bacteria and to degrade bacterial virulence factors. Thus, the resistance of
P. aeruginosa
to the bactericidal effect of neutrophil elastase, as well as this organism's ability to sense this enzyme's presence and downregulate the synthesis of a PAMP, may be the key factors in allowing
P. aeruginosa
to colonize the lungs. These findings demonstrate the dynamic nature of this bacterium's response to host defenses that ensures its success as a colonizer and also highlights the dual nature of defense molecules that confer advantages and disadvantages to both hosts and pathogens.
Lack of In Vitro and In Vivo Recognition of
Francisella tularensis
Subspecies Lipopolysaccharide by Toll-Like Receptors
Authors: Hajjar Adeline M. , Harvey Megan D. , Shaffer Scott A. , Goodlett David R. , Sjöstedt Anders , Edebro Helen , Forsman Mats , Byström Mona , Pelletier Mark , Wilson Christopher B. , Miller Samuel I. , Skerrett Shawn J. , Ernst Robert K. 
Published: November 2006

ABSTRACT

Francisella tularensis
is an intracellular gram-negative bacterium that is highly infectious and potentially lethal. Several subspecies exist of varying pathogenicity. Infection by only a few organisms is sufficient to cause disease depending on the model system. Lipopolysaccharide (LPS) of gram-negative bacteria is generally recognized by Toll-like receptor 4 (TLR4)/MD-2 and induces a strong proinflammatory response. Examination of human clinical
F. tularensis
isolates revealed that human virulent type A and type B strains produced lipid A of similar structure to the nonhuman model pathogen of mice,
Francisella novicida. F. novicida
LPS or lipid A is neither stimulatory nor an antagonist for human and murine cells through TLR4 or TLR2. It does not appear to interact with TLR4 or MD-2, as it is not an antagonist to other stimulatory LPS. Consistent with these observations, aerosolization of
F. novicida
LPS or whole bacteria induced no inflammatory response in mice. These results suggest that poor innate recognition of
F. tularensis
allows the bacterium to evade early recognition by the host innate immune system to promote its pathogenesis for mammals.
Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with
Streptococcus pneumoniae
Authors: Graham Rikki M. A. , Paton James C. 
Published: November 2006

ABSTRACT

Respiratory epithelial cells play an active part in the host response to respiratory pathogens, such as
Streptococcus pneumoniae
, by releasing chemokines responsible for neutrophil recruitment. In order to investigate the role of specific pneumococcal virulence factors in eliciting CXC chemokine responses, type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected with
S. pneumoniae
D39 or mutants lacking choline-binding protein A (CbpA), pneumococcal surface protein A (PspA), or specific domains thereof. In response to wild-type D39, both A549 and Detroit-562 cells showed a significant increase in CXC chemokine mRNA and interleukin-8 protein. This response was increased twofold when a
cbpA
deletion mutant (ΔCbpA) was used, suggesting that CbpA inhibits CXC chemokine induction. All three N-terminal domains of CbpA are required for this effect, as in-frame deletion of the respective region of
cbpA
had the same effect on the CXC chemokine response as deletion of
cbpA
altogether. Infection with a
pspA
deletion mutant (ΔPspA) led to a twofold decrease in the CXC chemokine response of A549 but not Detroit-562 cells, compared to infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate early CXC chemokine release from A549 cells. Deletion of the region of
pspA
encoding the first N-terminal α-helical domain reduced the ability of
S. pneumoniae
to elicit a chemokine response to the same degree as deletion of
pspA
altogether. Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected with
S. pneumoniae
.
Disruption of Tight Junctions and Induction of Proinflammatory Cytokine Responses in Colonic Epithelial Cells by
Campylobacter jejuni
Authors: Chen Ming L. , Ge Zhongming , Fox James G. , Schauer David B. 
Published: November 2006

ABSTRACT

Campylobacter jejuni
is a leading cause of human enterocolitis and is associated with postinfectious complications, including irritable bowel syndrome and Guillain-Barré syndrome. However, the pathogenesis of
C. jejuni
infection remains poorly understood. Paracellular pathways in intestinal epithelial cells are gated by intercellular junctions (tight junctions and adherens junctions), providing a functional barrier between luminal microbes and host immune cells in the lamina propria. Here we describe alterations in tight junctions in intestinal epithelial monolayers following
C. jejuni
infection. Apical infection of polarized T84 monolayers caused a time-dependent decrease in transepithelial electrical resistance (TER). Immunofluorescence microscopy revealed a redistribution of the tight junctional transmembrane protein occludin from an intercellular to an intracellular location. Subcellular fractionation using equilibrium sucrose density gradients demonstrated decreased hyperphosphorylated occludin in lipid rafts, Triton X-100-soluble fractions, and the Triton X-100-insoluble pellet following apical infection. Apical infection with
C. jejuni
also caused rapid activation of NF-κB and AP-1, phosphorylation of extracellular signal-regulated kinase, Jun N-terminal protein kinase, and p38 mitogen-activated protein kinases, and basolateral secretion of the CXC chemokine interleukin-8 (IL-8). Basolateral infection with
C. jejuni
caused a more rapid decrease in TER, comparable redistribution of tight-junction proteins, and secretion of more IL-8 than that seen with apical infection. These results suggest that compromised barrier function and increased chemokine expression contribute to the pathogenesis of
C. jejuni
-induced enterocolitis.
The SecA2 Secretion Factor ofMycobacterium tuberculosisPromotes Growth in Macrophages and Inhibits the Host Immune Response
Authors: Kurtz Sherry , McKinnon Karen P. , Runge Marschall S. , Ting Jenny P.-Y. , Braunstein Miriam 
Published: November 2006

ABSTRACTThe SecA protein is present in all bacteria, and it is a central component of the general Sec-dependent protein export pathway. An unusual property ofMycobacterium tuberculosisis the presence of two SecA proteins: SecA1, the essential “housekeeping” SecA, and SecA2, the accessory secretion factor. Here, we report that a ΔsecA2mutant ofM. tuberculosiswas defective for growth in the early stages of low-dose aerosol infection of C57BL/6 mice, a time during which the bacillus is primarily replicating in macrophages. Consistent with this in vivo phenotype, we found that the ΔsecA2mutant was defective for growth in macrophages from C57BL/6 mice. The ΔsecA2mutant was also attenuated for growth in macrophages from phox−/−mice and from NOS2−/−mice. These mice are defective in the reactive oxygen intermediate (ROI)-generating phagocyte oxidase and the reactive nitrogen intermediate (RNI)-generating inducible nitric oxide synthase, respectively. This indicated a role for SecA2 in the intracellular growth ofM. tuberculosisthat is independent of protecting against these ROIs or RNIs. Macrophages infected with the ΔsecA2mutant produced higher levels of tumor necrosis factor alpha, interleukin-6, RNI, and gamma interferon-induced major histocompatibility complex class II. This demonstrated a function forM. tuberculosisSecA2 in suppressing macrophage immune responses, which could explain the role of SecA2 in intracellular growth. Our results provide another example of a relationship betweenM. tuberculosisvirulence and inhibition of the host immune response.
Rapid Onset of Ulcerative Typhlocolitis in B6.129P2-IL10

tm1Cgn

(IL-10
−/−
) Mice Infected with
Helicobacter trogontum
Is Associated with Decreased Colonization by Altered Schaedler's Flora
Authors: Whary M. T. , Danon S. J. , Feng Y. , Ge Z. , Sundina N. , Ng V. , Taylor N. S. , Rogers A. B. , Fox J. G. 
Published: November 2006

ABSTRACT

Infection with
Helicobacter trogontum
, a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-IL10

tm1Cgn

(interleukin-10
−/−
[IL-10
−/−
]) and C57BL/6 (B6) mice. In a first experiment, IL-10
−/−
mice naturally infected with
Helicobacter rodentium
had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with
H. trogontum
. A second experiment demonstrated that helicobacter-free IL-10
−/−
mice dosed with
H. trogontum
also developed severe clinical signs and typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with
H. trogontum
were resistant to disease. In a third experiment, using helicobacter-free IL-10
−/−
mice, dosing with
H. trogontum
resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of
Escherichia coli
and
Proteus
spp. from the livers of infected mice. Quantitative PCR data revealed that
H. rodentium
and
H. trogontum
may compete for colonization of the lower bowel, as
H. trogontum
established higher colonization levels in the absence of
H. rodentium
(
P
< 0.003).
H. trogontum
-induced typhlocolitis was also associated with a significant decrease in the levels of colonization by five of eight anaerobes that comprise altered Schaedler's flora (
P
< 0.002). These results demonstrate for the first time that
H. rodentium
infection in IL-10
−/−
mice causes subclinical typhlocolitis and that infection with
H. trogontum
(with or without
H. rodentium
) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis.
Dual Role of MyD88 in Rapid Clearance of Relapsing FeverBorreliaspp
Authors: Bolz Devin D. , Sundsbak Rhianna S. , Ma Ying , Akira Shizuo , Weis John H. , Schwan Tom G. , Weis Janis J. 
Published: November 2006

ABSTRACTRelapsing feverBorreliaspp. undergo antigenic variation, achieve high levels in blood, and require rapid production of immunoglobulin M (IgM) for clearance. MyD88-deficient mice display defective clearance of many pathogens; however, the IgM response to persistent infection is essentially normal. Therefore, MyD88−/−mice provided a unique opportunity to study the effect of nonantibody, innate host defenses to relapsing feverBorrelia. Infected MyD88−/−mice harbored extremely high levels ofB. hermsiiin the blood compared to wild-type littermates. In the comparison of MyD88−/−mice and B- and T-cell-deficientscidmice, two features stood out: (i) bacterial numbers in blood were at least 10-fold greater in MyD88−/−mice thanscidmice, even though the production of IgM still occurred in MyD88−/−mice; and (ii) many of the MyD88−/−mice were able to exert partial clearance, although with delayed kinetics relative to wild-type mice, a feature not seen inscidmice. Further analysis revealed a delay in the IgM response to lipoproteins expressed by the original inoculum; however, by 6 days of infection antibodies were produced in MyD88−/−mice that could clear spirochetemia inscidmice. While these results indicated that the production of IgM was delayed in MyD88−/−mice, they also point to a second, antibody-independent role for MyD88 signaling in host defense to relapsing feverBorrelia. This second defect was apparent only when antibody levels were limiting.
Microneedle-Based Intradermal Delivery of the Anthrax Recombinant Protective Antigen Vaccine
Authors: Mikszta John A. , Dekker John P. , Harvey Noel G. , Dean Cheryl H. , Brittingham John M. , Huang Joanne , Sullivan Vincent J. , Dyas Beverly , Roy Chad J. , Ulrich Robert G. 
Published: November 2006

ABSTRACT

The recombinant protective antigen (rPA) of
Bacillus anthracis
is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 μg of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.
Single Nucleotide Polymorphism in the Cytolethal Distending Toxin B Gene Confers Heterogeneity in the Cytotoxicity of
Actinobacillus actinomycetemcomitans
Authors: Nishikubo Shuichi , Ohara Masaru , Ikura Masae , Katayanagi Katsuo , Fujiwara Tamaki , Komatsuzawa Hitoshi , Kurihara Hidemi , Sugai Motoyuki 
Published: November 2006

ABSTRACT

Clinical
Actinobacillus actinomycetemcomitans
produces cytolethal distending toxin (CDT) with titers ranging from 10
2
to 10
8
U/mg. Single nucleotide polymorphism analysis of the
cdt
gene in clinical isolates identified a variation of a single amino acid at residue 281 of CdtB, which significantly affected CDT toxicity by modulating the chromatin-degrading activity of CdtB.
DEVELOPMENT OF PAVING MATERIAL FOR FOOTPATH AND CAR PARK PAVEMENT USING GRANITE SOIL
Authors: NAGAMACHI MASAHARU , MIZUGUCHI HIROYUKI , INOUE KENTARO , KAMADA KOICHI 
Published: November 2006

It is required to develop new paving materials for pavements, such as footpaths, car parks, etc., in parks, having good landscape. Such paving materials have been already developed, but these do not have sufficient strength, abrasion resistance and frost resistance. In this study, a new paving was examined material using cement, sand and granite soil. The mix proportion of this material tested was 2:4:4 of cement, sand and granite soil by mass. The maximum flexural and compressive strength were both obtained at a water content of 14% of the total mass, and the strength were several times larger than that of paving material on the market consisting of 10% of cement and 90% granite soil. The abrasion resistance was tested according to ASTM C 779, and this resistance was about four times greater than that of the paving material on the market. The frost resistance was obtained high value compared with the concrete of 72% in water cement ratio by a new simple resisting test method for freezing and thawing using liquid nitrogen and warm water. It is considered that this new paving material is applicable to pavement for footpath, car park, etc.
THE LIFE ASSESSMENT OF STEAM TURBINE ROTORS FOR FOSSIL POWER PLANTS
Authors: CHANG SUNGHO , SONG GEEWOOK , KIM BUMSHIN , HYUN JUNGSEB , HA JEONGSOO 
Published: November 2006

The operational mode of thermal power plants has been changed from base load to duty cycle. From the changeover, fossil power plants cannot avoid frequent thermal transient states, for example, start up and stop, which results in thermal fatigue damage at the heavy section components. The rotor is the highest capital cost component in a steam turbine and requires long outage for replacing with a new one. For an optimized power plant operational life, inspection management of the rotor is necessary. It is known in general that the start-up and shutdown operations greatly affect the steam turbine life. The start-up operational condition is especially severe because of the rapid temperature and rotational speed increase, which causes damage and reduction of life of the main components life of the steam turbine. The start-up stress of a rotor which is directly related to life is composed of thermal and rotational stresses. The thermal stress is due to the variation of steam flow temperature and rotational stress is due to the rotational speed of the turbine. In this paper, the analysis method for the start-up stress of a rotor is proposed, which considers simultaneously temperature and rotational speed transition, and includes a case study regarding a 500MW fossil power plant steam turbine rotor. Also, the method of quantitative damage estimation for fatigue-creep damage to operational conditions, is described. The method can be applied to find weak points for fatigue-creep damage. Using the method, total life consumption can be obtained, and can be also be used for determining future operational modes and life extension of old fossil power units.
Gene Expression Patterns Distinguish Colonoscopically Isolated Human Aberrant Crypt Foci from Normal Colonic Mucosa
Authors: Glebov Oleg K. , Rodriguez Luz M. , Soballe Peter , DeNobile John , Cliatt Janet , Nakahara Kenneth , Kirsch Ilan R. 
Published: November 2006

Abstract
Aberrant crypt foci (ACF) are considered the earliest identifiable preneoplastic colonic lesions; thus, a greater understanding of the nature of genetic changes underlying the transformation of normal colonic mucosa (NM) into ACF may provide insight into the mechanisms of carcinogenesis. ACF were identified by indigo carmine spraying onto colonic mucosa during colonoscopy and isolated as standard pinch biopsies of the mucosal areas containing the ACF. RNAs isolated from ACF and matched NM biopsies from the ascending and descending colons of 13 patients were analyzed on arrays containing 9128 cDNAs. Thirty-four differentially expressed (P &lt; 0.001) genes were found in a paired comparison of the ACF and NM samples, and 25 of 26 matched pairs of ACF and NM could be correctly classified in leave-one-out cross-validation. Differential expression for seven of eight genes was confirmed by real-time reverse transcription-PCR. Furthermore, ACF and NM samples, including six pairs of ACF and NM samples that had not previously been analyzed by array hybridization, can be correctly classified on the basis of the overexpression in ACF of three selected genes (REG4, SRPN-B5, and TRIM29) evaluated by real-time reverse transcription-PCR. In a separate analysis of 13 biopsy pairs from either ascending or descending colon, ACF and NM samples could also be correctly classified by the gene expression patterns. Analysis of gene expression differences in ACF from the ascending and descending colon versus NM samples indicates that ACF from these distinct colonic locations are converging toward similar gene expression profiles and losing differences in gene expression characteristic of NM from the ascending versus descending colon. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2253–62)