bluuebunny/crossref_metadata_2025 huggingface dataset:
IpaD Localizes to the Tip of the Type III Secretion System Needle of
Shigella flexneri
Authors: Espina Marianela , Olive Andrew J. , Kenjale Roma , Moore David S. , Ausar S. Fernando , Kaminski Robert W. , Oaks Edwin V. , Middaugh C. Russell , Picking William D. , Picking Wendy L.
Published: July 2006

Shigella flexneri
, the causative agent of shigellosis, is a gram-negative bacterial pathogen that initiates infection by invading cells within the colonic epithelium. Contact with host cell surfaces induces a rapid burst of protein secretion via the
Shigella
type III secretion system (TTSS). The first proteins secreted are IpaD, IpaB, and IpaC, with IpaB and IpaC being inserted into the host cell membrane to form a pore for translocating late effectors into the target cell cytoplasm. The resulting pathogen-host cross talk results in localized actin polymerization, membrane ruffling, and, ultimately, pathogen entry. IpaD is essential for host cell invasion, but its role in this process is just now coming to light. IpaD is a multifunctional protein that controls the secretion and presentation of IpaB and IpaC at the pathogen-host interface. We show here that antibodies recognizing the surface-exposed N terminus of IpaD neutralize
Shigella
's ability to promote pore formation in erythrocyte membranes. We further show that MxiH and IpaD colocalize on the bacterial surface. When TTSS needles were sheared from the
Shigella
surface, IpaD was found at only the needle tips. Consistent with this, IpaD localized to the exposed tips of needles that were still attached to the bacterium. Molecular analyses then showed that the IpaD C terminus is required for this surface localization and function. Furthermore, mutations that prevent IpaD surface localization also eliminate all IpaD-related functions. Thus, this study demonstrates that IpaD localizes to the TTSA needle tip, where it functions to control the secretion and proper insertion of translocators into host cell membranes.
Antibody-Mediated Disease Remission in the Mouse Model of Lyme Borreliosis
Authors: Barthold Stephen W. , Hodzic Emir , Tunev Stefan , Feng Sunlian
Published: July 2006

In the mouse model of Lyme borreliosis, the host immune response during infection withBorrelia burgdorferiresults in the remission of carditis and arthritis, as well as global reduction of spirochete numbers in tissues, without elimination of infection (28). These events were recapitulated by passive transfer of immune serum from infected immunocompetent mice or T-cell-deficient mice to severe combined immunodeficient (SCID) mice. Previous studies have shown that immune serum is reactive against arthritis-related protein (Arp) and that Arp antiserum induces arthritis remission (16). However, although immune serum from T-cell-deficient mice induced disease remission, it was not reactive against Arp, suggesting that antibody to another antigen may be responsible. T-cell-deficient mouse immune serum was reactive to decorin binding protein A (DbpA). Therefore, DbpA antiserum was tested to determine its ability to induce disease remission in SCID mice. Antisera to Arp or DbpA induced both carditis and arthritis remission but did not significantly reduce spirochete numbers in tissues, based upon quantitativeflaBDNA analysis, nor did treatment affect RNA levels of several genes, includingarpanddbpA. Immunohistochemical labeling of spirochetes in hearts and joints during disease remission induced by adoptive transfer of lymphocytes, passive transfer of immune serum, or passive transfer of DbpA antiserum revealed that such treatment resulted in elimination of spirochetes from heart base and synovium but not vascular walls, tendons, or ligaments. These results suggest that Arp and DbpA antibodies may be active as disease-resolving components in immune serum but antibody against other antigens may be involved in reductions of spirochetes in tissues.
Homologous and Cross-Reactive Immune Responses to Enterotoxigenic
Escherichia coli
Colonization Factors in Bangladeshi Children
Authors: Qadri Firdausi , Ahmed Firoz , Ahmed Tanvir , Svennerholm Ann-Mari
Published: July 2006

We have studied homologous (HoM) and cross-reacting (CR) immunoglobulin A (IgA) antibody responses to colonization factors (CFs) in Bangladeshi children with diarrhea due to enterotoxigenic
E. coli
(ETEC) strains of the CF antigen I (CFA/I) group (CFA/I,
n
= 25; coli surface antigen 4 [CS4],
n
= 8; CS14,
n
= 11) and the CS5 group (CS5,
n
= 15; CS7,
n
= 8), respectively. The responses to the HoM, CR, and heterologous (HeT) CF antigens in each group of patient were studied and compared to that seen in healthy children (
n
= 20). In the CFA/I group (CFA/I and CS14), patients responded with antibody-secreting cell (ASC) responses to HoM CFs (geometric mean, 156 to 329 ASCs/10
6
peripheral blood mononuclear cells [PBMCs]) and to CR CFs (≈15 to 38 ASCs/10
6
PBMCs) but least of all to the HeT CS5 antigen (2 to 4 ASCs/10
6
PBMCs). For the CS5 group of patients with ETEC (CS5 and CS7), likewise, responses to HoM CFs (230 to 372 ASCs/10
6
PBMCs) and CR CFs (27 to 676 ASCs/10
6
PBMCs) were seen, along with lower responses to the HeT CFA/I antigen (9 to 38 ASCs/10
6
PBMCs). Both groups of patients responded with CF-specific IgA antibodies to HoM and CR antigens in plasma but responded less to the HeT CFs. The responses in patients were seen very soon after the onset of diarrhea and peaked around 1 week after onset. Vaccinees who had received two doses of the oral, killed whole-cell ETEC vaccine (CF-BS-ETEC) responded with plasma IgA antibodies to CFA/I, a component of the vaccine, but also to the CR CS14 antigen, which was not included in the vaccine, showing that antibody responses can be stimulated by a CFA/I-containing ETEC vaccine to a CR-reacting antigen in individuals in countries where ETEC is endemic.
Maltodextrin Utilization Plays a Key Role in the Ability of Group A
Streptococcus
To Colonize the Oropharynx
Authors: Shelburne Samuel A. , Sumby Paul , Sitkiewicz Izabela , Okorafor Nnaja , Granville Chanel , Patel Payal , Voyich Jovanka , Hull Richard , DeLeo Frank R. , Musser James M.
Published: July 2006

Analysis of multiple group A
Streptococcus
(GAS) genomes shows that genes encoding proteins involved in carbohydrate utilization comprise some 15% of the core GAS genome. Yet there is a limited understanding of how carbohydrate utilization contributes to GAS pathogenesis. Previous genome-wide GAS studies led us to a focused investigation of MalE, a putative maltodextrin-binding protein. Analysis of 28 strains of 22 distinct M protein serotypes showed that MalE is highly conserved among diverse GAS strains.
malE
transcript levels were significantly increased during growth in human saliva compared to growth in a chemically defined glucose-containing medium or a nutrient-rich medium. MalE was accessible to antibody binding, indicating that it is expressed on the GAS cell surface. Moreover, growth in human saliva appeared to increase MalE surface expression compared to growth in a nutrient-rich medium. Analysis of a Δ
malE
isogenic mutant strain revealed decreased growth in human saliva compared to wild-type GAS. Radiolabeled carbohydrate binding assays showed that MalE was required for the binding of maltose but not glucose. The Δ
malE
isogenic mutant strain colonized a lower percentage of GAS-challenged mice compared to wild-type and genetically complemented strains. Furthermore, decreased numbers of CFU were recovered from mice infected with the Δ
malE
strain compared to those infected with wild-type GAS. These data demonstrate that maltodextrin acquisition is likely to be a key factor in the ability of GAS to successfully infect the oropharynx. Further investigation into carbohydrate transport and metabolism pathways may yield novel insights into GAS pathogenesis.
Reduction of the Ganglioside Binding Activity of the Tetanus Toxin H
C
Fragment Destroys Immunogenicity: Implications for Development of Novel Tetanus Vaccines
Authors: Qazi Omar , Sesardic Dorothea , Tierney Robert , Söderbäck Zahra , Crane Dennis , Bolgiano Barbara , Fairweather Neil
Published: July 2006

In this study, the immunogenicities of the nontoxic H
C
fragment of tetanus toxin and derivatives lacking ganglioside binding activity were compared with that of tetanus toxoid after subcutaneous immunization of mice. Wild-type H
C
(H
C
WT) protein and tetanus toxoid both elicited strong antibody responses against toxoid and H
C
antigens and provided complete protection against toxin challenge. Mutants of H
C
containing deletions essential for ganglioside binding elicited lower responses than H
C
WT. H
C
M115, containing two amino acid substitutions within the ganglioside binding site, provided reduced protection against tetanus toxin challenge compared with H
C
WT, consistent with lower anti-H
C
and anti-toxoid antibody titers. Circular-dichroism spectroscopy and intrinsic fluorescence spectroscopy showed minimal structural perturbation in H
C
M115. We conclude that the presence of the ganglioside binding site within H
C
may be essential for induction of a fully protective anti-tetanus response comparable to that induced by tetanus toxoid by subcutaneous injection.
Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral
Mycobacterium bovis
BCG Immunization against Pulmonary Tuberculosis
Authors: Santosuosso Michael , McCormick Sarah , Zhang Xizhong , Zganiacz Anna , Xing Zhou
Published: July 2006

Parenterally administered
Mycobacterium bovis
BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary
Mycobacterium tuberculosis
challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.
Role and Regulation of the
Shigella flexneri
Sit and MntH Systems
Authors: Runyen-Janecky Laura , Dazenski Ellyn , Hawkins Stephanie , Warner Lisa
Published: July 2006

Shigella flexneri
possesses at least two putative high-affinity manganese acquisition systems, SitABCD and MntH. Mutations in the genes encoding the components of both of these systems were constructed in
S. flexneri
. The
sitA mntH
mutant showed reduced growth, relative to the wild type, in Luria broth (L broth) containing the divalent metal chelator ethylene diamino-
o
-dihydroxyphenyl acetic acid, and the addition of either iron or manganese restored growth to the level of the wild-type strain. Although the
sitA mntH
mutant was not defective in surviving exposure to superoxide generators, it was defective in surviving exposure to hydrogen peroxide. The
sitA mntH
mutant formed wild-type plaques on Henle cell monolayers but had a reduced ability to survive in activated macrophage lines. Expression of the
S. flexneri sit
and
mntH
promoters was higher when
Shigella
was in Henle cells than when it was in L broth. Expression of both the
sit
and
mntH
promoters was repressed by either iron or manganese, and this repression was partially dependent upon Fur and MntR, respectively. The
mntH
promoter, but not the
sit
promoter, exhibited OxyR-dependent induction in the presence of hydrogen peroxide.
Deletion of the Regulatory Subunit of Protein Kinase A in
Aspergillus fumigatus
Alters Morphology, Sensitivity to Oxidative Damage, andVirulence
Authors: Zhao Wei , Panepinto John C. , Fortwendel Jarrod R. , Fox Lauren , Oliver Brian G. , Askew David S. , Rhodes Judith C.
Published: July 2006

Aspergillus
fumigatus
is an important opportunistic fungal pathogen. The
cAMP-dependent protein kinase (PKA) signaling pathway plays an
important role in regulating morphology, growth, and virulence in a
number of fungal pathogens of plants and animals. We have constructed a
mutant of
A. fumigatus
that lacks the regulatory subunit of
PKA,
pkaR
, and analyzed the growth and development,
sensitivity to oxidative damage, and virulence of the mutant, along
with those of the wild type and a complemented mutant. Both growth and
germination rates of the mutant are reduced, and there are
morphological abnormalities in conidiophores, leading to reduced
conidiation. Conidia from the Δ
pkaR
mutant are more
sensitive to killing by hydrogen peroxide, menadione, paraquat, and
diamide. However, the hyphae of the mutant are killed to a greater
extent only by paraquat and diamide, whereas they are less susceptible
to the effects of hydrogen peroxide. In an immunosuppressed mouse
model, intranasally administered conidia of the mutant are
significantly less virulent than those of the wild type or a
complemented mutant. Unregulated PKA signaling is detrimental to the
virulence of
A. fumigatus
, perhaps through the reduced
susceptibility of the mutant to damage by oxidizing agents and reduced
growth
kinetics.
Swapping of Periplasmic Domains between
Brucella suis
VirB8 and a pSB102 VirB8 Homologue Allows Heterologous Complementation
Authors: Patey Gilles , Qi Zhong , Bourg Gisele , Baron Christian , O'Callaghan David
Published: July 2006

A
Brucella suis
mutant with a nonpolar deletion in the
virB8
gene was attenuated in a macrophage infection model. Complementation with the
B. suis
VirB8 protein expressed from the
virB
promoter restored virulence. Expression of TraJ, a VirB8 homologue from plasmid pSB102, did not restore virulence; however, virulence was partially restored by a chimeric protein containing the N terminus of the
B. suis
VirB8 protein and the C-terminal periplasmic domain of TraJ.
Cytotoxic Necrotizing Factor Type 1 Delivered by Outer Membrane Vesicles of Uropathogenic
Escherichia coli
Attenuates Polymorphonuclear Leukocyte Antimicrobial Activity and Chemotaxis
Authors: Davis Jon M. , Carvalho Humberto M. , Rasmussen Susan B. , O'Brien Alison D.
Published: July 2006

Cytotoxic necrotizing factor type 1 (CNF1), a toxin produced by many strains of uropathogenic
Escherichia coli
(UPEC), constitutively activates small GTPases of the Rho family by deamidating a single amino acid within these target proteins. Such activated GTPases not only stimulate actin polymerization within affected cells but also, as we previously reported, decrease membrane fluidity on mouse polymorphonuclear leukocytes (PMNs). In that same investigation we found that this diminished membrane movement impedes the clustering of the complement receptor CD11b/CD18 on PMNs and, in turn, decreases PMN phagocytic capacity and microbicidal activity on PMNs in direct contact with CNF1-expressing UPEC as well as on those in proximity to wild-type UPEC. The latter observation suggested to us that CNF1 is released from neighboring bacteria, although at the time of initiation of the study described here, no specific mechanism for export of CNF1 from UPEC had been described. Here we present evidence that CNF1 is released from the CNF1-expressing UPEC strain CP9 (serotype O4/H5/K54) in a complex with outer membrane vesicles (OMVs) and that these CNF1-bearing vesicles transfer biologically active CNF1 to PMNs and attenuate phagocyte function. Furthermore, we show that CNF1-bearing vesicles act in a dose-dependent fashion on PMNs to inhibit their chemotactic response to formyl-Met-Leu-Phe, while purified CNF1 does not. We conclude that OMVs provide a means for delivery of CNF1 from a UPEC strain to PMNs and thus negatively affect the efficacy of the acute inflammatory response to these organisms.
Construction and Characterization of an Attenuated Purine Auxotroph in aFrancisella tularensisLive Vaccine Strain
Authors: Pechous Roger , Celli Jean , Penoske Renee , Hayes Stanley F. , Frank Dara W. , Zahrt Thomas C.
Published: July 2006

Francisella tularensisis a facultative intracellular pathogen and is the etiological agent of tularemia. It is capable of escaping from the phagosome, replicating to high numbers in the cytosol, and inducing apoptosis in macrophages of a variety of hosts.F. tularensishas received significant attention recently due to its potential use as a bioweapon. Currently, there is no licensed vaccine againstF. tularensis, although a partially protective live vaccine strain (LVS) that is attenuated in humans but remains fully virulent for mice was previously developed. AnF. tularensisLVS mutant deleted in thepurMCDpurine biosynthetic locus was constructed and partially characterized by using an allelic exchange strategy. TheF. tularensisLVS ΔpurMCDmutant was auxotrophic for purines when grown in defined medium and exhibited significant attenuation in virulence when assayed in murine macrophages in vitro or in BALB/c mice. Growth and virulence defects were complemented by the addition of the purine precursor hypoxanthine or by introduction ofpurMCDNintrans. TheF. tularensisLVS ΔpurMCDmutant escaped from the phagosome but failed to replicate in the cytosol or induce apoptotic and cytopathic responses in infected cells. Importantly, mice vaccinated with a low dose of theF. tularensisLVSΔpurMCDmutant were fully protected against subsequent lethal challenge with the LVS parental strain. Collectively, these results suggest thatF. tularensismutants deleted in thepurMCDbiosynthetic locus exhibit characteristics that may warrant further investigation of their use as potential live vaccine candidates.
Filaria-Induced Monocyte Dysfunction and Its Reversal following Treatment
Authors: Semnani Roshanak Tolouei , Keiser Paul B. , Coulibaly Yaya I. , Keita Falaye , Diallo Abdallah A. , Traore Diakaridia , Diallo Dapa A. , Doumbo Ogobara K. , Traore Sekou F. , Kubofcik Joseph , Klion Amy D. , Nutman Thomas B.
Published: July 2006

Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from filaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation withStaphylococcus aureusCowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1α, MIP-1β, and IL-1α and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1α, MIP-1α, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment.
Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection
Authors: Goellner Stefanie , Schubert Evelyn , Liebler-Tenorio Elisabeth , Hotzel Helmut , Saluz Hans Peter , Sachse Konrad
Published: July 2006

The obligatory intracellular bacteriumChlamydophila psittaciis the causative agent of psittacosis in birds and humans. The capability of this zoonotic pathogen to develop a persistent phase is likely to play a role in chronicity of infections, as well as in failure of antibiotic therapy and immunoprophylaxis. To elucidate three different in vitro models for transition ofC. psittacito persistence (iron depletion, penicillin G treatment, and gamma interferon [IFN-γ] exposure), a set of 27 genes was examined by mRNA expression analysis using quantitative real-time PCR. While the phenotypical characteristics were the same as in other chlamydiae, i.e., aberrant morphology of reticulate bodies, loss of cultivability, and rescue of infectivity upon removal of inducers, the transcriptional response ofC. psittacito persistence-inducing factors included several new and distinctive features. Consistent downregulation of membrane proteins, chlamydial sigma factors, cell division protein, and reticulate body-elementary body differentiation proteins from 24 h postinfection onward proved to be a general feature ofC. psittacipersistence. However, other genes displayed considerable variations in response patterns from one model to another, which suggests that there is no persistence model per se. In contrast to results forChlamydia trachomatis, late shutdown of essential genes inC. psittaciwas more comprehensive with IFN-γ-induced persistence, which is probably due to the absence of a functional tryptophan synthesis operon.
Immunogenicity ofMycobacterium tuberculosisAntigens inMycobacterium bovisBCG-Vaccinated andM. bovis-Infected Cattle
Authors: Mustafa A. S. , Skeiky Y. A. , Al-Attiyah R. , Alderson M. R. , Hewinson R. G. , Vordermeier H. M.
Published: July 2006

The development of novel vaccine strategies supplementingMycobacterium bovisBCG (BCG) constitutes an urgent research challenge. To identify potential subunit vaccine candidates, we have tested a series of eight recently identifiedMycobacterium tuberculosisantigens inM. bovis-infected and BCG-vaccinated cattle. These antigens were characterized on the basis of their ability to induce in vitro gamma interferon responses in infected or BCG-vaccinated calves. We were able to establish a hierarchy of these antigens based on how frequently they were recognized in both groups of animals. In particular, we were able to prioritize frequently recognized proteins like Rv0287, Rv1174, and Rv1196 for future evaluation as subunit vaccines to be used in BCG-protein heterologous prime-boost vaccination scenarios. In addition, the antigen most dominantly recognized inM. bovis-infected cattle in this study, Rv3616c, was significantly less frequently recognized by BCG vaccinees and could be a target to improve BCG, for example, by increasing its secretion, in a recombinant BCG vaccine.
Immunity to RecombinantPlasmodium falciparumMerozoite Surface Protein 1 (MSP1): Protection inAotus nancymaiMonkeys Strongly Correlates with Anti-MSP1 Antibody Titer and In Vitro Parasite-Inhibitory Activity
Authors: Singh Sanjay , Miura Kazutoyo , Zhou Hong , Muratova Olga , Keegan Brian , Miles Aaron , Martin Laura B. , Saul Allan J. , Miller Louis H. , Long Carole A.
Published: July 2006

A number of malarial blood-stage candidate vaccines are currently being tested in human clinical trials, but our understanding of the relationship between clinical immunity and data obtained from in vitro assays remains inadequate. An in vitro assay which could reliably predict protective immunity in vivo would facilitate vaccine development. Merozoite surface protein1 (MSP1) is a leading blood-stage malaria vaccine candidate, and anti-MSP1 antibodies from individuals that are clinically immune to malaria inhibit the invasion ofPlasmodiummerozoites into erythrocytes in vitro. Using expression inEscherichia coliand subsequent refolding, we have produced two allelic forms of MSP142(FVO and 3D7).Aotus nancymaimonkeys were immunized with MSP142-FVO, MSP142-3D7, or a combination of FVO and 3D7 allelic forms, (MSP142-C1) and were subsequently challenged withPlasmodium falciparumFVO parasites. Sera obtained prior to challenge were tested by standardized enzyme-linked immunosorbent assay (ELISA) to determine antibody titer, and immunoglobulin G (IgG) fractions were also obtained from the same sera; the IgG fractions were tested in an in vitro growth inhibition (GI) assay to evaluate biological activity of the antibodies. Regardless of the immunogen used, all monkeys that had >200,000 ELISA units against MSP142-FVO antigen before challenge controlled their infections. By contrast, all monkeys whose purified IgGs gave <60% inhibition activity in an in vitro GI assay withP. falciparumFVO required treatment for high parasitemia after challenge. There is a strong correlation between ELISA units (Spearman rank correlation of greater than 0.75) or GI activity (Spearman rank correlation of greater than 0.70) and protective immunity judged by various parameters (e.g., cumulative parasitemia or day of patency). These data indicate that, in this monkey model, the ELISA and GI assay values can significantly predict protective immunity induced by a blood-stage vaccine, and they support the use of these assays as part of evaluation of human clinical trials of MSP1-based vaccines.
Role of Transcription Factor T-bet Expression by CD4+Cells in Gastritis Due toHelicobacter pyloriin Mice
Authors: Eaton Kathryn A. , Benson Lucy H. , Haeger Jennifer , Gray Brian M.
Published: July 2006

Gastritis due toHelicobacter pyloriis induced by a Th1-mediated response that is CD4 cell and gamma interferon (IFN-γ) dependent. T-bet is a transcription factor that directs differentiation of and IFN-γ secretion by CD4+Th1 T cells. The goal of this study was to use two mouse models to elucidate the role of T-bet in gastritis due toH. pylori. C57BL/6J mice, congenic T-bet knockout (KO) mutants, or congenic SCID (severe, combined immunodeficient) mutants were given liveH. pyloriby oral inoculation. SCID mice were given CD4+splenocytes from C57BL/6J or T-bet KO mice by intraperitoneal injection. Twelve or 24 weeks after bacterial inoculation, C57BL/6J mice developed moderate gastritis but T-bet KO mice and SCID mice did not. In contrast, SCID recipients of either C57BL/6J T cells or T-bet KO T cells developed gastritis 4 or 8 weeks after adoptive transfer. In recipients of C57BL/6J CD4+cells but not recipients of T-bet KO cells, gastritis was associated with a delayed-type hypersensitivity response toH. pyloriantigen and elevated gastric and serum IFN-γ, interleukin 6, and tumor necrosis factor alpha. In spite of the absence of IFN-γ expression, indicating failure of Th1 differentiation, CD4+T cells from T-bet KO mice induce gastritis inH. pylori-infected recipient SCID mice. This indicates that Th1-independent mechanisms can cause gastric inflammation and disease due toH. pylori.
Hemin-Dependent Modulation of the Lipid A Structure of
Porphyromonas gingivalis
Lipopolysaccharide
Authors: Al-Qutub Montaser N. , Braham Pamela H. , Karimi-Naser Lisa M. , Liu Xinyan , Genco Caroline A. , Darveau Richard P.
Published: July 2006

Porphyromonas gingivalis
is a periopathogen strongly associated with the development of adult-type periodontitis. Both the virulence characteristics of periopathogens and host-related factors are believed to contribute to periodontitis.
P. gingivalis
lipopolysaccharide (LPS) displays a significant amount of lipid A structural heterogeneity, containing both penta- and tetra-acylated lipid A structures. However, little is known concerning how the lipid A structural content of
P. gingivalis
is regulated. Alterations in the lipid A content may facilitate the ability of
P. gingivalis
to modulate the innate host response to this bacterium. In this report, it is shown that the concentration of hemin in the growth medium significantly modulates the lipopolysaccharide lipid A structural content of
P. gingivalis
. Hemin is a key microenvironmental component of gingival cervicular fluid which is believed to vary depending upon the state of vascular ulceration. At low hemin concentrations, one major penta-acylated lipid A structure was found, whereas at high concentrations of hemin, multiple tetra- and penta-acylated lipid A structures were observed. Hemin concentrations, not iron acquisition, were responsible for the alterations in the lipid A structural content. The modifications of the lipid A structural content were independent of the LPS extraction procedure and occurred in a variety of laboratory strains as well as a freshly obtained clinical isolate. The known hemin binding proteins Kgp and HmuR contributed to the lipid A modulation sensing mechanism. To the best of our knowledge, this is the first report that hemin, a clinically relevant microenvironmental component for
P. gingivalis
, can modulate the lipid A structure found in a bacterium. Since tetra- and penta-acylated
P. gingivalis
lipid A structures have opposing effects on Toll-like receptor 4 activation, the alteration of the lipid A structural content may have significant effects on the host response to this bacterium.
Expression and Antimicrobial Function of Bactericidal Permeability-Increasing Protein in Cystic Fibrosis Patients
Authors: Aichele Diana , Schnare Markus , Saake Marc , Röllinghoff Martin , Gessner Andre
Published: July 2006

In cystic fibrosis (CF), the condition limiting the prognosis of affected children is the chronic obstructive lung disease accompanied by chronic and persistent infection with mostly mucoid strains ofPseudomonas aeruginosa. The majority of CF patients have antineutrophil cytoplasmic antibodies (ANCA) primarily directed against the bactericidal permeability-increasing protein (BPI) potentially interfering with antimicrobial effects of BPI. We analyzed the expression of BPI in the airways of patients with CF. In their sputum samples or bronchoalveolar lavage specimens, nearly all patients expressed BPI mRNA and protein, which were mainly products of neutrophil granulocytes as revealed by intracellular staining and subsequent flow cytometry. Repeated measurements revealed consistent individual BPI expression levels during several months quantitatively correlating with interleukin-8. In vitro,P. aeruginosaisolates from CF patients initiated the rapid release of BPI occurring independently of protein de novo syntheses. Furthermore, purified natural BPI as well as a 27-mer BPI-derived peptide displayed antimicrobial activity against even patient-derived mucoidP. aeruginosastrains and bacteria resistant against all antibiotics tested. Thus, BPI that is functionally active against mucoidP. aeruginosastrains is expressed in the airways of CF patients but may be hampered by autoantibodies, resulting in chronic infection.
Plasmid Diversity in Neisseriae
Authors: van Passel Mark W. J. , van der Ende Arie , Bart Aldert
Published: July 2006

Horizontal gene transfer constitutes an important force in prokaryotic genome evolution, and it is well-known that plasmids are vehicles for DNA transfer. Chromosomal DNA is frequently exchanged between pathogenic and commensal neisseriae, but relatively little is known about plasmid diversity and prevalence among these nasopharyngeal inhabitants. We investigated the plasmid contents of 18
Neisseria lactamica
isolates and 20 nasopharyngeal
Neisseria meningitidis
isolates. Of 18
N. lactamica
strains, 9 harbored one or more plasmids, whereas only one
N. meningitidis
isolate contained a plasmid. Twelve plasmids were completely sequenced, while five plasmid sequences from the public databases were also included in the analyses. On the basis of nucleic acid sequences, mobilization, and replicase protein alignments, we distinguish six different plasmid groups (I to VI). Three plasmids from
N. lactamica
appeared to be highly similar on the nucleotide level to the meningococcal plasmids pJS-A (>99%) and pJS-B (>75%). The genetic organizations of two plasmids show a striking resemblance with that of the recently identified meningococcal disease-associated (MDA) phage, while four putative proteins encoded by these plasmids show 25% to 39% protein identity to those encoded by the MDA phage. The putative promoter of the gene encoding the replicase on these plasmids contains a polycytidine tract, suggesting that replication is subjected to phase variation. In conclusion, extensive plasmid diversity is encountered among commensal neisseriae. Members of three plasmid groups are found in both pathogenic and commensal neisseriae, indicating plasmid exchange between these species. Resemblance between plasmids and MDA phage may be indicative of dissemination of phage-related sequences among pathogenic and commensal neisseriae.
SOLUTION FOR THE EIGENENERGIES OF SEXTIC ANHARMONIC OSCILLATOR POTENTIAL V(x)=A6x6+A4x4+A2x2
Authors: SOUS A. J.
Published: July 2006

In this paper a study of the sextic anharmonic oscillator potential V(x)=A6x6+A4x4+A2x2 (A6≠0) using the asymptotic iteration method is presented. We calculate the eigenenergies for different excited states. The used method works very well for this potential and in fact one is able to obtain high accuracy with the asymptotic iteration method. A comparison between our results with other methods found in literature is presented.
REPRESENTATIONS OF GENERALIZED Ar STATISTICS AND EIGENSTATES OF JACOBSON GENERATORS
Authors: DAOUD M.
Published: July 2006

We investigate a generalization of Ar statistics discussed recently in the literature. The explicit complete set of state vectors for the Ar statistics system is given. We consider a Bargmann or an analytic function description of the Fock space corresponding to Ar statistics of bosonic kind. This brings, in a natural way, the so-called Gazeau–Klauder coherent states defined as eigenstates of the Jacobson annihilation operators. The minimization of Robertson uncertainty relation is also considered.
VON NEUMANN COORDINATIZATION IS NOT FIRST-ORDER
Authors: WEHRUNG FRIEDRICH
Published: July 2006

A lattice L is coordinatizable, if it is isomorphic to the lattice L(R) of principal right ideals of some von Neumann regular ring R. This forces L to be complemented modular. All known sufficient conditions for coordinatizability, due first to von Neumann, then to Jónsson, are first-order. Nevertheless, we prove that coordinatizability of lattices is not first-order, by finding a non-coordinatizable lattice K with a coordinatizable countable elementary extension L. This solves a 1960 problem of Jónsson. We also prove that there is no [Formula: see text] statement equivalent to coordinatizability. Furthermore, the class of coordinatizable lattices is not closed under countable directed unions; this solves another problem of Jónsson from 1962.
Eventrons
Authors: Spoonhower Daniel , Auerbach Joshua , Bacon David F. , Cheng Perry , Grove David
Published: July 2006

While real-time garbage collection has achieved worst-case latencies on the order of a millisecond, this technology is approaching its practical limits. For tasks requiring extremely low latency, and especially periodic tasks with frequencies above 1 KHz, Java programmers must currently resort to the NoHeapRealtimeThread construct of the Real-Time Specification for Java. This technique requires expensive run-time checks, can result in unpredictable low-level exceptions, and inhibits communication with the rest of the garbage-collected application. We present
Eventrons
, a programming construct that can arbitrarily preempt the garbage collector, yet guarantees safety
and
allows its data to be visible to the garbage-collected heap. Eventrons are a strict subset of Java, and require no run-time memory access checks. Safety is enforced using a
data-sensitive
analysis and simple run-time support with extremely low overhead. We have implemented Eventrons in IBM's J9 Java virtual machine, and present experimental results in which we ran Eventrons at frequencies up to 22 KHz (a 45
μ
s period). Across 10 million periods, 99.997% of the executions ran within 10
μ
ss of their deadline, compared to 99.999% of the executions of the equivalent program written in C.
Developing a superset language of smalltalk for modeling distributed mechanical design systems
Authors: Xue Deyi
Published: July 2006

This paper presents our experience on further development of a superset language of Smalltalk for modeling distributed mechanical design systems. In this language, mechanical system modeling primitives are called features. Features are described at two levels, class level and instance level, representing standard product libraries and special product data, respectively. Features modeled at different locations are associated by Internet. Class features at remote locations can be used for generating instance features at the local site. Instance features at remote locations can be accessed from the local site. This new language was implemented using Smalltalk.
The Josephus Flavius' problem
Authors: Henderson Peter B.
Published: July 2006

You may have used the Josephus Problem as a programming assignment in one of your courses. I have been using this problem for many years in CS1 or CS2, primarily to illustrate applications of various data structures and algorithmic problem solving. The resulting "brute force" solution works, but is not elegant. Accordingly, I challenge students to analyze the problem more mathematically and use mathematical thinking to seek a more precise solution. Few students are successful. However, computer science students should develop the skills necessary to find both solutions, algorithmic and mathematical model. The latter provides an efficient solution that can be used to validate the algorithmic solution -- very important for critical systems components.
Las Vegas does n-queens
Authors: Rolfe Timothy J.
Published: July 2006

This paper presents two Las Vegas algorithms to generate single solutions to the n-queens problem. One algorithm generates and improves on random permutation vectors until it achieves one that is a successful solution, while the other algorithm randomly positions queens within each row in positions not under attack from above.
It is time for a computer application degree
Authors: Wang Yang
Published: July 2006

Contemporary computer technology has spread computing activity to almost every field. The computing industry's need for application software developers who have not only proficient programming skills but also a good understanding of subjects in a specific application field has grown rapidly. Continuing to use existing degree programs in computer science to train expected application software developers would not only be a disservice to students but also hamper the further development of computer science programs themselves. Thus, a new degree program is called for in the sub-discipline of computer applications.
PL/I bulletin no. 5
Authors: Southworth R. N.
Published: July 2006

This issue contains (PB5.3.4) the proceedings of the PL/I Forum held on Z8 August 1967, (PB5.3.5) a survey taken at the forum and (PB5.3.6 thru .9) several papers presented at the forum. Several other papers which were presented at the forum are being held over for PB6.
Fortran information bulletin no. 1
Authors: Golde Hellmut
Published: July 2006

This first issue of the FIB may be considered a "trial balloon" as to its contents. While it does not contain a large amount of information, I have tried to gather a number of items which I feel might be of interest to you, the readers. I hope to get some feed- back about the material in this first issue, particularly with regard to desirable and undesirable features.Since the FIB was announced only a short time ago, I have not yet received many contributions. I hope that this will improve after you see this first, albeit skimpy, issue, since the frequency and content of the future issues will depend entirely on contributions from the readership.I have started to establish contact with a fairly sizable number of users groups in the hope that they will contribute to the FIB either through their membership or directly by permission to reprint or abstract their minutes. As an example of this kind of contribution see the report from the SHARE FORTRAN Project in this issue. (Incidentally, what is the accepted way of writing, FORTRAN or Fortran?)
Editor's message
Authors: Diot Christophe
Published: July 2006

Many good news in this issue. First, the increasing quality of the submissions is reflected by 6 articles being published. We received 20 papers for this issue.The editorial section is structuring with the third "10 recommended readings" by David Wetherall. This column is so successful that we appointed Jim Kurose as honorary 10 recommended readings editor. For next issues, you can send him your contribution directly. We also decided to show our support to the SIGCOMM conference's "test of time" award by starting a new column: Test of time: rejected 10 years ago, but still worth reading. Greg Minshall's paper on IP Switching is the first paper to be published in this column, with an introduction from Jon Crowcroft. Michalis Faloutsos' column is also addressing a serious problem with a non serious tone: who is the real father of the Internet? Michalis does a great job at demystifying the topic. We hope nobody feels insulted (we tried to avoid that); but we hope someone will react.Last, we are about to launch an on-line CCR virtual community and it is a coincidence that we publish the short paper by Fabio Ricciato making the case for a WiKi to support paper discussion. Ernst Biersack (from EURECOM) and his student Moritz Steiner have been prototyping a CCR community that we will make available to privileged users this summer, and that will be discussed at SIGCOMM. This community will allow researchers to publish articles on-line, apply for papers to review, comment on papers, give their opinion and interact, etc. Contact us if you want to help with the test and design of this new community service. We hope to launch it before the end of this year.
Flow labelled IP over ATM
Authors: Minshall Greg , Hinden Bob , Hoffman Eric , Liaw Fong Ching , Lyon Tom , Newman Peter
Published: July 2006

We describe a system in which layer 2 switching is placed directly under the control of layer 3 routing protocols on a hop-by-hop basis. Specifically, ATM switching is controlled by IP. We couple each ATM switch with a general purpose computer running IP routing and management protocols. We define a default ATM virtual channel identifier (VCI) to be used for transmitting IP packets over ATM links. We then define mechanisms which allow specific
flows
to be transmitted on specific ATM VCIs. The resulting system obeys IP's semantics for routing and forwarding, and takes advantage of ATM's switching hardware to accelerate the forwarding of packets. While this system takes advantage of ATM hardware, the ATM signalling, routing, and management architecture (as specified by the ATM Forum) is replaced by the protocols and practices currently in use for IP routing and management.
Design and implementation of a modern compiler course
Authors: Waite William M. , Jarrahian Assad , Jackson Michele H. , Diwan Amer
Published: July 2006

Current literature states that the undergraduate curriculum can no longer afford the luxury of a traditional compiler construction course. Nevertheless, there is an increasing need for an understanding of how to design and implement domain-specific languages. This paper presents a modern course in compiler construction, designed to provide a student with the capability of quickly constructin robust processors for a variety of language-related applications.
Student attitudes toward pair programming
Authors: Hanks Brian
Published: July 2006

Students in four introductory programming classes who participated in a pair programming study had very positive attitudes toward pair programming: they liked it, thought that it was fun, would like to do it again, and believed that they learned more because they paired. Although the students as a whole had positive attitudes, the results were not consistent between instructors; in particular, the students in one of the courses were significantly less positive about pair programming. The implications of instructor-based differences in attitude are discussed.This paper also examines the relationship between student confidence and attitudes toward pair programming. The most confident students liked pairing the most, while the least confident students liked it the least. This finding contradicts results that have been reported elsewhere.
Design and applications of an algorithm benchmark system in a computational problem solving environment
Authors: Chen Ming-Yu , Wei Jyh-Da , Huang Jeng-Hung , Lee D. T.
Published: July 2006

Benchmark tests are often used to evaluate the quality of products by a set of common criteria. In this paper we describe a computational problem solving environment based on open source codes and an algorithm benchmark system, which is embedded in the environment as a plug-in system. The algorithm benchmark system can be used to compare the performance of various algorithms or to evaluate the behavior of an algorithm with different input instances. The current implementation allows users to compare or evaluate algorithms written in C/C++. Some examples of the algorithm benchmark system that evaluates the memory utilization, time complexity and the output of algorithms are also presented. Algorithm benchmark impresses the learning effect; students can not only comprehend the performance of respective algorithms but also write their own programs to challenge the best known results.
The use of community-based non-profit organizations in information systems capstone projects
Authors: Leidig Paul M. , Ferguson Roger , Leidig Jonathan
Published: July 2006

Complaints often expressed about undergraduate computer science or information systems programs,,, is that students graduate with adequate technical skills but often lack an understanding of organizational processes, team project experience, and the ability to integrate information technology in an organizational setting. To address this, educators have historically created service-learning group projects, which leverage local organizations. These types of projects can be very rewarding for students and offer excellent educational opportunities for the students within the group. Educators who have taught service-learning group projects know there are significant problems with using this type of project. These problems include: motivation of students to do their best work, fair individual and overall group assessment, appropriate workload for a semester, and minimizing disruptive outside influences. In addition, the creation of new projects on a continuous semester basis would be very useful for the instructor of a project course. To solve these issues and problems, the following capstone course design was used with success at Grand Valley State University (GVSU). A socially-relevant, community-based assignment with local non-profit organizations provided the basis for the capstone information systems project course described in this paper. This project course produced working applications for actual clients that gave students a unique capstone experience.
Fast application development to demonstrate computer graphics concepts
Authors: Gómez-Martín Pedro Pablo , Gómez-Martín Marco Antonio
Published: July 2006

Computer graphics concepts have a high visual component. For that reason, teaching this subject should be enriched with the use of small applications showing concepts like near and far plane or objects hierarchy in real time. However, their development is usually time consuming. In this paper we propose the use of an open source engine called Nebula to create such examples. We will show that Nebula applications are easy to develop and modify, presenting three small applications that help to explain important concepts in Computer Graphics curriculum.