bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Fifty Putative Inclusion Membrane Proteins Encoded in theChlamydia trachomatisGenome
Authors: Li Zhongyu , Chen Chaoqun , Chen Ding , Wu Yimou , Zhong Youmin , Zhong Guangming 
Published: April 2008

ABSTRACTAlthough theChlamydia trachomatisgenome is predicted to encode 50 inclusion membrane proteins, only 18 have been experimentally localized in the inclusion membrane ofC. trachomatis-infected cells. Using fusion proteins and anti-fusion protein antibodies, we have systematically evaluated all 50 putative inclusion membrane proteins for their localization in the infected cells, distribution patterns, and effects on subsequent chlamydial infection when expressed ectopically, as well as their immunogenicity during chlamydial infection in humans. Twenty-two of the 50 proteins were localized in the inclusion membrane, and 7 were detected inside the inclusions, while the location of the remaining 21 was not defined. Four (CT225, CT228, CT358, and CT440) of the 22 inclusion membrane-localized proteins were visualized in the inclusion membrane ofChlamydia-infected cells for the first time in the current study. The seven intra-inclusion-localized proteins were confirmed to be chlamydial organism proteins in a Western blot assay. Further characterization of the 50 proteins revealed that neither colocalization with host cell endoplasmic reticulum nor inhibition of subsequent chlamydial infection by ectopically expressed proteins correlated with the inclusion membrane localization. Interestingly, antibodies from women withC. trachomatisurogenital infection preferentially recognized proteins localized in the inclusion membrane, and the immunodominant regions were further mapped to the region predicted to be on the cytoplasmic side of the inclusion membrane. These observations suggest that most of the inclusion membrane-localized proteins are both expressed and immunogenic duringC. trachomatisinfection in humans and that the cytoplasmic exposure may enhance the immunogenicity.
Role of the Mannose Receptor in a Murine Model ofCryptococcus neoformansInfection
Authors: Dan Jennifer M. , Kelly Ryan M. , Lee Chrono K. , Levitz Stuart M. 
Published: April 2008

ABSTRACTCryptococcus neoformansis an encapsulated fungal pathogen with a predilection to infect persons with suppressed T-cell function. Cryptococcal mannoproteins (MP) are highly mannosylated antigens which elicit T-cell responses in infected mice and in convalescent patients. Key to the immunogenicity of MP is its capacity to bind to the conserved mannose receptor (MR), CD206, on dendritic cells (DCs). To test the role of the MR in the immune response toC.neoformans, wild-type and MR knockout (MR KO) mice were compared by using in vivo and ex vivo models of cryptococcosis. Following a pulmonary challenge withC.neoformans, MR KO mice died significantly faster than wild-type mice and had higher lung fungal burdens after 4 weeks of infection. Uptake of MP was similar when DCs obtained from wild-type and MR KO mice were compared. Additionally, MP did not upregulate the maturation markers major histocompatibility complex class II, CD86, and CD40 in either wild-type or MR KO DCs. However, MP stimulated lymphoproliferation in CD4+T cells obtained from the peripheral lymph nodes of infected wild-type but not MR KO mice. These studies demonstrate a nonredundant role for the MR in the development of CD4+T-cell responses to MP and protection fromC.neoformans.
Protection against Nasopharyngeal Colonization byStreptococcus pneumoniaeIs Mediated by Antigen-Specific CD4+T Cells
Authors: Trzciński Krzysztof , Thompson Claudette M. , Srivastava Amit , Basset Alan , Malley Richard , Lipsitch Marc 
Published: April 2008

ABSTRACTCD4+T-cell-dependent acquired immunity confers antibody-independent protection against pneumococcal colonization. Since this mechanism is poorly understood for extracellular bacteria, we assessed the antigen specificity of the induction and recall of this immune response by using BALB/c DO11.10Rag−/−mice, which lack mature B and T cells except for CD4+T cells specific for the OVA323-339peptide derived from ovalbumin. Serotype 6BStreptococcus pneumoniaestrain 603S and unencapsulated strain Rx1ΔlytA were modified to express OVA323-339as a fusion protein with surface protein A (PspA) (strains 603OVA1and Rx1ΔlytAOVA1) or with PspA, neuraminidase A, and pneumolysin (Rx1ΔlytAOVA3). Whole-cell vaccines (WCV) were made of ethanol-killed cells of Rx1ΔlytAplus cholera toxin (CT) adjuvant, of Rx1ΔlytAOVA1+ CT (WCV-OVA1), and of Rx1ΔlytAOVA3+ CT (WCV-OVA3). Mice intranasally immunized with WCV-OVA1, but not with WCV or CT alone, were protected against intranasal challenge with 603OVA1. There was no protection against strain 603S in mice immunized with WCV-OVA1. These results indicate antigen specificity of both immune induction and the recall response. Effector action was not restricted to antigen-bearing bacteria since colonization by 603S was reduced in animals immunized with vaccines made of OVA-expressing strains when ovalbumin or killed Rx1ΔlytAOVA3antigen was administered around the time of challenge. CD4+T-cell-mediated protection against pneumococcal colonization can be induced in an antigen-specific fashion and requires specific antigen for effective bacterial clearance, but this activity may extend beyond antigen-expressing bacteria. These results are consistent with the recruitment and/or activation of phagocytic or other nonspecific effectors by antigen-specific CD4+T cells.
Role of
Porphyromonas gingivalis
SerB in Gingival Epithelial Cell Cytoskeletal Remodeling and Cytokine Production
Authors: Hasegawa Yoshiaki , Tribble Gena D. , Baker Henry V. , Mans Jeffrey J. , Handfield Martin , Lamont Richard J. 
Published: April 2008

ABSTRACT

The SerB protein of
Porphyromonas gingivalis
is a HAD family serine phosphatase that plays a critical role in entry and survival of the organism in gingival epithelial cells. SerB is secreted by
P. gingivalis
upon contact with epithelial cells. Here it is shown by microarray analysis that SerB impacts the transcriptional profile of gingival epithelial cells, with pathways involving the actin cytoskeleton and cytokine production among those significantly overpopulated with differentially regulated genes. Consistent with the transcriptional profile, a SerB mutant of
P. gingivalis
exhibited defective remodeling of actin in epithelial cells. Interaction between gingival epithelial cells and isolated SerB protein resulted in actin rearrangement and an increase in the F/G actin ratio. SerB protein was also required for
P. gingivalis
to antagonize interleukin-8 accumulation following stimulation of epithelial cells with
Fusobacterium nucleatum
. SerB is thus capable of modulating host cell signal transduction that impacts the actin cytoskeleton and cytokine production.
Acquisition of the Vacuolar ATPase Proton Pump and Phagosome Acidification Are Essential for Escape of
Francisella tularensis
into the Macrophage Cytosol
Authors: Santic Marina , Asare Rexford , Skrobonja Ivana , Jones Snake , Abu Kwaik Yousef 
Published: April 2008

ABSTRACT

The
Francisella tularensis
-containing phagosome (FCP) matures to a late-endosome-like phagosome prior to bacterial escape into the cytosols of macrophages, where bacterial proliferation occurs. Our data show that within the first 15 min after infection of primary human monocyte-derived macrophages (hMDMs), ∼90% of the FCPs acquire the proton vacuolar ATPase (vATPase) pump and the lysomotropic dye LysoTracker, which concentrates in acidic compartments, similar to phagosomes harboring the
Listeria monocytogenes
control. The acquired proton vATPase pump and lysomotropic dye are gradually lost by 30 to 60 min postinfection, which coincides with bacterial escape into the cytosols of hMDMs. Colocalization of phagosomes harboring the
iglD
mutant with the vATPase pump and the LysoTracker dye was also transient, and the loss of colocalization was faster than that observed for the wild-type strain, which is consistent with the faster escape of the
iglD
mutant into the macrophage cytosol. In contrast, colocalization of both makers with phagosomes harboring the
iglC
mutant was persistent, which is consistent with fusion to the lysosomes and failure of the
iglC
mutant to escape into the macrophage cytosol. We have utilized a fluorescence microscopy-based phagosome integrity assay for differential labeling of vacuolar versus cytosolic bacteria, using antibacterial antibodies loaded into the cytosols of live hMDMs. We show that specific inhibition of the proton vATPase pump by bafilomycin A1 (BFA) blocks rapid bacterial escape into the cytosols of hMDMs, but 30% to 50% of the bacteria escape into the cytosol by 6 to 12 h after BFA treatment. The effect of BFA on the blocking of bacterial escape into the cytosol is completely reversible, as the bacteria escape after removal of BFA. We also show that the limited fusion of the FCP to lysosomes is not due to failure to recruit the late-endosomal fusion regulator Rab7. Therefore, within few minutes of its biogenesis, the FCP transiently acquires the proton vATPase pump to acidify the phagosome, and this transient acidification is essential for subsequent bacterial escape into the macrophage cytosol.
Identification of
Streptococcus sanguinis
Genes Required for Biofilm Formation and Examination of Their Role in Endocarditis Virulence
Authors: Ge Xiuchun , Kitten Todd , Chen Zhenming , Lee Sehmi P. , Munro Cindy L. , Xu Ping 
Published: April 2008

ABSTRACT

Streptococcus sanguinis
is one of the pioneers in the bacterial colonization of teeth and is one of the most abundant species in the oral biofilm called dental plaque.
S. sanguinis
is also the most common viridans group streptococcal species implicated in infective endocarditis. To investigate the association of biofilm and endocarditis, we established a biofilm assay and examined biofilm formation with a signature-tagged mutagenesis library of
S. sanguinis
. Four genes that have not previously been associated with biofilm formation in any other bacterium,
purB, purL, thrB
, and
pyrE
, were putatively identified as contributing to in vitro biofilm formation in
S. sanguinis
. By examining 800 mutants for attenuation in the rabbit endocarditis model and for reduction in biofilm formation in vitro, we found some mutants that were both biofilm defective and attenuated for endocarditis. However, we also identified mutants with only reduced biofilm formation or with only attenuation in the endocarditis model. This result indicates that the ability to form biofilms in vitro is not associated with endocarditis virulence in vivo in
S. sanguinis
.
Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility toCryptococcus neoformansin a Mouse Model
Authors: Chen Gwo-hsiao , McNamara David A. , Hernandez Yadira , Huffnagle Gary B. , Toews Galen B. , Olszewski Michal A. 
Published: April 2008

ABSTRACTGenetic background variation between inbred strains accounts for different levels of susceptibility toCryptococcus neoformansin the mouse infection model. To elucidate the inheritance of immunophenotypic traits and their associations with clearance outcomes during cryptococcal infection, we compared C57BL/6, BALB/c, and their first-generation hybrid, CB6F1 (F1), mice. Mice from each group were infected withC. neoformans(104CFU) and analyzed at weekly intervals over a 6-week period. BALB/c mice progressively cleared the cryptococcal infection in the lungs and showed a Th1-skewed immune response: a Th1-shifted cytokine profile, modest lung pathology, and no significant elevation in the systemic immunoglobulin E (IgE) level. In contrast, C57BL/6 mice developed a chronic infection with a Th2-skewed immune response: a Th2-shifted cytokine profile, pulmonary eosinophilia, severe lung pathology, elevated serum IgE, fungemia, and cryptococcal dissemination in the central nervous system. F1 mice demonstrated intermediate resistance toC. neoformans, with a stronger resemblance to the immunophenotype of the resistant (BALB/c) mice. F1 mice also demonstrated enhanced pulmonary recruitment of lymphocytes, especially CD8+T cells, in comparison to both parental strains, suggesting positive heterosis. We conclude that the inheritance of traits responsible for early cytokine induction in the infected lungs and dendritic-cell maturation/activation status in draining nodes is responsible for the intermediate immune response polarization and clearance outcome observed initially in the lungs of F1 mice. The enhanced pulmonary lymphocyte recruitment could be responsible for a gradual shutdown of the undesirable Th2 arm of the immune response and subsequently improved anticryptococcal resistance in F1 mice.
Immune Recognition ofStreptococcus pyogenesby Dendritic Cells
Authors: Loof Torsten G. , Goldmann Oliver , Medina Eva 
Published: April 2008

ABSTRACTStreptococcus pyogenesis one of the most frequent human pathogens. Recent studies have identified dendritic cells (DCs) as important contributors to host defense againstS. pyogenes. The objective of this study was to identify the receptors involved in immune recognition ofS. pyogenesby DCs. To determine whether Toll-like receptors (TLRs) were involved in DC sensing ofS. pyogenes, we evaluated the response of bone marrow-derived DCs obtained from mice deficient in MyD88, an adapter molecule used by almost all TLRs, followingS. pyogenesstimulation. Despite the fact that MyD88−/−DCs did not differ from wild-type DCs in the ability to internalize and killS. pyogenes, the up-regulation of maturation markers, such as CD40, CD80, and CD86, and the production of inflammatory cytokines, such as interleukin-12 (IL-12), IL-6, and tumor necrosis factor alpha, were dramatically impaired inS. pyogenes-stimulated MyD88−/−DCs. These results suggest that signaling through TLRs is the principal pathway by which DCs senseS. pyogenesand become activated. Surprisingly, DCs deficient in signaling through each of the TLRs reported as potential receptors for gram-positive cell components, such as TLR1, TLR2, TLR4, TLR9, and TLR2/6, were not impaired in the secretion of proinflammatory cytokines and the up-regulation of costimulatory molecules afterS. pyogenesstimulation. In conclusion, our results exclude a major involvement of a single TLR or the heterodimer TLR2/6 inS. pyogenessensing by DCs and argue for a multimodal recognition in which a combination of several different TLR-mediated signals is essential for a rapid and effective response to the pathogen.
Injury surveillance in multi-sport events: the International Olympic Committee approach
Authors: Junge A , Engebretsen L , Alonso J M , Renström P , Mountjoy M , Aubry M , Dvorak J 
Published: April 2008

Background:The protection of athletes’ health by preventing injuries is an important task for international sports federations. Standardised injury surveillance provides not only important epidemiological information, but also directions for injury prevention, and the opportunity for monitoring long-term changes in the frequency and circumstances of injury. Numerous studies have evaluated sports injuries during the season, but few have focused on injuries during major sport events such as World Championships, World Cups or the Olympic Games.Objectives:To provide an injury surveillance system for multi-sports tournaments, using the 2008 Olympic Games in Beijing as an example.Methods:A group of experienced researchers reviewed existing injury report systems and developed a scientific sound and concise injury surveillance system for large multi-sport events.Results:The injury report system for multi-sport events is based on an established system for team sports tournaments and has proved feasible for individual sports during the International Association of Athletics Federations World Championships in Athletics 2007. The most important principles and advantages of the system are comprehensive definition of injury, injury report by the physician responsible for the athlete, a single-page report of all injuries, and daily report irrespective of whether or not an injury occurred. Implementation of the injury surveillance system, all definitions, the report form, and the analysis of data are described in detail to enable other researchers to implement the injury surveillance system in any sports tournament.Conclusion:The injury surveillance system has been accepted by experienced team physicians and shown to be feasible for single-sport and multi-sport events. It can be modified depending on the specific objectives of a certain sport or research question; however, a standardised use of injury definition, report forms and methodology will ensure the comparability of results.
Use of field-based tests to identify risk factors for injury to fast bowlers in cricket
Authors: Dennis R J , Finch C F , McIntosh A S , Elliott B C 
Published: April 2008

Objective:To identify risk factors for injury to cricket fast bowlers using field-based tests.Design:Prospective cohort study.Setting:High performance Australian cricket.Participants:Ninety-one male adolescent and adult fast bowlers (aged 12–33 years).Assessment of risk factors:A field-based pre-participation screening, consisting of musculoskeletal, fitness and anthropometric assessments and analysis of bowling technique was undertaken. Bowlers were prospectively monitored over the 2003–4 season and bowling workload and injuries were recorded. Logistic regression was used to identify injury risk factors.Main outcome measurement:Repetitive microtrauma injury to the trunk, back or lower limb associated with fast bowling.Results:Two variables were identified as independent predictors of injury in the multivariate logistic regression analysis. Bowlers with hip internal rotation of ⩽30° on the leg ipsilateral to the bowling arm were at a significantly reduced risk of injury (OR 0.20, 95% CI 0.06 to 0.73) compared with bowlers with >40° of rotation. Bowlers with an ankle dorsiflexion lunge of 12.1–14.0 cm on the leg contralateral to the bowling arm were at a significantly increased risk (OR 4.03, 95% CI 1.07 to 15.21) than bowlers with a lunge of >14 cm. Bowlers with a lunge of ⩽12 cm were also at an increased risk, but not significantly so (OR 1.38, 95% CI 0.40 to 4.84).Conclusions:Biomechanical research is needed to investigate how these two intrinsic risk factors increase injury risk so that appropriate interventions can be developed.
Interim evaluation of the effect of a new scrum law on neck and back injuries in rugby union
Authors: Gianotti S , Hume P A , Hopkins W G , Harawira J , Truman R 
Published: April 2008

Background:In January 2007 the International Rugby Board implemented a new law for scrum engagement aimed at improving player welfare by reducing impact force and scrum collapses. In New Zealand the new law was included in RugbySmart, an annual compulsory workshop for coaches and referees.Objective:To determine the effect of the new law on scrum-related moderate to serious neck and back injury claims in 2007.Methods:Claims filed with the Accident Compensation Corporation (the provider of no-fault injury compensation and rehabilitation in New Zealand) were combined with numbers of registered players to estimate moderate to serious scrum-related claims for players who take part in scrums (forwards). Poisson linear regression was used to compare the observed claims per 100 000 forwards for 2007 with the rate predicted from data for 2002–6.Results:The observed and predicted claims per 100 000 forwards were 52 and 76, respectively (rate ratio 0.69; 90% CI 0.42 to 1.12). The likelihoods of substantial benefit (rate ratio <0.90) and harm (rate ratio >1.1) attributable to the scrum law were 82% and 5%, respectively.Conclusion:The decline in scrum-related injury claims is consistent with a beneficial effect of the new scrum law in the first year of its implementation. Another year of monitoring should provide more evidence for the efficacy of the new law.
HÖLDER-TYPE INEQUALITIES FOR THE POLYGAMMA FUNCTIONS
Authors: ALZER HORST 
Published: April 2008

The nth polygamma function is defined by ψ(n) = (Γ′/Γ)(n), where Γ denotes Euler's gamma function. We prove: let n ≥ 1 be an integer and let p, q be non-zero real numbers. (i) The inequality [Formula: see text] holds for all positive numbers x, y if and only if p > 0, q > 0, 1/p + 1/q ≥ 1. (ii) The inequality [Formula: see text] holds for all positive numbers x, y if and only if either p < 0, q < 0 or pq < 0, 1/p + 1/q ≤ 1.
Hang analysis
Authors: Wang Xi , Guo Zhenyu , Liu Xuezheng , Xu Zhilei , Lin Haoxiang , Wang Xiaoge , Zhang Zheng 
Published: April 2008

Soft hang is an action that was expected to respond instantly but instead drives an application into a coma. While the application usually responds eventually, users cannot issue other requests while waiting. Such hang problems are widespread in productivity tools such as desktop applications; similar issues arise in server programs as well. Hang problems arise because the software contains blocking or time-consuming operations in graphical user interface (GUI) and other time-critical call paths that should not.
This paper proposes HangWiz to find hang bugs in source code, which are difficult to eliminate before release by testing, as they often depend on a user's environment. HangWiz finds hang bugs by finding hang points: an invocation that is expected to complete quickly, such as a GUI action, but calls a blocking function. HangWiz collects hang patterns from runtime traces supplemented with expert knowledge, and feed these patterns into a static analysis framework that searches exhaustively for hang points that involve potential hang bugs.
Experiments with several large, real-world software packages (including a source control client, a graphics editor and a web server) show that there are several hang bugs in these applications, and that HangWiz is effective in finding them. The experiments also demonstrate that HangWiz is scalable and can analyze millions of lines of code. We further discuss related techniques and report our experience on fixing hang bugs.
30 seconds is not enough!
Authors: Peter Simon , Baumann Andrew , Roscoe Timothy , Barham Paul , Isaacs Rebecca 
Published: April 2008

The basic system timer facilities used by applications and OS kernels for scheduling timeouts and periodic activities have remained largely unchanged for decades, while hardware architectures and application loads have changed radically. This raises concerns with CPU overhead power management and application responsiveness.
In this paper we study how kernel timers are used in the Linux and Vista kernels, and the instrumentation challenges and tradeoffs inherent in conducting such a study. We show how the same timer facilities serve at least five distinct purposes, and examine their performance characteristics under a selection of application workloads. We show that many timer parameters supplied by application and kernel programmers are somewhat arbitrary, and examine the potential benefit of adaptive timeouts.
We also discuss the further implications of our results, both for enhancements to the system timer functionality in existing kernels, and for the clean-slate design of a system timer subsystem for new OS kernels, including the extent to which applications might require such an interface at all.