bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza A Virus Neuraminidase Enhances Meningococcal Adhesion to Epithelial Cells through Interaction with Sialic Acid-Containing Meningococcal Capsules
Authors: Rameix-Welti Marie-Anne , Zarantonelli Maria Leticia , Giorgini Dario , Ruckly Corinne , Marasescu Monica , van der Werf Sylvie , Alonso Jean-Michel , Naffakh Nadia , Taha Muhamed-Kheir 
Published: June 2009

ABSTRACTThe underlying mechanisms of the epidemiological association between influenza virus infections andNeisseria meningitidisinvasive infections are not fully understood. Here we report that adhesion ofN. meningitidisto human Hec-1-B epithelial cells is enhanced by influenza A virus (IAV) infection. A potential role of the viral neuraminidase (NA) in facilitating meningococcal adhesion to influenza virus-infected epithelial cells was examined. Expression of a recombinant IAV NA in Hec-1-B human epithelial cells increased the adhesion of strains ofN. meningitidisbelonging to the sialic acid-containing capsular serogroups B, C, and W135 but not to the mannosamine phosphate-containing capsular serogroup A. Adhesion enhancement was not observed with an inactive NA mutant or in the presence of an NA inhibitor (zanamivir). Furthermore, purified IAV NA was shown to cleave sialic acid-containing capsular polysaccharides ofN. meningitidis. On the whole, our findings suggest that a direct interaction between the NA of IAV and the capsule ofN. meningitidisenhances bacterial adhesion to cultured epithelial cells, most likely through cleavage of capsular sialic acid-containing polysaccharides. A better understanding of the association between IAV and invasive meningococcal infections should help to set up improved control strategies against these seasonal dual viral-bacterial infections.
Streptococcus pneumoniaeAutolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines
Authors: Martner Anna , Skovbjerg Susann , Paton James C. , Wold Agnes E. 
Published: June 2009

ABSTRACTStreptococcus pneumoniaeis a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-typeS. pneumoniaefor inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-γ), and only negligible amounts of interleukin-12 (IL-12) compared with other closely relatedStreptococcusspecies, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-γ, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-γ, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.
Antigen-Specific Memory B-Cell Responses to
Vibrio cholerae
O1 Infection in Bangladesh
Authors: Harris Aaron M. , Bhuiyan M. Saruar , Chowdhury Fahima , Khan Ashraful I. , Hossain Azim , Kendall Emily A. , Rahman Atiqur , LaRocque Regina C. , Wrammert Jens , Ryan Edward T. , Qadri Firdausi , Calderwood Stephen B. , Harris Jason B. 
Published: June 2009

ABSTRACT

Cholera, caused by
Vibrio cholerae
, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with
V. cholerae
elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to
V. cholerae
infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with
V. cholerae
. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to
V. cholerae
protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to
V. cholerae
.
Identification of Specific and Universal Virulence Factors in
Burkholderia cenocepacia
Strains by Using Multiple Infection Hosts
Authors: Uehlinger Susanne , Schwager Stephan , Bernier Steve P. , Riedel Kathrin , Nguyen David T. , Sokol Pamela A. , Eberl Leo 
Published: June 2009

ABSTRACT

Over the past few decades, strains of the
Burkholderia cepacia
complex have emerged as important pathogens for patients suffering from cystic fibrosis. Identification of virulence factors and assessment of the pathogenic potential of
Burkholderia
strains have increased the need for appropriate infection models. In previous studies, different infection hosts, including mammals, nematodes, insects, and plants, have been used. At present, however, the extent to which the virulence factors required to infect different hosts overlap is not known. The aim of this study was to analyze the roles of various virulence factors of two closely related
Burkholderia cenocepacia
strains, H111 and the epidemic strain K56-2, in a multihost pathogenesis system using four different model organisms, namely,
Caenorhabditis elegans
,
Galleria mellonella
, the alfalfa plant, and mice or rats. We demonstrate that most of the identified virulence factors are specific for one of the infection models, and only three factors were found to be essential for full pathogenicity in several hosts: mutants defective in (i) quorum sensing, (ii) siderophore production, and (iii) lipopolysaccharide biosynthesis were attenuated in at least three of the infection models and thus may represent promising targets for the development of novel anti-infectives.
Streptococcus gordonii
Modulates
Candida albicans
Biofilm Formation through Intergeneric Communication
Authors: Bamford Caroline V. , d'Mello Anita , Nobbs Angela H. , Dutton Lindsay C. , Vickerman M. Margaret , Jenkinson Howard F. 
Published: June 2009

ABSTRACT

The fungus
Candida albicans
colonizes human oral cavity surfaces in conjunction with a complex microflora.
C. albicans
SC5314 formed biofilms on saliva-coated surfaces that in early stages of development consisted of ∼30% hyphal forms. In mixed biofilms with the oral bacterium
Streptococcus gordonii
DL1, hyphal development by
C. albicans
was enhanced so that biofilms consisted of ∼60% hyphal forms. Cell-cell contact between
S. gordonii
and
C. albicans
involved
Streptococcus
cell wall-anchored proteins SspA and SspB (antigen I/II family polypeptides). Repression of
C. albicans
hyphal filament and biofilm production by the quorum-sensing molecule farnesol was relieved by
S. gordonii
. The ability of a
luxS
mutant of
S. gordonii
deficient in production of autoinducer 2 to induce
C. albicans
hyphal formation was reduced, and this mutant suppressed farnesol inhibition of hyphal formation less effectively. Coincubation of the two microbial species led to activation of
C. albicans
mitogen-activated protein kinase Cek1p, inhibition of Mkc1p activation by H
2
O
2
, and enhanced activation of Hog1p by farnesol, which were direct effects of streptococci on morphogenetic signaling. These results suggest that interactions between
C. albicans
and
S. gordonii
involve physical (adherence) and chemical (diffusible) signals that influence the development of biofilm communities. Thus, bacteria may play a significant role in modulating
Candida
carriage and infection processes in the oral cavity.
Impact of Preexisting Vector-Specific Immunity on Vaccine Potency: Characterization ofListeria monocytogenes-Specific Humoral and Cellular Immunity in Humans and Modeling Studies Using Recombinant Vaccines in Mice
Authors: Leong Meredith L. , Hampl Johannes , Liu Weiqun , Mathur Shruti , Bahjat Keith S. , Luckett William , Dubensky Thomas W. , Brockstedt Dirk G. 
Published: June 2009

ABSTRACTRecombinant live-attenuatedListeria monocytogenesis currently being developed as a vaccine platform for treatment or prevention of malignant and infectious diseases. The effectiveness of complex biologic vaccines, such as recombinant viral and bacterial vectors, can be limited by either preexisting or vaccine-induced vector-specific immunity. We characterized the level ofL. monocytogenes-specific cellular and humoral immunity present in more than 70 healthy adult subjects as a first step to understanding its possible impact on the efficacy ofL. monocytogenes-based vaccines being evaluated in early-phase clinical trials. SignificantL. monocytogenes-specific humoral immunity was not measured in humans, consistent with a lack of antibodies in mice immunized with wild-typeL. monocytogenes. Cellular immune responses specific for listeriolysin O, a secreted bacterial protein required for potency ofL. monocytogenes-derived vaccines, were detected in approximately 60% of human donors tested. In mice, while wild-typeL. monocytogenesdid not induce significant humoral immunity, attenuatedL. monocytogenesvaccine strains induced high-titerL. monocytogenes-specific antibodies when given at high doses used for immunization. Passive transfer ofL. monocytogenes-specific antiserum to naïve mice had no impact on priming antigen-specific immunity in mice immunized with a recombinantL. monocytogenesvaccine. In mice with preexistingL. monocytogenes-specific immunity, priming of naïve T cells was not prevented, and antigen-specific responses could be boosted by additional vaccinations. For the first time, our findings establish the level ofL. monocytogenes-specific cellular immunity in healthy adults, and, together with modeling studies performed with mice, they support the scientific rationale for repeatedL. monocytogenesvaccine immunization regimens to elicit a desired therapeutic effect.
Inhibition of
Staphylococcus epidermidis
Biofilm Formation by Rabbit Polyclonal Antibodies against the SesC Protein
Authors: Shahrooei Mohammad , Hira Vishal , Stijlemans Benoit , Merckx Rita , Hermans Peter W. M. , Van Eldere Johan 
Published: June 2009

ABSTRACT

Several well-studied proteins with defined roles in
Staphylococcus epidermidis
biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (
S
. epidermidis
surface protein C; accession no. NP_765787) as a target for antibodies to prevent biofilm formation. In vitro and in a in vivo rat model of catheter infection, gene and protein expression analysis showed that SesC is expressed more strongly in biofilm-associated cells than in planktonic cells and is expressed particularly during the late phase of in vivo biofilm formation. Polyclonal rabbit antibodies raised against SesC reduced the fibrinogen-binding ability of
S. epidermidis
RP62A and
Staphylococcus aureus
RN4220 transformants expressing SesC, inhibited in vitro biofilm formation by
S. epidermidis
strains 10b and 1457, and significantly reduced the numbers of bacteria in a 1-day-old in vivo biofilm (
P
< 0.001, one-way analysis of variance). Our findings revealed that SesC is a promising target for prevention and treatment of
S. epidermidis
biofilms because it affects both the primary attachment and biofilm accumulation phases. The precise role of SesC in biofilm formation remains to be identified.
Loa loaMicrofilariae Evade Complement Attack In Vivo by Acquiring Regulatory Proteins from Host Plasma
Authors: Haapasalo Karita , Meri Taru , Jokiranta T. Sakari 
Published: June 2009

ABSTRACTLoa loais a filarial nematode that infects humans. The adults live in subcutaneous tissues and produce microfilariae that live for several weeks in the blood circulation in order to be transmitted to another person via blood meals of a dipterian vector. As microfilariae live in continuous contact with plasma, it is obvious that they evade the complement system. We studied markers of complement activation and signs of complement regulation onLoa loamicrofilariae in vivo. The microfilariae were isolated from anticoagulated blood samples of aLoa loa-infected Caucasian patient. C1q and some mannose-binding lectin but only a limited amount of C3b or C4b fragments and practically no C5 or C5b-9 were present on the microfilariae. The covalently microfilaria-bound C3 and C4 depositions were mainly inactive iC3b, C3c, and iC4b fragments indicating that microfilariae had regulated complement activation in vivo. Also, in vitro deposition of C3b onto the microfilariae upon serum exposure was limited. The patient-isolated microfilariae were found to carry the host complement regulators factor H and C4b-binding protein on the outermost layer, so called sheath. The microfilaria-bound factor H was functionally active. Binding of the complement regulators to the microfilariae was confirmed in vitro using125I-labeled factor H and C4b-binding protein. In conclusion, our study shows thatLoa loamicrofilariae block complement activation and acquire the host complement regulators factor H and C4b-binding protein in blood circulation. This is the first time that binding of complement regulators onto nonviral pathogens has been demonstrated to occur in humans in vivo.
Association between passive jobs and low levels of leisure-time physical activity: the Whitehall II cohort study
Authors: Gimeno D , Elovainio M , Jokela M , De Vogli R , Marmot M G , Kivimäki M 
Published: June 2009

Background:There is mixed evidence on the association between psychosocial work exposures (ie, passive jobs) and physical activity, but previous studies did not take into account the effect of cumulative exposures nor did they examine different trajectories in exposure. We investigated whether exposure to passive jobs, measured three times over an average of 5 years, is associated with leisure-time physical activity (LTPA).Methods:Data were from working men (n = 4291) and women (n = 1794) aged 35–55 years who participated in the first three phases of the Whitehall II prospective cohort. Exposure to passive jobs was measured at each phase and LTPA at phases 1 and 3. Participants were categorised according to whether or not they worked in a passive job at each phase, leading to a scale ranging from 0 (non-passive job at all three phases) to 3 (passive job at all three phases). Poisson regression with robust variance estimates were used to assess the prevalence ratios of low LTPA.Results:An association was found in men between exposure to passive jobs over 5 years and low LTPA at follow-up, independently of other relevant risk factors. The prevalence ratio for low LTPA in men was 1.16 (95% CI 1.01 to 1.33) times greater for employees with three reports of passive job than for those who had never worked in passive jobs. No association was observed in women.Conclusion:This study provides evidence that working in passive jobs may encourage a passive lifestyle in men.
Population-based asbestosis surveillance in British Columbia
Authors: Gan W Q , Demers P A , McLeod C B , Koehoorn M 
Published: June 2009

Objectives:To investigate the use of multiple health data sources for population-based asbestosis surveillance in British Columbia, Canada.Methods:Provincial health insurance registration records, workers’ compensation records, hospitalisation records, and outpatient medical service records were linked using individual-specific study identifiers. The study population was restricted to individuals ⩾15 years of age living in the province during 1992–2004.Results:1170 new asbestosis cases were identified from 1992 to 2004 for an overall incidence rate of 2.82 (men: 5.48, women: 0.23) per 100 000 population; 96% of cases were male and average (SD) age was 69 (10) years. Although the annual number of new cases increased by 30% during the surveillance period (β = 2.36, p = 0.019), the observed increase in annual incidence rates was not significant (β = 0.02, p = 0.398). Workers’ compensation, hospitalisation and outpatient databases identified 23%, 48% and 50% of the total new cases, respectively. Of the new cases, 82% were identified through single data sources, 10% were only recorded in the workers’ compensation records, and 36% only in each of the hospitalisation and outpatient records. 84% of hospitalisation cases and 83% of outpatient cases were not included in the workers’ compensation records. The three data sources showed different temporal trends in the annual number of new cases and annual incidence rates.Conclusions:Single data sources were not sufficient to identify all new cases, thus leading to serious underestimations of the true burden of asbestosis. Integrating multiple health data sources could provide a more complete picture in population-based surveillance of asbestosis and other occupational diseases.
ProtoFlex
Authors: Chung Eric S. , Papamichael Michael K. , Nurvitadhi Eriko , Hoe James C. , Mai Ken , Falsafi Babak 
Published: June 2009

Functional full-system simulators are powerful and versatile research tools for accelerating architectural exploration and advanced software development. Their main shortcoming is limited throughput when simulating large multiprocessor systems with hundreds or thousands of processors or when instrumentation is introduced. We propose theProtoFlexsimulation architecture, which uses FPGAs to accelerate full-system multiprocessor simulation and to facilitate high-performance instrumentation. Prior FPGA approaches that prototype a complete system in hardware are either too complex when scaling to large-scale configurations or require significant effort to provide full-system support. In contrast,ProtoFlexvirtualizes the execution of many logical processors onto a consolidated number of multiple-context execution engines on the FPGA. Through virtualization, the number of engines can be judiciously scaled, as needed, to deliver on necessary simulation performance at a large savings in complexity. Further, to achieve low-complexity full-system support, a hybrid simulation technique called transplanting allows implementing in the FPGA only the frequently encountered behaviors, while a software simulator preserves the abstraction of a complete system.We have created a first instance of theProtoFlexsimulation architecture, which is an FPGA-based, full-system functional simulator for a 16-way UltraSPARC III symmetric multiprocessor server, hosted on a single Xilinx Virtex-II XCV2P70 FPGA. On average, the simulator achieves a 38x speedup (and as high as 49×) over comparable software simulation across a suite of applications, including OLTP on a commercial database server. We also demonstrate the advantages of minimal-overhead FPGA-accelerated instrumentation through a CMP cache simulation technique that runs orders-of-magnitude faster than software.
PetaBricks
Authors: Ansel Jason , Chan Cy , Wong Yee Lok , Olszewski Marek , Zhao Qin , Edelman Alan , Amarasinghe Saman 
Published: June 2009

It is often impossible to obtain a one-size-fits-all solution for high performance algorithms when considering different choices for data distributions, parallelism, transformations, and blocking. The best solution to these choices is often tightly coupled to different architectures, problem sizes, data, and available system resources. In some cases, completely different algorithms may provide the best performance. Current compiler and programming language techniques are able to change some of these parameters, but today there is no simple way for the programmer to express or the compiler to choose different algorithms to handle different parts of the data. Existing solutions normally can handle only coarse-grained, library level selections or hand coded cutoffs between base cases and recursive cases.
We present PetaBricks, a new implicitly parallel language and compiler where having multiple implementations of multiple algorithms to solve a problem is the natural way of programming. We make algorithmic choice a first class construct of the language. Choices are provided in a way that also allows our compiler to tune at a finer granularity. The PetaBricks compiler autotunes programs by making both fine-grained as well as algorithmic choices. Choices also include different automatic parallelization techniques, data distributions, algorithmic parameters, transformations, and blocking.
Additionally, we introduce novel techniques to autotune algorithms for different convergence criteria. When choosing between various direct and iterative methods, the PetaBricks compiler is able to tune a program in such a way that delivers near-optimal efficiency for any desired level of accuracy. The compiler has the flexibility of utilizing different convergence criteria for the various components within a single algorithm, providing the user with accuracy choice alongside algorithmic choice.
Stretching transactional memory
Authors: Dragojević Aleksandar , Guerraoui Rachid , Kapalka Michal 
Published: June 2009

Transactional memory (TM) is an appealing abstraction for programming multi-core systems. Potential target applications for TM, such as business software and video games, are likely to involve complex data structures and large transactions, requiring specific software solutions (STM). So far, however, STMs have been mainly evaluated and optimized for smaller scale benchmarks.
We revisit the main STM design choices from the perspective of complex workloads and propose a new STM, which we call SwissTM. In short, SwissTM is lock- and word-based and uses (1) optimistic (commit-time) conflict detection for read/write conflicts and pessimistic (encounter-time) conflict detection for write/write conflicts, as well as (2) a new two-phase contention manager that ensures the progress of long transactions while inducing no overhead on short ones. SwissTM outperforms state-of-the-art STM implementations, namely RSTM, TL2, and TinySTM, in our experiments on STMBench7, STAMP, Lee-TM and red-black tree benchmarks.
Beyond SwissTM, we present the most complete evaluation to date of the individual impact of various STM design choices on the ability to support the mixed workloads of large applications.