bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector
Authors: Battisti James M. , Bono James L. , Rosa Patricia A. , Schrumpf Merry E. , Schwan Tom G. , Policastro Paul F. 
Published: September 2008

ABSTRACT

The Lyme disease spirochete
Borrelia burgdorferi
alters the expression of outer surface protein (
osp
) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of
ospA
in strain B31-A3. The
ospA
mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naïve mice were compared with those in the vector fed on immune mice. The
ospA
mutant proliferates in larvae if it is exposed to blood from naïve mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the
ospA
mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector.
Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection
Authors: Sanabria Mayra X. Hernandez , Vargas-Inchaustegui Diego A. , Xin Lijun , Soong Lynn 
Published: September 2008

ABSTRACTThe importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well-documented; however, limited information on DC-NK cell interaction during parasitic infections is available. Given that someLeishmaniaparasites are known to prevent or suppress DC activation, we developed a DC-NK cell coculture system to examine the role of NK cells in modulating the functions ofLeishmania-infected DCs. We found that the addition of freshly isolated, resting NK cells significantly promoted the activation of DCs that were preinfected withLeishmania amazonensispromastigotes and that these activated DCs, in turn, stimulated NK cell activation mostly via cell contact-dependent mechanisms. Notably,L. amazonensisamastigote infection failed to activate DCs, and this lack of DC activation could be partially reversed by the addition of preactivated NK (ANK) cells but not resting NK cells. Moreover, the adoptive transfer of ANK cells intoL. amazonensis-infected mice markedly increased DC and T-cell activation and reduced tissue parasite loads at 1 and 3 weeks postinfection. These results suggest differential roles of DC-NK cell cross talk at different stages ofLeishmaniainfection and provide new insight into the interplay of components of the innate immune system during parasitic infection.
Association ofMycoplasma arthritidisMitogen with Lethal Toxicity but Not with Arthritis in Mice
Authors: Luo Wenyi , Yu Huilan , Cao Zuhua , Schoeb Trenton R. , Marron Michele , Dybvig Kevin 
Published: September 2008

ABSTRACTMycoplasma arthritidisinduces an acute to chronic arthritis in rodents. Arthritis induced in mice histologically resembles human rheumatoid arthritis and can be associated with lethal toxicity following systemic injection. TheM. arthritidismitogen (MAM) superantigen has long been implicated as having a role in pathogenesis, but its significance with respect to toxicity and arthritogenicity in mycoplasma-induced disease is unclear. To study the pathogenic significance of MAM,M. arthritidismutants that overproduced or failed to produce MAM were developed. MAM overproduction and knockout mutants were more and less mitogenic, respectively, than the wild-type strain. The degree of mitogenic activity correlated with lethal toxicity in DBA/2J mice. In contrast, histopathological studies detected no correlation between MAM production and the severity of arthritis induced in DBA/2J and CBA/J mice.
Trypanosoma cruziInfection Is Enhanced by Vector Saliva through Immunosuppressant Mechanisms Mediated by Lysophosphatidylcholine
Authors: Mesquita Rafael D. , Carneiro Alan Brito , Bafica André , Gazos-Lopes Felipe , Takiya Christina M. , Souto-Padron Thaís , Vieira Danielle P. , Ferreira-Pereira Antônio , Almeida Igor C. , Figueiredo Rodrigo T. , Porto Bárbara N. , Bozza Marcelo T. , Graça-Souza Aurélio V. , Lopes Angela H. C. S. , Atella Geórgia C. , Silva-Neto Mário A. C. 
Published: September 2008

ABSTRACTTrypanosoma cruzi, the etiological agent of Chagas disease, is transmitted by bug feces deposited on human skin during a blood meal. However, parasite infection occurs through the wound produced by insect mouthparts. Saliva of the Triatominae bugRhodnius prolixusis a source of lysophosphatidylcholine (LPC). Here, we tested the role of both triatomine saliva and LPC on parasite transmission. We show that vector saliva is a powerful inducer of cell chemotaxis. A massive number of inflammatory cells were found at the sites where LPC or saliva was inoculated into the skin of mice. LPC is a known chemoattractant for monocytes, but neutrophil recruitment induced by saliva is LPC independent. The preincubation of peritoneal macrophages with saliva or LPC increased fivefold the association ofT. cruziwith these cells. Moreover, saliva and LPC block nitric oxide production byT. cruzi-exposed macrophages. The injection of saliva or LPC into mouse skin in the presence of the parasite induces an up-to-sixfold increase in blood parasitemia. Together, our data suggest that saliva of the Triatominae enhancesT. cruzitransmission and that some of its biological effects are attributed to LPC. This is a demonstration that a vector-derived lysophospholipid may act as an enhancing factor of Chagas disease.
RecombinantBacillus subtilisExpressing theClostridium perfringensAlpha Toxoid Is a Candidate Orally Delivered Vaccine against Necrotic Enteritis
Authors: Hoang Tran H. , Hong Huynh A. , Clark Graeme C. , Titball Richard W. , Cutting Simon M. 
Published: September 2008

ABSTRACTRecombinantBacillus subtilisendospores have been used to vaccinate against tetanus and anthrax. In this work, we have developed spores that could be used to vaccinate againstClostridium perfringensalpha toxin and that could be used to protect against gas gangrene in humans and necrotic enteritis in poultry. The primary active agent in both cases is alpha toxin. A carboxy-terminal segment of the alpha toxin gene (cpa) fused to the glutathione-S-transferase (GST) gene was cloned inB. subtilissuch that the encoded GST-Cpa247-370polypeptide had been expressed in the following three different ways: expression in the vegetative cell, expression on the surface of the spore coat (fused to the CotB spore coat protein), and a combined approach of spore coat expression coupled with expression in the vegetative cell. Mice immunized orally or nasally with three doses of recombinant spores that carried GST-Cpa247-370on the spore surface showed the most striking responses. This included seroconversion with anti-Cpa247-370-specific immunoglobulin G (IgG) responses in their sera, a Th2 bias, and secretory IgA responses in saliva, feces, and lung samples. Neutralizing IgG antibodies to alpha toxin were detected using in vitro and in vivo assays, and a toxin challenge established protection. Mice immunized nasally or orally with recombinant spores were protected against a challenge with 12 median lethal doses of alpha toxin. Existing use of spores as competitive exclusion agents in animal feeds supports their use as a potentially economical and heat-stable vaccine for the poultry industry.
Characterization of a Unique ClpB Protein of
Mycoplasma pneumoniae
and Its Impact on Growth
Authors: Kannan T. R. , Musatovova Oxana , Gowda Pramod , Baseman Joel B. 
Published: September 2008

ABSTRACT

Mycoplasma pneumoniae
accounts for 20 to 30% of all community-acquired pneumonia and has been associated with other airway pathologies, including asthma, and a range of extrapulmonary manifestations. Although the entire genomic sequence of
M. pneumoniae
has been completed, the functions of many of these genes in mycoplasma physiology are unknown. In this study, we focused on
clpB
, a well-known heat shock gene in other bacteria, to examine its role in mycoplasma growth. Transcriptional and translational analyses of heat shock in
M. pneumoniae
indicated that
clpB
is significantly upregulated, reinforcing its status as a critical responder to heat stress. Interestingly,
M. pneumoniae
ClpB does not use dual translational start points for ClpB synthesis, like other ClpB-characterized bacteria. Biochemical characterization of purified
M. pneumoniae
recombinant ClpB revealed casein- and lysine-independent ATPase activity and DnaK-DnaJ-GrpE-dependent chaperone activity. An
M. pneumoniae
mini-Tn
4001
-integrated,
clpB
-null mutant was impaired in its ability to replicate under permissive growth conditions, demonstrating the growth-promoting status of ClpB.
Serotype-Specific Immune Unresponsiveness to Pneumococcal Conjugate Vaccine following Invasive Pneumococcal Disease
Authors: Borrow Ray , Stanford Elaine , Waight Pauline , Helbert Matthew , Balmer Paul , Warrington Rosalind , Slack Mary , George Robert , Miller Elizabeth 
Published: September 2008

ABSTRACT

Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of ≥0.35 μg/ml. Eight children failed to develop a response to their infecting serotype (6B [
n
= 4], 18C [
n
= 2], 4 [
n
= 1], and 14 [
n
= 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.
The
Cryptococcus neoformans
Rho-GDP Dissociation Inhibitor Mediates Intracellular Survival and Virulence
Authors: Price Michael S. , Nichols Connie B. , Alspaugh J. Andrew 
Published: September 2008

ABSTRACT

Rho-GDP dissociation inhibitors (Rho-GDI) are repressors of Rho-type monomeric GTPases that control fundamental cellular processes, such as cytoskeletal arrangement, vesicle trafficking, and polarized growth. We identified and altered the expression of the gene encoding a Rho-GDI homolog in the human fungal pathogen
Cryptococcus neoformans
and investigated its impact on pathogenicity in animal models of cryptococcosis. Consistent with its predicted function to inhibit and sequester Rho-type GTPases, overexpression of
RDI1
results in cytosolic localization of Cdc42. Likely as a result of this finding,
RDI1
-overexpressing strains exhibited altered morphology compared to that of the wild type, with apparent defects in maintaining proper cell polarity and cytokinesis.
RDI1
deletion resulted in increased vacuole size in tissue culture medium and aberrant cell morphology at neutral pH. Maintenance of normal cell morphology is vital for
C. neoformans
pathogenicity. Accordingly, the
rdi1
Δ mutant strain also showed reduced intracellular survival in macrophages and severe attenuation of virulence in two murine models of cryptococcosis. This reduction in virulence of the
rdi1
Δ mutant occurs in the absence of major growth defects in rich medium and with classical virulence-associated phenotypes.
Recruitment of Rab27a to Phagosomes Controls Microbial Antigen Cross-Presentation by Dendritic Cells
Authors: Kim Seong Hyun , Visser Annelies , Cruijsen Carin , van der Velden Adrianus W. M. , Boes Marianne 
Published: September 2008

ABSTRACTPolyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8+T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8+T cells through recruitment of Rab27a.
The effect of head protection on the hearing of rugby players: Table 1
Authors: Kieran S M , Dunne J , Hughes J P , Fenton J E 
Published: September 2008

Objective:Professional rugby players utilise various methods of head protection to prevent against the development of a pinna haematoma. This study tests the hypothesis that these measures, whilst preventing injury, decrease the wearers’ hearing threshold and therefore their performance.Design and participants:Eight patients had free field audiometry performed in a soundproof room, with warble tones. All patients were young men (mean 24.75 years (range 22–34)). No participant had ear symptomatology or a past history of ear surgery. Three separate audiological assessments were performed on each patient: normal free field audiometry in a sound field room, following application of adhesive tape and whilst wearing a scrum cap. All measurements were performed by a single audiological scientist. A significant clinical drop in hearing threshold was defined as an increase of 10 dB.Results:No patient demonstrated a significant drop in hearing threshold following the application of either tape or a scrum cap, nor was there a significant difference in the mean (SD) warble tone average: air 7.03 (5.47); tape 7.19 (6.40); scrum cap 6.56 (5.58).Conclusion:Theoretical concerns that “ear taping” and scrum caps affect hearing of rugby players are unfounded and should not discourage their use.
INFRARED SPECTRAL SIGNATURES: CREATION OF REFERENCE DATA FOR VAPORS AND LIQUIDS
Authors: SHARPE STEVEN , JOHNSON TIMOTHY , SAMS ROBERT , HYLDEN JEFFREY , KLEIMEYER JAMES , ROWLAND BRAD 
Published: September 2008

Two primary goals of infrared spectroscopic detection are chemical identification and quantification. In order to accomplish these goals, a comprehensive and quantitative spectral library suitable for digital manipulation is required. To a large degree, the contents of such a library depend on the application. Since the primary application of the PNNL/DOE spectral library is for environmental monitoring, we have focused our efforts on hazardous pollutants, as well as a large variety of natural and anthropogenic chemicals. As a spin-off project and in collaboration with Dugway Proving Ground, we also had the opportunity to analyze a limited set of chemical warfare agents (CWAs). An example of such data appears below. [Formula: see text] Infrared optical properties of VX [O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate] in the vapor and liquid phases. Refractive index data (top traces) are critical for modeling aerosol and reflection phenomena.
Some Extensions of Banach's Contraction Principle in Complete Cone Metric Spaces
Authors: Raja P. , Vaezpour S. M. 
Published: September 2008

AbstractIn this paper we consider complete cone metric spaces. We generalize some definitions such as "Equation missing"-nonexpansive and "Equation missing"-uniformly locally contractive functions "Equation missing"-closure, "Equation missing"-isometric in cone metric spaces, and certain fixed point theorems will be proved in those spaces. Among other results, we prove some interesting applications for the fixed point theorems in cone metric spaces.
Quasicontraction Mappings in Modular Spaces without Δ2-Condition
Authors: Khamsi M.A. 
Published: September 2008

AbstractAs a generalization to Banach contraction principle, Ćirić introduced the concept of quasi-contraction mappings. In this paper, we investigate these kinds of mappings in modular function spaces without the "Equation missing"2-condition. In particular, we prove the existence of fixed points and discuss their uniqueness.
Multiple Primary Sporadic Gastrointestinal Stromal Tumors in the Adult: An Underestimated Entity
Authors: Gasparotto Daniela , Rossi Sabrina , Bearzi Italo , Doglioni Claudio , Marzotto Alessandra , Hornick Jason L. , Grizzo Alessandra , Sartor Chiara , Mandolesi Alessandra , Sciot Raf , Debiec-Rychter Maria , Dei Tos Angelo Paolo , Maestro Roberta 
Published: September 2008

Abstract
Purpose: Gastrointestinal stromal tumors (GIST) are commonly regarded as solitary tumors. The occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions. Beyond these well-defined situations, the presentation of multiple synchronous lesions is commonly viewed as the result of the metastatic spreading of a single primary GIST. Based on this axiom, patients with multifocal disease are classified as advanced stage and treated as such. Whether, indeed, the detection of several lesions in sporadic adult GIST patients may be suggestive of phenomena of tumor multiplicity still needs to be clarified.
Experimental Design: From a multicentric series of 442 consecutive cases, 26 of which with advanced disease, we selected 5 patients who presented up to three distinct GIST nodules. Five additional cases with similar characteristics were also contributed by two other institutions. The clonal relationship between the synchronous lesions was assessed by comparing KIT/PDGFRA mutation and microsatellite pattern.
Results: An independent origin of the synchronous lesions was established in 6 of 10 cases. Notably, in one patient, one lesion arose in the peritoneum, which is ordinarily regarded as a site of metastasis.
Conclusions: Our data indicate that a significant fraction of GIST patients with multifocal presentation are actually affected by multiple primary tumors, suggesting that mesenchymal GIST precursor cells of these individuals are somehow primed to transformation. Thus, in the presence of multifocal GIST manifestations, an accurate characterization of the different tumor sites should be undertaken for a proper patient staging and therapy planning.
The Advisory Centre on WTO Law: A Success Story, But for Whom?
Authors: Schunken Kenneth Ruwan 
Published: September 2008

AbstractDeveloping countries are facing problems in their efforts to access the WTO Dispute Settlement system. This article deals with the several problems these counties are facing. The Advisory Centre on WTO Law was founded to contribute to the greater participation of developing and least developed countries in the WTO dispute settlement system and to enhance the credibility of the WTO dispute settlement system. I will discuss the legal foundations and current operations of the ACWL. In addition, I will provide practical solutions in order to improve the operations of the Advisory Centre. These solutions contribute to a more fair and equal participation of developing and least developed countries in the WTO dispute settlement system.
Ireland and Medical Research with Minors: Some Medico-Legal Aspects
Authors: Sheikh Asim 
Published: September 2008

AbstractThe practice of medical research with minors in Ireland consist of practices pertaining to therapeutic and non-therapeutic medical research. Clinical trials (a category of therapeutic research), is governed by legislation. However, any other therapeutic research (non-clinical trials research) and non-therapeutic research, e.g. observational medical research such as a longitudinal study of children or non-therapeutic research such as blood sample collection for analysis of cause of disease, are unregulated by legislation. This, article will outline and describe some of the medico-legal issues involved in both types of research and will comment on matters such as what national law exists, how the directive on good clinical practice has been implemented, what guidelines, if any, exist.
Doppler Lidar Estimation of Mixing Height Using Turbulence, Shear, and Aerosol Profiles
Authors: Tucker Sara C. , Senff Christoph J. , Weickmann Ann M. , Brewer W. Alan , Banta Robert M. , Sandberg Scott P. , Law Daniel C. , Hardesty R. Michael 
Published: September 2008

Abstract
The concept of boundary layer mixing height for meteorology and air quality applications using lidar data is reviewed, and new algorithms for estimation of mixing heights from various types of lower-tropospheric coherent Doppler lidar measurements are presented. Velocity variance profiles derived from Doppler lidar data demonstrate direct application to mixing height estimation, while other types of lidar profiles demonstrate relationships to the variance profiles and thus may also be used in the mixing height estimate. The algorithms are applied to ship-based, high-resolution Doppler lidar (HRDL) velocity and backscattered-signal measurements acquired on the R/V Ronald H. Brown during Texas Air Quality Study (TexAQS) 2006 to demonstrate the method and to produce mixing height estimates for that experiment. These combinations of Doppler lidar–derived velocity measurements have not previously been applied to analysis of boundary layer mixing height—over the water or elsewhere. A comparison of the results to those derived from ship-launched, balloon-radiosonde potential temperature and relative humidity profiles is presented.