bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Levels of Interleukin-10 Impair Resistance to Pulmonary Coccidioidomycosis in Mice in Part through Control of Nitric Oxide Synthase 2 Expression
Authors: Jimenez Maria del Pilar , Walls Lorraine , Fierer Joshua 
Published: May 2006

ABSTRACTWe have shown previously that there is a direct correlation between IL-10 levels and susceptibility toCoccidioides immitisperitonitis in C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice. We now show that B6 mice are also more susceptible toC. immitispneumonia and that interleukin-10 (IL-10)-deficient (IL-10−/−) B6 mice are more resistant toC. immitispneumonia. In addition, we established that high levels of IL-10 are sufficient to make genetically resistant mice susceptible to bothC. immitisperitonitis and pneumonia by infecting h.IL-10 transgenic mice. Infected h.IL-10 transgenic mice express lower levels of gamma interferon, IL-12 p40, and inducible nitric oxide synthetase 2 (NOS2) mRNA in their lungs, implicating inducible NOS as a defense mechanism in this disease. We treated DBA/2 mice with aminoguanidine, and they became more susceptible toC. immitisperitonitis and pneumonia. We conclude that high levels of IL-10 are both necessary and sufficient to make mice susceptible toC. immitis, regardless of the genetic background of the mice, and that IL-10 impairs resistance toC. immitisin part by suppressing NO synthesis.
Differential Expression of the Bhmp39 Major Outer Membrane Proteins of
Brachyspira hyodysenteriae
Authors: Witchell Timothy D. , Coutts Scott A. J. , Bulach Dieter M. , Adler Ben 
Published: May 2006

ABSTRACT

The enteric, anaerobic spirochete
Brachyspira hyodysenteriae
is the causative agent of swine dysentery, a severe mucohemorrhagic diarrheal disease of pigs that has economic significance in every major pork-producing country. Recent investigation into potential vaccine candidates has focused on the outer membrane proteins of
B. hyodysenteriae
. Bhmp39 (formerly Vsp39) is the most abundant surface-exposed outer membrane protein of
B. hyodysenteriae
; its predicted gene sequence has previously been shown to share sequence similarity to eight genes divided evenly between two paralogous loci. The peptide sequence suggested that Bhmp39 is encoded by one of these genes,
bhmp39h
. The biological significance of maintaining eight homologous
bhmp39
genes is unclear, though it has been proposed that this may play a role in antigenic variation. In this study, real-time, reverse transcription-PCR was used to demonstrate that
bhmp39f
and
bhmp39h
were the transcripts most abundantly expressed by
B. hyodysenteriae
strain B204 cultured under in vitro growth conditions. Mass spectrometry data of the purified 39-kDa membrane protein showed that both Bhmp39f and Bhmp39h were present. Northern blot analysis across predicted Rho-independent terminators demonstrated that the genes of the
bhmp39efgh
locus result in monocistronic transcripts.
DifferentialRequirements for Soluble and Transmembrane Tumor Necrosis Factor in theImmunological Control of Primary and SecondaryListeria monocytogenesInfection
Authors: Musicki Korana , Briscoe Helen , Tran Stephen , Britton Warwick J. , Saunders Bernadette M. 
Published: May 2006

ABSTRACTThe relative contributions of transmembrane tumor necrosis factor (memTNF) and soluble tumor necrosis factor (solTNF) in innate and adaptive immunity are poorly defined. We examined the capacities of wild-type (WT) mice, TNF−/−mice, and memTNF mice, which express only transmembrane TNF, to control primary and secondaryListeria monocytogenesinfections. Soluble TNF was not required for induction or maintenance of protective immunity against a low-dose (200-CFU)Listeriainfection. In contrast to TNF−/−mice, both WT and memTNF mice cleared the bacilli within 10 days and were fully protected against rechallenge with a lethal infective dose. Furthermore, T cells transferred from immune mice, but not from naïve, WT, and memTNF mice, protected TNF−/−recipients against an otherwise lethal infection. By contrast, infection with a higher dose ofListeria(2,000 CFU) clearly demonstrated that solTNF is required to coordinate an optimal protective inflammatory response. memTNF mice were more susceptible to a high-dose infection, and they exhibited delayed bacterial clearance, increased inflammation, and necrosis in the liver that resulted in 55% mortality. The dysregulated inflammation was accompanied by prolonged elevated expression of mRNAs for several chemokines as well as the macrophage effector molecules inducible nitric oxide synthase and LRG-47 in the livers of memTNF mice but not in the livers of WT mice. These data demonstrated that memTNF is sufficient for establishing protective immunity against a primary low-doseListeriainfection but that solTNF is required for optimal control of cellular inflammation and resistance to a primary high-dose infection. By contrast, memTNF alone is sufficient for resolution of a secondary, high-dose infection and for the transfer of protective immunity with memory T cells.
Basis for the Failure ofFrancisella tularensisLipopolysaccharide To Prime Human Polymorphonuclear Leukocytes
Authors: Barker Jason H. , Weiss Jerrold , Apicella Michael A. , Nauseef William M. 
Published: May 2006

ABSTRACTFrancisella tularensisis the intracellular gram-negative coccobacillus that causes tularemia, and its virulence and infectiousness make it a potential agent of bioterrorism. Previous studies using mononuclear leukocytes have shown that the lipopolysaccharide (LPS) ofF. tularensisis neither a typical proinflammatory endotoxin nor an endotoxin antagonist. This inertness suggests thatF. tularensisLPS does not bind host LPS-sensing molecules such as LPS-binding protein (LBP). Using priming of the polymorphonuclear leukocyte (PMN) oxidase as a measure of endotoxicity, we found thatF. tularensislive vaccine strain LPS did not behave like either a classic endotoxin or an endotoxin antagonist in human PMNs, even when the concentration of LBP was limiting. Furthermore,F. tularensisLPS did not compete with a radiolabeled lipooligosaccharide fromNeisseria meningitidisfor binding to LBP or to the closely related PMN granule protein, bactericidal/permeability-increasing protein. Our results suggest that the inertness ofF. tularensisLPS and the resistance ofF. tularensisto oxygen-independent PMN killing may result from the inability ofF. tularensisLPS to be recognized by these important LPS-sensing molecules of the innate immune system.
Borrelia burgdorferi
Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity
Authors: Li Xin , Liu Xianzhong , Beck Deborah S. , Kantor Fred S. , Fikrig Erol 
Published: May 2006

ABSTRACT

BBK32, a fibronectin-binding protein of
Borrelia burgdorferi
, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in
B. burgdorferi
is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type
B. burgdorferi
B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the
Borrelia
life cycle. Our data indicated that
B. burgdorferi
lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional
B. burgdorferi
proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.
Members of a
Legionella pneumophila
Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells
Authors: VanRheenen Susan M. , Luo Zhao-Qing , O'Connor Tamara , Isberg Ralph R. 
Published: May 2006

ABSTRACT

Legionella
pneumophila
replicates within alveolar macrophages, causing a
severe pneumonia termed Legionnaires' disease. The bacterium resides
within a vacuole that escapes immediate transport to the host lysosome.
Instead, the vacuole interacts with the early secretory pathway to
establish an environment suitable for rapid multiplication. A type IV
secretion system is central to the pathogenicity of the bacterium, and
many protein substrates that are translocated by this system to the
host cell have been identified. One of these, VipD, was found to
interrupt the late secretory pathway when overproduced in
Saccharomyces cerevisiae
. We independently identified VipD in
a previous study and have further characterized this protein as well as
its three paralogs. The
vipD
gene belongs to a family of
L. pneumophila
open reading frames that are predicted to
contain a phospholipase A domain with sequence similarity to the type
III-secreted toxin ExoU from
Pseudomonas aeruginosa
. Similarly
to other known translocated proteins of
L. pneumophila
, VipD
is strongly induced in early stationary phase, a time when the
bacterium is most virulent. Detergent extraction studies of infected
macrophages confirm that VipD is translocated into host cells via the
type IV secretion system. A second assay for translocation revealed
that two paralogs of VipD, VpdA and VpdB, also have translocation
signals recognized by the type IV system. A strain lacking VipD and its
three paralogs grew at wild-type rates in murine macrophages, although
secondary mutations that cause growth defects in strains lacking VipD
accumulate. The quadruple mutant displayed a growth advantage in the
amoebal host
Dictyostelium discoideum
, indicating that the
protein family may modulate intracellular growth in a complex fashion.
VipD is mildly toxic when overproduced in eukaryotic cells, and the
toxicity is partially dependent on the putative phospholipase active
site. VipD and its paralogs therefore define a family of translocated
proteins that may assist in the establishment of a vacuole suitable for
bacterial replication through functioning as a
phospholipase.
Eosinophils Can Function as Antigen-Presenting Cells To Induce Primary and Secondary Immune Responses toStrongyloides stercoralis
Authors: Padigel Udaikumar M. , Lee James J. , Nolan Thomas J. , Schad Gerhard A. , Abraham David 
Published: May 2006

ABSTRACTSeveral studies have demonstrated roles for eosinophils during innate and adaptive immune responses to helminth infections. However, evidence that eosinophils are capable of initiating an immune response to parasite antigens is lacking. The goal of the present in vitro study was to investigate the potential of eosinophils to serve as antigen-presenting cells (APC) and initiate an immune response to parasite antigens. Purified eosinophils were exposed to solubleStrongyloides stercoralisantigens, and the expression of various surface markers involved in cell activation was examined. Antigen-exposed eosinophils showed a sixfold increase in expression levels of CD69 and major histocompatibility complex (MHC) class II, a fourfold increase in levels of T-cell costimulatory molecule CD86, and a twofold decrease in levels of CD62L compared to eosinophils cultured in medium containing granulocyte-macrophage colony-stimulating factor. The ability of eosinophils to present antigen to T cells was determined by culturing them with T cells in vitro. Eosinophils pulsed with antigen stimulated antigen-specific primed T cells and CD4+T cells to increase interleukin-5 (IL-5) production. The blocking of MHC class II expression on eosinophils inhibited their ability to induce IL-5 production by CD4+T cells in culture. Antigen-pulsed eosinophils were able to prime naïve T cells and CD4+T cells in culture and polarized them into Th2 cells producing IL-5 similar to that induced by antigen-loaded dendritic cells. These results demonstrate that eosinophils are capable of activating antigen-specific Th2 cells inducing the release of cytokines and assist in the priming of naïve T cells to initiate Th2 responses against infection. This study highlights the potential of eosinophils to actively induce immune responses against infection by amplifying antigen-specific Th2-cell responses.
Immunoglobulin A Antibodies against Ricin A and B Subunits Protect Epithelial Cells from Ricin Intoxication
Authors: Mantis Nicholas J. , McGuinness Carolyn R. , Sonuyi Oluwakemi , Edwards Gary , Farrant Stephanie A. 
Published: May 2006

ABSTRACTEpithelial cells of the respiratory and gastrointestinal tracts are extremely vulnerable to the cytotoxic effects of ricin, a Shiga-like toxin with ribosome-inactivating properties. While mucosal immunity to ricin correlates with secretory immunoglobulin A (IgA) antibody levels in vivo, the potential of IgA to protect epithelial cells from ricin in vitro has not been examined due to the unavailability of well-defined antitoxin IgA antibodies. Here we report the characterization of four monoclonal IgA antibodies (IgA MAbs) produced from the Peyer's patches and mesenteric lymph nodes of BALB/c mice immunized intragastrically with ricin toxoid. Two IgA MAbs (33G2 and 35H6) were active against ricin's lectin subunit (RTB), and two (23D7 and 25A4) reacted with the toxin's enzymatic subunit (RTA). All four IgA MAbs neutralized ricin in a Vero cell cytotoxicity assay, blocked toxin-induced interleukin-8 release by the human monocyte/macrophage cell line 28SC, and protected polarized epithelial cell monolayers from ricin-mediated protein synthesis inhibition. 33G2 and 35H6 reduced ricin binding to the luminal surfaces of human intestinal epithelial cells to undetectable levels in tissue section overlay assays, whereas 23D7 had no effect on toxin attachment. 23D7 and 25A4 did, however, reduce ricin transcytosis across MDCK II cell monolayers, possibly by interfering with intracellular toxin transport. We conclude that IgA antibodies against RTA and RTB can protect mucosal epithelial cells from ricin intoxication.
Inorganic Phosphate Induces Spore Morphogenesis and Enterotoxin Production in the Intestinal Pathogen
Clostridium perfringens
Authors: Philippe Valeria A. , Méndez Marcelo B. , Huang I-Hsiu , Orsaria Lelia M. , Sarker Mahfuzur R. , Grau Roberto R. 
Published: May 2006

ABSTRACT

Clostridium perfringens
enterotoxin (CPE) is an important virulence factor for food poisoning and non-food borne gastrointestinal (GI) diseases. Although CPE production is strongly regulated by sporulation, the nature of the signal(s) triggering sporulation remains unknown. Here, we demonstrated that inorganic phosphate (P
i
), and not pH, constitutes an environmental signal inducing sporulation and CPE synthesis. In the absence of P
i
-supplementation,
C. perfringens
displayed a
spo0A
phenotype, i.e., absence of polar septation and DNA partitioning in cells that reached the stationary phase of growth. These results received support from our Northern blot analyses which demonstrated that P
i
was able to counteract the inhibitory effect of glucose at the onset of sporulation and induced
spo0A
expression, indicating that P
i
acts as a key signal triggering spore morphogenesis. In addition to being the first study reporting the nature of a physiological signal triggering sporulation in clostridia, these findings have relevance for the development of antisporulation drugs to prevent or treat CPE-mediated GI diseases in humans.
The triad of shift work, occupational noise, and physical workload and risk of coronary heart disease
Authors: Virkkunen H , Härmä M , Kauppinen T , Tenkanen L 
Published: May 2006

Background:Shift work, noise, and physical workload are very common occupational exposures and they tend to cluster in the same groups of workers.Objectives:To study the short and long term effects of these exposures on risk of coronary heart disease (CHD) and to estimate the joint effects of these factors.Methods:The study population in this prospective 13 year follow up study of 1804 middle aged industrially employed men was collected at the first screening for the Helsinki Heart Study. The CHD end points (ICD-9 codes 410–414 and ICD-10 codes I20–I25) were obtained from official Finnish registers. The Finnish job-exposure matrix FINJEM provided information on occupational exposures. Relative risks (RR) of CHD for the exposures were estimated using Cox’s proportional hazard models adjusting for classical risk factors of CHD.Results:The RR in the five year follow up for continuous noise combined with impulse noise was 1.28; for shift work it was 1.59, and for physical workload 1.18, while in the 13 year follow up the RRs were 1.58, 1.34, and 1.31, respectively. When adjusted for white-collar/blue-collar status the RRs decreased markedly. The RR in the 13 year follow up for those exposed to two risk factors was close to 1.7 and for those exposed to all three, 1.87.Conclusion:Shift work and continuous noise entailed an excess risk for CHD in the shortest follow up with only a few retired workers but a decreasing risk during the longer follow up. For physical workload and impulse noise the trend was opposite: the CHD risk was increasing with increasing follow up time despite increasing numbers of retired workers.
Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1
Authors: Chen Yabing , Budd Ralph C. , Kelm Robert J. , Sobel Burton E. , Schneider David J. 
Published: May 2006

Objective—Proliferation of vascular smooth muscle cells (VSMCs) contributes to restenosis after coronary intervention. We have shown previously that increased expression of plasminogen activator inhibitor type 1 (PAI-1) limits VSMC apoptosis. Because apoptosis and proliferation appear to be linked, we sought to determine whether increased PAI-1 would affect VSMC proliferation.Methods and Results—VSMCs were explanted from control and transgenic mice (SM22-PAI+) in which VSMC expression of PAI-1 was increased. Increased growth of SM22-PAI+-VSMCs (2.3±0.4-fold) reflected, at least partially, increased proliferation. Greater expression of FLICE-like inhibitory protein (FLIP; 2.7-fold) and its cleaved active form were seen in SM22-PAI+-VSMCs. The balance between caspase-8 and FLIP favored proliferation in SM22-PAI+-VSMCs. Increased expression of NF-κB and activation of extracellular signal-regulated kinase (ERK) were demonstrated in SM22-PAI+-VSMCs (fold=NF-κB=2.2±0.1, fold=phosphorylated-ERK=1.6±0.1). Results were confirmed when expression of PAI-1 was increased by transfection. Inhibition of NF-κB and ERK attenuated proliferation in SM22-PAI+-VSMCs. Increased expression of PAI-1 promoted proliferation when VSMCs were exposed to tumor necrosis factor (TNF).Conclusions—Increased expression of PAI-1 is associated with greater activity of FLIP that promotes VSMC proliferation through NF-κB and ERK. Thus, when vascular wall expression of PAI-1 is increased, restenosis after coronary intervention is likely to be potentiated by greater proliferation of VSMC and resistance to apoptosis.
Seasonality and Meridional Propagation of the MJO
Authors: Wu Man-Li C. , Schubert Siegfried D. , Suarez Max J. , Pegion Philip J. , Waliser Duane E. 
Published: May 2006

AbstractThe Madden–Julian oscillation (MJO) is known to have a substantial impact on the variability of the Asian–Australian summer monsoons. An important, but not well understood, aspect of the MJO–monsoon connection is the meridional propagation of bands of enhanced or reduced precipitation that are especially pronounced during the northern summer. In this study, the nature of the seasonality of the MJO is examined, with a focus on the meridional propagation, using both observations and simulations with an atmospheric general circulation model (AGCM).A key result is that the AGCM, when forced with idealized eastward propagating equatorial dipole heating anomalies, reproduces the salient features of the observed seasonality in the precipitation and wind fields associated with the MJO, including meridional propagation into the Indian and Australian summer monsoon regions. An analysis of the simulations and observations shows that the off-equatorial precipitation anomalies are initiated by surface frictional convergence/divergence associated with the Rossby wave response to the leading pole of the equatorial heating dipole. The off-equatorial precipitation anomalies develop further by interacting with the trailing pole of the equatorial dipole heating to produce a northwest–southeast (or southwest–northeast) oriented line of surface convergence/divergence that propagates to the east. Since the prescribed heating does not vary by season, the seasonal asymmetry in the response must be the result of the seasonal changes in the background state. In particular, the results suggest that seasonal changes in both the vertical wind shear and static stability play a role.
Preferred Modes of Variability and Their Relationship with Climate Change
Authors: Son Seok-Woo , Lee Sukyoung 
Published: May 2006

Abstract
Spatial structure of annular modes shows a remarkable resemblance to that of the recent trend in the observed circulation (Thompson et al.). This study performs a series of multilevel primitive equation model simulations to examine the extent to which the annular mode is capable of predicting changes in the zonal-mean flow response to external heat perturbations. Each of these simulations represents a statistically steady state and differs from each other in the values of the imposed tropical heating (ℋ) and high-latitude cooling (𝒞).
Defining the annular mode as the first empirical orthogonal function (EOF1) of zonal-mean tropospheric zonal wind, it is found that the “climate predictability” is generally high in the small 𝒞–large ℋ region of the parameter space, but is markedly low in the large 𝒞–small ℋ region. In the former region, EOF1 represents meridional meandering of the midlatitude jet, while in the latter region, EOF1 and EOF2 combine to represent coherent poleward propagation of zonal-mean flow anomalies. It is also found that the climate predictability tends to be higher with respect to changes in 𝒞 than to changes in ℋ. The implications of these findings for the Southern Hemisphere climate predictability are also presented.
An Operational Dynamical Downscaling Prediction System for Nordeste Brazil and the 2002–04 Real-Time Forecast Evaluation
Authors: Sun Liqiang , Li Huilan , Zebiak Stephen E. , Moncunill David F. , Filho Francisco D. A. D. S. , Moura Antonio D. 
Published: May 2006

Abstract
The International Research Institute for Climate Prediction (IRI) and Ceará Foundation for Meteorology and Water Resources (FUNCEME) in Brazil have developed a dynamical downscaling prediction system for Northeast Brazil (the Nordeste) and have been issuing seasonal rainfall forecasts since December 2001. To the authors’ knowledge, this is the first operational climate dynamical downscaling prediction system. The ECHAM4.5 AGCM and the NCEP Regional Spectral Model (RSM) are the core of this prediction system. This is a two-tiered prediction system. SST forecasts are produced first, which then serve as the lower boundary condition forcing for the ECHAM4.5 AGCM–NCEP RSM nested system. Hindcasts for January–June 1971–2000 with the nested model, using observed SSTs, provided estimates of model potential predictability and characteristics of the model climatology. During 2002–04, the overall rainfall forecast skill, measured by the ranked probability skill score (RPSS), is positive over a majority of the Nordeste. Higher skill is found for the March–May (MAM) and April–June (AMJ) seasons with forecast lead times up to 3 months. The skill of the downscaled forecasts is generally higher than that of the driving global model forecasts.