bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Major Subunit, CfaB, of Colonization Factor Antigen I from Enterotoxigenic
Escherichia coli
Is a Glycosphingolipid Binding Protein
Authors: Jansson Lena , Tobias Joshua , Lebens Michael , Svennerholm Ann-Mari , Teneberg Susann 
Published: May 2006

ABSTRACT

Bacterial adherence to mucosal surfaces is an important virulence trait of pathogenic bacteria. Adhesion of enterotoxigenic
Escherichia coli
(ETEC) to the intestine is mediated by a number of antigenically distinct colonization factors (CFs). One of the most common CFs is CFA/I. This has a fimbrial structure composed of a major repeating subunit, CfaB, and a single tip subunit, CfaE. The potential carbohydrate recognition by CFA/I was investigated by binding CFA/I-fimbriated bacteria and purified CFA/I fimbriae to a large number of variant glycosphingolipids separated on thin-layer chromatograms. For both fimbriated bacteria and purified fimbriae, specific interactions could be identified with a number of nonacid glycosphingolipids. These included glucosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, neolactotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, the H5 type 2 pentaglycosylceramide, the Le
a
-5 glycosphingolipid, the Le
x
-5 glycosphingolipid, and the Le
y
-6 glycosphingolipid. These glycosphingolipids were also recognized by recombinant
E. coli
expressing CFA/I in the absence of tip protein CfaE, as well as by purified fimbriae from the same strain. This demonstrates that the glycosphingolipid-binding capacity of CFA/I resides in the major CfaB subunit.
Localization of the C3-Like ADP-Ribosyltransferase from
Staphylococcus aureus
during Bacterial Invasion of Mammalian Cells
Authors: Molinari Gabriella , Rohde Manfred , Wilde Christian , Just Ingo , Aktories Klaus , Chhatwal Gursharan S. 
Published: May 2006

ABSTRACT

The C3stau2 exoenzyme from
Staphylococcus aureus
is a C3-like ADP-ribosyltransferase which possesses no specific receptor-binding domain or translocation unit required for entry in target cells where its substrate is located. Here we show that C3stau2 can reach its target after invasion of staphylococci in eukaryotic cells without needing translocation.
Toll-Like Receptor 2 Is Required for Control of Pulmonary Infection withFrancisella tularensis
Authors: Malik Meenakshi , Bakshi Chandra Shekhar , Sahay Bikash , Shah Aaloki , Lotz Steven A. , Sellati Timothy J. 
Published: May 2006

ABSTRACTToll-like receptor 2 (TLR2) deficiency enhances murine susceptibility to infection byFrancisella tularensisas indicated by accelerated mortality, higher bacterial burden, and greater histopathology. Analysis of pulmonary cytokine levels revealed that TLR2 deficiency results in significantly lower levels of tumor necrosis factor alpha and interleukin-6 but increased amounts of gamma interferon and monocyte chemoattractant protein 1. This pattern of cytokine production may contribute to the exaggerated pathogenesis seen in TLR2−/−mice. Collectively, these findings suggest that TLR2 plays an important role in tempering the host response to pneumonic tularemia.
MyD88-Dependent Responses Involving Toll-Like Receptor 2 Are Important for Protection and Clearance ofLegionella pneumophilain a Mouse Model of Legionnaires' Disease
Authors: Archer Kristina A. , Roy Craig R. 
Published: May 2006

ABSTRACTLegionella pneumophilais a gram-negative facultative intracellular parasite of macrophages. AlthoughL. pneumophilais the causative agent of a severe pneumonia known as Legionnaires' disease, it is likely that most infections caused by this organism are cleared by the host innate immune system. It is predicted that host pattern recognition proteins belonging to the Toll-like receptor (TLR) family are involved in the protective innate immune responses. We examined the role of TLR-mediated responses inL. pneumophiladetection and clearance using genetically altered mouse hosts in which the macrophages are permissive forL. pneumophilaintracellular replication. Our data demonstrate that cytokine production by bone marrow-derived macrophages (BMMs) in response toL. pneumophilainfection requires the TLR adapter protein MyD88 and is reduced in the absence of TLR2 but not in the absence of TLR4. Bacterial growth ex vivo in BMMs from MyD88-deficient mice was not enhanced compared to bacterial growth ex vivo in BMMs from heterozygous littermate controls. Wild-type mice were able to clearL. pneumophilafrom the lung, whereas respiratory infection of MyD88-deficient mice caused death that resulted from robust bacterial replication and dissemination. In contrast to an infection with virulentL. pneumophila, MyD88-deficient mice were able to clear infections withL. pneumophila dotAmutants, indicating that MyD88-independent responses in the lung are sufficient to clear bacteria that are unable to replicate intracellularly. In vivo growth ofL. pneumophilawas enhanced in the lungs of TLR2-deficient mice, which resulted in a delay in bacterial clearance. No significant differences were observed in the growth and clearance ofL. pneumophilain the lungs of TLR4-deficient mice and heterozygous littermate control mice. Our data indicate that MyD88 is crucial for eliciting a protective innate immune response against virulentL. pneumophilaand that TLR2 is one of the pattern recognition receptors involved in initiating this MyD88-dependent response.
Mycobacterium marinum
Erp Is a Virulence Determinant Required for Cell Wall Integrity and Intracellular Survival
Authors: Cosma Christine L. , Klein Kathryn , Kim Rosa , Beery Dana , Ramakrishnan Lalita 
Published: May 2006

ABSTRACT

The
Mycobacterium tuberculosis
exported repetitive protein (Erp) is a virulence determinant required for growth in cultured macrophages and in vivo. To better understand the role of Erp in
Mycobacterium
pathogenesis, we generated a mutation in the
erp
homologue of
Mycobacterium marinum
, a close genetic relative of
M. tuberculosis. erp
-deficient
M. marinum
was growth attenuated in cultured macrophage monolayers and during chronic granulomatous infection of leopard frogs, suggesting that Erp function is similarly required for the virulence of both
M. tuberculosis
and
M. marinum
. To pinpoint the step in infection at which Erp is required, we utilized a zebrafish embryo infection model that allows
M. marinum
infections to be visualized in real-time, comparing the
erp
-deficient strain to a ΔRD1 mutant whose stage of attenuation was previously characterized in zebrafish embryos. A detailed microscopic examination of infected embryos revealed that bacteria lacking Erp were compromised very early in infection, failing to grow and/or survive upon phagocytosis by host macrophages. In contrast, ΔRD1 mutant bacteria grow normally in macrophages but fail to induce host macrophage aggregation and subsequent cell-to-cell spread. Consistent with these in vivo findings,
erp
-deficient but not RD1-deficient bacteria exhibited permeability defects in vitro, which may be responsible for their specific failure to survive in host macrophages.
High Frequency of CD4+T Cells Specific for the TB10.4 Protein Correlates with Protection againstMycobacterium tuberculosisInfection
Authors: Hervas-Stubbs Sandra , Majlessi Laleh , Simsova Marcela , Morova Jana , Rojas Marie-Jesus , Nouzé Clémence , Brodin Priscille , Sebo Peter , Leclerc Claude 
Published: May 2006

ABSTRACTTB10.4 is a newly identified antigen ofMycobacterium tuberculosisrecognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization withMycobacterium bovisBCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 peptide was identified as an immunodominant CD4+T-cell epitope forH-2dmice. Since recent results, as well as the present study, have raised interest in TB10.4 as a subunit vaccine, we analyzed immune responses induced by this antigen delivered by a new vector, the adenylate cyclase (CyaA) ofBordetella pertussis. CyaA is able to target dendritic cells and to deliver CD4+or CD8+T-cell epitopes to the major histocompatibility complex class II/I molecule presentation pathways, triggering specific Th1 or cytotoxic T-lymphocyte (CTL) responses. Several CyaA harboring either the entire TB10.4 protein or various subfragments containing the TB10.4:20-28 CTL epitope were shown to induce TB10.4-specific Th1 CD4+and CD8+T-cell responses. However, none of the recombinant CyaA, injected in the absence of adjuvant, was able to induce protection againstM. tuberculosisinfection. In contrast, TB10.4 protein administered with a cocktail of strong adjuvants that triggered a strong Th1 CD4+T-cell response induced significant protection againstM. tuberculosischallenge. These results confirm the potential value of the TB10.4 protein as a candidate vaccine and show that the presence of high frequencies of CD4+T cells specific to this strong immunogen correlates with protection againstM. tuberculosisinfection.
Elevated Plasma Phenylalanine in Severe Malaria and Implications for Pathophysiology of Neurological Complications
Authors: Lopansri Bert K. , Anstey Nicholas M. , Stoddard Gregory J. , Mwaikambo Esther D. , Boutlis Craig S. , Tjitra Emiliana , Maniboey Helena , Hobbs Maurine R. , Levesque Marc C. , Weinberg J. Brice , Granger Donald L. 
Published: May 2006

ABSTRACTCerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor,l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid abnormalities are associated with disease severity in falciparum malaria. Subjects were enrolled in Dar es Salaam, Tanzania (children) (n= 126), and Papua, Indonesia (adults) (n= 156), in two separate studies. Plasma samples were collected from subjects with WHO-defined cerebral malaria (children), all forms of severe malaria (adults), and uncomplicated malaria (children and adults). Healthy children and adults without fever or illness served as controls. Plasma amino acids were measured using reverse-phase high-performance liquid chromatography with fluorescence detection. Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 μM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] μM;P< 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] μM;P< 0.0001). In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement (P= 0.0002). Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.
Laminar Shear Stress Inhibits Cathepsin L Activity in Endothelial Cells
Authors: Platt Manu O. , Ankeny Randall F. , Jo Hanjoong 
Published: May 2006

Objective—The cysteine proteases, cathepsins, have been implicated in vascular remodeling and atherosclerosis, processes known to be regulated by shear stress. It is not known, however, whether shear regulates cathepsins. We examined the hypothesis that shear stress regulates cathepsin activity in endothelial cells.Methods and Results—Mouse aortic endothelial cells (MAECs) exposed to atheroprotective, unidirectional laminar shear (LS) degraded significantly less BODIPY-labeled elastin and gelatin in comparison to static and proatherogenic oscillatory shear (OS). The cathepsin inhibitor E64 also reduced this activity. Gelatin zymography showed that cathepsin activity of MAECs was blunted by LS exposure and by a cathepsin L inhibitor but not by cathepsin B and S inhibitors, whereas a cathepsin K inhibitor had a minor effect. Cathepsin L siRNA knocked down cathepsin L expression, gelatinase, and elastase activity in OS and static MAECs. A partial reduction of cathepsin B protein raised the possibility that the siRNA effect on the matrix protease activity could have been attributable to cathepsin L or B. Cathepsin B activity study using the synthetic peptide showed it was not regulated by shear.Conclusions—These results suggest that cathepsin L is a shear-sensitive matrix protease and that it may play an important role in flow-mediated vascular remodeling and atherogenic responses.
Interannual Rainfall Extremes over Southwest Western Australia Linked to Indian Ocean Climate Variability
Authors: England Matthew H. , Ummenhofer Caroline C. , Santoso Agus 
Published: May 2006

Abstract
Interannual rainfall extremes over southwest Western Australia (SWWA) are examined using observations, reanalysis data, and a long-term natural integration of the global coupled climate system. The authors reveal a characteristic dipole pattern of Indian Ocean sea surface temperature (SST) anomalies during extreme rainfall years, remarkably consistent between the reanalysis fields and the coupled climate model but different from most previous definitions of SST dipoles in the region. In particular, the dipole exhibits peak amplitudes in the eastern Indian Ocean adjacent to the west coast of Australia. During dry years, anomalously cool waters appear in the tropical/subtropical eastern Indian Ocean, adjacent to a region of unusually warm water in the subtropics off SWWA. This dipole of anomalous SST seesaws in sign between dry and wet years and appears to occur in phase with a large-scale reorganization of winds over the tropical/subtropical Indian Ocean. The wind field alters SST via anomalous Ekman transport in the tropical Indian Ocean and via anomalous air–sea heat fluxes in the subtropics. The winds also change the large-scale advection of moisture onto the SWWA coast. At the basin scale, the anomalous wind field can be interpreted as an acceleration (deceleration) of the Indian Ocean climatological mean anticyclone during dry (wet) years. In addition, dry (wet) years see a strengthening (weakening) and coinciding southward (northward) shift of the subpolar westerlies, which results in a similar southward (northward) shift of the rain-bearing fronts associated with the subpolar front. A link is also noted between extreme rainfall years and the Indian Ocean Dipole (IOD). Namely, in some years the IOD acts to reinforce the eastern tropical pole of SST described above, and to strengthen wind anomalies along the northern flank of the Indian Ocean anticyclone. In this manner, both tropical and extratropical processes in the Indian Ocean generate SST and wind anomalies off SWWA, which lead to moisture transport and rainfall extremes in the region. An analysis of the seasonal evolution of the climate extremes reveals a progressive amplification of anomalies in SST and atmospheric circulation toward a wintertime maximum, coinciding with the season of highest SWWA rainfall. The anomalies in SST can appear as early as the summertime months, however, which may have important implications for predictability of SWWA rainfall extremes.
Synoptic-Scale Atmospheric Circulation and Boreal Canada Summer Drought Variability of the Past Three Centuries
Authors: Girardin Martin-Philippe , Tardif Jacques C. , Flannigan Mike D. , Bergeron Yves 
Published: May 2006

Abstract
Five independent multicentury reconstructions of the July Canadian Drought Code and one reconstruction of the mean July–August temperature were developed using a network of 120 well-replicated tree-ring chronologies covering the area of the eastern Boreal Plains to the eastern Boreal Shield of Canada. The reconstructions were performed using 54 time-varying reconstruction submodels that explained up to 50% of the regional drought variance during the period of 1919–84. Spatial correlation fields on the six reconstructions revealed that the meridional component of the climate system from central to eastern Canada increased since the mid–nineteenth century. The most obvious change was observed in the decadal scale of variability. Using 500-hPa geopotential height and wind composites, this zonal to meridional transition was interpreted as a response to an amplification of long waves flowing over the eastern North Pacific into boreal Canada, from approximately 1851 to 1940. Composites with NOAA Extended Reconstructed SSTs indicated a coupling between the meridional component and tropical and North Pacific SST for a period covering at least the past 150 yr, supporting previous findings of a summertime global ocean–atmosphere–land surface coupling. This change in the global atmospheric circulation could be a key element toward understanding the observed temporal changes in the Canadian boreal forest fire regimes over the past 150 yr.
Factors Limiting Convective Cloud-Top Height at the ARM Nauru Island Climate Research Facility
Authors: Jensen Michael P. , Del Genio Anthony D. 
Published: May 2006

Abstract
Cumulus congestus clouds, with moderate shortwave albedos and cloud-top temperatures near freezing, occur fairly often in the Tropics. These clouds may play an important role in the evolution of the Madden–Julian oscillation and the regulation of relative humidity in the midtroposphere. Despite this importance they are not necessarily simulated very well in global climate models. Surface remote sensing observations and soundings from the Atmospheric Radiation Measurement (ARM) climate research facility at Nauru Island are coupled with a simple parcel model in order to address the following questions about these cloud types: 1) Which environmental factors play a role in determining the depth of tropical convective clouds? 2) What environmental parameters are related to entrainment rate in cumulus congestus clouds? The results presented herein suggest that at Nauru Island a drying of the midtroposphere is more likely to be responsible for limiting congestus cloud-top heights than is a stabilizing of the freezing level. It is also found that low-level CAPE and the RH profile account for the largest portion of the variance in cumulus congestus entrainment rates, consistent with the idea that entrainment rate depends on the buoyant production of turbulent kinetic energy. If the analysis is limited to cases where there is a sounding during the hour preceding the cumulus congestus observations, it is found that the low-level CAPE accounts for 85% of the total variance in entrainment rate.
Anthropogenic Warming of the Oceans: Observations and Model Results
Authors: Pierce David W. , Barnett Tim P. , AchutaRao Krishna M. , Gleckler Peter J. , Gregory Jonathan M. , Washington Warren M. 
Published: May 2006

Abstract
Observations show the oceans have warmed over the past 40 yr, with appreciable regional variation and more warming at the surface than at depth. Comparing the observations with results from two coupled ocean–atmosphere climate models [the Parallel Climate Model version 1 (PCM) and the Hadley Centre Coupled Climate Model version 3 (HadCM3)] that include anthropogenic forcing shows remarkable agreement between the observed and model-estimated warming. In this comparison the models were sampled at the same locations as gridded yearly observed data. In the top 100 m of the water column the warming is well separated from natural variability, including both variability arising from internal instabilities of the coupled ocean–atmosphere climate system and that arising from volcanism and solar fluctuations. Between 125 and 200 m the agreement is not significant, but then increases again below this level, and remains significant down to 600 m. Analysis of PCM’s heat budget indicates that the warming is driven by an increase in net surface heat flux that reaches 0.7 W m−2 by the 1990s; the downward longwave flux increases by 3.7 W m−2, which is not fully compensated by an increase in the upward longwave flux of 2.2 W m−2. Latent and net solar heat fluxes each decrease by about 0.6 W m−2. The changes in the individual longwave components are distinguishable from the preindustrial mean by the 1920s, but due to cancellation of components, changes in the net surface heat flux do not become well separated from zero until the 1960s. Changes in advection can also play an important role in local ocean warming due to anthropogenic forcing, depending on the location. The observed sampling of ocean temperature is highly variable in space and time, but sufficient to detect the anthropogenic warming signal in all basins, at least in the surface layers, by the 1980s.
Climatology and ENSO-Related Variability of North American Extratropical Cyclone Activity
Authors: Eichler Timothy , Higgins Wayne 
Published: May 2006

Abstract
The climatology and interannual variability of North American extratropical cyclones are examined using 6-hourly sea level pressure data from the NCEP–NCAR reanalysis for the period 1950–2002 and ECMWF 40-yr Re-Analysis (ERA-40) data from 1971 to 2000. The climatology includes an evaluation of the seasonal frequency and intensity of storms as well as an analysis of extreme event intensity. ENSO variability is evaluated by ENSO phase with emphasis on boreal winter. Results show an enhanced East Coast storm track during El Niño as well as an equatorward shift in storm tracks in the North Pacific for storms generated from both the NCEP–NCAR reanalysis and ERA-40 datasets. Observed precipitation close to a storm’s center is used to determine which phase of the ENSO cycle is associated with the most productive storms and where they occur. During El Niño winters, a precipitation maximum is located east of the Appalachians and is associated with an enhanced East Coast storm track. During La Niña winters, the precipitation maximum shifts to the Ohio Valley and is associated with an enhanced Great Lakes storm track. Along the U.S. west coast, there is a precipitation maximum in the Pacific Northwest during La Niña winters, which is due to a storm track west of Washington State.