bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tea Catechin Epigallocatechin Gallate Suppresses Cariogenic Virulence Factors of
Streptococcus mutans
Authors: Xu Xin , Zhou Xue D. , Wu Christine D. 
Published: December 2010

ABSTRACT

Streptococcus mutans
, the primary etiologic agent of dental caries, possesses a series of virulence factors associated with its cariogenicity. Alternatives to traditional antimicrobial treatment, agents selectively inhibiting the virulence factors without necessarily suppressing the resident oral species, are promising. The anticariogenic properties of tea have been suggested in experimental animals and humans. Tea polyphenols, especially epigallocatechin gallate (EGCg), have been shown to inhibit the growth and glucosyltransferases activity of
S. mutans
. However, their effects on biofilm and cariogenic virulence factors of oral streptococci other than glucosyltransferases have not been well documented. In this study, we investigated the biological effect of EGCg on the virulence factors of
S. mutans
associated with its acidogenicity and acidurity. The antimicrobial effects of EGCg on
S. mutans
biofilm grown in chemically defined medium were also examined. EGCg inhibited growth of
S. mutans
planktonic cells at an MIC of 31.25 μg/ml and a minimal bactericidal concentration (MBC) of 62.5 μg/ml. EGCg also inhibited
S. mutans
biofilm formation at 15.6 μg/ml (minimum concentration that showed at least 90% inhibition of biofilm formation) and reduced viability of the preformed biofilm at 625 μg/ml (sessile MIC
80
). EGCg at sub-MIC levels inhibited acidogenicity and acidurity of
S. mutans
cells. Analysis of the data obtained from real-time PCR showed that EGCg significantly suppressed the
ldh
,
eno
,
atpD
, and
aguD
genes of
S. mutans
UA159. Inhibition of the enzymatic activity of F
1
F
o
-ATPase and lactate dehydrogenase was also noted (50% inhibitory concentration between 15.6 and 31.25 μg/ml). These findings suggest that EGCg is a natural anticariogenic agent in that it exhibits antimicrobial activity against
S. mutans
and suppresses the specific virulence factors associated with its cariogenicity.
A Two-Component Regulatory System Interconnects Resistance to Polymyxins, Aminoglycosides, Fluoroquinolones, and β-Lactams inPseudomonas aeruginosa
Authors: Muller Cédric , Plésiat Patrick , Jeannot Katy 
Published: December 2010

ABSTRACTConstitutive overexpression of the active efflux system MexXY/OprM is a major cause of resistance to aminoglycosides, fluoroquinolones, and cefepime in clinical strains ofPseudomonas aeruginosa. Upregulation of this pump often results from mutations occurring inmexZ, the local repressor gene of themexXYoperon. In this study, analysis of MexXY-overproducing mutants selectedin vitrofrom reference strain PAO1Bes on amikacin (at a concentration 1.5-fold higher than the MIC) led to identification of a new class of mutants harboring an intactmexZgene and exhibiting increased resistance to colistin and imipenem in addition to aminoglycosides, fluoroquinolones, and cefepime. Reverse transcription-quantitative PCR (RT-qPCR) experiments on a selected clone named PAOW2 demonstrated thatmexXYoverexpression was independent ofmexZand the PA5471 gene, which is required for drug-dependent induction ofmexXY. Furthermore, the transcript levels of theoprDgene, which encodes the carbapenem-selective porin OprD, were found to be reduced drastically in PAOW2. Whole-genome sequencing revealed a single mutation resulting in an M59I substitution in the ParR protein, the response regulator of the ParRS two-component regulatory system (with ParS being the sensor kinase), which is required for adaptive resistance ofP. aeruginosato polycationic peptides such as colistin. The multidrug resistance phenotype was suppressed in PAOW2 by deletion of theparSandparRSgenes and conferred to PAO1Bes by chromosomal insertion of the mutatedparRSlocus from PAOW2. As shown by transcriptomic analysis, only a very small number of genes were expressed differentially between PAOW2 and PAO1Bes, including the lipopolysaccharide (LPS) modification operonarnBCADTEF-ugd, responsible for resistance to polycationic agents. Exposure of wild-type PAO1Bes to different polycationic peptides, including colistin, was shown to result in increasedmexYand repressedoprDexpression via ParRS, independent of PA5471. In agreement with these results, colistin antagonized activity of the MexXY/OprM substrates in PAO1Bes but not in a ΔparRSderivative. Finally, screening of clinical strains exhibiting the PAOW2 resistance phenotype allowed the identification of additional alterations in ParRS. Collectively, our data indicate that ParRS may promote either induced or constitutive multidrug resistance to four different classes of antibiotics through the activation of three distinct mechanisms (efflux, porin loss, and LPS modification).
Thrombopoietin Contributes to Neuronal Damage in Experimental Bacterial Meningitis
Authors: Hoffmann Olaf , Rung Olga , Im Ae-Rie , Freyer Dorette , Zhang Juan , Held Josephin , Stenzel Werner , Dame Christof 
Published: December 2010

ABSTRACTThrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons. In the present study, we investigated the implication ofTpoin experimental pneumococcal meningitis. Following intrathecal infection with the encapsulatedStreptococcus pneumoniaestrain D39, we observed upregulation ofTpomRNA expression at 12 h and 24 h in brain homogenates of wild-type C57BL/6 mice. c-MplmRNA expression was upregulated at 12 h and returned to baseline at 24 h. Compared to wild-type mice, mutants with homozygous Tpo receptor ablation (c-Mpl−/−) displayed reduced microglial activation and neuronal apoptosis in the dentate gyrus. Concentrations of bacteria in blood or cerebrospinal fluid (CSF), as well as CSF pleocytosis, were not significantly different between wild-type and c-Mpl−/−mice. In human postmortem brain, Tpo protein was colocalized to macrophages during encephalitis. In murine primary microglia and RAW264.7 macrophages, upregulation ofTpomRNA was induced by D39-conditioned medium but not by bacterial lipopeptide or by medium conditioned by pneumococcal mutants defective in hydrogen peroxide formation (ΔspxB) or pneumolysin (Δpln). We conclude that Tpo acts as a mediator of neuronal damage in bacterial meningitis.
Activation of Motility by Sensing Short-Chain Fatty Acids via Two Steps in a Flagellar Gene Regulatory Cascade in Enterohemorrhagic
Escherichia coli
Authors: Tobe Toru , Nakanishi Noriko , Sugimoto Nakaba 
Published: December 2010

ABSTRACT

The regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. Orally ingested enterohemorrhagic
Escherichia coli
(EHEC) travels through the gastrointestinal tract and encounters a variety of environmental factors, some of which act as triggering signals for the induction of virulence genes. Butyrate, one of the main short-chain fatty acids (SCFAs), is such a signal, enhancing the expression of genes for intimate attachment and type III secretion. We further explored the role of SCFAs and found a positive effect of SCFAs on flagellar expression. Although EHEC did not produce flagella when grown in Dulbecco's modified Eagle's medium (DMEM), a tissue culture medium that enhances virulence gene expression, the addition of SCFAs to the medium induced the production of flagella, and the EHEC bacteria became motile. Among SCFAs, butyrate simultaneously activates both virulence and flagellar genes. Flagella did not affect initial adherence, and they were not expressed in adherent bacteria during microcolony formation. SCFAs activated flagellar genes via two regulatory steps. Butyrate activated the
flhDC
regulatory genes through leucine-responsive regulatory protein (Lrp), which is also a regulator of virulence genes. However, butyrate, acetate, and propionate also activated downstream genes independently of
flhDC
activation. Consequently, when encountering increased concentrations of SCFAs, which are abundant in acetate, in the intestine, EHEC first activates flagellar production and motility, followed by genes involved in adherence and type III secretion, which leads to efficient adherence in a preferable niche.
Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood
Authors: Oakley Miranda S. , Anantharaman Vivek , Venancio Thiago M. , Zheng Hong , Mahajan Babita , Majam Victoria , McCutchan Thomas F. , Myers Timothy G. , Aravind L. , Kumar Sanjai 
Published: December 2010

ABSTRACTCerebral malaria (CM) is a primary cause of deaths caused byPlasmodium falciparumin young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using thePlasmodium bergheiANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, β-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathioneS-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation inP. falciparum-infected young African children as diagnostic markers of CM.
Reticulocyte and Erythrocyte Binding-Like Proteins Function Cooperatively in Invasion of Human Erythrocytes by Malaria Parasites
Authors: Lopaticki Sash , Maier Alexander G. , Thompson Jennifer , Wilson Danny W. , Tham Wai-Hong , Triglia Tony , Gout Alex , Speed Terence P. , Beeson James G. , Healer Julie , Cowman Alan F. 
Published: December 2010

ABSTRACT

Plasmodium falciparum
causes the most severe form of malaria in humans and invades erythrocytes using multiple ligand-receptor interactions. Two important protein families involved in erythrocyte binding are the erythrocyte binding-like (EBL) and the reticulocyte binding-like (RBL or
P. falciparum
Rh [PfRh]) proteins. We constructed
P. falciparum
lines lacking expression of EBL proteins by creating single and double knockouts of the corresponding genes for
eba-175
,
eba-181
, and
eba-140
and show that the EBL and PfRh proteins function cooperatively, consistent with them playing a similar role in merozoite invasion. We provide evidence that PfRh and EBL proteins functionally interact, as loss of function of EBA-181 ablates the ability of PfRh2a/b protein antibodies to inhibit merozoite invasion. Additionally, loss of function of some
ebl
genes results in selection for increased transcription of the
PfRh
family. This provides a rational basis for considering PfRh and EBL proteins for use as a combination vaccine against
P. falciparum
. We immunized rabbits with combinations of PfRh and EBL proteins to test the ability of antibodies to block merozoite invasion in growth inhibition assays. A combination of EBA-175, PfRh2a/b, and PfRh4 recombinant proteins induced antibodies that potently blocked merozoite invasion. This validates the use of a combination of these ligands as a potential vaccine that would have broad activity against
P. falciparum
.
Bifunctional Role of theTreponema pallidumExtracellular Matrix Binding Adhesin Tp0751
Authors: Houston Simon , Hof Rebecca , Francescutti Teresa , Hawkes Aaron , Boulanger Martin J. , Cameron Caroline E. 
Published: December 2010

ABSTRACTTreponema pallidum, the causative agent of syphilis, is a highly invasive pathogenic spirochete capable of attaching to host cells, invading the tissue barrier, and undergoing rapid widespread dissemination via the circulatory system. TheT. pallidumadhesin Tp0751 was previously shown to bind laminin, the most abundant component of the basement membrane, suggesting a role for this adhesin in host tissue colonization and bacterial dissemination. We hypothesized that similar to that of other invasive pathogens, the interaction ofT. pallidumwith host coagulation proteins, such as fibrinogen, may also be crucial for dissemination via the circulatory system. To test this prediction, we used enzyme-linked immunosorbent assay (ELISA) methodology to demonstrate specific binding of soluble recombinant Tp0751 to human fibrinogen. Click-chemistry-based palmitoylation profiling of heterologously expressed Tp0751 confirmed the presence of a lipid attachment site within this adhesin. Analysis of the Tp0751 primary sequence revealed the presence of a C-terminal putative HEXXH metalloprotease motif, andin vitrodegradation assays confirmed that recombinant Tp0751 purified from both insect andEscherichia coliexpression systems degrades human fibrinogen and laminin. The proteolytic activity of Tp0751 was abolished by the presence of the metalloprotease inhibitor 1,10-phenanthroline. Further, inductively coupled plasma-mass spectrometry showed that Tp0751 binds zinc and calcium. Collectively, these results indicate that Tp0751 is a zinc-dependent, membrane-associated protease that exhibits metalloprotease-like characteristics. However, site-directed mutagenesis of the HEXXH motif to HQXXH did not abolish the proteolytic activity of Tp0751, indicating that further mutagenesis studies are required to elucidate the critical active site residues associated with this protein. This study represents the first published description of aT. pallidumprotease capable of degrading host components and thus provides novel insight into the mechanism ofT. pallidumdissemination.
Global topographical exploration and analysis with the SRTM and ASTER elevation models
Authors: Crippen Robert E. 
Published: December 2010

Abstract
One of the most fundamental geophysical measurements of the Earth is that which describes the shape of its land surface. Topographical data are required by virtually all Earth science disciplines engaged in studies at or near the land surface. Topography is also civilization's most heavily used non-atmospheric geophysical measurement. NASA's Shuttle Radar Topography Mission (SRTM) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) projects have each completed independent near-global digital elevation measurements at comparable resolutions that approach 30 m spatially and 10 m vertically. Exploration of these datasets provides a new perspective of our planet. Fusion of these datasets will produce a more complete global elevation database, and differentiation of these datasets can be used to quantify select geomorphic processes.
An assessment of ASTER elevation data over glaciated terrain on Pourquois Pas Island, Antarctic Peninsula
Authors: Cziferszky A. , Fleming A. H. , Fox A. 
Published: December 2010

Abstract
This paper assesses the accuracy of digital elevation models (DEMs) generated from ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery in glaciated and mountainous terrain. This is an especially attractive technique for inaccessible glaciated regions of the Antarctic Peninsula. Our aims are to determine the best option for generating elevation data from ASTER data and to determine the errors involved for different terrain types. We use a near-coincident and contemporaneous airborne photogrammetric dataset to provide sufficiently accurate reference data. Three different software options for derivation of the ASTER DEM are assessed in order to determine the best available method of generating elevation data for this type of terrain. DEM accuracy is highly correlated to the steepness of the terrain. For areas of low to moderate relief errors are less than 20 m RMSE (root mean square error), but areas of high relief show much larger errors of up to 200 m RMSE.
Selecting the appropriate digital terrain model: an example from a hazard mapping exercise
Authors: Rutter H. K. , Newsham R. , Morris D. G. , McKenzie A. A. 
Published: December 2010

Abstract
In the UK national derived geological datasets are increasingly being produced, many of which are based on NEXTMap digital terrain model (DTM) or digital surface model (DSM) data. These include groundwater level and land stability datasets. Any DTM is a model of the land surface and under different conditions may have differing degrees of accuracy. This paper compares the NEXTMap data, derived from airborne Interferometric Synthetic Aperture Radar (IfSAR) data, with other frequently used datasets derived from contours and point data; in particular, the Integrated Hydrological Digital Terrain Model (IHDTM), a terrain model that was originally derived from Ordnance Survey (OS) 1:50 000 scale contours, and a DTM interpolated from Land-Form PROFILE data. This initial comparison of the DTMs has highlighted some issues with the NEXTMap data: first, that of elevation inaccuracy in woodland areas; and, secondly, the shadowing effect caused by the side-looking scanner. It also highlights the problems of using DTMs created from contour data in areas of low relief. The development of an uncertainty layer would enable a user to decide whether the DTM was appropriate in certain areas, and could also be incorporated into uncertainty models for the derived national datasets.
The use of elevation models to predict areas at risk of groundwater flooding
Authors: McKenzie A. A. , Rutter H. K. , Hulbert A. G. 
Published: December 2010

Abstract
Groundwater flooding, which occurs when the groundwater table rises in response to exceptional recharge rates either to the ground surface or to a point where subsurface infrastructure is affected, has been recognized as a significant issue with real economic impacts.
A methodology has been developed to produce maps of groundwater flooding susceptibility, using geological and hydrogeological data. While good geological map data are available in digital form for England and Wales, there are much less data on water levels. These levels are usually measured during the construction of water boreholes, and while there is a national groundwater level monitoring network for regulatory purposes, at a national level data are sparse. To assist in developing a comprehensive map of water levels, the British Geological Survey (BGS) has adopted a number of strategies for data interpolation for areas with limited water level data and a surface has been derived from a terrain model by considering interactions between groundwater and surface water in rivers and lakes. When comparing the calculated levels against the available field measurements, a high correlation was found to exist. However, it was considered that in areas where bedrock aquifers dominate, this interpolated surface was probably inaccurate, and so refinements were developed to improve the modelled water levels surfaces.
The resulting groundwater levels have been used to develop maps of areas where shallow groundwater may pose a risk. With potential changes in groundwater recharge postulated as a result of global climate change, identifying areas prone to flooding from groundwater, or areas where groundwater is likely to increase the impact of surface water flooding, is increasingly important.
Modeling the interactions between MAC and higher layer
Authors: Begum Shamim , Helmy Ahmed , Gupta Sandeep 
Published: December 2010

We propose a new framework for worst-case performance evaluation of MAC protocols for wireless ad hoc networks. Given a protocol, its performance metrics and a network topology, our framework first generates MAC scenarios which achieve poor performance at MAC level. In order to evaluate the impact of these MAC scenarios on the end performance, we model the interactions between MAC interface and the MAC layer using a state transition graph and generate high-level scenarios using enumeration techniques. These high-level scenarios can be simulated and compared with heuristics developed by others to identify high-level scenarios that are expected to lead to the worst-case end performance.
In order to demonstrate its usefulness, we use our framework to evaluate the worst-case performance of IEEE 802.11 DCF protocol by generating a library of MAC- and high-level scenarios. We simulate the high-level scenarios to demonstrate that the scenarios we generate exhibit the worst performance among all the scenarios, including those generated by using heuristics recently proposed by other researchers.
Controlling dynamic module composition through an extensible meta-level API
Authors: Axelsen Eyvind W. , Krogdahl Stein , Møller-Pedersen Birger 
Published: December 2010

In addition to traditional object-oriented (OO) concepts such as inheritance and polymorphism, several modularization and composition mechanisms like e.g. traits, mixins and virtual classes have emerged. The Package Template mechanism is another attempt at providing a flexible mechanism for modularization, composition and adaption.
Dynamic languages have traditionally employed strong support for meta-programming, with hooks to control OO concepts such as method invocation and object construction, by utilizing meta-classes and meta-object protocols.
In this work, we attempt to bring a corresponding degree of meta-level control to composition primitives, with a concrete starting point in the package template mechanism as developed for the dynamic language Groovy. We wish to support a wide range of possible composition semantics, and to make such choices available to the developer through a meta-level API. This API should be extensible, and the semantic variations should be applied within well-defined scopes.
Cyclophosphamide Synergizes with Type I Interferons through Systemic Dendritic Cell Reactivation and Induction of Immunogenic Tumor Apoptosis
Authors: Schiavoni Giovanna , Sistigu Antonella , Valentini Mara , Mattei Fabrizio , Sestili Paola , Spadaro Francesca , Sanchez Massimo , Lorenzi Silvia , D'Urso Maria Teresa , Belardelli Filippo , Gabriele Lucia , Proietti Enrico , Bracci Laura 
Published: December 2010

Abstract
Successful chemotherapy accounts for both tumor-related factors and host immune response. Compelling evidence suggests that some chemotherapeutic agents can induce an immunogenic type of cell death stimulating tumor-specific immunity. Here, we show that cyclophosphamide (CTX) exerts two types of actions relevant for the induction of antitumor immunity in vivo: (i) effect on dendritic cell (DC) homeostasis, mediated by endogenous type I interferons (IFN-I), leading to the preferential expansion of CD8α+ DC, the main subset involved in the cross-presentation of cell-derived antigens; and (ii) induction of tumor cell death with clear-cut immunogenic features capable of stimulating tumor infiltration, engulfment of tumor apoptotic material, and CD8 T-cell cross-priming by CD8α+ DC. Notably, the antitumor effects of CTX were efficiently amplified by IFN-I, the former providing a source of antigen and a “resetting” of the DC compartment and the latter supplying optimal costimulation for T-cell cross-priming, resulting in the induction of a strong antitumor response and tumor rejection. These results disclose new perspectives for the development of targeted and more effective chemoimmunotherapy treatments of cancer patients. Cancer Res; 71(3); 768–78. ©2010 AACR.