bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfated K5
Escherichia coli
Polysaccharide Derivatives as Wide-Range Inhibitors of Genital Types of Human Papillomavirus
Authors: Lembo David , Donalisio Manuela , Rusnati Marco , Bugatti Antonella , Cornaglia Maura , Cappello Paola , Giovarelli Mirella , Oreste Pasqua , Landolfo Santo 
Published: February 2008

ABSTRACT

Genital human papillomaviruses (HPV) represent the most common sexually transmitted agents and are classified into low or high risk by their propensity to cause genital warts or cervical cancer, respectively. Topical microbicides against HPV may be a useful adjunct to the newly licensed HPV vaccine. A main objective in the development of novel microbicides is to block HPV entry into epithelial cells through cell surface heparan sulfate proteoglycans. In this study, selective chemical modification of the
Escherichia coli
K5 capsular polysaccharide was integrated with innovative biochemical and biological assays to prepare a collection of sulfated K5 derivatives with a backbone structure resembling the heparin/heparan biosynthetic precursor and to test them for their anti-HPV activity. Surface plasmon resonance assays revealed that O-sulfated K5 with a high degree of sulfation [K5-OS(H)] and N,O-sulfated K5 with a high [K5-N,OS(H)] or low [K5-N,OS(L)] sulfation degree, but not unmodified K5, N-sulfated K5, and O-sulfated K5 with low levels of sulfation, prevented the interaction between HPV-16 pseudovirions and immobilized heparin. In cell-based assays, K5-OS(H), K5-N,OS(H), and K5-N,OS(L) inhibited HPV-16, HPV-18, and HPV-6 pseudovirion infection. Their 50% inhibitory concentration was between 0.1 and 0.9 μg/ml, without evidence of cytotoxicity. These findings provide insights into the design of novel, safe, and broad-spectrum microbicides against genital HPV infections.
Roles of Trypanothione
S
-Transferase and Tryparedoxin Peroxidase in Resistance to Antimonials
Authors: Wyllie Susan , Vickers Tim J. , Fairlamb Alan H. 
Published: February 2008

ABSTRACT

The clinical value of antimonial drugs, the mainstay therapy for leishmaniasis, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is required. Using the model organism
Leishmania tarentolae
, we have examined the role of trypanothione
S
-transferase (TST) in trivalent antimony [Sb(III)] resistance. TST has
S
-transferase activity with substrates such as chlorodinitrobenzene as well as peroxidase activity with alkyl and aryl hydroperoxides but not with hydrogen peroxide. Although
S
-transferase activity and TST protein levels were unchanged in Sb(III)-sensitive and -resistant lines, rates of metabolism of hydrogen peroxide,
t
-butyl hydroperoxide, and cumene hydroperoxide were significantly increased. Elevated peroxidase activities were shown to be both trypanothione and tryparedoxin dependent and were associated with the overexpression of classical tryparedoxin peroxidase (TryP) in the cytosol of
L. tarentolae
. The role of TryP in Sb(III) resistance was verified by overexpression of the recombinant
Leishmania major
protein in Sb(III)-sensitive promastigotes. An approximate twofold increase in the level of TryP activity in this transgenic cell line was accompanied by a significant decrease in sensitivity to Sb(III) (twofold;
P
< 0.001). Overexpression of an enzymatically inactive TryP failed to result in Sb(III) resistance. This indicates that TryP-dependent resistance is not due to sequestration of Sb(III) and suggests that enhanced antioxidant defenses may well be a key feature of mechanisms of clinical resistance to antimonial drugs.
The Presence of Capsule inCryptococcus neoformansInfluences the Gene Expression Profile in Dendritic Cells during Interaction with the Fungus
Authors: Lupo P. , Chang Y. C. , Kelsall B. L. , Farber J. M. , Pietrella D. , Vecchiarelli A. , Leon F. , Kwon-Chung K. J. 
Published: February 2008

ABSTRACTThe aim of this investigation was to study the effect of polysaccharide capsule on the gene expression in dendritic cells (DC) during their interaction withCryptococcus neoformans. To this end, we used an encapsulated virulent strain ofC. neoformansand acap59gene-disrupted acapsular avirulent strain derived from the same genetic background. DC were exposed to encapsulated and acapsularC. neoformansstrains for 4 h and 18 h, and their transcriptional profiles were analyzed using the Affymetrix mouse gene chip U74Av2. A large number of DC genes were up-regulated after treatment with the acapsular strain. In particular, we observed the up-regulation of the genes involved in DC maturation, such as cell surface receptors, cytokines, and chemokines (interleukin-12 [IL-12], IL-2, IL-1α, IL-1β, IL-6, IL-10, tumor necrosis factor alpha, CCR7, CCL17, CCL22, CCL3, CCL4, CCL7, and CXCL10), membrane proteins, and the genes involved in antigen processing and presentation as well as cell cycle or apoptosis. The chemokine gene expression data were confirmed by real-time reverse transcription-PCR, while the expression of cytokine genes was correlated with their secretion. A completely different pattern of gene expression was observed for DC treated with an encapsulated strain ofC. neoformans. In particular, no significant induction was observed in the expression of the genes mentioned above. Moreover, a number of genes, such as those coding for chemokines, were down-regulated. These results suggest that the polysaccharide capsule shrouding the cell wall ofC. neoformansplays a fundamental role in inducing DC response, highlighting the molecular basis of the true nature of immune silencing exerted by capsular material.
Proteomic Characterization of the Whole Secretome of
Legionella pneumophila
and Functional Analysis of Outer Membrane Vesicles
Authors: Galka Frank , Wai Sun Nyunt , Kusch Harald , Engelmann Susanne , Hecker Michael , Schmeck Bernd , Hippenstiel Stefan , Uhlin Bernt Eric , Steinert Michael 
Published: February 2008

ABSTRACT

Secretion of effector molecules is one of the major mechanisms by which the intracellular human pathogen
Legionella pneumophila
interacts with host cells during infection. Specific secretion machineries which are responsible for the subfraction of secreted proteins (soluble supernatant proteins [SSPs]) and the production of bacterial outer membrane vesicles (OMVs) both contribute to the protein composition of the extracellular milieu of this lung pathogen. Here we present comprehensive proteome reference maps for both SSPs and OMVs. Protein identification and assignment analyses revealed a total of 181 supernatant proteins, 107 of which were specific to the SSP fraction and 33 of which were specific to OMVs. A functional classification showed that a large proportion of the identified OMV proteins are involved in the pathogenesis of Legionnaires' disease. Zymography and enzyme assays demonstrated that the SSP and OMV fractions possess proteolytic and lipolytic enzyme activities which may contribute to the destruction of the alveolar lining during infection. Furthermore, it was shown that OMVs do not kill host cells but specifically modulate their cytokine response. Binding of immunofluorescently stained OMVs to alveolar epithelial cells, as visualized by confocal laser scanning microscopy, suggested that there is delivery of a large and complex group of proteins and lipids in the infected tissue in association with OMVs. On the basis of these new findings, we discuss the relevance of protein sorting and compartmentalization of virulence factors, as well as environmental aspects of the vesicle-mediated secretion.
Elevated Gamma Interferon-Producing NK Cells, CD45RO Memory-Like T Cells, and CD4 T Cells Are Associated with Protection against Malaria Infection in Pregnancy
Authors: Othoro Caroline , Moore Julie M. , Wannemuehler Kathleen A. , Moses Sichangi , Lal Altaf , Otieno Juliana , Nahlen Bernard , Slutsker Laurence , Shi Ya Ping 
Published: February 2008

ABSTRACTPrevious studies have shown that gamma interferon (IFN-γ) production in the placenta is associated with protection against placental malaria. However, it remains unknown which IFN-γ-producing cell subpopulations are involved in this protection and whether the cellular immune components of protection are the same in the peripheral and the placental blood compartments. We investigated cell subpopulations for CD4, CD8, and CD45RO memory-like T cells and CD56+/CD3−natural killer (NK) cells and for IFN-γ production by these cells in maternal peripheral and placental intervillous blood in relation to the status of malaria infection in pregnancy. Of 52 human immunodeficiency virus-negative enrolled pregnant women residing in Western Kenya, 20 had placental parasitemia. We found that the percentages of CD45RO memory-like and CD4 T cells were significantly higher in the periphery than in the placenta, while the CD56/CD3−NK-cell percentage was higher in the placenta than in the periphery, suggesting differences in immune cell profiles between the two blood compartments. Furthermore, the percentages of peripheral CD45RO memory-like and CD4 T cells were significantly elevated in aparasitemic women compared to levels in the parasitemic group, with aparasitemic multigravid women having the highest percentages of CD45RO memory-like and CD4 T cells. In contrast, at the placental level, IFN-γ production by innate NK cells was significantly increased in aparasitemic women compared to parasitemic women, regardless of gravidity. These results suggest that the elevated IFN-γ-producing NK cells in the placenta and CD45RO memory-like and CD4 T cells in peripheral blood may be involved in protection against malaria infection in pregnancy.
Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA
Authors: Avril Marion , Kulasekara Bridget R. , Gose Severin O. , Rowe Chris , Dahlbäck Madeleine , Duffy Patrick E. , Fried Michal , Salanti Ali , Misher Lynda , Narum David L. , Smith Joseph D. 
Published: February 2008

ABSTRACT

Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of
Plasmodium falciparum
-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size (∼350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in
Pichia pastoris
or
var2csa
plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines.
Vibrio vulnificus rtxE
Is Important for Virulence, and Its Expression Is Induced by Exposure to Host Cells
Authors: Lee Byung Cheol , Lee Jeong Hyun , Kim Myung Won , Kim Byoung Sik , Oh Man Hwan , Kim Kun-Soo , Kim Tae Sung , Choi Sang Ho 
Published: February 2008

ABSTRACT

Numerous secreted virulence factors have been proposed to account for the fulminating and destructive nature of
Vibrio vulnificus
infections. A mutant of
V. vulnificus
that exhibited less cytotoxicity to INT-407 human intestinal epithelial cells was screened from a library of mutants constructed by random transposon mutagenesis. A transposon-tagging method was used to identify and clone an open reading frame encoding an RTX toxin secretion ATP binding protein, RtxE, from
V. vulnificus
. The deduced amino acid sequence of RtxE from
V. vulnificus
was 91% identical to that reported from
Vibrio cholerae
. Functions of the
rtxE
gene in virulence were assessed by constructing an isogenic mutant whose
rtxE
gene was inactivated by allelic exchanges and by evaluating the differences between its virulence phenotype and that of the wild type in vitro and in mice. The disruption of
rtxE
blocked secretion of RtxA to the cell exterior and resulted in a significant reduction in cytotoxic activity against epithelial cells in vitro. Also, the intraperitoneal 50% lethal dose of the
rtxE
mutant was 10
4
to 10
5
times higher than that of the parental wild type, indicating that RtxE is essential for the virulence of
V. vulnificus
. Furthermore, the present study demonstrated that the
rtxBDE
genes are transcribed as one transcriptional unit under the control of a single promoter, P

rtxBDE

. The activity of
V. vulnificus
P

rtxBDE

is induced by exposure to INT-407 cells, and the induction requires direct contact of the bacteria with the host cells.
A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response
Authors: DiFeo Analisa , Feld Lauren , Rodriguez Estefania , Wang Christine , Beer David G. , Martignetti John A. , Narla Goutham 
Published: February 2008

Abstract
Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer. [Cancer Res 2008;68(4):965–70]
Betting on Hitler—The Value of Political Connections in Nazi Germany*
Authors: Ferguson Thomas , Voth Hans-Joachim 
Published: February 2008

AbstractThis paper examines the value of connections between German industry and the Nazi movement in early 1933. Drawing on previously unused contemporary sources about management and supervisory board composition and stock returns, we find that one out of seven firms, and a large proportion of the biggest companies, had substantive links with the National Socialist German Workers' Party. Firms supporting the Nazi movement experienced unusually high returns, outperforming unconnected ones by 5% to 8% between January and March 1933. These results are not driven by sectoral composition and are robust to alternative estimators and definitions of affiliation.
Evaluating the Effects of Height-Variable Reflectivity and Antenna Sidelobes on the Radar Equation
Authors: Campos Edwin F. , Hocking Wayne , Fabry Frédéric 
Published: February 2008

Abstract
Using radar observations to quantify precipitation intensity requires the intervention of the radar equation, which converts the precipitation signal into reflectivity units. This equation generally assumes that the reflectivity is uniform within each sampling gate and that the sidelobes of the antenna pattern are negligible. The purpose here is to provide a more realistic approach that eliminates these assumptions when computing profiles of precipitation intensity (by using a height-variable reflectivity and antenna pattern of significant sidelobes to compute profiles of a radar reflectivity factor). To achieve this, simultaneous observations of collocated vertically pointing radars operating in the VHF and X bands were obtained. Raindrop measurements were used to correct for attenuation in the precipitation signal at the X band. Then the precipitation signal in the VHF radar was simulated by combining this X-band signal and the VHF antenna pattern into a general version of the radar equation. The simulated precipitation signal at VHF compares well with actual measurements of the rain signal (range gates centered at 2.5, 3.0, and 3.5 km) by the VHF radar, and this validates the analysis methods. In conclusion, the analysis indicates that VHF reflectivity at gates above the melting layer is artificially enhanced by the precipitation signal collected in the sidelobe direction. Similar enhancement will be expected wherever there is a strong vertical gradient of reflectivity (i.e., on the order of 10 dB km−1 or larger).
Detection of Fog and Low Cloud Boundaries with Ground-Based Remote Sensing Systems
Authors: Nowak Daniela , Ruffieux Dominique , Agnew Judith L. , Vuilleumier Laurent 
Published: February 2008

Abstract
The performance of the boundary determination of fog and low stratiform cloud layers with data from a frequency-modulated continuous-wave (FMCW) cloud radar and a Vaisala ceilometer is assessed. During wintertime stable episodes, fog and low stratiform cloud layers often occur in the Swiss Plateau, where the aerological station of Payerne, Switzerland, is located. During the international COST 720 Temperature, Humidity, and Cloud (TUC) profiling experiment in winter 2003/04, both a cloud radar and a ceilometer were operated in parallel, among other profiling instruments. Human eye observations (“synops”) and temperature and humidity profiles from radiosoundings were used as reference for the validation. In addition, two case studies were chosen to demonstrate the possibilities and limitations of such ground-based remote sensing systems in determining low clouds. In these case studies the cloud boundaries determined by ceilometer and cloud radar were furthermore compared with wind profiler signal-to-noise ratio time series. Under dry conditions, cloud-base and -top detection was possible in 59% and 69% of the cases for low stratus clouds and fog situations, respectively. When cases with any form of precipitation were included, performances were reduced with detection rates of 41% and 63%, respectively. The combination of ceilometer and cloud radar has the potential for providing the base and top of a cloud layer with optimal efficiency in the continuous operational mode. The cloud-top height determination by the cloud radar was compared with cloud-top heights detected using radiosounding humidity profiles. The average height difference between the radiosounding and cloud radar determination of the cloud upper boundary is 53 ± 32 m.
An Atmospheric Soliton Observed with Doppler Radar, Differential Absorption Lidar, and a Molecular Doppler Lidar
Authors: Koch Steven E. , Flamant Cyrille , Wilson James W. , Gentry Bruce M. , Jamison Brian D. 
Published: February 2008

Abstract
Airborne Leandre II differential absorption lidar (DIAL), S-band dual-polarization Doppler radar (S-Pol), and Goddard Lidar Observatory for Winds (GLOW) Doppler lidar data are used, in conjunction with surface mesonet and special sounding data, to derive the structure and dynamics of a bore and associated solitary wave train (soliton) that were generated in southwestern Kansas during the International H20 Project (IHOP_2002). Vertical cross sections of S-Pol reflectivity, S-Pol radial velocity, and DIAL water vapor mixing ratio show a stunning amplitude-ordered train of trapped solitary waves. DIAL data reveal that the leading wave in the soliton increasingly flattened with time as the soliton dissipated.
A method is developed for using the GLOW Doppler winds to obtain the complex two-dimensional vertical circulation accompanying the dissipating soliton. The results show multiple circulations identical in number to the oscillations seen in the S-Pol and DIAL data. The leading updraft occurred precisely at the time that the bore passed over the GLOW facility, as well as when the photon count values suddenly ramped up (suggesting lifting of the low-level inversion by the bore). Additional evidence in support of the validity of the results is provided by the fact that layer displacements computed using the derived vertical motions agree well with those implied by the changes in height of the DIAL mixing ratio surfaces.
The depth and speed of propagation of the bore seen in the DIAL and surface mesoanalyses were shown to be consistent with the predictions from bore hydraulic theory. Analysis of National Center for Atmospheric Research (NCAR) Integrated Sounding System (ISS) data shows that a highly pronounced curvature in the profile of bore-relative winds, related to the existence of a very strong low-level jet, effectively trapped the upward leakage of solitary wave energy below 3 km. This finding explains the trapped lee wave–type structures seen in the DIAL, GLOW, and S-Pol data.
In Situ Samplings and Remote Sensing Measurements to Characterize Aerosol Properties over Southeast Italy
Authors: Bellantone V. , Carofalo I. , De Tomasi F. , Perrone M. R. , Santese M. , Tafuro A. M. , Turnone A. 
Published: February 2008

Abstract
Ground-based particulate matter (PM) samplers, an XeF Raman lidar operating in the framework of the European Aerosol Research Lidar Network (EARLINET), and a sun/sky radiometer operating in the framework of the Aerosol Robotic Network (AERONET) have been used to characterize vertical profiles, optical and microphysical properties, and chemical composition of aerosols during the 29 June–1 July 2005 dust outbreak that occurred over the central-eastern Mediterranean. Aerosol backscatter coefficient, total depolarization, and lidar ratio vertical profiles revealed that a well-mixed dust layer extending from ∼0.5 to 6 km was present over southeastern Italy on 30 June. Sun/sky radiometer measurements revealed a bimodal lognormal size distribution during all measurement days. The particle volume distribution was found to be well correlated either to the PM mass distribution measured at ground by a seven-stage cascade impactor and to the fine to total suspended PM mass ratio measured by ground-based PM samplers. Scanning electron microscopy and ion chromatography analyses on PM samples revealed that coarse-mode aerosols were mainly made of carbonate, aluminum-silicate, and sea salt particles. Carbon, sulfate, and nitrate particles were the main components of fine-mode aerosols representing more than 50% of the total aerosol load; the significant role of fine-mode anthropogenic particles during a dust event is highlighted.
Finally, the potential capabilities of complementary measurements by passive and active remote sensing techniques and in situ observations to retrieve the vertical distribution of the particle number and mass concentration are analyzed and discussed.