bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Dualtropic Human Immunodeficiency Virus Type 1 by the CXCR4 Antagonist AMD3100 Is Associated with Efficiency of CXCR4 Use and Baseline Virus Composition
Authors: Fransen Signe , Bridger Gary , Whitcomb Jeannette M. , Toma Jonathan , Stawiski Eric , Parkin Neil , Petropoulos Christos J. , Huang Wei 
Published: April 2008

ABSTRACT

In a phase I/II evaluation of the CXCR4 antagonist AMD3100, human immunodeficiency virus RNA levels were significantly reduced in a single study subject who harbored CXCR4 (X4)-tropic virus, but not in subjects who harbored either dual/mixed (DM)-tropic or CCR5 (R5)-tropic virus (C. W. Hendrix et al., J. Acquir. Immune Defic. Syndr.
37
:1253-1262, 2004). In this study, we analyzed the envelope clones of DM-tropic virus in baseline and treated virus populations from 14 subjects. Ten subjects exhibited significant reductions in CXCR4-mediated infectivity after 10 days of AMD3100 therapy relative to baseline (X4 suppressor group), while four subjects had no reduction of CXCR4-mediated infectivity (X4 nonsuppressor group). The baseline viruses of the X4 suppressor group infected CXCR4-expressing cells less efficiently than those of the X4 nonsuppressor group. Clonal analysis indicated that the baseline viruses from the X4 suppressor group contained a higher proportion of R5-tropic variants mixed with CXCR4-using variants, while the X4 nonsuppressor group was enriched for CXCR4-using variants. AMD3100 suppressed X4-tropic variants in all subjects studied, but not all dualtropic variants. Furthermore, dualtropic variants that used CXCR4 efficiently were suppressed by AMD3100, while dualtropic variants that used CXCR4 poorly were not. This study demonstrated that AMD3100 has the ability to suppress both X4-tropic and certain dualtropic variants in vivo. The suppression of CXCR4-using variants by AMD3100 is dependent on both the tropism composition of the virus population and the efficiency of CXCR4 usage of individual variants.
Synergy of Human Immunodeficiency Virus Protease Inhibitors with Chloroquine against
Plasmodium falciparum
In Vitro and
Plasmodium chabaudi
In Vivo
Authors: He Zhengxiang , Qin Li , Chen Lili , Peng Nanzheng , You Jianlan , Chen Xiaoping 
Published: April 2008

ABSTRACT
The synergy of the activities between chloroquine and various human immunodeficiency virus protease inhibitors was investigated in chloroquine-resistant and -sensitive malaria parasites. In both in vitro and in vivo assay systems, ritonavir was found to be the most potent in potentiating the antimalarial action of chloroquine.
Gene Amplification of the Multidrug Resistance 1 Gene of
Plasmodium vivax
Isolates from Thailand, Laos, and Myanmar
Authors: Imwong Mallika , Pukrittayakamee Sasithon , Pongtavornpinyo Wirichada , Nakeesathit Supatchara , Nair Shalini , Newton Paul , Nosten Francois , Anderson Timothy J. C. , Dondorp Arjen , Day Nicholas P. J. , White Nicholas J. 
Published: April 2008

ABSTRACT

Plasmodium vivax mdr1
gene amplification, quantified by real-time PCR, was significantly more common on the western Thailand border (6 of 66 samples), where mefloquine pressure has been intense, than elsewhere in southeast Asia (3 of 149;
P
= 0.02). Five coding mutations in
pvmdr1
, independent of gene amplification, were also found.
Convergence of Regulatory Networks on the Pilus Locus of
Streptococcus pneumoniae
Authors: Rosch Jason W. , Mann Beth , Thornton Justin , Sublett Jack , Tuomanen Elaine 
Published: April 2008

ABSTRACT

The
rlrA
pilus locus of
Streptococcus pneumoniae
is an example of a pathogenicity island acquired through genetic recombination. Many acquired genetic elements commandeer preexisting networks of the new organism for transcriptional regulation. We hypothesized that the
rlrA
locus has integrated into transcriptional regulatory networks controlling expression of virulence factors important in adhesion and invasion. To test this hypothesis, we determined the impact on pilus expression of known regulators controlling adherence, including the two-component systems CbpR/S and HK/RR03 and the transcriptional regulators of divalent cation transporters MerR and PsaR in vitro and in vivo. It was determined that the pilus locus is down-regulated by preexisting networks designed for adhesion and cation transport/response and that its regulation occurs through RlrA. The pilus locus was found to participate in invasion specifically restricted to lung epithelial cells in vitro. While expression of pili had only a small effect on virulence with an intranasal infection model, pili were critically important with an intratracheal infection model. Thus, expression of pili appears to have become integrated into the regulatory circuits for lung-specific invasion by pneumococci.
Burkholderia pseudomallei
Type III Secretion System Mutants Exhibit Delayed Vacuolar Escape Phenotypes in RAW 264.7 Murine Macrophages
Authors: Burtnick Mary N. , Brett Paul J. , Nair Vinod , Warawa Jonathan M. , Woods Donald E. , Gherardini Frank C. 
Published: April 2008

ABSTRACT

Burkholderia pseudomallei
is a facultative intracellular pathogen capable of surviving and replicating within eukaryotic cells. Recent studies have shown that
B. pseudomallei
Bsa type III secretion system 3 (T3SS-3) mutants exhibit vacuolar escape and replication defects in J774.2 murine macrophages. In the present study, we characterized the interactions of a
B. pseudomallei bsaZ
mutant with RAW 264.7 murine macrophages. Following uptake, the mutant was found to survive and replicate within infected RAW 264.7 cells over an 18-h period. In addition, high levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES, but not IL-1α and IL-1β, were detected in culture supernatants harvested from infected monolayers. The subcellular location of
B. pseudomallei
within infected RAW 264.7 cells was determined, and as expected, the
bsaZ
mutant demonstrated early-vacuolar-escape defects. Interestingly, however, experiments also indicated that this mutant was capable of delayed vacuolar escape. Consistent with this finding, evidence of actin-based motility and multinucleated giant cell formation were observed between 12 and 18 h postinfection. Further studies demonstrated that a triple mutant defective in all three
B. pseudomallei
T3SSs exhibited the same phenotype as the
bsaZ
mutant, indicating that functional T3SS-1 and T3SS-2 did not appear to be responsible for the delayed escape phenotype in RAW 264.7 cells. Based upon these findings, it appears that
B. pseudomallei
may not require T3SS-1, -2, and -3 to facilitate survival, delayed vacuolar escape, and actin-based motility in activated RAW 264.7 macrophages.
Pathogenesis of Renal Disease Due to Enterohemorrhagic
Escherichia coli
in Germ-Free Mice
Authors: Eaton Kathryn A. , Friedman David I. , Francis Gayle J. , Tyler Jessica S. , Young Vincent B. , Haeger Jennifer , Abu-Ali Galeb , Whittam Thomas S. 
Published: April 2008

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) is a food-borne pathogen that causes hemorrhagic colitis and acute renal failure. We used a germ-free mouse model to investigate the role of host factors, Shiga toxin 2 (Stx2), and bacterial strain in disease due to EHEC. Germ-free male and female Swiss-Webster mice that were 3 days to 12 weeks old were orally inoculated with 1 of 10 EHEC strains or derivatives of two of these strains with Stx2 deleted. All inoculated mice became infected regardless of the inoculum dose. All bacterial strains colonized the intestines, reaching levels of 10
9
to 10
12
CFU/g of feces by 4 days after inoculation. Seven of the 10 wild-type strains caused disease. However, the two Stx2 deletion mutants, unlike the Stx2
+
parental strains, did not cause disease. The clinical signs of disease in mice included lethargy, dehydration, polyuria, polydypsia, and death. Postmortem examination of affected mice revealed dehydration and luminal cecal fluid accumulation. Histologic examination revealed close adherence of bacteria to the intestinal epithelium in the ileum and cecum but not in the colon. Other lesions included progressive renal tubular necrosis, glomerular fibrin thrombosis, and red blood cell sludging. The severity of disease varied according to the bacterial strain and age, but not sex, of the host. This study demonstrated that EHEC colonizes germ-free mice in large numbers, adheres to the intestinal epithelium, and causes luminal cecal fluid accumulation and progressive renal failure. The disease in mice was Stx2 and bacterial strain dependent. This animal model should be a useful tool for studying the pathogenesis of renal disease secondary to EHEC infection.
The
Streptococcus pneumoniae
Competence Regulatory System Influences Respiratory Tract Colonization
Authors: Kowalko J. E. , Sebert M. E. 
Published: April 2008

ABSTRACT

The
Streptococcus pneumoniae
ComDE two-component signaling system controls the development of genetic competence in the bacterium and affects virulence in models of pneumonia and bacteremia. We have investigated the impact of the competence pathway during colonization of the nasopharynx, the principal ecological niche of the pneumococcus. Previous work showed that deletion of the pneumococcal CiaRH signaling system inhibited colonization and increased expression of genes required for competence. We anticipated that signaling by the competence pathway might similarly reduce carriage. Consistent with this expectation, a
comE
deletion that blocked transformation increased colonization fitness such that the mutant outcompeted the wild type in an infant rat model of asymptomatic carriage. Deletion of
comD
—immediately upstream of
comE
and likewise required for competence—similarly increased colonization fitness if the orientation of the antibiotic resistance cassette inserted into the
comD
locus was such that it reduced transcription of
comE
. However, an alternative
comD
deletion mutation that caused an increase in
comE
transcription impaired colonization instead. Activation of the competence system through a
comE
(
D143Y
) mutation did not affect colonization, but an inability to secrete the competence-stimulating peptide due to deletion of
comAB
produced a density-dependent reduction in colonization fitness. These results suggest a model in which signaling by the unactivated form of ComE reduces colonization fitness compared to that of bacteria in which it is either activated or absent entirely, with the most substantial fitness gain accompanying deletion of
comE
. This observation demonstrates that the pneumococcus incurs a substantial fitness cost in order to retain a functional competence regulatory system.
Relationship between methylene blue values of concrete aggregate fines and some concrete properties
Authors: Topçu İlker Bekir , Demir Abdullah 
Published: April 2008

The fine granular structure and surface activity of clay minerals increase the amount of mixing water needed to provide workability in concrete. Even when the microfine material percentage in fine aggregate is low, the methylene blue value of the fine aggregate increases when materials of clay origin are present. In this study, methylene blue values were determined in fine aggregate samples used to produce ready-mixed concrete. Samples were taken from four different aggregate quarries, and relationships between methylene blue values of the concrete samples produced with these aggregates and some of their properties were investigated. Tests were done to determine the quality of microfine material (i.e., passing 0.063 mm sieve). Slump, ultrasonic pulse velocity, compressive strength, and surface abrasion resistance tests were performed on concretes made with these aggregate fines. It is shown that clay content, as indicated by the methylene blue value test, affects the concrete properties, but the microfine material percentage does not give any hint about clay content.
Characterization of a Novel, Water-Soluble Hydrogen Sulfide–Releasing Molecule (GYY4137)
Authors: Li Ling , Whiteman Matthew , Guan Yan Yi , Neo Kay Li , Cheng Yvonne , Lee Shiau Wei , Zhao Yujun , Baskar Rajamanian , Tan Choon-Hong , Moore Philip K. 
Published: April 2008

Background—The potential biological significance of hydrogen sulfide (H2S) has attracted growing interest in recent years. The aim of this study was to characterize a novel, water-soluble, slow-releasing H2S compound [morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate (GYY4137)] and evaluate its use as a tool to investigate the cardiovascular biology of this gas.Methods and Results—The acute vasorelaxant effect of drugs was assessed in rat aortic rings and perfused rat kidney in vitro and in the anesthetized rat in vivo. The chronic effect of GYY4137 on blood pressure in normotensive and spontaneously hypertensive rats was determined by tail-cuff plethysmography. GYY4137 released H2S slowly both in aqueous solution in vitro and after intravenous or intraperitoneal administration in anesthetized rats in vivo. GYY4137 caused a slow relaxation of rat aortic rings and dilated the perfused rat renal vasculature by opening vascular smooth muscle KATPchannels. GYY4137 did not affect rat heart rate or force of contraction in vitro. GYY4137 exhibited antihypertensive activity as evidenced by ability to reduceNG-nitro-l-arginine methyl ester–evoked hypertension in the anesthetized rat and after chronic (14-day) administration in spontaneously hypertensive rats.Conclusions—These results identify GYY4137 as a slow-releasing H2S compound with vasodilator and antihypertensive activity. GYY4137 is likely to prove useful in the study of the many and varied biological effects of H2S. GYY4137 may also prove of therapeutic value in cardiovascular disease.
Elated Citizenry: Deception and the Democratic Task of Bearing Witness
Authors: Birmingham Peg 
Published: April 2008

AbstractIt has become nearly a truism for contemporary theorists of democracy to understand the democratic space as agonistic and contested. The shadow that haunts thinkers of democracy today, and out of which this assumption emerges, is the specter of totalitarianism with its claims to a totalizing knowledge in the form of ideology and a totalizing power of a sovereign will that claims to be the embodiment of the law. Caught up in these totalizing claims, the citizenry becomes elated. The only remedy to totalitarianism is a democratic space wherein no one can claim to know the truth, no one can claim to occupy the space of power, and no one can claim to embody the law. The problem with this remedy is that it fails entirely to take account of what Arendt understands to be the fundamental condition of totalitarianism, namely, the institution of a "lying world order" whereby reality is replaced with a lie. For Arendt therefore the remedy for totalitarianism and its elated citizenry depends first and foremost upon the existence of factual truth. Following Arendt as well as Shoshana Felman's work on testimony, I argue that bearing witness to factual reality is the ground of the democratic public space and the remedy to an elated citizenry caught up in a lying world order.
Dialectic as Method in Public Theology: Recalling Jacques Ellul
Authors: Neville David 
Published: April 2008

AbstractThis article recalls the contribution of Jacques Ellul's theological methodology as a resource for public theology. The first part of the study surveys Ellul's contribution as a public theologian, while the second responds to Ellul's reflections on the theme of dialectic and evaluates the significance of Ellulian-style dialectical theology for public theology. The term 'dialectic' is one Ellul used to describe his own mode of theological engagement. For Ellul, dialectic implies dialogue, which entails both presence (being with, so as to be able to converse) and distance (being apart, so as to be able to contribute something different). What Ellul affirms about a dialectical stance is valuable in so far as it enables theology to grapple with complexity and contradiction, which is important for public theology because the conversation between theology and the wider public now usually occurs in the absence of shared assumptions and values.
Which of These Was Neighbour?: Spiritual Dimensions of the US Immigration Question
Authors: Schaab Gloria 
Published: April 2008

AbstractIn the present climate of debate surrounding United States immigration, both legal and illegal, the call to be neighbour and to exercise hospitality that echoes throughout the biblical tradition provides valid and unequivocal dimensions of a Christian spirituality within the horizon of the immigration discussion. This article traces the development of such a spirituality beginning with the Jewish scriptures, the ministry of Jesus in the gospels and Catholic social teaching. It concludes with a spirituality rooted in the American memory that offers promise and hope and proclaims the best of the American spirit.
Public Theology in the Market State
Authors: Drayton Dean 
Published: April 2008

AbstractThe accepted view that the modern state arose out of the 'wars of religion' is countered with evidence that the late fifteenth century reification of the state used a new category of religion as a human universal impulse to disempower the church and contain the church within the bounds of the state. As a further five successive forms of the state have come into existence new forms of communal and religious life have emerged: first, religious toleration; secondly, the development of a new 'public' realm; thirdly, the denominational form of church; fourthly, the appearance of mass media; fifthly, the embedding of the private citizen in a media world. In this last context either the church opts to reify the denominational church emphasizing individual democratic religious experience, or it realizes that an eschatological view of the gospel calls it to be a public church with a public theology.
Impact of ECCO Ocean-State Estimates on the Initialization of Seasonal Climate Forecasts
Authors: Cazes-Boezio Gabriel , Menemenlis Dimitris , Mechoso Carlos R. 
Published: April 2008

Abstract
The impact of ocean-state estimates generated by the consortium for Estimating the Circulation and Climate of the Ocean (ECCO) on the initialization of a coupled general circulation model (CGCM) for seasonal climate forecasts is examined. The CGCM consists of the University of California, Los Angeles, Atmospheric GCM (UCLA AGCM) and an ECCO ocean configuration of the Massachusetts Institute of Technology GCM (MITgcm). The forecasts correspond to ensemble seasonal hindcasts for the period 1993–2001. For the forecasts, the ocean component of the CGCM is initialized in either early March or in early June using ocean states provided either by an unconstrained forward ocean integration of the MITgcm (the “baseline” hindcasts) or by data-constrained ECCO results (the “ECCO” hindcasts). Forecast skill for both the baseline and the ECCO hindcasts is significantly higher than persistence and compares well with the skill of other state-of-the art CGCM forecast systems. For March initial conditions, the standard errors of sea surface temperature (SST) anomalies in ECCO hindcasts (relative to observed anomalies) are up to 1°C smaller than in the baseline hindcasts over the central and eastern equatorial Pacific (150°–120°W). For June initial conditions, the errors of ECCO hindcasts are up to 0.5°C smaller than in the baseline hindcasts. The smaller standard error of the ECCO hindcasts is, in part, due to a more realistic equatorial thermocline structure of the ECCO initial conditions. This study confirms the value of physically consistent ocean-state estimation for the initialization of seasonal climate forecasts.
On Annular Modes and Zonal Jets
Authors: Monahan Adam H. , Fyfe John C. 
Published: April 2008

Abstract
This study considers the relation of the annular mode to the kinematics of a fluctuating jet in zonal-mean zonal wind and to the zonal index, using an idealized model of fluctuations in the eddy-driven jet. When the sphericity of the domain is accounted for, observed and numerically simulated annular modes for the Southern Hemisphere summertime are found to be in excellent agreement. In particular, the annular mode and zonal index mode are shown to be related but distinct. Although the annular mode is strongly (but not identically) related to fluctuations in jet position, fluctuations in jet strength and width are shown to also be important for its simulation. When the sphericity of the domain is neglected, analytic expressions for the leading empirical orthogonal function (EOF) modes of zonal-mean geopotential for the cases of individual fluctuations in jet strength, position, and width can be obtained. None of these EOF modes have the characteristics of the annular mode. In the presence of simultaneous fluctuations in jet strength and position, the leading zonal-mean geopotential EOF mode (strongly resembling the annular mode) is shown to mix the zonal index mode of zonal-mean zonal wind with other EOF modes, demonstrating why the annular mode and zonal index mode are related but distinct. The greater sensitivity to domain size of EOF modes of geopotential relative to the EOF modes of zonal-mean zonal wind is also discussed. This study focuses on the Southern Hemisphere summertime, which is characterized by a single, eddy-driven jet; the generality of the results presented suggest that the conclusions should be qualitatively unchanged in the presence of both subtropical and eddy-driven jets.
The North Pacific Oscillation–West Pacific Teleconnection Pattern: Mature-Phase Structure and Winter Impacts
Authors: Linkin Megan E. , Nigam Sumant 
Published: April 2008

Abstract
The North Pacific Oscillation (NPO) in sea level pressure and its upper-air geopotential height signature, the west Pacific (WP) teleconnection pattern, constitute a prominent mode of winter midlatitude variability, the NPO/WP. Its mature-phase expression is identified from principal component analysis of monthly sea level pressure variability as the second leading mode just behind the Pacific–North American variability pattern.
NPO/WP variability, primarily on subseasonal time scales, is characterized by a large-scale meridional dipole in SLP and geopotential height over the Pacific and is linked to meridional movements of the Asian–Pacific jet and Pacific storm track modulation. The hemispheric height anomalies at upper levels resemble the climatological stationary wave pattern attributed to transient eddy forcing. The NPO/WP divergent circulation is thermal wind restoring, pointing to independent forcing of jet fluctuations.
Intercomparison of sea level pressure, geopotential height, and zonal wind anomaly structure reveals that NPO/WP is a basin analog of the NAO, which is not surprising given strong links to storm track variability in both cases.
The NPO/WP variability is influential: its impact on Alaskan, Pacific Northwest, Canadian, and U.S. winter surface air temperatures is substantial—more than that of PNA or ENSO. It is likewise more influential on the Pacific Northwest, western Mexico, and south-central Great Plains winter precipitation.
Finally, and perhaps, most importantly, NPO/WP is strongly linked to marginal ice zone variability of the Arctic seas with an influence that surpasses that of other Pacific modes. Although NPO/WP variability and impacts have not been as extensively analyzed as its Pacific cousins (PNA, ENSO), it is shown to be more consequential for Arctic sea ice and North American winter hydroclimate.