bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Cohort Analysis of the Antiviral Activities of Zidovudine and Tenofovir in the Presence of the K65R Mutation in Reverse Transcriptase
Authors: Grant Philip M. , Taylor Jonathan , Nevins Andrew B. , Calvez Vincent , Marcelin Anne-Geneviève , Wirden Marc , Zolopa Andrew R. 
Published: February 2010

ABSTRACTA K65R mutation in HIV-1 reverse transcriptase can occur with the failure of tenofovir-, didanosine-, abacavir-, and, in some cases, stavudine-containing regimens and leads to reduced phenotypic susceptibility to these drugs and hypersusceptibility to zidovudine, but its clinical impact is poorly described. We identified isolates with the K65R mutation within the Stanford Resistance Database and a French cohort for which subsequent treatment and virological response data were available. The partial genotypic susceptibility score (pGSS) was defined as the genotypic susceptibility score (GSS) excluding the salvage regimen's nucleoside reverse transcriptase inhibitor (NRTI) component. A three-part virologic response variable was defined (e.g., complete virologic response, partial virologic response, and no virologic response). Univariate, multivariate, and bootstrap analyses evaluated factors associated with the virologic response, focusing on the contributions of zidovudine and tenofovir. Seventy-one of 130 patients (55%) achieved a complete virologic response (defined as an HIV RNA level of <200 copies/ml). In univariate analyses, pGSS and zidovudine use in the salvage regimen were predictors of the virologic response. In a multivariate analysis, pGSS and zidovudine and tenofovir use were associated with the virologic response. Bootstrap analyses showed similar reductions in HIV RNA levels with zidovudine or tenofovir use (0.5 to 0.9 log10). In the presence of K65R, zidovudine and tenofovir are associated with similar reductions in HIV RNA levels. Given its tolerability, tenofovir may be the preferred agent over zidovudine even in the presence of the K65R mutation.
Combination of V106I and V179D Polymorphic Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confers Resistance to Efavirenz and Nevirapine but Not Etravirine
Authors: Gatanaga Hiroyuki , Ode Hirotaka , Hachiya Atsuko , Hayashida Tsunefusa , Sato Hironori , Oka Shinichi 
Published: February 2010

ABSTRACT

Etravirine (ETV) is a second-generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) introduced recently for salvage antiretroviral treatment after the emergence of NNRTI-resistant human immunodeficiency virus type 1 (HIV-1). Following its introduction, two naturally occurring mutations in HIV-1 RT, V106I and V179D, were listed as ETV resistance-associated mutations. However, the effect of these mutations on the development of NNRTI resistance has not been analyzed yet. To select highly NNRTI-resistant HIV-1
in vitro
, monoclonal HIV-1 strains harboring V106I and V179D (HIV-1
V106I
and HIV-1
V179D
) were propagated in the presence of increasing concentrations of efavirenz (EFV). Interestingly, V179D emerged in one of three selection experiments from HIV-1
V106I
and V106I emerged in two of three experiments from HIV-1
V179D
. Analysis of recombinant HIV-1 clones showed that the combination of V106I and V179D conferred significant resistance to EFV and nevirapine (NVP) but not to ETV. Structural analysis indicated that ETV can overcome the repulsive interactions caused by the combination of V106I and V179D through fine-tuning of its binding module to RT facilitated by its plastic structure, whereas EFV and NVP cannot because of their rigid structures. Analysis of clinical isolates showed comparable drug susceptibilities, and the same combination of mutations was found in some database patients who experienced virologic NNRTI-based treatment failure. The combination of V106I and V179D is a newly identified NNRTI resistance pattern of mutations. The combination of polymorphic and minor resistance-associated mutations should be interpreted carefully.
Contribution ofCandida albicansCell Wall Components to Recognition by and Escape from Murine Macrophages
Authors: McKenzie C. G. J. , Koser U. , Lewis L. E. , Bain J. M. , Mora-Montes H. M. , Barker R. N. , Gow N. A. R. , Erwig L. P. 
Published: February 2010

ABSTRACTThe pathogenicity of the opportunistic human fungal pathogenCandida albicansdepends on its ability to escape destruction by the host immune system. Using mutant strains that are defective in cell surface glycosylation, cell wall protein synthesis, and yeast-hypha morphogenesis, we have investigated three important aspects ofC. albicansinnate immune interactions: phagocytosis by primary macrophages and macrophage cell lines, hyphal formation within macrophage phagosomes, and the ability to escape from and kill macrophages. We show that cell wall glycosylation is critically important for the recognition and ingestion ofC. albicansby macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4Δ,pmr1Δ, andmnt3 mnt5Δ), whereas O- and N-linked mannan defects (mnt1Δmnt2Δ andmns1Δ) were associated with increased ingestion, compared to the parent wild-type strains and genetically complemented controls. In contrast, macrophage uptake of mutants deficient in cell wall proteins such as adhesins (ece1Δ,hwp1Δ, andals3Δ) and yeast-locked mutants (clb2Δ,hgc1Δ,cph1Δ,efg1Δ, andefg1Δcph1Δ), was similar to that observed for wild-typeC. albicans. Killing of macrophages was abrogated in hypha-deficient strains, significantly reduced in all glycosylation mutants, and comparable to wild type in cell wall protein mutants. The diminished ability of glycosylation mutants to kill macrophages was not a consequence of impaired hyphal formation within macrophage phagosomes. Therefore, cell wall composition and the ability to undergo yeast-hypha morphogenesis are critical determinants of the macrophage's ability to ingest and processC. albicans.
CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of
Bacillus anthracis
Lethal Toxin-Neutralizing Antibodies
Authors: Devera T. Scott , Aye Lindsay M. , Lang Gillian A. , Joshi Sunil K. , Ballard Jimmy D. , Lang Mark L. 
Published: February 2010

ABSTRACT

The current
Bacillus anthracis
vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against
Bacillus anthracis
but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (α-galactosylceramide [α-GC]) at the time of immunization improves PA-specific Ab responses. We observed that α-GC enhanced PA-specific Ab titers in C57BL/6 mice. In CD1d
−/−
mice deficient in type I and type II NKT cells the anti-PA Ab response was diminished. In Jα281
−/−
mice expressing CD1d but lacking type I α-GC-reactive NKT cells, α-GC did not enhance the Ab response.
In vitro
neutralization assays were performed and showed that the Ab titers correlated with protection of macrophages against anthrax lethal toxin (LT). The neutralization capacity of the Ab was further tested in lethal challenge studies, which revealed that NKT activation leads to enhanced
in vivo
protection against LT. Anti-PA Ab titers, neutralization, and protection were then measured over a period of several months, and this revealed that NKT activation leads to a sustained protective Ab response. These results suggest that NKT-activating CD1d ligands could be exploited for the development of improved vaccines for
Bacillus anthracis
that increase not only neutralizing Ab titers but also the duration of the protection afforded by Ab.
GroEL and Lipopolysaccharide fromFrancisella tularensisLive Vaccine Strain Synergistically Activate Human Macrophages
Authors: Noah Courtney E. , Malik Meenakshi , Bublitz DeAnna C. , Camenares Devin , Sellati Timothy J. , Benach Jorge L. , Furie Martha B. 
Published: February 2010

ABSTRACTFrancisella tularensis, the causative agent of tularemia, interacts with host cells of innate immunity in an atypical manner. For most Gram-negative bacteria, the release of lipopolysaccharide (LPS) from their outer membranes stimulates an inflammatory response. When LPS from the attenuated live vaccine strain (LVS) or the highly virulent Schu S4 strain ofF. tularensiswas incubated with human umbilical vein endothelial cells, neither species of LPS induced expression of the adhesion molecule E-selectin or secretion of the chemokine CCL2. Moreover, a high concentration (10 μg/ml) of LVS or Schu S4 LPS was required to stimulate production of CCL2 by human monocyte-derived macrophages (huMDM). A screen for alternative proinflammatory factors ofF. tularensisLVS identified the heat shock protein GroEL as a potential candidate. Recombinant LVS GroEL at a concentration of 10 μg/ml elicited secretion of CXCL8 and CCL2 by huMDM through a TLR4-dependent mechanism. When 1 μg of LVS GroEL/ml was added to an equivalent amount of LVS LPS, the two components synergistically activated the huMDM to produce CXCL8. Schu S4 GroEL was less stimulatory than LVS GroEL and showed a lesser degree of synergy when combined with Schu S4 LPS. These findings suggest that the intrinsically low proinflammatory activity ofF. tularensisLPS may be increased in the infected human host through interactions with other components of the bacterium.
Comparative Genomic Analyses of Attenuated Strains of
Mycoplasma gallisepticum
Authors: Szczepanek S. M. , Tulman E. R. , Gorton T. S. , Liao X. , Lu Z. , Zinski J. , Aziz F. , Frasca S. , Kutish G. F. , Geary S. J. 
Published: February 2010

ABSTRACT

Mycoplasma gallisepticum
is a significant respiratory and reproductive pathogen of domestic poultry. While the complete genomic sequence of the virulent, low-passage
M. gallisepticum
strain R (R
low
) has been reported, genomic determinants responsible for differences in virulence and host range remain to be completely identified. Here, we utilize genome sequencing and microarray-based comparative genomic data to identify these genomic determinants of virulence and to elucidate genomic variability among strains of
M. gallisepticum
. Analysis of the high-passage, attenuated derivative of R
low
, R
high
, indicated that relatively few total genomic changes (64 loci) occurred, yet they are potentially responsible for the observed attenuation of this strain. In addition to previously characterized mutations in cytadherence-related proteins, changes included those in coding sequences of genes involved in sugar metabolism. Analyses of the genome of the
M. gallisepticum
vaccine strain F revealed numerous differences relative to strain R, including a highly divergent complement of
vlhA
surface lipoprotein genes, and at least 16 genes absent or significantly fragmented relative to strain R. Notably, an R
low
isogenic mutant in one of these genes (MGA_1107) caused significantly fewer severe tracheal lesions in the natural host compared to virulent
M. gallisepticum
R
low
. Comparative genomic hybridizations indicated few genetic loci commonly affected in F and vaccine strains ts-11 and 6/85, which would correlate with proteins affecting strain R virulence. Together, these data provide novel insights into inter- and intrastrain
M. gallisepticum
genomic variability and the genetic basis of
M. gallisepticum
virulence.
Critical Role of Dispensable Genes inMycoplasma agalactiaeInteraction with Mammalian Cells
Authors: Baranowski Eric , Guiral Sébastien , Sagné Eveline , Skapski Agnès , Citti Christine 
Published: February 2010

ABSTRACTMycoplasmas are minimal bacteria whose genomes barely exceed the smallest amount of information required to sustain autonomous life. Despite this apparent simplicity, several mycoplasmas are successful pathogens of humans and animals, in which they establish intimate interactions with epithelial cells at mucosal surfaces. To identify biological functions mediating mycoplasma interactions with mammalian cells, we produced a library of transposon knockout mutants in the ruminant pathogenMycoplasma agalactiaeand used this library to identify mutants displaying a growth-deficient pheonotype in cell culture.M. agalactiaemutants displaying a 3-fold reduction in CFU titers to nearly complete extinction in coculture with HeLa cells were identified. Mapping of transposon insertion sites revealed 18 genomic regions putatively involved in the interaction ofM. agalactiaewith HeLa cells. Several of these regions encode proteins with features of membrane lipoproteins and/or were involved in horizontal gene transfer with phylogenetically distant pathogenic mycoplasmas of ruminants. Two mutants with the most extreme phenotype carry a transposon in a genomic region designated the NIF locus which encodes homologues of SufS and SufU, two proteins presumably involved in [Fe-S] cluster biosynthesis in Gram-positive bacteria. Complementation studies confirmed the conditional essentiality of the NIF locus, which was found to be critical for proliferation in the presence of HeLa cells and several other mammalian cell lines but dispensable for axenic growth. While our results raised questions regarding essential functions in mycoplasmas, they also provide a means for studying the role of mycoplasmas as minimal pathogens.
Transmission of Diverse Oral Bacteria to Murine Placenta: Evidence for the Oral Microbiome as a Potential Source of Intrauterine Infection
Authors: Fardini Yann , Chung Peter , Dumm Rochelle , Joshi Nishiant , Han Yiping W. 
Published: February 2010

ABSTRACT
Microbial infection of the intrauterine environment is a major cause of preterm birth. The current paradigm indicates that intrauterine infections predominantly originate from the vaginal tract, with the organisms ascending into the sterile uterus. With the improvements in technology, an increasing number of bacterial species have been identified in intrauterine infections that do not belong to the vaginal microflora. We have demonstrated previously that intrauterine infections can originate from the oral cavity following hematogenous transmission. In this study, we begin to systemically examine what proportion of the oral microbiome can translocate to the placenta. Pooled saliva and pooled subgingival plaque samples were injected into pregnant mice through tail veins to mimic bacteremia, which occurs frequently during periodontal infections. The microbial species colonizing the murine placenta were detected using 16S rRNA gene-based PCR and clone analysis. A diverse group of bacterial species were identified, many of which have been associated with adverse pregnancy outcomes in humans although their sources of infection were not determined. Interestingly, the majority of these species were oral commensal organisms. This may be due to a dose effect but may also indicate a unique role of commensal species in intrauterine infection. In addition, a number of species were selectively “enriched” during the translocation, with a higher prevalence in the placenta than in the pooled saliva or subgingival plaque samples. These observations indicate that the placental translocation was species specific. This study provides the first insight into the diversity of oral bacteria associated with intrauterine infection.
Filet-o-fish
Authors: Dagand Pierre-Evariste , Baumann Andrew , Roscoe Timothy 
Published: February 2010

We address a persistent problem with using domain-specific languages to write operating systems: the effort of implementing, checking, and debugging the DSL usually outweighs any of its benefits. Because these DSLs generate C by templated string concatenation, they are tedious to write, fragile, and incompatible with automated verification tools.
We present Filet-o-Fish (FoF), a semantic language to ease DSL construction. Building a DSL using FoF consists of safely composing semantically-rich building blocks. This has several advantages: input files for the DSL are formal specifications of the system's functionality, automated testing of the DSL is possible via existing tools, and we can prove that the C code generated by a given DSL respects the semantics expected by the developer. Early experience has been good: FoF is in daily use as part of the tool chain of the Barrelfish multicore OS, which makes extensive use of domain-specific languages to generate low-level OS code. We have found that the ability to rapidly generate DSLs we can rely on has changed how we have designed the OS.
Robustness of Mann Type Algorithm with Perturbed Mapping for Nonexpansive Mappings in Banach Spaces
Authors: Ceng LC , Liou YC , Yao JC 
Published: February 2010

AbstractThe purpose of this paper is to study the robustness of Mann type algorithm in the sense that approximately perturbed mapping does not alter the convergence of Mann type algorithm. It is proven that Mann type algorithm with perturbed mapping "Equation missing" remains convergent in a Banach space setting where "Equation missing", "Equation missing" a nonexpansive mapping, "Equation missing", "Equation missing", errors and "Equation missing" a strongly accretive and strictly pseudocontractive mapping.
Factors Affecting the Predictability of Hurricane Humberto (2007)
Authors: Sippel Jason A. , Zhang Fuqing 
Published: February 2010

Abstract
This study uses ensemble Kalman filter analyses and short-range ensemble forecasts to study factors affecting the predictability of Hurricane Humberto, which made landfall along the Texas coast in 2007. Humberto is known for both its rapid intensification and extreme forecast uncertainty, which makes it an ideal case in which to examine the origins of tropical cyclone strength forecast error. Statistical correlation is used to determine why some ensemble members strengthen the incipient low into a hurricane and others do not. During the analysis period, it is found that variations in midlevel moisture, low-level convective instability, and strength of a front to the north of the cyclone likely lead to differences in net precipitation, which ultimately leads to storm strength spread. Stronger storms are favored when the atmosphere is more moist and unstable and when the front is weaker, possibly because some storms in the ensemble begin entraining cooler and drier postfrontal air during this period. Later during the free forecast, variable entrainment of postfrontal air becomes a leading cause of strength spread. Surface moisture differences are the primary contributor to intensity forecast differences, and convective instability differences play a secondary role. Eventually mature tropical cyclone dynamics and differences in landfall time result in very rapid growth of ensemble spread. These results are very similar to a previous study that investigated a 2004 Gulf of Mexico low with a different model and analysis technique, which gives confidence that they are relevant to tropical cyclone formation and intensification in general. Finally, the rapid increase in forecast uncertainty despite relatively modest differences in initial conditions highlights the need for ensembles and advanced data assimilation techniques.
Subtropics-Related Interannual Sea Surface Temperature Variability in the Central Equatorial Pacific
Authors: Yu Jin-Yi , Kao Hsun-Ying , Lee Tong 
Published: February 2010

Abstract
Interannual sea surface temperature (SST) variability in the central equatorial Pacific consists of a component related to eastern Pacific SST variations (called Type-1 SST variability) and a component not related to them (called Type-2 SST variability). Lead–lagged regression and ocean surface-layer temperature balance analyses were performed to contrast their control mechanisms. Type-1 variability is part of the canonical, which is characterized by SST anomalies extending from the South American coast to the central Pacific, is coupled with the Southern Oscillation, and is associated with basinwide subsurface ocean variations. This type of variability is dominated by a major 4–5-yr periodicity and a minor biennial (2–2.5 yr) periodicity. In contrast, Type-2 variability is dominated by a biennial periodicity, is associated with local air–sea interactions, and lacks a basinwide anomaly structure. In addition, Type-2 SST variability exhibits a strong connection to the subtropics of both hemispheres, particularly the Northern Hemisphere. Type-2 SST anomalies appear first in the northeastern subtropical Pacific and later spread toward the central equatorial Pacific, being generated in both regions by anomalous surface heat flux forcing associated with wind anomalies. The SST anomalies undergo rapid intensification in the central equatorial Pacific through ocean advection processes, and eventually decay as a result of surface heat flux damping and zonal advection. The southward spreading of trade wind anomalies within the northeastern subtropics-to-central tropics pathway of Type-2 variability is associated with intensity variations of the subtropical high. Type-2 variability is found to become stronger after 1990, associated with a concurrent increase in the subtropical variability. It is concluded that Type-2 interannual variability represents a subtropical-excited phenomenon that is different from the conventional ENSO Type-1 variability.
Links between Rossby Wave Breaking and the North Atlantic Oscillation–Arctic Oscillation in Present-Day and Last Glacial Maximum Climate Simulations
Authors: Rivière Gwendal , Laîné Alexandre , Lapeyre Guillaume , Salas-Mélia David , Kageyama Masa 
Published: February 2010

Abstract
Upper-tropospheric Rossby wave–breaking processes are examined in coupled ocean–atmosphere simulations of the Last Glacial Maximum (LGM) and of the modern era. LGM statistics of the Northern Hemisphere in winter, computed from the Paleoclimate Modeling Intercomparison Project Phase II (PMIP2) dataset, are compared with those from preindustrial simulations and from the 40-yr ECMWF Re-Analysis (ERA-40). Particular attention is given to the role of wave-breaking events in the North Atlantic Oscillation (NAO) for each simulation. Anticyclonic (AWB) and cyclonic (CWB) wave-breaking events during LGM are shown to be less and more frequent, respectively, than in the preindustrial climate, especially in the Pacific. This is consistent with the slight equatorward shift of the eddy-driven jets in the LGM runs. The most remarkable feature of the simulated LGM climate is that it presents much weaker latitudinal fluctuations of the eddy-driven jets. This is accompanied by less dispersion in the wave-breaking events. A physical interpretation is provided in terms of the fluctuations of the low-level baroclinicity at the entrance of the storm tracks. The NAO in the preindustrial simulations and in ERA-40 is characterized by strong latitudinal fluctuations of the Atlantic eddy-driven jet as well as by significant changes in the nature of the wave breaking. During the positive phase, the eddy-driven jet moves to the north with more AWB events than usual and is well separated from the subtropical African jet. The negative phase exhibits a more equatorward Atlantic jet and more CWB events. In contrast, the LGM NAO is less well marked by the latitudinal vacillation of the Atlantic jet and for some models this property disappears entirely. The LGM NAO corresponds more to acceleration–deceleration or extension–retraction of the Atlantic jet. The hemispheric point of view of the Arctic Oscillation exhibits similar changes.