bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with LiveLeishmania majorand CpG DNA Promotes Interleukin-2 Production by Dermal Dendritic Cells and NK Cell Activation
Authors: Laabs Eva Maria , Wu Wenhui , Mendez Susana 
Published: September 2009

ABSTRACTCutaneous leishmaniasis due toLeishmania majoris an emerging, chronic parasitic disease that causes disfigurement and social stigmatization. Drug therapy is inadequate, and there is no vaccine. Inoculation of virulent parasites (leishmanization) is the only intervention that has ever provided protection, because it mimics natural infection and immunity, but it was discontinued due to safety concerns (uncontrolled vaccinal lesions). In an effort to retain the benefits (immunity) while avoiding the side effects (lesions) of leishmanization, we immunized C57BL/6 mice withL. majorand CpG DNA (Lm/CpG). This combination prevented lesions while inducing immunity. Also, the vaccination with live parasites and the Toll-like receptor 9 agonist enhanced innate immune responses by activating dermal dendritic cells (DCs) to produce cytokines. Here we report that the Lm/CpG vaccine induced dermal DCs, but not bone marrow-derived DCs, to produce interleukin-2 (IL-2). The release of this unusual DC-derived cytokine was concomitant with a peak in numbers of NK cells that produced gamma interferon (IFN-γ) and also enhanced activation of proliferation of IFN-γ+CD4+T cells. Parasite growth was controlled in Lm/CpG-vaccinated animals. This is the first demonstration of the ability of dermal DCs to produce IL-2 and of the activation of NK cells by vaccination in the context of leishmaniasis. Understanding how the Lm/CpG vaccine enhances innate immunity may provide new tools to develop vaccines againstL. major, other chronic infectious diseases, or other conditions, such as cancer.
High Interlaboratory Reproducibility of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based Species Identification of Nonfermenting Bacteria
Authors: Mellmann A. , Bimet F. , Bizet C. , Borovskaya A. D. , Drake R. R. , Eigner U. , Fahr A. M. , He Y. , Ilina E. N. , Kostrzewa M. , Maier T. , Mancinelli L. , Moussaoui W. , Prévost G. , Putignani L. , Seachord C. L. , Tang Y. W. , Harmsen D. 
Published: September 2009

ABSTRACT
Matrix-assisted laser desorption ionization-time of flight mass spectrometry has emerged as a rapid, cost-effective alternative for bacterial species identification. Identifying 60 blind-coded nonfermenting bacteria samples, this international study (using eight laboratories) achieved 98.75% interlaboratory reproducibility. Only 6 of the 480 samples were misidentified due to interchanges (4 samples) or contamination (1 sample) or not identified because of insufficient signal intensity (1 sample).
Large Dissemination of VIM-2-Metallo-β-Lactamase-Producing
Pseudomonas aeruginosa
Strains Causing Health Care-Associated Community-Onset Infections
Authors: Tsakris Athanassios , Poulou Aggeliki , Kristo Ioulia , Pittaras Theodore , Spanakis Nicholas , Pournaras Spyros , Markou Fani 
Published: September 2009

ABSTRACT

During a 3-year period (May 2005 to April 2008), a series of 45 outpatients presented with community-onset urinary tract infections due to carbapenem-resistant
Pseudomonas aeruginosa
isolates. Forty of them had a history of previous hospitalization or exposure to healthcare facilities, while the remaining five had not been previously admitted to our healthcare facilities or elsewhere within the preceding 12 months. In 18 outpatients, the carbapenem-resistant organisms caused recurrent community-onset urinary tract infections, while in three outpatients the organisms were also implicated in bacteremic episodes. All 45 single-patient
P. aeruginosa
isolates harbored the
bla
VIM-2
metallo-β-lactamase (MBL) gene in a common class 1 integron structure. They belonged to one predominant pulsed-field gel electrophoresis type and three sporadically detected types; two of the sporadic clonal types were identified among outpatients without previous exposure to healthcare facilities, while the predominant clonal type was also identified to cause infections in hospitalized patients. This is the first study documenting that MBL-producing
P. aeruginosa
isolates cause community-onset infections that are related or not with exposure to healthcare facilities. Community-onset infections in our patients most likely resulted from the nosocomial acquisition of MBL producers, followed by a prolonged digestive carriage. The high rate of recurrent infections in the community underlies the difficulty of constraining infections caused by such microorganisms in the extrahospital setting.
Replication Mode and Landscape Topology Differentially Affect RNA Virus Mutational Load and Robustness
Authors: Sardanyés Josep , Solé Ricard V. , Elena Santiago F. 
Published: September 2009

ABSTRACT
Regardless of genome polarity, intermediaries of complementary sense must be synthesized and used as templates for the production of new genomic strands. Depending on whether these new genomic strands become themselves templates for producing extra antigenomic ones, thus giving rise to geometric growth, or only the firstly synthesized antigenomic strands can be used to this end, thus following Luria's stamping machine model, the abundances and distributions of mutant genomes will be different. Here we propose mathematical and bit string models that allow distinguishing between stamping machine and geometric replication. We have observed that, regardless the topology of the fitness landscape, the critical mutation rate at which the master sequence disappears increases as the mechanism of replication switches from purely geometric to stamping machine. We also found that, for a wide range of mutation rates, large-effect mutations do not accumulate regardless the scheme of replication. However, mild mutations accumulate more in the geometric model. Furthermore, at high mutation rates, geometric growth leads to a population collapse for intermediate values of mutational effects at which the stamping machine still produces master genomes. We observed that the critical mutation rate was weakly dependent on the strength of antagonistic epistasis but strongly dependent on synergistic epistasis. In conclusion, we have shown that RNA viruses may increase their robustness against the accumulation of deleterious mutations by replicating as stamping machines and that the magnitude of this benefit depends on the topology of the fitness landscape assumed.
The Myxoma Virus M-T5 Ankyrin Repeat Host Range Protein Is a Novel Adaptor That Coordinately Links the Cellular Signaling Pathways Mediated by Akt and Skp1 in Virus-Infected Cells
Authors: Werden Steven J. , Lanchbury Jerry , Shattuck Donna , Neff Chris , Dufford Max , McFadden Grant 
Published: September 2009

ABSTRACT
Most poxviruses express multiple proteins containing ankyrin (ANK) repeats accounting for a large superfamily of related but unique determinants of poxviral tropism. Recently, select members of this novel family of poxvirus proteins have drawn considerable attention for their potential roles in modulating intracellular signaling networks during viral infection. The rabbit-specific poxvirus, myxoma virus (MYXV), encodes four unique ANK repeat proteins, termed M-T5, M148, M149, and M150, all of which include a carboxy-terminal PRANC domain which closely resembles a cellular protein motif called the F-box domain. Here, we show that each MYXV-encoded ANK repeat protein, including M-T5, interacts directly with the Skp1 component of the host SCF ubiquitin ligase complex, and that the binding of M-T5 to cullin 1 is indirect via binding to Skp1 in the host SCF complex. To understand the significance of these virus-host protein interactions, the various binding domains of M-T5 were mapped. The N-terminal ANK repeats I and II were identified as being important for interaction with Akt, whereas the C-terminal PRANC/F-box-like domain was essential for binding to Skp1. We also report that M-T5 can bind Akt and the host SCF complex (via Skp1) simultaneously in MYXV-infected cells. Finally, we report that M-T5 specifically mediates the relocalization of Akt from the nucleus to the cytoplasm during infection with the wild-type MYXV, but not the M-T5 knockout version of the virus. These results indicate that ANK/PRANC proteins play a critical role in reprogramming disparate cellular signaling cascades to establish a new cellular environment more favorable for virus replication.
Protonation of Individual Histidine Residues Is Not Required for the pH-Dependent Entry of West Nile Virus: Evaluation of the “Histidine Switch” Hypothesis
Authors: Nelson Steevenson , Poddar Subhajit , Lin Tsai-Yu , Pierson Theodore C. 
Published: September 2009

ABSTRACT
Histidine residues have been hypothesized to function as sensors of environmental pH that can trigger the activity of viral fusion proteins. We investigated a requirement for histidine residues in the envelope (E) protein of West Nile virus during pH-dependent entry into cells. Each histidine was individually replaced with a nonionizable amino acid and tested functionally. In each instance, mutants capable of orchestrating pH-dependent infection were identified. These results do not support a requirement for any single histidine as a pH-sensing “switch,” and they suggest that additional features of the E protein are involved in triggering pH-dependent steps in the flavivirus life cycle.
Analysis of Human Immunodeficiency Virus Type 1 Matrix Binding to Membranes and Nucleic Acids
Authors: Alfadhli Ayna , Still Amelia , Barklis Eric 
Published: September 2009

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein targets HIV-1 precursor Gag (PrGag) proteins to assembly sites at plasma membrane (PM) sites that are enriched in cholesterol and phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P
2
]. MA is myristoylated, which enhances membrane binding, and specifically binds PI(4,5)P
2
through headgroup and 2′ acyl chain contacts. MA also binds nucleic acids, although the significance of this association with regard to the viral life cycle is unclear. We have devised a novel MA binding assay and used it to examine MA interactions with membranes and nucleic acids. Our results indicate that cholesterol increases the selectivity of MA for PI(4,5)P
2
-containing membranes, that PI(4,5)P
2
binding tolerates 2′ acyl chain variation, and that the MA myristate enhances membrane binding efficiency but not selectivity. We also observed that soluble PI(4,5)P
2
analogues do not compete effectively with PI(4,5)P
2
-containing liposomes for MA binding but surprisingly do increase nonspecific binding to liposomes. Finally, we have demonstrated that PI(4,5)P
2
-containing liposomes successfully outcompete nucleic acids for MA binding, whereas other liposomes do not. These results support a model in which RNA binding protects MA from associating with inappropriate cellular membranes prior to PrGag delivery to PM assembly sites.
Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes
Authors: Wagner Melany J. , Smiley James R. 
Published: September 2009

ABSTRACTHerpes simplex virus (HSV) tegument proteins are released into the cytoplasm during viral entry and hence are among the first viral proteins encountered by an infected cell. Despite the implied importance of these proteins in the evasion of host defenses, the function of some, like virion protein 11/12 (VP11/12), have not been clearly defined. Previously, we reported that VP11/12 is strongly tyrosine phosphorylated during the infection of lymphocytes but not in fibroblasts or an epithelial cell line (G. Zahariadis, M. J. Wagner, R. C. Doepker, J. M. Maciejko, C. M. Crider, K. R. Jerome, and J. R. Smiley, J. Virol.82:6098-6108, 2008). We also showed that tyrosine phosphorylation depends in part on the activity of the lymphocyte-specific Src family kinase (SFK) Lck in Jurkat T cells. These data suggested that VP11/12 is a substrate of Lck and that Lck is activated during HSV infection. Here, we show that HSV infection markedly increases the fraction of Lck phosphorylated on its activation loop tyrosine (Y394), a feature characteristic of activated Lck. A previous report implicated the immediate-early protein ICP0 and the viral serine/threonine kinases US3 and UL13 in the induction of a similar activated phenotype of SFKs other than Lck in fibroblasts and suggested that ICP0 interacts directly with SFKs through their SH3 domain. However, we were unable to detect an interaction between ICP0 and Lck in T lymphocytes, and we show that ICP0, US3, and UL13 are not strictly required for Lck activation. In contrast, VP11/12 interacted with Lck or Lck signaling complexes and was strictly required for Lck activation during HSV infection. Thus, VP11/12 likely modulates host cell signaling pathways for the benefit of the virus.
A Single Point Mutation in Nonstructural Protein NS2 of Bovine Viral Diarrhea Virus Results in Temperature-Sensitive Attenuation of Viral Cytopathogenicity
Authors: Pankraz Alexander , Preis Simone , Thiel Heinz-Jürgen , Gallei Andreas , Becher Paul 
Published: September 2009

ABSTRACTForBovine viral diarrhea virus(BVDV), the type species of the genusPestivirusin the familyFlaviviridae, cytopathogenic (cp) and noncytopathogenic (ncp) viruses are distinguished according to their effect on cultured cells. It has been established that cytopathogenicity of BVDV correlates with efficient production of viral nonstructural protein NS3 and with enhanced viral RNA synthesis. Here, we describe generation and characterization of a temperature-sensitive (ts) mutant of cp BVDV strain CP7, termed TS2.7. Infection of bovine cells with TS2.7 and the parent CP7 at 33°C resulted in efficient viral replication and a cytopathic effect. In contrast, the ability of TS2.7 to cause cytopathogenicity at 39.5°C was drastically reduced despite production of high titers of infectious virus. Further experiments, including nucleotide sequencing of the TS2.7 genome and reverse genetics, showed that a Y1338H substitution at residue 193 of NS2 resulted in the temperature-dependent attenuation of cytopathogenicity despite high levels of infectious virus production. Interestingly, TS2.7 and the reconstructed mutant CP7-Y1338H produced NS3 in addition to NS2-3 throughout infection. Compared to the parent CP7, NS2-3 processing was slightly decreased at both temperatures. Quantification of viral RNAs that were accumulated at 10 h postinfection demonstrated that attenuation of the cytopathogenicity of thetsmutants at 39.5°C correlated with reduced amounts of viral RNA, while the efficiency of viral RNA synthesis at 33°C was not affected. Taken together, the results of this study show that a mutation in BVDV NS2 attenuates viral RNA replication and suppresses viral cytopathogenicity at high temperature without altering NS3 expression and infectious virus production in a temperature-dependent manner.
Inhibition of Protein Kinase R Activation and Upregulation of GADD34 Expression Play a Synergistic Role in Facilitating Coronavirus Replication by Maintaining De Novo Protein Synthesis in Virus-Infected Cells
Authors: Wang Xiaoxing , Liao Ying , Yap Pei Ling , Png Kim J. , Tam James P. , Liu Ding Xiang 
Published: September 2009

ABSTRACT
A diversity of strategies is evolved by RNA viruses to manipulate the host translation machinery in order to create an optimal environment for viral replication and progeny production. One of the common viral targets is the α subunit of eukaryotic initiation factor 2 (eIF-2α). In this report, we show that phosphorylation of eIF-2α was severely suppressed in human and animal cells infected with the coronavirus infectious bronchitis virus (IBV). To understand whether this suppression is through inhibition of protein kinase R (PKR), the double-stranded-RNA-dependent kinase that is one of the main kinases responsible for phosphorylation of eIF-2α, cells infected with IBV were analyzed by Western blotting. The results showed that the level of phosphorylated PKR was greatly reduced in IBV-infected cells. Overexpression of IBV structural and nonstructural proteins (nsp) demonstrated that nsp2 is a weak PKR antagonist. Furthermore, GADD34, a component of the protein phosphatase 1 (PP1) complex, which dephosphorylates eIF-2α, was significantly induced in IBV-infected cells. Inhibition of the PP1 activity by okadaic acid and overexpression of GADD34, eIF-2α, and PKR, as well as their mutant constructs in virus-infected cells, showed that these viral regulatory strategies played a synergistic role in facilitating coronavirus replication. Taken together, these results confirm that IBV has developed a combination of two mechanisms, i.e., blocking PKR activation and inducing GADD34 expression, to maintain de novo protein synthesis in IBV-infected cells and, meanwhile, to enhance viral replication.
Numerical Investigation of Collision-Induced Breakup of Raindrops. Part II: Parameterizations of Coalescence Efficiencies and Fragment Size Distributions
Authors: Straub Winfried , Beheng Klaus Dieter , Seifert Axel , Schlottke Jan , Weigand Bernhard 
Published: September 2009

Abstract
Results of numerically investigated binary collisions of 32 drop pairs presented in Part I of this study are used to parameterize coalescence efficiencies and size distributions of breakup fragments of large raindrops.
In contrast to the well-known results of Low and List, it is shown that coalescence efficiencies Ec can be described best by means of the Weber number We yielding Ec = exp(−1.15We). The fragment size distributions gained from our numerical investigations were parameterized by fitting normal, lognormal, and delta distributions and relating the parameters of the distribution functions to physical quantities relevant for the breakup event. Thus, this parameterization has formally a substantial similarity to the one of Low and List, although no reference is made to breakup modes such as filament, disk, and sheet. Additionally, mass conservation is guaranteed in the present approach. The parameterizations from Low and List, as well as the new parameterizations, are applied to compute a stationary size distribution (SSD) from solving the kinetic coagulation–breakup equation until a time-independent state is reached. Although with the parameterizations of Low and List, the SSD shows an often-reported three-peak structure, with the new parameterizations the second peak vanishes completely.
Response of Summer Precipitation over Eastern China to Large Volcanic Eruptions
Authors: Peng Youbing , Shen Caiming , Wang Wei-Chyung , Xu Ying 
Published: September 2009

Abstract
Studies of the effects of large volcanic eruptions on regional climate so far have focused mostly on temperature responses. Previous studies using proxy data suggested that coherent droughts over eastern China are associated with explosive low-latitude volcanic eruptions. Here, the authors present an investigation of the responses of summer precipitation over eastern China to large volcanic eruptions through analyzing a 1000-yr global climate model simulation driven by natural and anthropogenic forcing. Superposed epoch analyses of 18 cases of large volcanic eruption indicate that summer precipitation over eastern China significantly decreases in the eruption year and the year after. Model simulation suggests that this reduction of summer precipitation over eastern China can be attributed to a weakening of summer monsoon and a decrease of moisture vapor over tropical oceans caused by large volcanic eruptions.
Implied Ocean Heat Transports in the Standard and Superparameterized Community Atmospheric Models
Authors: DeMott Charlotte A. , Randall David A. , Khairoutdinov Marat 
Published: September 2009

Abstract
Implied ocean heat transport (To) based on net surface energy budgets is computed for two versions of the Community Atmospheric Model (CAM, version 3.0) general circulation model (GCM). The first version is the standard CAM with parameterized convection. The second is the multiscale modeling framework (MMF), in which parameterized convection is replaced with a two-dimensional cloud-resolving model in each GCM grid column. Although global-mean net surface energy totals are similar for both models, differences in the geographic distributions of the component errors lead to distinctly different To for each model, with CAM’s To generally agreeing with observationally based To estimates, and the MMF’s To producing northward transport at all latitudes north of ∼50°S.
Analysis of component error sources in the To calculation identifies needed improvements in the MMF. Net surface shortwave radiation and latent heat fluxes over the oceans are the primary causes of To errors in the MMF. Surface shortwave radiation biases in the MMF are associated with liquid and/or ice water content biases in tropical and extratropical convection and a deficit of marine stratocumulus clouds. It is expected that tropical ice water contents in the MMF can be made more realistic via improvements to the cloud microphysics parameterization. MMF marine stratocumulus clouds are overly sensitive to low-level relative humidity and form only with nearly saturated conditions and a shallow boundary layer. Latent heat flux errors in the MMF are amplifications of those found in the CAM and are concentrated in the trade wind regime and the Asian monsoon region and the adjacent western Pacific Ocean.
Potential improvements to To are estimated by replacing either simulated net surface shortwave or latent heat fluxes with those from observations and recomputing To. When observed shortwave fluxes are used, both CAM and MMF produce greatly improved To curves for both hemispheres. When To is computed using observed latent heat fluxes, CAM To degrades slightly and MMF To improves, especially in the sign of Southern Hemisphere transport.
Implications of Ensemble Quantitative Precipitation Forecast Errors on Distributed Streamflow Forecasting
Authors: Mascaro Giuseppe , Vivoni Enrique R. , Deidda Roberto 
Published: September 2009

Abstract
Evaluating the propagation of errors associated with ensemble quantitative precipitation forecasts (QPFs) into the ensemble streamflow response is important to reduce uncertainty in operational flow forecasting. In this paper, a multifractal rainfall downscaling model is coupled with a fully distributed hydrological model to create, under controlled conditions, an extensive set of synthetic hydrometeorological events, assumed as observations. Subsequently, for each event, flood hindcasts are simulated by the hydrological model using three ensembles of QPFs—one reliable and the other two affected by different kinds of precipitation forecast errors—generated by the downscaling model. Two verification tools based on the verification rank histogram and the continuous ranked probability score are then used to evaluate the characteristics of the correspondent three sets of ensemble streamflow forecasts. Analyses indicate that the best forecast accuracy of the ensemble streamflows is obtained when the reliable ensemble QPFs are used. In addition, results underline (i) the importance of hindcasting to create an adequate set of data that span a wide range of hydrometeorological conditions and (ii) the sensitivity of the ensemble streamflow verification to the effects of basin initial conditions and the properties of the ensemble precipitation distributions. This study provides a contribution to the field of operational flow forecasting by highlighting a series of requirements and challenges that should be considered when hydrologic ensemble forecasts are evaluated.