bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Downregulation of Rhesus Macaque and Sooty Mangabey Major Histocompatibility Complex Class I Molecules by Nef Alleles of Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2
Authors: DeGottardi M. Quinn , Specht Anke , Metcalf Benjamin , Kaur Amitinder , Kirchhoff Frank , Evans David T. 
Published: January 2008

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) Nef downregulates HLA-A and -B molecules, but not HLA-C or -E molecules, based on amino acid differences in their cytoplasmic domains to simultaneously evade cytotoxic T lymphocyte (CTL) and natural killer cell surveillance. Rhesus macaques and sooty mangabeys express orthologues of HLA-A, -B, and -E, but not HLA-C, and many of these molecules have unique amino acid differences in their cytoplasmic tails. We found that these differences also resulted in differential downregulation by primary simian immunodeficiency virus (SIV) SIVsmm/macand HIV-2 Nef alleles. Thus, selective major histocompatibility complex class I downregulation is a conserved mechanism of immune evasion for pathogenic SIV infection of rhesus macaques and nonpathogenic SIV infection of sooty mangabeys.
Targets of Small Interfering RNA Restriction during Human Immunodeficiency Virus Type 1 Replication
Authors: Gao Yong , Lobritz Michael A. , Roth Justin , Abreha Measho , Nelson Kenneth N. , Nankya Immaculate , Moore-Dudley Dawn M. , Abraha Awet , Gerson Stanton L. , Arts Eric J. 
Published: January 2008

ABSTRACT

Small interfering RNAs (siRNAs) have been shown to effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro. The mechanism(s) for this inhibition is poorly understood, as siRNAs may interact with multiple HIV-1 RNA species during different steps of the retroviral life cycle. To define susceptible HIV-1 RNA species, siRNAs were first designed to specifically inhibit two divergent primary HIV-1 isolates via
env
and
gag
gene targets. A self-inactivating lentiviral vector harboring these target sequences confirmed that siRNA cannot degrade incoming genomic RNA. Disruption of the incoming core structure by rhesus macaque TRIM5α did, however, provide siRNA-RNA-induced silencing complex access to HIV-1 genomic RNA and promoted degradation. In the absence of accelerated core disruption, only newly transcribed HIV-1 mRNA in the cytoplasm is sensitive to siRNA degradation. Inhibitors of HIV-1 mRNA nuclear export, such as leptomycin B and camptothecin, blocked siRNA restriction. All HIV-1 RNA regions and transcripts found 5′ of the target sequence, including multiply spliced HIV-1 RNA, were degraded by unidirectional 3′-to-5′ siRNA amplification and spreading. In contrast, HIV-1 RNA 3′ of the target sequence was not susceptible to siRNA. Even in the presence of siRNA, full-length HIV-1 RNA is still encapsidated into newly assembled viruses. These findings suggest that siRNA can target only a relatively “naked” cytoplasmic HIV-1 RNA despite the involvement of viral RNA at nearly every step in the retroviral life cycle. Protection of HIV-1 RNA within the core following virus entry, during encapsidation/virus assembly, or within the nucleus may reflect virus evolution in response to siRNA, TRIM5α, or other host restriction factors.
Class VIII Myosins Are Required for Plasmodesmatal Localization of a Closterovirus Hsp70 Homolog
Authors: Avisar Dror , Prokhnevsky Alexey I. , Dolja Valerian V. 
Published: January 2008

ABSTRACT

The Hsp70 homolog (Hsp70h) of
Beet yellows virus
(BYV) functions in virion assembly and cell-to-cell movement and is autonomously targeted to plasmodesmata in association with the actomyosin motility system (A. I. Prokhnevsky, V. V. Peremyslov, and V. V. Dolja, J. Virol. 79:14421-14428, 2005). Myosins are a diverse category of molecular motors that possess a motor domain and a tail domain involved in cargo binding. Plants have two classes of myosins, VIII and XI, whose specific functions are poorly understood. We used dominant negative inhibition to identify myosins required for Hsp70h localization to plasmodesmata. Six full-length myosin cDNAs from the BYV host plant
Nicotiana benthamiana
were sequenced and shown to encode apparent orthologs of the
Arabidopsis thaliana
myosins VIII-1, VIII-2, VIII-B, XI-2, XI-F, and XI-K. We found that the ectopic expression of the tail domains of each of the class VIII, but not the class XI, myosins inhibited the plasmodesmatal localization of Hsp70h. In contrast, the overexpression of the motor domains or the entire molecules of the class VIII myosins did not affect Hsp70h targeting. Further mapping revealed that the minimal cargo-binding part of the myosin VIII tails was both essential and sufficient for the inhibition of the proper Hsp70h localization. Interestingly, plasmodesmatal localization of the
Tobacco mosaic virus
movement protein and
Arabidopsis
protein RGP2 was not affected by myosin VIII tail overexpression. Collectively, our data implicate class VIII myosins in protein delivery to plasmodesmata and suggest that more than one mechanism of such delivery exist in plants.
Characterization of Hypovirus-Derived Small RNAs Generated in the Chestnut Blight Fungus by an Inducible DCL-2-Dependent Pathway
Authors: Zhang Xuemin , Segers Gert C. , Sun Qihong , Deng Fuyou , Nuss Donald L. 
Published: January 2008

ABSTRACT

The disruption of one of two dicer genes,
dcl-2
, of the chestnut blight fungus
Cryphonectria parasitica
was recently shown to increase susceptibility to mycovirus infection (G. C. Segers, X. Zhang, F. Deng, Q. Sun, and D. L. Nuss, Proc. Natl. Acad. Sci. USA 104:12902-12906, 2007). We now report the accumulation of virus-derived small RNAs (vsRNAs) in hypovirus CHV1-EP713-infected wild-type and dicer gene
dcl-1
mutant
C. parasitica
strains but not in hypovirus-infected
dcl-2
mutant and
dcl-1 dcl-2
double-mutant strains. The CHV1-EP713 vsRNAs were produced from both the positive and negative viral RNA strands at a ratio of 3:2 in a nonrandom distribution along the viral genome. We also show that
C. parasitica
responds to hypovirus and mycoreovirus infections with a significant increase (12- to 20-fold) in
dcl-2
expression while the expression of
dcl-1
is increased only modestly (2-fold). The expression of
dcl-2
is further increased (∼35-fold) following infection with a hypovirus CHV1-EP713 mutant that lacks the p29 suppressor of RNA silencing. The combined results demonstrate the biogenesis of mycovirus-derived small RNAs in a fungal host through the action of a specific dicer gene,
dcl-2
. They also reveal that
dcl-2
expression is significantly induced in response to mycovirus infection by a mechanism that appears to be repressed by the hypovirus-encoded p29 suppressor of RNA silencing.
Inhibition of IRF-3 Activation by VP35 Is Critical for the High Level of Virulence of Ebola Virus
Authors: Hartman Amy L. , Bird Brian H. , Towner Jonathan S. , Antoniadou Zoi-Anna , Zaki Sherif R. , Nichol Stuart T. 
Published: January 2008

ABSTRACT

Zaire ebolavirus
causes a rapidly progressing hemorrhagic disease with high mortality. Identification of the viral virulence factors that contribute to the severity of disease induced by Ebola virus is critical for the design of therapeutics and vaccines against the disease. Given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely plays an important role in determining the outcome of the disease. The Ebola virus VP35 protein inhibits the activation of IRF-3, a critical transcription factor for the induction of early antiviral immunity. Previous studies revealed that a single amino acid change (R312A) in VP35 renders the protein unable to inhibit IRF-3 activation. A reverse-genetics-generated, mouse-adapted, recombinant Ebola virus that encodes the R312A mutation in VP35 was produced. We found that relative to the case for wild-type virus containing the authentic VP35 sequence, this single amino acid change in VP35 renders the virus completely attenuated in mice. Given that these viruses differ by only a single amino acid in the IRF-3 inhibitory domain of VP35, the level of alteration of virulence is remarkable and highlights the importance of VP35 for the pathogenesis of Ebola virus.
Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge
Authors: Rockx Barry , Corti Davide , Donaldson Eric , Sheahan Timothy , Stadler Konrad , Lanzavecchia Antonio , Baric Ralph 
Published: January 2008

ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.
Emergence of Polyfunctional CD8+T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral Therapy
Authors: Rehr Manuela , Cahenzli Julia , Haas Anna , Price David A. , Gostick Emma , Huber Milo , Karrer Urs , Oxenius Annette 
Published: January 2008

ABSTRACTProgressive human immunodeficiency virus type 1 (HIV-1) infection is often associated with high plasma virus load (pVL) and impaired CD8+T-cell function; in contrast, CD8+T cells remain polyfunctional in long-term nonprogressors. However, it is still unclear whether CD8+T-cell dysfunction is the cause or the consequence of high pVLs. Here, we conducted a longitudinal functional and phenotypic analysis of virus-specific CD8+T cells in a cohort of patients with chronic HIV-1 infection. During the initiation and maintenance of successful antiretroviral therapy (ART), we assessed whether the level of pVL was associated with the degree of CD8+T-cell dysfunction. Under viremic conditions, HIV-specific CD8+T cells were dysfunctional with respect to cytokine secretion (gamma interferon, interleukin-2 [IL-2], and tumor necrosis factor alpha), and their phenotype suggested limited potential for proliferation. During ART, cytokine secretion by HIV-specific CD8+T cells was gradually restored, IL-7Rα and CD28 expression increased dramatically, and PD-1 levels declined. Thus, prolonged ART-induced reduction of viral replication and, hence, presumably antigen exposure in vivo, allows a significant functional restoration of CD8+T cells with the appearance of polyfunctional cells. These findings indicate that the level of pVL as a surrogate for antigen load has a dominant influence on the phenotypic and functional profile of virus-specific CD8+T cells.
Mitochondrial and Secretory Human Cytomegalovirus UL37 Proteins Traffic into Mitochondrion-Associated Membranes of Human Cells
Authors: Bozidis Petros , Williamson Chad D. , Colberg-Poley Anamaris M. 
Published: January 2008

ABSTRACT

The human cytomegalovirus (HCMV) UL37 exon 1 protein (pUL37x1), also known as vMIA, is the predominant UL37 isoform during permissive infection. pUL37x1 is a potent antiapoptotic protein, which prevents cytochrome
c
release from mitochondria. The UL37x1 NH
2
-terminal bipartite localization signal, which remains uncleaved, targets UL37 proteins to the endoplasmic reticulum (ER) and then to mitochondria. Based upon our findings, we hypothesized that pUL37x1 traffics from the ER to mitochondria through direct contacts between the two organelles, provided by mitochondrion-associated membranes (MAMs). To facilitate its identification, we cloned and tagged the human phosphatidylserine synthase 1 (huPSS-1) cDNA, whose mouse homologue localizes almost exclusively in the MAM. Using subcellular fractionation of stable HeLa cell transfectants expressing mEGFP-huPSS-1, we found that HCMV pUL37x1 is present in purified microsomes, mitochondria, and MAM fractions. We further examined the trafficking of the full-length UL37 glycoprotein cleavage products, which divergently traffic either through the secretory apparatus or into mitochondria. Surprisingly, pUL37
NH2
and gpUL37
COOH
were both detected in the ER and MAM fraction, even though only pUL37
NH2
is preferentially imported into mitochondria but gpUL37
COOH
is not. To determine the sequences required for MAM importation, we examined pUL37x1 mutants that were partially defective for mitochondrial importation. Deletion mutants of the NH
2
-terminal UL37x1 mitochondrial localization signal were reduced in trafficking into the MAM, indicating partial overlap of MAM and mitochondrial targeting signals. Taken together, these results suggest that HCMV UL37 proteins traffic from the ER into the MAM, where they are sorted into either the secretory pathway or to mitochondrial importation.
Rift Valley Fever Virus Lacking the NSs and NSm Genes Is Highly Attenuated, Confers Protective Immunity from Virulent Virus Challenge, and Allows for Differential Identification of Infected and Vaccinated Animals
Authors: Bird Brian H. , Albariño César G. , Hartman Amy L. , Erickson Bobbie Rae , Ksiazek Thomas G. , Nichol Stuart T. 
Published: January 2008

ABSTRACTRift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping “abortion storms” and high mortality among young animals. Human infection results in self-limiting febrile disease that in ∼1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 × 104PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, ∼1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas.
Rice Yellow Mottle Virus
, an RNA Plant Virus, Evolves as Rapidly as Most RNA Animal Viruses
Authors: Fargette D. , Pinel A. , Rakotomalala M. , Sangu E. , Traoré O. , Sérémé D. , Sorho F. , Issaka S. , Hébrard E. , Séré Y. , Kanyeka Z. , Konaté G. 
Published: January 2008

ABSTRACT

The rate of evolution of an RNA plant virus has never been estimated using temporally spaced sequence data, by contrast to the information available on an increasing range of animal viruses. Accordingly, the evolution rate of
Rice yellow mottle virus
(RYMV) was calculated from sequences of the coat protein gene of isolates collected from rice over a 40-year period in different parts of Africa. The evolution rate of RYMV was estimated by pairwise distance linear regression on five phylogeographically defined groups comprising a total of 135 isolates. It was further assessed from 253 isolates collected all over Africa by Bayesian coalescent methods under strict and relaxed molecular clock models and under constant size and skyline population genetic models. Consistent estimates of the evolution rate between 4 × 10
−4
and 8 × 10
−4
nucleotides (nt)/site/year were obtained whatever method and model were applied. The synonymous evolution rate was between 8 × 10
−4
and 11 × 10
−4
nt/site/year. The overall and synonymous evolution rates of RYMV were within the range of the rates of 50 RNA animal viruses, below the average but above the distribution median. Experimentally, in host change studies, substitutions accumulated at an even higher rate. The results show that an RNA plant virus such as RYMV evolves as rapidly as most RNA animal viruses. Knowledge of the molecular clock of plant viruses provides methods for testing a wide range of biological hypotheses.
Superior performance in WAIS-R block design among top-level rugby players: Table 1
Authors: Kasahara S , Mashiko H , Niwa S-I 
Published: January 2008

Objective and design:Following a report that a well-known soccer player achieved a perfect score on the Block Design subtest of WAIS-R, WAIS-R was conducted on 31 skilled rugby players.Participants:Twenty-seven of the 31 players were recruited for further analyses.Results:In 14 of 27 players, Block Design scores were the highest of the 11 subtests. In addition to Block Design scores that exceeded the scores for the other subtests, the players’ Block Design scores were also better than scores for the standard sample.Conclusions:The Block Design is related to spatial cognitive ability. These results showed that highly skilled players of field and ball games possess high spatial cognitive abilities.
Analysis of heart rate variability at rest and during aerobic exercise: a study in healthy people and cardiac patients
Authors: de la Cruz Torres B , López C López , Orellana J Naranjo 
Published: January 2008

Objective:To analyse HRV at rest in healthy people and in patients with acute myocardial infarction (AMI) and how it changes during aerobic exercise.Methods:The heartbeat signal was recorded beat to beat for 15 minutes at rest and 15 minutes while pedalling in 10 healthy and active men (H group) and 10 cardiac patients (C group). The statistical parameters in the time domain were calculated as well as the spectral analysis applying the Fast Fourier Transform (FFT) and Poincare’s graphic analysis (PGA).Results:At rest, H group have an average SDRR (standard deviation of RR intervals) of 71.24 msec, a pRR50 (percentage of differences higher than 50 msec in RR intervals) of 9.97% and a PGA called “comet-type”. The C group have a SDRR of 36.69 msec, a pRR50 of 1.69%, and a PGA “torpedo-type”. These data show a low or moderate risk for healthy people and a high risk for patients. The FFT analysis lies in the very-low-frequency (VLF) zone in both groups.During exercise, H group shows a significant decrease in all parameters; the PGA turns to “torpedo-type” and the FFT remains in the VLF zone. However, C group is characterised by the maintenance of pRR50, no change in PGA and a second peak in FFT in the high-frequency zone.Conclusion:The HRV at rest and during aerobic exercise follows a different pattern in healthy people and in patients and it provides further information about performance during exercise.
URBAN SAFETY MANAGEMENT: HOW TO DEAL WITH COMPLEXITY
Authors: FLEURY DOMINIQUE 
Published: January 2008

Urban safety management remains a field of action in cities that is unanimously considered as being a necessity as well as being difficult to apprehend in its theoretical, disciplinary and spatial dimensions. The analysis frameworks that are today consensual are based on system approaches and on analyses of the complexity of urban dynamics and dysfunctional situations. We propose a panorama of models that can be used for action and combined for effective interventions. Notably, the analysis of microregulation carried out in real time in driving situations uses psychoergonomic and cognitive psychology models, while the analysis of traffic accidents uses models developed for the more general diagnosis of safety. Macroregulation of the travel system, carried out with a time delay by network managers, should work in favor of research for consistency among the various actions on the one hand, and the various levels of intervention on space on the other. Safety actions thus require a good understanding of the cognitive models at work in public policies.
A COLLISION-AVOIDING MECHANISM BASED ON A THEORY OF MIND
Authors: ZANLUNGO FRANCESCO 
Published: January 2008

We develop a collision-avoiding mechanism for a system of individual agents (pedestrians) that move in a crowd trying to reach their different goal points. The agents avoid collisions on the basis of a model of the other agents' behavior, a "theory of mind," which is realized at different levels through an iterative process (the first level, or level 0, corresponds to ignoring the other agents' behavior, level 1 to assuming that the other agents will ignore each other, and so on). The model is conceived in order to perform an evolutionary simulation of some basic parameters that determine the agent's sensorial, cognitive and behavioral system (the perception of the agent's own size, the attraction to the goal, the radius and angle of the field of view and the level of the theory of mind). In this preliminary work we present our model, show that it reproduces some of the simplest organized behaviors of a system of pedestrians, and focus on some features of the theory of mind, as the difference between odd and even levels.