bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-Fused and/or Multiple Early Genes from Cottontail Rabbit Papillomavirus as DNA Vaccines
Authors: Leachman Sancy A. , Shylankevich Mark , Slade Martin D. , Levine Dana , K. Sundaram Ranjini , Xiao Wei , Bryan Marianne , Zelterman Daniel , Tiegelaar Robert E. , Brandsma Janet L. 
Published: July 2002

ABSTRACTHuman papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.
Different Patterns of Immune Responses but Similar Control of a Simian-Human Immunodeficiency Virus 89.6P Mucosal Challenge by Modified Vaccinia Virus Ankara (MVA) and DNA/MVA Vaccines
Authors: Amara Rama Rao , Villinger Francois , Staprans Silvija I. , Altman John D. , Montefiori David C. , Kozyr Natalia L. , Xu Yan , Wyatt Linda S. , Earl Patricia L. , Herndon James G. , McClure Harold M. , Moss Bernard , Robinson Harriet L. 
Published: July 2002

ABSTRACT
Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (DNA/MVA) vaccine. Here we evaluate the ability of the MVA component of this vaccine to serve as both a prime and a boost for an AIDS vaccine. The same immunization schedule, MVA dose, and challenge conditions were used as in the prior DNA/MVA vaccine trial. Compared to the DNA/MVA vaccine, the MVA-only vaccine raised less than 1/10 the number of vaccine-specific T cells but 10-fold-higher titers of binding antibody for Env. Postchallenge, the animals vaccinated with MVA alone increased their CD8 cell numbers to levels that were similar to those seen in DNA/MVA-vaccinated animals. However, they underwent a slower emergence and contraction of antiviral CD8 T cells and were slower to generate neutralizing antibodies than the DNA/MVA-vaccinated animals. Despite this, by 5 weeks postchallenge, the MVA-only-vaccinated animals had achieved as good control of the viral infection as the DNA/MVA group, a situation that has held up to the present time in the trial (48 weeks postchallenge). Thus, MVA vaccines, as well as DNA/MVA vaccines, merit further evaluation for their ability to control the current AIDS pandemic.
Explant-Induced Reactivation of Herpes Simplex Virus Occurs in Neurons Expressing Nuclear cdk2 and cdk4
Authors: Schang Luis M. , Bantly Andrew , Schaffer Priscilla A. 
Published: July 2002

ABSTRACTHerpes simplex virus (HSV) establishes productive (lytic) infections in nonneuronal cells and nonproductive (latent) infections in neurons. It has been proposed that HSV establishes latency because quiescent neurons lack cellular factors required for productive infection. It has been further proposed that these putative factors are induced following neuronal stress, as a requirement for HSV reactivation. To date, the identity of these putative cellular factors remains unknown. We have demonstrated that cyclin-dependent kinase (cdk) 1, 2, or 7 is required for HSV replication in nonneuronal cells. Interestingly, cdks 1 and 2 are not expressed in quiescent neurons but can be induced in stressed neurons. Thus, cdks may be among the cellular proteins required for HSV reactivation whose neuronal expression is differentially regulated during stress. Herein, we determined that neuronal expression of nuclear cdk2, cdk4, and cyclins E and D2 (which activate cdks 2 and 4, respectively) was induced following explant cultivation, a stressful stimulus that induces HSV reactivation. In contrast, neuronal expression of cdk7 and cytoplasmic cdk4 decreased during explant cultivation, whereas cdk3 was detected in the same small percentage of neurons before and after explant cultivation and cdks 1, 5, and 6 were not detected in neuronal cell bodies. HSV-1 reactivated specifically in neurons expressing nuclear cdk2 and cdk4, and an inhibitor specific for cdk2 inhibited HSV-1 reactivation. We conclude that neuronal levels of cdk2 are among the factors that determine the outcome of HSV infections of neurons.
Successful Boosting of a DNA Measles Immunization with an Oral Plant-Derived Measles Virus Vaccine
Authors: Webster Diane E. , Cooney Michelle L. , Huang Zhongjun , Drew Damien R. , Ramshaw Ian A. , Dry Ian B. , Strugnell Richard A. , Martin Jenny L. , Wesselingh Steve L. 
Published: July 2002

ABSTRACT
Despite eradication attempts, measles remains a global health concern. Here we report results that demonstrate that a single-dose DNA immunization followed by multiple boosters, delivered orally as a plant-derived vaccine, can induce significantly greater quantities of measles virus-neutralizing antibodies than immunization with either DNA or plant-derived vaccines alone. This represents the first demonstration of an enhanced immune response to a prime-boost vaccination strategy combining a DNA vaccine with edible plant technology.
Given the Opportunity, the Sendai Virus RNA-Dependent RNA Polymerase Could as Well Enter Its Template Internally
Authors: Vulliémoz Diane , Roux Laurent 
Published: July 2002

ABSTRACT
The negative-stranded RNA viral genome is an RNA-protein complex of helicoidal symmetry, resistant to nonionic detergent and high salt, in which the RNA is protected from RNase digestion. The 15,384 nucleotides of the Sendai virus genome are bound to 2,564 subunits of the N protein, each interacting with six nucleotides so tightly that the bases are poorly accessible to soluble reagents. With such a uniform structure, the question of template recognition by the viral RNA polymerase has been raised. In a previous study, the N-phase context has been proposed to be crucial for this recognition, a notion referring to the importance of the position in which the nucleotides interact with the N protein. The N-phase context ruled out the role of the template 3′-OH congruence, a feature resulting from the obedience to the rule of six that implies the precise interaction of the last six 3′-OH nucleotides with the last N protein. The N-phase context then allows prediction of the recognition by the RNA polymerase of a replication promoter sequence even if internally positioned, a promoter which normally lies at the template extremity. In this study, with template minireplicons bearing tandem replication promoters separated by intervening sequences, we present data that indeed show that initiation of RNA synthesis takes place at the internal promoter. This internal initiation can best be interpreted as the result of the polymerase entering the template at the internal promoter. In this way, the data are consistent with the importance of the N-phase context in template recognition. Moreover, by introducing between the two promoters a stretch of 10 A residues which represent a barrier for RNA synthesis, we found that the ability of the RNA polymerase to cross this barrier depends on the type of replication promoter, strong or weak, that the RNA polymerase starts on, a sign that the RNA polymerase may be somehow imprinted in its activity by the nature of the promoter on which it starts synthesis.
The Carboxy-Terminal Region of the Human Immunodeficiency Virus Type 1 Protein Rev Has Multiple Roles in Mediating CRM1-Related Rev Functions
Authors: Hakata Yoshiyuki , Yamada Masami , Mabuchi Naoto , Shida Hisatoshi 
Published: July 2002

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Rev, mediates the nuclear export of unspliced and singly spliced viral mRNAs by bridging viral RNA and export receptor human CRM1 (hCRM1). Ribonucleoprotein complex formation, including the oligomerization of Rev proteins on viral RNA, must occur to allow export. We show here that Rev-Rev interactions, which are a basis of complex formation, can be initiated without cellular factors and are subsequently enhanced by hCRM1-Ran-GTP. Furthermore, we reveal functions for the Rev carboxy-terminal (C-terminal) region, which is well conserved among many HIV-1 strains, and for which no function has been reported. This region is required for the efficient binding of Rev to hCRM1 and consequently for nuclear export, Rev-Rev dimerization, and full Rev transactivator activity. Consistent with these results, a HIV-1 proviral plasmid that expresses a C-terminally truncated Rev mutant protein produces smaller amounts of the p24 antigen than does a plasmid that possesses an intact
rev
gene. These results indicate the functional importance of the C-terminal region for full Rev activity, which leads to efficient HIV-1 replication.
The Herpes Simplex Virus Type 1 US11 Protein Binds the Coterminal UL12, UL13, and UL14 RNAs and Regulates UL13 Expression In Vivo
Authors: Attrill Helen L. , Cumming Sarah A. , Clements J. Barklie , Graham Sheila V. 
Published: July 2002

ABSTRACT
The US11 protein of herpes simplex virus type 1 (HSV-1) is a small, highly basic phosphoprotein expressed at late times during infection. US11 localizes to the nucleolus in infected cells, can associate with ribosomes, and has been shown to bind RNA. The RNA substrates of US11 identified thus far have no apparent role in the virus lytic cycle, so we set out to identify a novel, biologically relevant RNA substrate(s) for this protein in HSV-1-infected cells. We designed a reverse transcriptase PCR-based protocol that allowed specific selection of a 600-bp RNA binding partner for US11. This RNA sequence, designated 12/14, is present in the coterminal HSV-1 mRNAs UL12, UL13, and UL14. We show that the binding of US11 to 12/14 is sequence-specific and mediated by the C-terminal domain of the protein. To elucidate the role of US11 in the virus life cycle, we infected cells with wild-type virus, a cosmid-reconstructed US11 HSV-1 null mutant, and a cosmid-reconstructed wild-type virus and analyzed expression of UL12, -13, and -14 during a time course of infection. These experiments revealed that this interaction has biological activity; at early times of infection, US11 down-regulates UL13 protein kinase mRNA and protein.
Identification of SRPK1 and SRPK2 as the Major Cellular Protein Kinases Phosphorylating Hepatitis B Virus Core Protein
Authors: Daub Henrik , Blencke Stephanie , Habenberger Peter , Kurtenbach Alexander , Dennenmoser Julia , Wissing Josef , Ullrich Axel , Cotten Matt 
Published: July 2002

ABSTRACT
Phosphorylation of hepatitis B virus (HBV) core protein has recently been shown to be a prerequisite for pregenomic RNA encapsidation into viral capsids, but the host cell kinases mediating this essential step of the HBV replication cycle have not been identified. We detected two kinases of 95 and 115 kDa in HuH-7 total cell lysates which interacted specifically with the HBV core protein and phosphorylated its arginine-rich C-terminal domain. The 95-kDa kinase was purified and characterized as SR protein-specific kinase 1 (SRPK1) by mass spectrometry. Based on this finding, the 115-kDa kinase could be identified as the related kinase SRPK2 by immunoblot analysis. In vitro, both SRPKs phosphorylated HBV core protein on the same serine residues which are found to be phosphorylated in vivo. Moreover, the major cellular HBV core kinase activity detected in the total cell lysate showed biochemical properties identical to those of SRPK1 and SRPK2, as examined by measuring binding to a panel of chromatography media. We also clearly demonstrate that neither the cyclin-dependent kinases Cdc2 and Cdk2 nor protein kinase C, previously implicated in HBV core protein phosphorylation, can account for the HBV core protein kinase activity. We conclude that both SRPK1 and SRPK2 are most likely the cellular protein kinases mediating HBV core protein phosphorylation during viral infection and therefore represent important host cell targets for therapeutic intervention in HBV infection.
Clinical validation of methods of diagnosis of neuropathy in a field study of United Kingdom sheep dippers
Authors: Buchanan D , Jamal G A , Pilkington A , Hansen S 
Published: July 2002

Objectives:To investigate the reproducibility of measured indices of chronic peripheral neuropathy from a field study of sheep dippers when compared with similar measurements carried out in a clinical setting.Methods:A stratified random sample of field study subjects was invited to attend a clinic. Neuropathy was measured both in the field and at the clinic with a modified version of a standard symptoms questionnaire and quantitative sensory thresholds for hot, cold, and vibration. These were combined into a classification of the likelihood of neuropathy with a neuropathy scoring system. Indicators of sensory abnormality were based on comparison of sensory thresholds to age dependent reference values derived from an external reference group.Results:Only 51% of subjects were assigned similar classifications in the field and clinic based on the neuropathy scoring system. Of the component indices, grouped symptom scores, with 65% of subjects showing exact agreement, proved to be more reproducible than quantitative sensory test indicators. There were biases in the comparison of field and clinic measurements of hot and vibration sensations, but no evidence of greater variation between individual people in sensory thresholds in the field relative to at the clinic.Conclusions:The neuropathy scoring system proved to be of limited reproducibility, due in a large part to the lack of reproducibility of the indicators of sensory test abnormality caused by inadequate temperature control. However, the symptoms score and measured sensory thresholds could be used separately as indices of neuropathy in exposure-response analyses.
Active epidemiological surveillance of musculoskeletal disorders in a shoe factory
Authors: Roquelaure Y , Mariel J , Fanello S , Boissière J-C , Chiron H , Dano C , Bureau D , Penneau-Fontbonne D 
Published: July 2002

Aims:(1) To evaluate an active method of surveillance of musculoskeletal disorders (MSDs). (2) To compare different criteria for deciding whether or not a work situation could be considered at high risk of MSDs in a large, modern shoe factory.Methods:A total of 253 blue collar workers were interviewed and examined by the same physician in 1996; 191 of them were re-examined in 1997. Risk factors of MSDs were assessed for each worker by standardised job site work analysis. Prevalence and incidence rates of carpal tunnel syndrome, rotator cuff syndrome, and tension neck syndrome were calculated for each of the nine main types of work situation. Different criteria used to assess situations with high risk of MSDs were compared.Results:On the basis of prevalence data, three types of work situation were detected to be at high risk of MSDs: cutting, sewing, and assembly preparation. The three types of work situations identified on the basis of incidence data (sewing preparation, mechanised assembling, and finishing) were different from those identified by prevalence data. At least one recognised risk factor for MSDs was identified for all groups of work situations. The ergonomic risk could be considered as serious for the four types of work situation having the highest ergonomic scores (sewing, assembly preparation, pasting, and cutting).Conclusion:The results of the health surveillance method depend largely on the definition of the criteria used to define the risk of MSDs. The criteria based on incidence data are more valid than those based on prevalence data. Health and risk factor surveillance must be combined to predict the risk of MSDs in the company. However, exposure assessment plays a greater role in determining the priorities for ergonomic intervention.
Superconducting States with the Lattice Distortion in the Extended Hubbard Model
Authors: Miyai Eiji , Ozaki Masa-Aki 
Published: July 2002

We give group theoretical classification of superconducting (SC) states with a single SC order parameter in the extended Hubbard model with uniform lattice distortion on the two-dimensional square lattice, by using the mean field approach. We obtain two singlet SCs (s-wave and d-wave) and eight triplet SCs by decomposing the pairing interaction into irreducible components (A1g, B1g and Eu) of point symmetry D4h. We show that in the singlet SC state with a single SC order parameter (s-wave or d-wave) no anisotropic lattice distortion occurs. In the case of triplet SC states, two SC states among eight must be accompanied with anisotropic lattice distortion. The symmetry of SC order parameter uniquely determines the lattice symmetry. We have performed numerical calculations for these SC states, and shown the possibility that one of the SC states with anisotropic lattice distortion becomes most stable of all SC states in the extended Hubbard model. We also discuss singlet SC states with multiple SC order parameters (s-wave and d-wave). It is shown that the anisotropic distortion must occur in (s+d)-SC states and not in (s+id)-SC state.
Spectral Function Analysis of Fermi Liquids and of Composite Fermions in A Finite Magnetic Field: Renormalised Gaps
Authors: Curnoe S. , Stamp P. C. E. 
Published: July 2002

We consider the self-energy and quasiparticle spectrum, for both electrons interacting with phonons, and composite fermions interacting with gauge fluctuations. In both cases we incorporate the singular structure arising from Landau level quantization in a finite field. This is then used to determine the renormalised gap between the Fermi energy and the first excited states. The electron–phonon problem is treated for both Debye and Einstein phonons. In the case of composite fermions, it is found that the singular Landau level structure strongly affects the renormalised gap in the intermediate coupling regime, which is relevant to experiments on the fractional quantum Hall effect. We compare our findings with measurements of the gap in fractional Hall states with filling fraction ν near ν=1/2.
INERTIAL PARTICLES IN A RANDOM FIELD
Authors: SIGURGEIRSSON H. , STUART A. M. 
Published: July 2002

The motion of an inertial particle in a Gaussian random field is studied. This is a model for the phenomenon of preferential concentration, whereby inertial particles in a turbulent flow can correlate significantly. Mathematically the motion is described by Newton's second law for a particle on a 2-D torus, with force proportional to the difference between a background fluid velocity and the particle velocity itself. The fluid velocity is defined through a linear stochastic PDE of Ornstein–Uhlenbeck type. The properties of the model are studied in terms of the covariance of the noise which drives the stochastic PDE. Sufficient conditions are found for almost sure existence and uniqueness of particle paths, and for a random dynamical system with a global random attractor. The random attractor is illustrated by means of a numerical experiment, and the relevance of the random attractor for the understanding of particle distributions is highlighted.
Covert Auditory Attention Generates Activation in the Rostral/Dorsal Anterior Cingulate Cortex
Authors: Benedict Ralph H. B. , Shucard David W. , Maria Michael P. Santa , Shucard Janet L. , Abara Jose P. , Coad Mary Lou , Wack David , Sawusch James , Lockwood Alan 
Published: July 2002

Abstract
The anterior cingulate cortex (ACC) is believed to mediate conscious information processing or high-capacity attention. However, previous functional imaging studies have largely relied on tasks that involve motor function as well as attention. The work from our group utilizing an auditory continuous performance task demonstrated increased activity in a caudal division of the ACC that borders the supplementary motor area (SMA). Activity in this region was attributed to motor responding as well as attention. In the present study, we used15O H2O positron emission tomography (PET) to map brain activation during nonmotor, covert auditory attention. Our hypothesis was that a different region within the ACC, anterior to the SMA, would be active during covert attention (CA). Six men and six women were asked to monitor aurally presented syllables presented at a 1-sec interstimulus interval. During the CA condition, subjects were asked to continuously discriminate target (.19 probability) from nontarget stimuli. Simultaneous recording of event-related potentials (ERPs) confirmed the discrimination of target and nontarget stimuli and the allocation of attention capacity. Comparison of the monitored versus nonmonitored presentation of stimuli demonstrated significant activity in a rostral/dorsal division of the right ACC, anterior to SMA. Other regions of activation included the lateral prefrontal cortex and posterior superior temporal gyrus in the left hemisphere, consistent with neurocognitive models of language and vigilance. We conclude that a rostral/dorsal subdivision of the right ACC is specific for conscious attention during auditory processing, in contrast to premotor response formation.
A Neural Model of Perceptual-Motor Alignment
Authors: Guigon Emmanuel , Baraduc Pierre 
Published: July 2002

Abstract
Sensorimotor systems face complex and frequent discrepancies among spatial modalities, for example, growth, optical distortion, and telemanipulation. Adaptive mechanisms must act continuously to restore perceptual-motor alignments necessary for perception of a coherent world. Experimental manipulations that exposed participants to localized discrepancies showed that adaptation is revealed by the acquisition of a constrained relation between entire modalities rather than associations between individual exemplars within these modalities. The computational problem faced by the human nervous system can thus be conceived as having to induce constrained relations between continuous stimulus and response dimensions from ambiguous or incomplete training sets, that is, performing interpolation and extrapolation. How biological neuronal networks solve this problem is unknown. Here we show that neural processing based on linear collective computation and least-square (LS) error learning in populations of frequency-coded neurons (i.e., whose discharge varies in a monotonic fashion with a parameter) has built-in interpolation and extrapolation capacities. This model can account for the properties of perceptual-motor adaptations in sensorimotor systems.