bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Inequality and Interaction
Authors: Bottero Wendy
Published: September 2007

This paper looks at the effects of social inequality on where we live, who we associate with and who we choose (and hang on to) as our friends and partners. We may feel that we freely choose our friends or lovers, but our most personal and intimate choices are constrained by patterns of social similarity and ‘differential association’. The pattern of ‘homophily’ (the principle that we are more likely to associate with people who are socially similar to ourselves) has a major impact on social networks creating ‘social interaction distance’ between unequals. There is a social sorting process in the way we form social ties, so that the people we interact with tend to be similar to ourselves in education, social class, race/ethnicity, religion and attitudes. This has major consequences for our routes through life and worldviews, and for how inequality is reproduced.
Structural Influences on Racial and Ethnic Disparities in Women's Health Care
Authors: Robbins Cheryl L. , Padavic Irene
Published: September 2007

This paper summarizes recent research about several structural influences on racial and ethnic disparities in women's health care. While disparities in women's health care access and quality emanate from a number of sources, this paper focuses on the intersection between race/ethnicity and several structural factors (access to insurance coverage, discrimination, neighborhood characteristics, and social isolation). We identify gaps in the literature and suggest directions for future research. Particularly needed are gender studies of the impact of race/ethnicity that transcend the black–white dichotomy, that attend to location, that examine variation in social networks, and that clarify the impact of discrimination on women's health care.
Framing Latina/o Immigration, Education, and Activism
Authors: Ochoa Gilda L. , Ochoa Enrique C.
Published: September 2007

Although Latinas/os have a long history in the USA and represent a growing percentage of the population, they remain largely invisible or stereotyped in dominant images and discourses. Such representations are often ahistorical, and they camouflage the effects of US power and inequality. However, the spring 2006 immigrant rights demonstrations disturbed dominant conceptions. The demonstrators called attention to the contradictory US practices that disrupt home countries, recruit labor migrants, and deny immigrants full participation. Likewise, the role of students in these demonstrations spurred reflections on why youth would walk out of their schools for immigrant rights. Inspired by these demonstrations, we combine materials from multiple disciplines to emphasize the significance of US imperialism, exploitation, and exclusion on Latina/o migration, education, and activism. Key to this article is a reframing of how the media, K‐12 curriculum, and popular discourse often engage in a cultural cover‐up that sustains inequality.
Heterogeneity in male horn growth and longevity in a highly sexually dimorphic ungulate
Authors: Bergeron P. , Festa‐Bianchet M. , Von Hardenberg A. , Bassano B.
Published: September 2007

In sexually dimorphic ungulates, sexual selection favoring rapid horn growth in males may be counterbalanced by a decrease in longevity if horns are costly to produce and maintain. Alternatively, if early horn growth varied with individual quality, it may be positively correlated with longevity. We studied Alpine ibex Capra ibex in the Gran Paradiso National Park, Italy, to test these alternatives by comparing early horn growth and longevity of 383 males that died from natural causes. After accounting for age at death, total horn length after age 5 was positively correlated with horn growth from two to four years. Individuals with the fastest horn growth as young adults also had the longest horns later in life. Annual horn growth increments between two and six years of age were independent of longevity for ibex whose age at death ranged from 8 to 16 years. Our results suggest that growing long horns does not constrain longevity. Of the variability in horn length, 22% could be explained by individual heterogeneity, suggesting persistent differences in phenotypic quality among males. Research on unhunted populations of sexually dimorphic ungulates documents how natural mortality varies according to horn or antler size, and can help reduce the impact of sport hunting on natural processes.
Gall‐forming and free‐feeding herbivory along vertical gradients in a lowland tropical rainforest: the importance of leaf sclerophylly
Authors: Pontes Ribeiro Sérvio , Basset Yves
Published: September 2007

In contrast to most insect guilds, gall‐forming insects are thought to reach highest diversity on sclerophyllous vegetation, such as Neotropical savannas and Mediterranean vegetation types. The water and nutrient stress endured by meristems of canopy trees in tall wet tropical rainforests may cause leaf sclerophylly. Hence, the upper canopies of such ecosystems may represent a suitable habitat for gall‐forming insects. At the San Lorenzo Protected Area, Panama, we estimated free‐feeding herbivory and gall densities within five sites in 2003 and 2004, by surveying leaves in vertical and horizontal transects. In each sample, we recorded leaf density (mature and young foliage), free‐feeding herbivore damage and number of galls, including the presence of live larvae, parasitoids or fungi. We surveyed 43 994 leaves, including 231 plants and 73 tree and liana species. We collected 5014 galls from 17 host‐plant species, including 32 gall species of which 59% were restricted to the canopy (overall infestation rates: 2.4% in 2003, 5.5% in 2004). In 2003, 16% of the galls were occupied by live larvae, against 5% in 2004. About 17–20% of leaves surveyed suffered from free‐feeding herbivory. Leaf sclerophylly increased significantly with sampling height, while free‐feeding herbivory decreased inversely. Conversely, the number of live galls collected in the canopy was 13–16 times higher than in the understorey, a pattern consistent across sites and years. Hence, the probability of gall survivorship increased with increasing leaf sclerophylly as death by fungi, parasitoids or accidental chewing were greater in the understorey. Increasing harsh ecophysiological conditions towards the upper canopy appear favourable to galls‐forming population maintenance, in support of the hypothesis of harsh environment. Hence, gall diversity and abundance in the upper canopy of tall tropical forests are perhaps among the highest in the world.
Methods to account for spatial autocorrelation in the analysis of species distributional data: a review
Authors: F. Dormann Carsten , M. McPherson Jana , B. Araújo Miguel , Bivand Roger , Bolliger Janine , Carl Gudrun , G. Davies Richard , Hirzel Alexandre , Jetz Walter , Daniel Kissling W. , Kühn Ingolf , Ohlemüller Ralf , R. Peres‐Neto Pedro , Reineking Björn , Schröder Boris , M. Schurr Frank , Wilson Robert
Published: September 2007

Species distributional or trait data based on range map (extent‐of‐occurrence) or atlas survey data often display spatial autocorrelation, i.e. locations close to each other exhibit more similar values than those further apart. If this pattern remains present in the residuals of a statistical model based on such data, one of the key assumptions of standard statistical analyses, that residuals are independent and identically distributed (i.i.d), is violated. The violation of the assumption of i.i.d. residuals may bias parameter estimates and can increase type I error rates (falsely rejecting the null hypothesis of no effect). While this is increasingly recognised by researchers analysing species distribution data, there is, to our knowledge, no comprehensive overview of the many available spatial statistical methods to take spatial autocorrelation into account in tests of statistical significance. Here, we describe six different statistical approaches to infer correlates of species’ distributions, for both presence/absence (binary response) and species abundance data (poisson or normally distributed response), while accounting for spatial autocorrelation in model residuals: autocovariate regression; spatial eigenvector mapping; generalised least squares; (conditional and simultaneous) autoregressive models and generalised estimating equations. A comprehensive comparison of the relative merits of these methods is beyond the scope of this paper. To demonstrate each method's implementation, however, we undertook preliminary tests based on simulated data. These preliminary tests verified that most of the spatial modeling techniques we examined showed good type I error control and precise parameter estimates, at least when confronted with simplistic simulated data containing spatial autocorrelation in the errors. However, we found that for presence/absence data the results and conclusions were very variable between the different methods. This is likely due to the low information content of binary maps. Also, in contrast with previous studies, we found that autocovariate methods consistently underestimated the effects of environmental controls of species distributions. Given their widespread use, in particular for the modelling of species presence/absence data (e.g. climate envelope models), we argue that this warrants further study and caution in their use. To aid other ecologists in making use of the methods described, code to implement them in freely available software is provided in an electronic appendix.
Effects of urbanization on ground beetle assemblages (Coleoptera, Carabidae) of grassland habitats in western Canada
Authors: J. Hartley Dustin , J. Koivula Matti , R. Spence John , Pelletier Rick , E. Ball George
Published: September 2007

We pitfall‐trapped carabid beetles across an urban‐rural gradient in central Alberta, Canada to assess the relative contributions of landscape structure and habitat quality in explaining variation in composition of assemblages. The gradient ranged from the “urban” zone in the city of Edmonton, through a “suburban” zone just outside the city, into a “rural” zone 25–60 km east of the city. We trapped beetles at three replicated sites for each of two habitats (unmanaged grasslands and highly managed graveyards) in each of the three zones. Most of the 24 species (3162 individuals) captured were commonly associated with open habitats.Pterostichus melanarius, an introduced species, made up 80% of the total catch. Carabid assemblages of grasslands and graveyards were distinct, with lower species richness and lower catch rates of native, introduced and brachypterous carabids in graveyards. Graveyard assemblages also had proportionally fewer brachypterous carabid individuals (32 vs 52%) and species (20 vs 36%), suggesting that populations recruit locally from elsewhere after disturbances. Native carabids were least abundant in the urban areas. Brachypterous carabids were similarly abundant across the gradient, but more occurred in the urban zone than elsewhere (32 vs 5–10%). Samples from graveyards were characterized by lower beta diversity (variation among samples) than those from grasslands, but beta diversity was more‐or‐less equally variable across the gradient within habitats. The amount of unmanaged grassland habitat and the degree of urbanization significantly influence carabid assemblages, and therefore are relevant to management and conservation of urban grassland areas.
A Whiff of Oxygen Before the Great Oxidation Event?
Authors: Anbar Ariel D. , Duan Yun , Lyons Timothy W. , Arnold Gail L. , Kendall Brian , Creaser Robert A. , Kaufman Alan J. , Gordon Gwyneth W. , Scott Clinton , Garvin Jessica , Buick Roger
Published: September 2007

High-resolution chemostratigraphy reveals an episode of enrichment of the redox-sensitive transition metals molybdenum and rhenium in the late Archean Mount McRae Shale in Western Australia. Correlations with organic carbon indicate that these metals were derived from contemporaneous seawater. Rhenium/osmium geochronology demonstrates that the enrichment is a primary sedimentary feature dating to 2501 ± 8 million years ago (Ma). Molybdenum and rhenium were probably supplied to Archean oceans by oxidative weathering of crustal sulfide minerals. These findings point to the presence of small amounts of O
2
in the environment more than 50 million years before the start of the Great Oxidation Event.
Comment on "A Semi-Empirical Approach to Projecting Future Sea-Level Rise"
Authors: Holgate Simon , Jevrejeva Svetlana , Woodworth Philip , Brewer Simon
Published: September 2007

Rahmstorf (Reports, 19 January 2007, p. 368) presented an approach for predicting sea-level rise based on a proposed linear relationship between global mean surface temperature and the rate of global mean sea-level change. We find no such linear relationship. Although we agree that there is considerable uncertainty in the prediction of future sea-level rise, this approach does not meaningfully contribute to quantifying that uncertainty.
Myths and Consequences
Authors: Witzel Michael
Published: September 2007

Aryan Idols
. Indo-European Mythology as Ideology and Science.
By Stefan Arvidsson
. Translated from the Swedish () by Sonia Wichmann. University of Chicago Press, Chicago, 2006. 366 pp. $55, £35. ISBN 9780226028606.

Examining two centuries of scholarship on Indo-European religion and mythology, Arvidsson explores the effects of the idea of an ancient, unified lineage.
The Slit Receptor EVA-1 Coactivates a SAX-3/Robo–Mediated Guidance Signal in
C. elegans
Authors: Fujisawa Kazuko , Wrana Jeffrey L. , Culotti Joseph G.
Published: September 2007

The SAX-3/roundabout (Robo) receptor has Shiga-like toxin 1 (SLT-1)/Slit–dependent and –independent functions in guiding cell and axon migrations. We identified enhancer of ventral-axon guidance defects of
unc-40
mutants (EVA-1) as a
Caenorhabditis elegans
transmembrane receptor for SLT-1. EVA-1 has two predicted galactose-binding ectodomains, acts cell-autonomously for SLT-1/Slit–dependent axon migration functions of SAX-3/Robo, binds to SLT-1 and SAX-3, colocalizes with SAX-3 on cells, and provides cell specificity to the activation of SAX-3 signaling by SLT-1. Double mutants of
eva-1
or
slt-1
with
sax-3
mutations suggest that SAX-3 can (when
slt-1
or
eva-1
function is reduced) inhibit a parallel-acting guidance mechanism, which involves UNC-40/deleted in colorectal cancer.
Symmetrized Characterization of Noisy Quantum Processes
Authors: Emerson Joseph , Silva Marcus , Moussa Osama , Ryan Colm , Laforest Martin , Baugh Jonathan , Cory David G. , Laflamme Raymond
Published: September 2007

A major goal of developing high-precision control of many-body quantum systems is to realize their potential as quantum computers. A substantial obstacle to this is the extreme fragility of quantum systems to “decoherence” from environmental noise and other control limitations. Although quantum computation is possible if the noise affecting the quantum system satisfies certain conditions, existing methods for noise characterization are intractable for present multibody systems. We introduce a technique based on symmetrization that enables direct experimental measurement of some key properties of the decoherence affecting a quantum system. Our method reduces the number of experiments required from exponential to polynomial in the number of subsystems. The technique is demonstrated for the optimization of control over nuclear spins in the solid state.
Probing Quantum Commutation Rules by Addition and Subtraction of Single Photons to/from a Light Field
Authors: Parigi Valentina , Zavatta Alessandro , Kim Myungshik , Bellini Marco
Published: September 2007

The possibility of arbitrarily “adding” and “subtracting” single photons to and from a light field may give access to a complete engineering of quantum states and to fundamental quantum phenomena. We experimentally implemented simple alternated sequences of photon creation and annihilation on a thermal field and used quantum tomography to verify the peculiar character of the resulting light states. In particular, as the final states depend on the order in which the two actions are performed, we directly observed the noncommutativity of the creation and annihilation operators, one of the cardinal concepts of quantum mechanics, at the basis of the quantum behavior of light. These results represent a step toward the full quantum control of a field and may provide new resources for quantum information protocols.
Rapid Emergence of Baculovirus Resistance in Codling Moth Due to Dominant, Sex-Linked Inheritance
Authors: Asser-Kaiser S. , Fritsch E. , Undorf-Spahn K. , Kienzle J. , Eberle K. E. , Gund N. A. , Reineke A. , Zebitz C. P. W. , Heckel D. G. , Huber J. , Jehle J. A.
Published: September 2007

Insect-specific baculoviruses are increasingly used as biological control agents of lepidopteran pests in agriculture and forestry, and they have been previously regarded as robust to resistance development by the insects. However, in more than a dozen cases of field resistance of the codling moth Cydia pomonella to commercially applied C. pomonella granulovirus (CpGV) in German orchards, resistance ratios exceed 1000. The rapid emergence of resistance is facilitated by sex-linkage and concentration-dependent dominance of the major resistance gene and genetic uniformity of the virus. When the gene is fixed, resistance levels approach 100,000-fold. Our findings highlight the need for development of resistance management strategies for baculoviruses.
Nuclei-Induced Frequency Focusing of Electron Spin Coherence
Authors: Greilich A. , Shabaev A. , Yakovlev D. R. , Efros Al. L. , Yugova I. A. , Reuter D. , Wieck A. D. , Bayer M.
Published: September 2007

The hyperfine interaction of an electron with the nuclei is considered as the primary obstacle to coherent control of the electron spin in semiconductor quantum dots. We show, however, that the nuclei in singly charged quantum dots act constructively by focusing the electron spin precession about a magnetic field into well-defined modes synchronized with a laser pulse protocol. In a dot with a synchronized electron, the light-stimulated fluctuations of the hyperfine nuclear field acting on the electron are suppressed. The information about electron spin precession is imprinted in the nuclei and thereby can be stored for tens of minutes in darkness. The frequency focusing drives an electron spin ensemble into dephasing-free subspaces with the potential to realize single frequency precession of the entire ensemble.
Whole-Genome Shotgun Sequencing of Mitochondria from Ancient Hair Shafts
Authors: Gilbert M. Thomas P. , Tomsho Lynn P. , Rendulic Snjezana , Packard Michael , Drautz Daniela I. , Sher Andrei , Tikhonov Alexei , Dalén Love , Kuznetsova Tatyana , Kosintsev Pavel , Campos Paula F. , Higham Thomas , Collins Matthew J. , Wilson Andrew S. , Shidlovskiy Fyodor , Buigues Bernard , Ericson Per G. P. , Germonpré Mietje , Götherström Anders , Iacumin Paola , Nikolaev Vladimir , Nowak-Kemp Malgosia , Willerslev Eske , Knight James R. , Irzyk Gerard P. , Perbost Clotilde S. , Fredrikson Karin M. , Harkins Timothy T. , Sheridan Sharon , Miller Webb , Schuster Stephan C.
Published: September 2007

Although the application of sequencing-by-synthesis techniques to DNA extracted from bones has revolutionized the study of ancient DNA, it has been plagued by large fractions of contaminating environmental DNA. The genetic analyses of hair shafts could be a solution: We present 10 previously unexamined Siberian mammoth (Mammuthus primigenius) mitochondrial genomes, sequenced with up to 48-fold coverage. The observed levels of damage-derived sequencing errors were lower than those observed in previously published frozen bone samples, even though one of the specimens was >50,00014C years old and another had been stored for 200 years at room temperature. The method therefore sets the stage for molecular-genetic analysis of museum collections.
Single Antigen Detects both Immunoglobulin M (IgM) and IgG Antibodies Elicited by All Four Dengue Virus Serotypes
Authors: Hapugoda Menaka D. , Batra Gaurav , Abeyewickreme W. , Swaminathan S. , Khanna N.
Published: September 2007

The resurgence of dengue (DEN) virus infections in the last few decades coupled with the lack of a preventive vaccine and specific antiviral drugs has jointly contributed to making this a significant global public health problem. Currently, symptomatic supportive treatment and fluid replacement therapy are the only means available to minimize DEN-induced mortality. As the clinical symptoms associated with DEN virus infections are indistinguishable from those of many other viral, bacterial, and parasitic infections, specific diagnostic tests assume critical importance in the unequivocal identification of DEN virus infections. We have designed a novel chimeric antigen based on envelope domain III (EDIII), a critical antigenic region of the major structural protein of DEN viruses. We fused EDIIIs corresponding to each of the four DEN virus serotypes using pentaglycyl linkers, overexpressed the resultant tetravalent chimeric protein in
Escherichia coli
, and affinity purified it in high yields, obtaining ∼30 mg protein of >95% purity per liter of culture. We show that this tetravalent antigen could specifically recognize anti-DEN virus antibodies of both the immunoglobulin M (IgM) and IgG classes. Using a large panel of IgM antibody capture-enzyme-linked immunosorbent assay- and hemagglutination inhibition-confirmed DEN virus-infected and uninfected patient sera (
n
= 289), we demonstrate that this tetravalent antigen can function as a diagnostic tool of high sensitivity and specificity.
Immunogenicity, Reactogenicity, and Safety of a P1.7b,4 Strain-Specific Serogroup B Meningococcal Vaccine Given to Preteens
Authors: Hosking Jamie , Rasanathan Kumanan , Mow Florina Chan , Jackson Catherine , Martin Diana , O'Hallahan Jane , Oster Philipp , Ypma Ellen , Reid Stewart , Aaberge Ingeborg , Crengle Sue , Stewart Joanna , Lennon Diana
Published: September 2007

New Zealand (NZ) has experienced a
Neisseria meningitidis
serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (
n
= 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (
n
= 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of ≥1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.
Use of Protein Antigens for Early Serological Diagnosis of Leprosy
Authors: Duthie Malcolm S. , Goto Wakako , Ireton Greg C. , Reece Stephen T. , Cardoso Ludimila P. V. , Martelli Celina M. T. , Stefani Mariane M. A. , Nakatani Maria , de Jesus Robson Crusue , Netto Eduardo M. , Balagon Ma V. F. , Tan Esterlina , Gelber Robert H. , Maeda Yumi , Makino Masahiko , Hoft Dan , Reed Steven G.
Published: September 2007

Leprosy is a chronic and debilitating human disease caused by infection with the
Mycobacterium leprae
bacillus. Despite the marked reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. This indicates that
M. leprae
is still being transmitted and that, without earlier diagnosis,
M. leprae
infection will continue to pose a health problem. Current diagnostic techniques, based on the appearance of clinical symptoms or of immunoglobulin M (IgM) antibodies that recognize the bacterial phenolic glycolipid I, are unable to reliably identify early-stage leprosy. In this study we examine the ability of IgG within leprosy patient sera to bind several
M. leprae
protein antigens. As expected, multibacillary leprosy patients provided stronger responses than paucibacillary leprosy patients. We demonstrate that the geographic locations of the patients can influence the antigens they recognize but that ML0405 and ML2331 are recognized by sera from diverse regions (the Philippines, coastal and central Brazil, and Japan). A fusion construct of these two proteins (designated leprosy IDRI diagnostic 1 [LID-1]) retained the diagnostic activity of the component antigens. Upon testing against a panel of prospective sera from individuals who developed leprosy, we determined that LID-1 was capable of diagnosing leprosy 6 to 8 months before the onset of clinical symptoms. A serological diagnostic test capable of identifying and allowing treatment of early-stage leprosy could reduce transmission, prevent functional disabilities and stigmatizing deformities, and facilitate leprosy eradication.
Anaplasma phagocytophilum
-
Borrelia burgdorferi
Coinfection Enhances Chemokine, Cytokine, and Matrix Metalloprotease Expression by Human Brain Microvascular Endothelial Cells
Authors: Grab Dennis J. , Nyarko Elvis , Barat Nicole C. , Nikolskaia Olga V. , Dumler J. Stephen
Published: September 2007

Borrelia burgdorferi
and
Anaplasma phagocytophilum
coinfect and are transmitted by
Ixodes
species ticks. Clinical indicators suggest that
A. phagocytophilum
coinfection contributes to the severity, dissemination, and, possibly, sequelae of Lyme disease. Previous in vitro studies showed that spirochete penetration through human brain microvascular endothelial cells of the blood-brain barrier is facilitated by endothelial cell-derived matrix metalloproteases (MMPs).
A. phagocytophilum
-infected neutrophils continuously release MMPs and other vasoactive biomediators. We examined
B. burgdorferi
infection of brain microvascular barriers during
A. phagocytophilum
coinfection and showed that coinfection enhanced reductions in transendothelial electrical resistance and enhanced or synergistically increased production of MMPs (MMP-1, -3, -7, -8, and -9), cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha), and chemokines (IL-8 and macrophage inflammatory protein 1α) known to affect vascular permeability and inflammatory responses.
Confirmatory Real-Time PCR Assay for Human Papillomavirus (HPV) Type 52 Infection in Anogenital Specimens Screened for HPV Infection with the Linear Array HPV Genotyping Test
Authors: Coutlée François , Rouleau Danielle , Ghattas Georges , Hankins Catherine , Vézina Sylvie , Coté Pierre , Macleod John , de Pokomandy Alexandra , Money Deborah , Walmsley Sharon , Voyer Hélène , Brassard Paul , Franco Eduardo
Published: September 2007

A novel real-time PCR assay for detection of human papillomavirus type 52 (HPV-52) DNA (RT-52) was evaluated on 265 anogenital samples. RT-52 had a sensitivity of 98.4% and a specificity of 100% compared to conventional HPV-52 typing assays, including hybridization of PGMY products with an HPV-52-specific probe and PCR sequencing of HPV-52 E6.
Improved COBAS TaqMan Hepatitis C Virus Test (Version 2.0) for Use with the High Pure System: Enhanced Genotype Inclusivity and Performance Characteristics in a Multisite Study
Authors: Colucci G. , Ferguson J. , Harkleroad C. , Lee S. , Romo D. , Soviero S. , Thompson J. , Velez M. , Wang A. , Miyahara Y. , Young S. , Sarrazin C.
Published: September 2007

We have evaluated the COBAS TaqMan hepatitis C virus (HCV) test (version 2.0) for use with the High Pure system (HCVHPS V2), a new, revised real-time reverse transcription-PCR assay developed to improve the genotype quantitation of version 1.0 (HCVHPS V1). Revisions were made in the wash buffer and in the reverse transcription temperature. The genotype inclusivity of HCVHPS V2 was evaluated at three different sites, using HCVHPS V2, HCVHPS V1, and the COBAS AMPLICOR HCV MONITOR test (version 2.0) (CAHCM). The fully automated COBAS Ampliprep/COBAS TaqMan HCV test was also used in one of the participating laboratories. The mean differences in HCV RNA values between HCVHPS V2 and CAHCM and between HCVHPS V2 and HCVHPS V1 ranged from −0.21 to 0.13 log and from 0.24 to 1.27 log, respectively, with >0.5-log differences for genotypes 2, 3, 4, and 5. With a NIBSC panel of HCV genotypes 1 through 6, the measured HCVHPS V2 values were within 0.25 log of the nominal values for all 6 genotypes. When serial dilutions of genotype-specific clinical HCV specimens were tested, the assay showed a limit of detection between 10 and 20 IU/ml and a linear range of 25 IU/ml to 3.91 × 108IU/ml. Clinical and analytical specificities of 100% were demonstrated with 100 HCV-seronegative specimens as well as with 12 non-HCV members ofFlaviviridaeand 22 additional microorganisms. These data indicate that HCVHPS V2 is a robust and accurate test for the quantitation of all six HCV genotypes and useful in monitoring viral load in all clinical HCV specimens.
Discovery of a Novel
Mycobacterium tuberculosis
Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil
Authors: Lazzarini Luiz Claudio Oliveira , Huard Richard C. , Boechat Neio L. , Gomes Harrison M. , Oelemann Maranibia C. , Kurepina Natalia , Shashkina Elena , Mello Fernanda C. Q. , Gibson Andrea L. , Virginio Milena J. , Marsico Ana Grazia , Butler W. Ray , Kreiswirth Barry N. , Suffys Philip N. , Lapa e Silva Jose Roberto , Ho John L.
Published: September 2007

The current study evaluated
Mycobacterium tuberculosis
isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in ∼30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD
Rio
. Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD
Rio
locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS
6110
-based restriction fragment length polymorphism analysis cumulatively support the idea that RD
Rio
strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD
Rio
lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD
Rio
strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD
Rio
strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD
Rio
M. tuberculosis
.
Cell-Cell Fusion Induced by Measles Virus Amplifies the Type I Interferon Response
Authors: Herschke F. , Plumet S. , Duhen T. , Azocar O. , Druelle J. , Laine D. , Wild T. F. , Rabourdin-Combe C. , Gerlier D. , Valentin H.
Published: September 2007

Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-β) production is amplified in vitro by the formation of virus-induced MGC derived from human epithelial cells or mature conventional dendritic cells. Both fusion and IFN-β response amplification were inhibited in a dose-dependent way by a fusion-inhibitory peptide after MeV infection of epithelial cells. This effect was observed at both low and high multiplicities of infection. While in the absence of virus replication, the cell-cell fusion mediated by MeV H/F glycoproteins did not activate any IFN-α/β production, an amplified IFN-β response was observed when H/F-induced MGC were infected with a nonfusogenic recombinant chimerical virus. Time lapse microscopy studies revealed that MeV-infected MGC from epithelial cells have a highly dynamic behavior and an unexpected long life span. Following cell-cell fusion, both of the RIG-I and IFN-β gene deficiencies were
trans
complemented to induce IFN-β production. Production of IFN-β and IFN-α was also observed in MeV-infected immature dendritic cells (iDC) and mature dendritic cells (mDC). In contrast to iDC, MeV infection of mDC induced MGC, which produced enhanced amounts of IFN-α/β. The amplification of IFN-β production was associated with a sustained nuclear localization of IFN regulatory factor 3 (IRF-3) in MeV-induced MGC derived from both epithelial cells and mDC, while the IRF-7 up-regulation was poorly sensitive to the fusion process. Therefore, MeV-induced cell-cell fusion amplifies IFN-α/β production in infected cells, and this indicates that MGC contribute to the antiviral immune response.
Distribution of Fitness and Virulence Effects Caused by Single-Nucleotide Substitutions inTobacco Etch Virus
Authors: Carrasco Purificación , de la Iglesia Francisca , Elena Santiago F.
Published: September 2007

Little is known about the fitness and virulence consequences of single-nucleotide substitutions in RNA viral genomes, and most information comes from the analysis of nonrandom sets of mutations with strong phenotypic effect or which have been assessed in vitro, with their relevance in vivo being unclear. Here we used site-directed mutagenesis to create a collection of 66 clones ofTobacco etch potyvirus, each carrying a different, randomly chosen, single-nucleotide substitution. Competition experiments between each mutant and the ancestral nonmutated clone were performed in planta to quantitatively assess the relative fitness of each mutant genotype. Among all mutations, 40.9% were lethal, and among the viable ones, 36.4% were significantly deleterious and 22.7% neutral. Not a single case of beneficial effects was observed within the level of resolution of our measures. On average, the fitness of a genotype carrying a deleterious but viable mutation was 49% smaller than that for its unmutated progenitor. Deleterious mutational effects conformed to a beta probability distribution. The virulence of a subset of viable mutants was assessed as the reduction in the number of viable seeds produced by infected plants. Mutational effects on virulence ranged between 17% reductions and 24.4% increases. Interestingly, the only mutations showing a significant effect on virulence were hypervirulent. Competitive fitness and virulence were uncorrelated traits.
Biochemical and Genetic Analyses of Murine Hepatitis Virus Nsp15 Endoribonuclease
Authors: Kang Hyojeung , Bhardwaj Kanchan , Li Yi , Palaninathan Satheesh , Sacchettini James , Guarino Linda , Leibowitz Julian L. , Kao C. Cheng
Published: September 2007

The goal of this project was to better define the relationship between the endoribonuclease activity of murine hepatitis virus (MHV) Nsp15 (mNsp15) and its role in virus infection. Molecular modeling demonstrated that the catalytic residues of mNsp15 are superimposable with its severe acute respiratory syndrome coronavirus ortholog. Alanine substitutions at three key residues in the mNsp15 catalytic pocket (H262, H277, and G275) and a double-mutant version (H262P and H277A) generated proteins with greatly reduced but detectable endoribonuclease activities. Furthermore, these mutant proteins demonstrated lower cleavage specificities for uridylate than wild-type (WT) mNsp15. These mutations were successfully incorporated into viruses named vH262A, vH277A, vG275A, and vH262P+H277A. All four mutant viruses formed plaques with diameters similar to that of MHV-A59 1000 (WT virus) on several different cell lines. Interestingly, viruses with a mutation at a noncatalytic residue, D324A, could not be recovered despite repeated attempts, and expression of mNsp15 containing the D324A mutation in
Escherichia coli
resulted in an insoluble protein. Plaques derived from vH262A produced approximately 6- to 13-fold fewer PFU than those from WT virus. Cells infected with mNsp15 mutant viruses accumulated lesser amounts of plus- and minus-sense subgenomic RNAs and spike protein than WT virus. The expression of mNsp15 in
trans
by transient transfection partially restored RNA synthesis by vH262A. These results demonstrate that mNsp15 is required for optimal infection by MHV.
Phylogenetic Surveillance of Viral Genetic Diversity and the Evolving Molecular Epidemiology of Human Immunodeficiency Virus Type 1
Authors: Gifford Robert J. , de Oliveira Tulio , Rambaut Andrew , Pybus Oliver G. , Dunn David , Vandamme Anne-Mieke , Kellam Paul , Pillay Deenan
Published: September 2007

With ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1
pol
gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201
pol
gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.
Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation
Authors: Hebner Christy , Beglin Melanie , Laimins Laimonis A.
Published: September 2007

The high-risk human papillomavirus (HPV) E6 and E7 proteins act cooperatively to mediate multiple activities in viral pathogenesis. For instance, E7 acts to increase p53 levels while E6 accelerates its rate of turnover through the binding of the cellular ubiquitin ligase E6AP. Interferons are important antiviral agents that modulate both the initial and persistent phases of viral infection. The expression of HPV type 16 E7 was found to sensitize keratinocytes to the growth-inhibitory effects of interferon, while coexpression of E6 abrogates this inhibition. Treatment of E7-expressing cells with interferon ultimately resulted in cellular senescence through a process that is dependent upon acetylation of p53 by p300/CBP at lysine 382. Cells expressing mutant forms of E6 that are unable to bind p300/CBP or bind p53 failed to block acetylation of p53 at lysine 382 and were sensitive to growth arrest by interferon. In contrast, mutant forms of E6 that are unable to bind E6AP remain resistant to the effects of interferon, demonstrating that the absolute levels of p53 are not the major determinants of this activity. Finally, p53 acetylation at lysine 382 was found not to be an essential determinant of other types of senescence such as that induced by overexpression of Ras in human fibroblasts. This study identifies an important physiological role for E6 binding to p300/CBP in blocking growth arrest of human keratinocytes in the presence of interferon and so contributes to the persistence of HPV-infected cells.
A Monoclonal Fab Derived from a Human Nonimmune Phage Library Reveals a New Epitope on gp41 and Neutralizes Diverse Human Immunodeficiency Virus Type 1 Strains
Authors: Gustchina Elena , Louis John M. , Lam Son N. , Bewley Carole A. , Clore G. Marius
Published: September 2007

A monoclonal Fab (Fab 3674) selected from a human nonimmune phage library by panning against the chimeric construct N
CCG
-gp41 (which comprises an exposed coiled-coil trimer of gp41 N helices fused in the helical phase onto the minimal thermostable ectodomain of gp41) is described. Fab 3674 is shown to neutralize diverse laboratory-adapted B strains of human immunodeficiency virus type 1 (HIV-1) and primary isolates of subtypes A, B, and C in an Env-pseudotyped-virus neutralization assay, albeit with reduced potency (approximately 25-fold) compared to that of 2F5 and 4E10. Alanine scanning mutagenesis maps a novel epitope to a shallow groove on the N helices of gp41 that is exposed between two C helices in the fusogenic six-helix bundle conformation of gp41. Bivalent Fab 3674 and the C34 peptide (a potent fusion inhibitor derived from the C helix of gp41) are shown to act at similar stages of the fusion reaction and to neutralize HIV-1 synergistically, providing additional evidence that the epitope of Fab 3674 is new and distinct from the binding site of C34.
Development of a Challenge-Protective Vaccine Concept by Modification of the Viral RNA-Dependent RNA Polymerase of Canine Distemper Virus
Authors: Silin D. , Lyubomska O. , Ludlow M. , Duprex W. P. , Rima B. K.
Published: September 2007

We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a “quick response” in vaccine development against well-known and “new” viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.
The Mre11/Rad50/Nbs1 Complex Limits Adeno-Associated Virus Transduction and Replication
Authors: Schwartz Rachel A. , Palacios Jose Alejandro , Cassell Geoffrey D. , Adam Sarah , Giacca Mauro , Weitzman Matthew D.
Published: September 2007

Adeno-associated virus (AAV) is a parvovirus with a small single-stranded DNA genome that relies on cellular replication machinery together with functions supplied by coinfecting helper viruses. The impact of host factors on AAV infection is not well understood. We explored the connection between AAV helper functions supplied by adenovirus and cellular DNA repair proteins. The adenoviral E1b55K/E4orf6 proteins induce degradation of the cellular Mre11 repair complex (MRN) to promote productive adenovirus infection. These viral proteins also augment recombinant AAV transduction and provide crucial helper functions for wild-type AAV replication. Here, we show that MRN poses a barrier to AAV and that the helper function provided by E1b55K/E4orf6 involves MRN degradation. Using a fluorescent method to visualize the viral genome, we show an effect at the viral DNA level. MRN components accumulate at AAV replication centers and recognize the viral inverted terminal repeats. Together, our data suggest that AAV is targeted by MRN and has evolved to exploit adenoviral proteins that degrade these cellular factors.
A Novel Virus Detected in Papillomas and Carcinomas of the Endangered Western Barred Bandicoot (
Perameles bougainville
) Exhibits Genomic Features of both the
Papillomaviridae
and
Polyomaviridae
Authors: Woolford Lucy , Rector Annabel , Van Ranst Marc , Ducki Andrea , Bennett Mark D. , Nicholls Philip K. , Warren Kristin S. , Swan Ralph A. , Wilcox Graham E. , O'Hara Amanda J.
Published: September 2007

Conservation efforts to prevent the extinction of the endangered western barred bandicoot (
Perameles bougainville
) are currently hindered by a progressively debilitating cutaneous and mucocutaneous papillomatosis and carcinomatosis syndrome observed in captive and wild populations. In this study, we detected a novel virus, designated the bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1), in lesional tissue from affected western barred bandicoots using multiply primed rolling-circle amplification and PCR with the cutaneotropic papillomavirus primer pairs FAP59/FAP64 and AR-L1F8/AR-L1R9. Sequencing of the BPCV1 genome revealed a novel prototype virus exhibiting genomic properties of both the
Papillomaviridae
and the
Polyomaviridae
. Papillomaviral properties included a large genome size (∼7.3 kb) and the presence of open reading frames (ORFs) encoding canonical L1 and L2 structural proteins. The genomic organization in which structural and nonstructural proteins were encoded on different strands of the double-stranded genome and the presence of ORFs encoding the nonstructural proteins large T and small t antigens were, on the other hand, typical polyomaviral features. BPCV1 may represent the first member of a novel virus family, descended from a common ancestor of the papillomaviruses and polyomaviruses recognized today. Alternatively, it may represent the product of ancient recombination between members of these two virus families. The discovery of this virus could have implications for the current taxonomic classification of
Papillomaviridae
and
Polyomaviridae
and can provide further insight into the evolution of these ancient virus families.