bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection of Human Airway Epithelium by Human and Avian Strains of Influenza A Virus
Authors: Thompson Catherine I. , Barclay Wendy S. , Zambon Maria C. , Pickles Raymond J. 
Published: July 2006

ABSTRACT
We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, α-2,6- and α-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of α-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.
Characterization of an Amino-Terminal Dimerization Domain from Retroviral Restriction Factor Fv1
Authors: Bishop Kate N. , Mortuza Gulnahar B. , Howell Steven , Yap Melvyn W. , Stoye Jonathan P. , Taylor Ian A. 
Published: July 2006

ABSTRACT

The Fv1 protein is an endogenous factor in mice that confers resistance to infection by certain classes of murine leukemia virus, a phenomenon referred to as restriction. The mechanism of restriction is not understood, and the low endogenous level of Fv1 in cells has prevented any biochemical or biophysical analysis of the protein. We have now purified recombinant Fv1
n
protein from a baculovirus system and demonstrate that Fv1 exists in a multimeric form. Furthermore, we have mapped the position of two domains within the protein using limited proteolysis. Biophysical characterization of the N-terminal domain reveals that it comprises a highly helical and extended dimeric structure. Based on these biochemical and biophysical data, we propose a model for the arrangement of domains in Fv1 and suggest that dimerization of the N-terminal domain is necessary for Fv1 function to allow the protein to interact with multiple capsid protomers in retroviral cores.
CD4+T-Cell Responses to Epstein-Barr Virus Nuclear Antigen EBNA1 in Chinese Populations Are Highly Focused on Novel C-Terminal Domain-Derived Epitopes
Authors: Tsang C. W. , Lin X. , Gudgeon N. H. , Taylor G. S. , Jia H. , Hui E. P. , Chan A. T. C. , Lin C. K. , Rickinson A. B. 
Published: July 2006

ABSTRACTEpstein-Barr virus nuclear antigen EBNA1, the one viral protein uniformly expressed in nasopharyngeal carcinoma (NPC), represents a prime target for T-cell-based immunotherapy. However, little is known about the EBNA1 epitopes, particularly CD4 epitopes, presented by HLA alleles in Chinese people, the group at highest risk for NPC. We analyzed the CD4+T-cell responses to EBNA1 in 78 healthy Chinese donors and found marked focusing on a small number of epitopes in the EBNA1 C-terminal region, including a DP5-restricted epitope that was recognized by almost half of the donors tested and elicited responses able to recognize EBNA1-expressing, DP5-positive target cells.
Prion Strain-Dependent Differences in Conversion of Mutant Prion Proteins in Cell Culture
Authors: Atarashi Ryuichiro , Sim Valerie L. , Nishida Noriyuki , Caughey Byron , Katamine Shigeru 
Published: July 2006

ABSTRACT

Although the protein-only hypothesis proposes that it is the conformation of abnormal prion protein (PrP
Sc
) that determines strain diversity, the molecular basis of strains remains to be elucidated. In the present study, we generated a series of mutations in the normal prion protein (PrP
C
) in which a single glutamine residue was replaced with a basic amino acid and compared their abilities to convert to PrP
Sc
in cultured neuronal N2a58 cells infected with either the Chandler or 22L mouse-adapted scrapie strain. In mice, these strains generate PrP
Sc
of the same sequence but different conformations, as judged by infrared spectroscopy. Substitutions at codons 97, 167, 171, and 216 generated PrP
C
that resisted conversion and inhibited the conversion of coexpressed wild-type PrP in both Chandler-infected and 22L-infected cells. Interestingly, substitutions at codons 185 and 218 gave strain-dependent effects. The Q185R and Q185K PrP were efficiently converted to PrP
Sc
in Chandler-infected but not 22L-infected cells. Conversely, Q218R and Q218H PrP were converted only in 22L-infected cells. Moreover, the Q218K PrP exerted a potent inhibitory effect on the conversion of coexpressed wild-type PrP in Chandler-infected cells but had little effect on 22L-infected cells. These results show that two strains with the same PrP sequence but different conformations have differing abilities to convert the same mutated PrP
C
.
Cleavage Map and Proteolytic Processing of the Murine Norovirus Nonstructural Polyprotein in Infected Cells
Authors: Sosnovtsev Stanislav V. , Belliot Gaël , Chang Kyeong-OK , Prikhodko Victor G. , Thackray Larissa B. , Wobus Christiane E. , Karst Stephanie M. , Virgin Herbert W. , Green Kim Y. 
Published: July 2006

ABSTRACT

Murine
norovirus (MNV) is presently the only member of the genus
Norovirus
in the
Caliciviridae
that can be propagated
in cell culture. The goal of this study was to elucidate the
proteolytic processing strategy of MNV during an authentic replication
cycle in cells. A proteolytic cleavage map of the ORF1 polyprotein was
generated, and the virus-encoded 3C-like (3CL) proteinase (Pro)
mediated cleavage at five dipeptide cleavage sites,
341
E/G
342
, Q
705
/N
706
,
870
E/G
871
,
994
E/A
995
, and
1177
Q/G
1178
, that defined the borders of six
proteins with the gene order p38.3 (Nterm)-p39.6
(NTPase)-p18.6-p14.3 (VPg)-p19.2 (Pro)-p57.5 (Pol). Bacterially
expressed MNV 3CL Pro was sufficient to mediate
trans
cleavage
of the ORF1 polyprotein containing the mutagenized Pro sequence into
products identical to those observed during cotranslational processing
of the authentic ORF1 polyprotein in vitro and to those observed in
MNV-infected cells. Immunoprecipitation and Western blot analysis of
proteins produced in virus-infected cells demonstrated efficient
cleavage of the proteinase-polymerase precursor. Evidence for
additional processing of the Nterm protein in MNV-infected cells by
caspase 3 was obtained, and Nterm sequences
118
DRPD
121
and
128
DAMD
131
were mapped as caspase 3 cleavage sites by site-directed mutagenesis.
The availability of the MNV nonstructural polyprotein cleavage map in
concert with a permissive cell culture system should facilitate studies
of norovirus
replication.
Requirement of the N-Terminal Region of Orthobunyavirus Nonstructural Protein NSm for Virus Assembly and Morphogenesis
Authors: Shi Xiaohong , Kohl Alain , Léonard Vincent H. J. , Li Ping , McLees Angela , Elliott Richard M. 
Published: July 2006

ABSTRACT

The nonstructural protein NSm of Bunyamwera virus (BUNV), the prototype of the
Bunyaviridae
family, is encoded by the M segment in a polyprotein precursor, along with the virion glycoproteins, in the order Gn-NSm-Gc. As little is known of its function, we examined the intracellular localization, membrane integrality, and topology of NSm and its role in virus replication. We confirmed that NSm is an integral membrane protein and that it localizes in the Golgi complex, together with Gn and Gc. Coimmunoprecipitation assays and yeast two-hybrid analysis demonstrated that NSm was able to interact with other viral proteins. NSm is predicted to contain three hydrophobic (I, III, and V) and two nonhydrophobic (II and IV) domains. The N-terminal nonhydrophobic domain II was found in the lumen of an intracellular compartment. A novel BUNV assembly assay was developed to monitor the formation of infectious virus-like-particles (VLPs). Using this assay, we showed that deletions of either the complete NSm coding region or domains I, II, and V individually seriously compromised VLP production. Consistently, we were unable to rescue viable viruses by reverse genetics from cDNA constructs that contained the same deletions. However, we could generate mutant BUNV with deletions in NSm domains III and IV and also a recombinant virus with the green fluorescent protein open reading frame inserted into NSm domain IV. The mutant viruses displayed differences in their growth properties. Overall, our data showed that the N-terminal region of NSm, which includes domain I and part of domain II, is required for virus assembly and that the C-terminal hydrophobic domain V may function as an internal signal sequence for the Gc glycoprotein.
PML Contributes to a Cellular Mechanism of Repression of Herpes Simplex Virus Type 1 Infection That Is Inactivated by ICP0
Authors: Everett Roger D. , Rechter Sabine , Papior Peer , Tavalai Nina , Stamminger Thomas , Orr Anne 
Published: July 2006

ABSTRACT
Promyelocytic leukemia (PML) nuclear bodies (also known as ND10) are nuclear substructures that contain several proteins, including PML itself, Sp100, and hDaxx. PML has been implicated in many cellular processes, and ND10 are frequently associated with the replicating genomes of DNA viruses. During herpes simplex virus type 1 (HSV-1) infection, the viral regulatory protein ICP0 localizes to ND10 and induces the degradation of PML, thereby disrupting ND10 and dispersing their constituent proteins. ICP0-null mutant viruses are defective in PML degradation and ND10 disruption, and concomitantly they initiate productive infection very inefficiently. Although these data are consistent with a repressive role for PML and/or ND10 during HSV-1 infection, evidence in support of this hypothesis has been inconclusive. By use of short interfering RNA technology, we demonstrate that depletion of PML increases both gene expression and plaque formation by an ICP0-negative HSV-1 mutant, while having no effect on wild-type HSV-1. We conclude that PML contributes to a cellular antiviral repression mechanism that is countered by the activity of ICP0.
The L2 Minor Capsid Protein of Low-Risk Human Papillomavirus Type 11 Interacts with Host Nuclear Import Receptors and Viral DNA
Authors: Bordeaux J. , Forte S. , Harding E. , Darshan M. S. , Klucevsek K. , Moroianu J. 
Published: July 2006

ABSTRACT

Analysis of the interactions of low-risk human papillomavirus type 11 (HPV11) L2 with karyopherin β (Kap β) nuclear import receptors revealed that L2 interacted with Kap β
1
, Kap β
2
, and Kap β
3
and formed a complex with the Kap α
2
β
1
heterodimer. HPV11 L2 contains two nuclear localization signals (NLSs)—in the N terminus and the C terminus—that could mediate its nuclear import via a classical pathway. Each NLS was functional in vivo, and deletion of both of them abolished L2 nuclear localization. Both NLSs interacted with the viral DNA. Thus, HPV11 L2 can interact with several karyopherins and the viral DNA and may enter the nucleus via multiple pathways.
Differential Role of Sp100 Isoforms in Interferon-Mediated Repression of Herpes Simplex Virus Type 1 Immediate-Early Protein Expression
Authors: Negorev Dmitri G. , Vladimirova Olga V. , Ivanov Alexey , Rauscher Frank , Maul Gerd G. 
Published: July 2006

ABSTRACTNuclear domains called ND10 or PML nuclear bodies contain interferon (IFN)-upregulated proteins like PML and Sp100. Paradoxically, herpes simplex virus 1 (HSV-1) begins its transcriptional cascade at aggregates of ND10-associated proteins, which in turn are destroyed by the HSV-1 immediate-early protein ICP0. While PML is essential in the formation of ND10, the function of Sp100 in the cells' defense against viral infection is unknown. In this study we investigated the potential antiviral effect of IFN-β-induced Sp100. We found that IFN-β treatment leads to a differential accumulation of four Sp100 isoforms in different cell lines. Using an HEK293 cell line derivative, 293-S, producing no detectable amounts of Sp100 even after IFN exposure, we analyzed individual Sp100 isoforms for their effect on HSV-1 infection. Sp100 isoforms B, C, and HMG, but not Sp100A, suppressed ICP0 and ICP4 early after infection. Isoforms B, C, and HMG suppressed expression from the ICP0 promoter in transient transfection, whereas Sp100A enhanced expression. Moreover, Sp100A localized in ND10, whereas the repressive isoforms were either dispersed within the nucleus or, at unphysiologically higher expression levels, formed new aggregates. The repressive activity was dependent on an intact SAND domain, since Sp100B bearing a W655Q mutation in the SAND domain lost this repressive activity and accumulated in ND10. Using RNA interference to knock down the repressive Sp100 isoforms B, C, and HMG, we find that they are an essential part of the IFN-β-mediated suppression of ICP0 expression. These data suggest that repression by the Sp100 isoforms B, C, and HMG takes place outside of ND10 and raise the possibility that viral genomes at Sp100A accumulations are more likely to start their transcription program because of a more permissive local environment.
Substantial Connections: Water and Identity in an English Cultural Landscape
Authors: Strang Veronica 
Published: July 2006

AbstractAs a material substance, essential to every organic process, water literally constitutes human "being", providing a vital "natural symbol" of sociality and of human-environmental interdependence. Its particular qualities of fluidity and transmutability lend themselves to a stream of metaphors about flows and interconnections, and to ideas about spatio-temporal change and transformation. Moving constantly between internal and external environments, water facilitates scheme transfers between conceptual models of physiological, social and ecological processes. Representing "orderly" flows and balances in each of these, it is vulnerable to pollution at various levels, with concerns about material pollution readily transferred to ideas about social and cultural disorder. In particular, metaphors employing water imagery dominate discourses about individual and cultural identities and the maintenance—or dissolution—of social boundaries.Based on ethnographic research in Dorset, this paper explores these themes and considers how human engagements with water—in the home, and through interaction with rivers and water supply infrastructure—mediate individual, familial and wider collective identities in a shifting cultural " fluidscape" of social, spatial, economic and political relationships. It suggests that, in a post-modern social milieu, images of water and identity vie with more grounded metaphors of landscape, place and location, assisting debates about the potential for fluidity in human constructions of identity.
Green and Extreme: Free-Flowing Through Seascape and Sewer
Authors: Laviolette Patrick 
Published: July 2006

AbstractActivities to do with the coastline and the aquatic environment such as fishing, boating and seaside holidays have been mainstays of the Cornish peninsula for generations. Building on this legacy of marine leisure, this paper explores both the fluidity and materiality of waves, tides and coastal seascapes through a metaphorical framework encompassing symbolic as well as literal issues of pollution and embodiment. It examines Cornwall's distinct surf culture with regard to concerns over the effects of sewage and other malignant discharges on public health and the quality of the seashore environment. Extreme water sports are an increasingly prominent factor in the formulation of Cornish identity. Hence, the paper outlines the ways in which certain environmental pressure groups, charity campaigners and corporate surf companies have become involved in attempts to safeguard the ecological sustainability of coastal leisure pursuits. It does so primarily through ethnographic case studies concerning Surfers Against Sewage, protest-art exhibitions and environmental campaigns. On the surface, the symbolism of fluidity and pollution may appear contradictory. But through an exploration of the materiality of waves, this paper illustrates the dialectical ways in which water and the sea relate to shifting local identities and to creative forms of extreme subversion.
Ultrasonographic Investigation of the Achilles Tendon in Elite Badminton Players Using Color Doppler
Authors: Boesen Morten Ilum , Boesen Anders , Koenig Merete Juhl , Bliddal Henning , Torp-Pedersen Soren 
Published: July 2006

Background The most frequent injuries in badminton players are in the lower extremities, especially in the Achilles tendon. Hypothesis The game of badminton may be related to abnormal intratendinous flow in the Achilles tendon as detected by color Doppler ultrasound. To a certain extent, this blood flow might be physiological, especially when examined after match. Study Design Cohort study (prevalence); Level of evidence, 3. Methods Seventy-two elite badminton players were interviewed regarding Achilles tendon pain (achillodynia) in the preceding 3 years. Color Doppler was used to examine the tendons of 64 players before their matches and 46 players after their matches. Intratendinous color Doppler flow was graded from 0 to 4. The Achilles tendon was divided into dominant (eg, right side for right-handed players and vice versa) and nondominant side and classified as midtendon, preinsertional, and calcaneal areas. Results Of 72 players, 26 had experienced achillodynia in 34 tendons, 18 on the dominant side and 16 on the nondominant side. In 62% of the players with achillodynia, the problems had begun slowly, and the median duration of symptoms was 4 months (range, 0-36 months). Thirty-five percent had ongoing pain in their tendons for a median duration of 12 months (range, 0-12 months). Achillodynia was not associated with the self-reported training load or with sex, age, weight, singles or doubles players, or racket side. Forty-six players were scanned before and after match. At baseline, color Doppler flow was present in the majority of players, and only 7 (16%) players had no color Doppler flow in either tendon. After match, all players had some color Doppler flow in 1 or both tendons. Achillodynia and color Doppler flow were related in the nondominant Achilles tendon (chi-square, P =. 008). The grades of Doppler flow also increased significantly after match in the preinsertional area in both the nondominant (P =. 0002) and dominant (P =. 005) side tendons. Conclusion A large proportion of the players had experienced achillodynia and habitually played with a degree of pain that demanded medication. The self-reported pain was associated with increased intratendinous color Doppler flow in the nondominant Achilles tendon. Doppler flow was found in most players before and in all players after the match and therefore may in part be a physiological response to activity.
Manganese enriched diffusion layers on NiAl alloy
Authors: Bartuška P. , Lašek J. , Paidar V. 
Published: July 2006

Materials based on Ni–Al intermetallics are prospective high temperature materials. Properties of these intermetallics can often be improved by surface diffusion layers enriched by various metals. In this contribution results of a study are presented about microstructure and composition of Mn enriched diffusion layers on a NiAl alloy. A pure Mn plate was annealed at 900°C for 4 h in contact with a prism of the NiAl phase. The ordered B2-NiAl ( β′) phase can absorb only a few per cent of manganese without structural changes. When absorbing more Mn, the ordrerd B2-NiAl phase transforms into the disordered bcc β′ NiMnAl phase forming the first structurally different (narrow) layer on NiAl. Its Mn content increases from 25 wt-% (in contact with B2-NiAl phase) up to 35 wt-% across this homogeneous layer. Higher average Mn content in the next layer manifests in precipitation of β-Mn particles (containing several per cent of Ni and Al) from the β″ matrix. Owing to diffusion of Ni and Al into the original Mn plate the β″ NiMnAl precipitates are formed in the Mn matrix containing several per cent of Ni and Al (when studying microstructure and composition at room temperature after annealing).
Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf gene
Authors: Lemmerhirt Heidi L. , Shavit Jordan A. , Levy Gallia G. , Cole Suzanne M. , Long Jeffrey C. , Ginsburg David 
Published: July 2006

Abstract
Both genetic and environmental influences contribute to the wide variation in plasma von Willebrand factor (VWF) levels observed in humans. Inbred mouse strains also have highly variable plasma VWF levels, providing a convenient model in which to study genetic modifiers of VWF. Previously, we identified a major modifier of VWF levels in the mouse (Mvwf1) as a regulatory mutation in murine Galgt2. We now report the identification of an additional murine VWF modifier (Mvwf2). Mvwf2 accounts for approximately 16% of the 8-fold plasma VWF variation (or ∼ 25% of the genetic variation) observed between the A/J and CASA/RkJ strains and maps to the murine Vwf gene itself. Twenty SNPs were identified within the coding regions of the A/J and CASA/RkJ Vwf alleles, and in vitro analysis of recombinant VWF demonstrated that a single SNP (+7970G>A) and the associated nonsynonymous amino acid change (R2657Q) confers a significant increase in VWF biosynthesis from the CASA/RkJ Vwf allele. This change appears to represent a unique gain of function that likely explains the mechanism of Mvwf2 in vivo. The identification of a natural Vwf gene variant among inbred mice affecting biosynthesis suggests that similar genetic variation may contribute to the wide range of VWF levels observed in humans.
Diurnal ventilationviamouthpiece: survival in end-stage Duchenne patients
Authors: Toussaint M. , Steens M. , Wasteels G. , Soudon P. 
Published: July 2006

The present study aimed to assess the impact of diurnal mouthpiece intermittent positive pressure ventilation (MIPPV) as the extension of the nasal intermittent positive pressure ventilation (NIPPV) in Duchenne muscular dystrophy (DMD). In total, 42 DMD patients aged 15–33 yrs, normocapnic at night with NIPPV and receiving MIPPV since end-diurnal hypercapnia, were studied.Transcutaneous CO2tension (Pt,CO2) was prospectively monitored at the end of the day, before and after MIPPV initiation. Vital capacity (VC), breathing pattern and maximal inspiratory strength were measured. Patients were asked to score the presence (1 point) or absence (0 point) of seven respiratory-linked symptoms before and after MIPPV establishment.Survival rates reached 88, 77, 58 and 51% after 1, 3, 5 and 7 yrs, respectively. The mean survival rate was 31 yrs. VC stabilised during 5 yrs with MIPPV. Symptom scores significantly decreased andPt,CO2normalised during the day (8.17±2.22 to 5.78±0.73 kPa). No accident and minor side-effects were observed in this 184 cumulated patient-yrs study.In conclusion, daytime mouthpiece ventilation is safe, prolongs survival and stabilises vital capacity in Duchenne muscular dystrophy patients. It is recommended on the condition that patients are equipped with a self-supporting harness.