bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caveolin-1-Dependent Infectious Entry of Human Papillomavirus Type 31 in Human Keratinocytes Proceeds to the Endosomal Pathway for pH-Dependent Uncoating
Authors: Smith Jessica L. , Campos Samuel K. , Wandinger-Ness Angela , Ozbun Michelle A. 
Published: July 2008

ABSTRACTHigh-risk human papillomaviruses (HPVs) are small nonenveloped DNA viruses with a strict tropism for squamous epithelium. The viruses are causative agents of cervical cancer and some head and neck cancers, but their differentiation-dependent life cycles have made them difficult to study in simple cell culture. Thus, many aspects of early HPV infection remain mysterious. We recently showed the high-risk HPV type 31 (HPV31) enters its natural host cell type via caveola-dependent endocytosis, a distinct mechanism from that of the closely related HPV16 (Smith et al., J. Virol. 81:9922-9931, 2007). Here, we determined the downstream trafficking events after caveolar entry of HPV31 into human keratinocytes. After initial plasma membrane binding, HPV31 associates with caveolin-1 and transiently localizes to the caveosome before trafficking to the early endosome and proceeding through the endosomal pathway. Caveosome-to-endosome transport was found to be Rab5 GTPase dependent. Although HPV31 capsids were observed in the lysosome, Rab7 GTPase was dispensable for HPV31 infection, suggesting that viral genomes escape from the endosomal pathway prior to Rab7-mediated capsid transport. Consistent with this, the acidic pH encountered by HPV31 within the early endosomal pathway induces a conformational change in the capsid resulting in increased DNase susceptibility of the viral genome, which likely aids in uncoating and/or endosomal escape. The entry and trafficking route of HPV31 into human keratinocytes represents a unique viral pathway by which the virions use caveolar entry to eventually access a low-pH site that appears to facilitate endosomal escape of genomes.
Gain, Preservation, and Loss of a Group 1a Coronavirus Accessory Glycoprotein
Authors: Lorusso Alessio , Decaro Nicola , Schellen Pepijn , Rottier Peter J. M. , Buonavoglia Canio , Haijema Bert-Jan , de Groot Raoul J. 
Published: July 2008

ABSTRACT
Coronaviruses are positive-strand RNA viruses of extraordinary genetic complexity and diversity. In addition to a common set of genes for replicase and structural proteins, each coronavirus may carry multiple group-specific genes apparently acquired through relatively recent heterologous recombination events. Here we describe an accessory gene, ORF3, unique to canine coronavirus type I (CCoV-I) and characterize its product, glycoprotein gp3. Whereas ORF3 is conserved in CCoV-I, only remnants remain in CCoV-II and CCoV-II-derived porcine and feline coronaviruses. Our findings provide insight into the evolutionary history of coronavirus group 1a and into the dynamics of gain and loss of accessory genes.
Sequestering of the Prehairpin Intermediate of gp41 by Peptide N36
Mut(e,g)
Potentiates the Human Immunodeficiency Virus Type 1 Neutralizing Activity of Monoclonal Antibodies Directed against the N-Terminal Helical Repeat of gp41
Authors: Gustchina Elena , Bewley Carole A , Clore G. Marius 
Published: July 2008

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) neutralization can be effected by several classes of inhibitors that target distinct regions of gp41 that are accessible in the prehairpin intermediate (PHI) state and block the formation of the six-helix bundle (6-HB) conformation of gp41. The N-heptad repeat (N-HR) of gp41 is the site of action of two classes of inhibitors. One class binds to the trimeric N-HR coiled coil, while the other, exemplified by the peptide N36
Mut(e,g)
, disrupts the trimer and sequesters the PHI through the formation of heterotrimers. We recently reported a neutralizing Fab (Fab 3674), selected from a nonimmune phage library, that binds to the trimeric N-HR coiled coil through an epitope that remains exposed in the 6-HB and is also present in heterotrimers of the N-HR and N36
Mut(e,g)
peptide. Here we show that N36
Mut(e,g)
prolongs the temporal window during which the virus is susceptible to neutralization by the bivalent Fab 3674 and that bivalent Fab 3674 and N36
Mut(e,g)
neutralize HXB2 and SF162 strains of HIV-1, as well as isolates of diverse primary B and C HIV-1 strains, synergistically in a Env-pseudotyped virus neutralization assay. N36
Mut(e,g)
also rescues neutralizing activity of Fab 3674 against resistant virus strains and renders a series of related nonneutralizing Fabs neutralizing. Moreover, N36
Mut(e,g)
exhibits the same effects on the broadly neutralizing 2F5 and 4E10 monoclonal antibodies directed against the membrane-proximal extended region of gp41. The mechanistic implications of these findings are discussed.
Impaired Hepatitis C Virus (HCV)-Specific Effector CD8
+
T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection
Authors: Radziewicz Henry , Ibegbu Chris C. , Hon Huiming , Osborn Melissa K. , Obideen Kamil , Wehbi Mohammad , Freeman Gordon J. , Lennox Jeffrey L. , Workowski Kimberly A. , Hanson Holly L. , Grakoui Arash 
Published: July 2008

ABSTRACT

A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8
+
T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8
+
T cells during the acute and chronic stages of infection. Although HCV-specific CD8
+
T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8
+
T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8
+
T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8
+
T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections.
Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8
+
Memory T Cells
Authors: Badr Gamal , Bédard Nathalie , Abdel-Hakeem Mohamed S. , Trautmann Lydie , Willems Bernard , Villeneuve Jean-Pierre , Haddad Elias K. , Sékaly Rafick P. , Bruneau Julie , Shoukry Naglaa H. 
Published: July 2008

ABSTRACT

The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-α) antiviral therapy achieves the highest rate of success when IFN-α is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-γ- and IL-2-producing and CD107a
+
) virus-specific CD8
+
T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8
+
T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-α rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.
Effector CD4+T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords
Authors: Johnson Alison J. , Chu Chin-Fun , Milligan Gregg N. 
Published: July 2008

ABSTRACTIn primary infection, CD8+T cells are important for clearance of infectious herpes simplex virus (HSV) from sensory ganglia. In this study, evidence of CD4+T-cell-mediated clearance of infectious HSV type 1 (HSV-1) from neural tissues was also detected. In immunocompetent mice, HSV-specific CD4+T cells were present in sensory ganglia and spinal cords coincident with HSV-1 clearance from these sites and remained detectable at least 8 months postinfection. Neural CD4+T cells isolated at the peak of neural infection secreted gamma interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), or IL-4 after stimulation with HSV antigen. HSV-1 titers in neural tissues were greatly reduced over time in CD8+T-cell-deficient and CD8+T-cell-depleted mice, suggesting that CD4+T cells could mediate clearance of HSV-1 from neural tissue. To examine possible mechanisms by which CD4+T cells resolved neural infection, CD8+T cells were depleted from perforin-deficient or FasL-defective mice. Clearance of infectious virus from neural tissues was not significantly different in perforin-deficient or FasL-defective mice compared to wild-type mice. Further, in spinal cords and brains after vaginal HSV-1 challenge of chimeric mice expressing both perforin and Fas or neither perforin nor Fas, virus titers were significantly lower than in control mice. Thus, perforin and Fas were not required for clearance of infectious virus from neural tissues. These results suggest that HSV-specific CD4+T cells are one component of a long-term immune cell presence in neural tissues following genital HSV-1 infection and play a role in clearance of infectious HSV-1 at neural sites, possibly via a nonlytic mechanism.
Remodeling of Endothelial Adherens Junctions by Kaposi's Sarcoma-Associated Herpesvirus
Authors: Mansouri Mandana , Rose Patrick P. , Moses Ashlee V. , Früh Klaus 
Published: July 2008

ABSTRACTVascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits α- and β-catenins and γ-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of α- and β-catenins and γ-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis.
Spontaneous Heteromerization of Gammaretrovirus Envelope Proteins: a Possible Novel Mechanism of Retrovirus Restriction
Authors: Dewannieux Marie , Collins Mary K. 
Published: July 2008

ABSTRACT

The
env
gene of gammaretroviruses encodes a glycoprotein conserved among diverse retroviruses, except for the domains involved in receptor binding. Here we show that pairs of gammaretrovirus envelope proteins (from Friend virus and GALV or xenotropic viruses) assemble into heteromers when coexpressed. This assembly results in a strong inhibition of infectivity. An unrelated envelope protein does not assemble in heteromers with the gammaretrovirus glycoproteins tested and does not affect their infectivity, demonstrating the specificity of the mechanism we describe. We propose that the numerous copies of endogenous retroviral
env
genes conserved within mammalian genomes act as restriction factors against infectious retroviruses.
Production and engineering application of C60 high-performance pump pebble concrete containing ultra-fine fly ash
Authors: Li Gao Ying , Guo Ma Bao , Zhou Shi Qiong 
Published: July 2008

C60 grade high-performance pump concrete incorporating river pebbles and ultra-fine fly ash (UFA) was successfully prepared, with UFA replacing 30% of the cement, for the second-stage of construction of the Hunan Xiangtan Power Plant. Some of the properties of this pump concrete were studied using both laboratory and on-site testing. The results indicated that workability of UFA concrete was excellent. The initial slump surpassed 180 mm, and the slump loss was small. The 28 d strength of the concrete met the engineering requirement of conforming to C60 strength grade. It is shown that the resistance–chloride ion penetration of UFA pump concrete is better than that of ordinary concrete in terms of Association for Testing and Materials test method C1202-94. Dry shrinkage of concrete slightly reduced with the addition of UFA, and UFA concrete shows better crack resistance compared with ordinary concrete. The production technology of UFA pump pebble concrete is summarized based on test and engineering applications.
Stage-Specific Alterations of DNA Methyltransferase Expression, DNA Hypermethylation, and DNA Hypomethylation during Prostate Cancer Progression in the Transgenic Adenocarcinoma of Mouse Prostate Model
Authors: Morey Kinney Shannon R. , Smiraglia Dominic J. , James Smitha R. , Moser Michael T. , Foster Barbara A. , Karpf Adam R. 
Published: July 2008

Abstract
We analyzed DNA methyltransferase (Dnmt) protein expression and DNA methylation patterns during four progressive stages of prostate cancer in the transgenic adenocarcinoma of mouse prostate (TRAMP) model, including prostatic intraepithelial neoplasia, well-differentiated tumors, early poorly differentiated tumors, and late poorly differentiated tumors. Dnmt1, Dnmt3a, and Dnmt3b protein expression were increased in all stages; however, after normalization to cyclin A to account for cell cycle regulation, Dnmt proteins remained overexpressed in prostatic intraepithelial neoplasia and well-differentiated tumors, but not in poorly differentiated tumors. Restriction landmark genomic scanning analysis of locus-specific methylation revealed a high incidence of hypermethylation only in poorly differentiated (early and late) tumors. Several genes identified by restriction landmark genomic scanning showed hypermethylation of downstream regions correlating with mRNA overexpression, including p16INK4a, p19ARF, and Cacna1a. Parallel gene expression and DNA methylation analyses suggests that gene overexpression precedes downstream hypermethylation during prostate tumor progression. In contrast to gene hypermethylation, genomic DNA hypomethylation, including hypomethylation of repetitive elements and loss of genomic 5-methyldeoxycytidine, occurred in both early and late stages of prostate cancer. DNA hypermethylation and DNA hypomethylation did not correlate in TRAMP, and Dnmt protein expression did not correlate with either variable, with the exception of a borderline significant association between Dnmt1 expression and DNA hypermethylation. In summary, our data reveal the relative timing of and relationship between key alterations of the DNA methylation pathway occurring during prostate tumor progression in an in vivo model system. (Mol Cancer Res 2008;6(8):1365–74)
'He Is He, and I Am I': Individual and Collective among China's Rural Elderly
Authors: Thøgersen Stig , Anru Ni 
Published: July 2008

AbstractChina's rural elderly strongly feel the tension between the life patterns they had expected to follow and the risks and possibilities presented by a more dynamic and individualised society. This paper discusses how the elderly react to the rapid changes in intergenerational relations. The focus is on their strategies towards the two most common types of living arrangements during old age: maintaining an independent household, and living with a son's family. Earlier generations of elderly perceived cohabitation with a son as the only natural arrangement, but interviews indicate that living in an independent household has become an accepted alternative. This illustrates how China's rural elderly are able to create and accept changes in family relations and new life patterns. Their problems are generated by the lack of social services in rural areas rather than by any culturally determined resistance to change. The last part of the paper discusses recent social engineering projects aimed at reintegrating the elderly into society. By looking at how the elderly adapt to changing family relations and how others imagine their reintegration, the paper highlights the complicated patterns of social change that have emerged in China's villages in the wake of decollectivisation.
Individualisation and Politics in China: The Political Identity and Agency of Private Business People
Authors: Yin Xiaoqing , Delman Jørgen 
Published: July 2008

AbstractThe article considers the dynamics in the nexus between the Chinese party-state and private entrepreneurs. It develops in response to both globalization and market reforms which promote accelerated individualisation and disembedding of citizens anchored in the new capitalist economy, such as private business people. It is argued that informal political agency is part of the political dynamics of the nexus and that it develops through critical tension between private business people and the autocratic party-state. This is illustrated through the case of Sun Dawu, a Hebei businessman turned political activist. Referring to both Bech and Bech-Gersheim's and Baumann's discussions about the effects of the twin processes of globalisation and individualisation, one of the main conclusions is that Sun Dawu has engaged in 'self-politics' through creating a sub-political or 'peg' community where he and others can exert informal political agency. The construction of such a community is an example of how assertive private business people may exploit the dynamics of the state-private business nexus through critical tension.
Me and My Family: Perceptions of Individual and Collective among Young Rural Chinese
Authors: Hansen Mette Halskov , Pang Cuiming 
Published: July 2008

AbstractThis article discusses how young people born and raised in rural areas of China perceive and account for individual choice and responsibility in relation to their family and the state. Based on personal narratives of more than 100 young people, the article shows how concepts of freedom, independence, free love and personal development are widespread among young villagers who are searching, not merely for economic prosperity, but for a self-fulfilling life. They express a remarkably strong sense of individual responsibility for success or failure, and even tend to idealise individual choice. The article argues that in spite of young people's growing demands for individual space and the rapid changes in the relations between the generations, the family remains the most important collective for these young people, emotionally and as their only source of social security and support.
A Collective of Their Own: Young Volunteers at the Fringes of the Party Realm
Authors: Rolandsen Unn Målfrid 
Published: July 2008

AbstractBased on fieldwork in an urban branch of the China Youth Volunteers' Association this article discusses how individual motivation for volunteering among young middle-class students plays a role in the internal reforming of one of the few officially authorised associations available for young people. Whereas Chinese volunteering was once a Party-driven effort supported by Maoist calls to 'Serve the people', contemporary Chinese volunteering is promoted with a focus on the volunteer's own experience and commitment. Interviews and participant observation demonstrate how young volunteers use the Party-linked Volunteers' Association not merely instrumentally to support their own personal ambitions, but also as a social space where the individual may find room to 'give and share beyond the family'. The analysis shows that volunteering is perceived differently by volunteers' families, the local media, the local community and the volunteers themselves. The article concludes that what attracts youth to the volunteer movement is the opportunity to be part of a collective where they can contribute to society while at the same time being recognised as individuals.
Critiquing the Idea of Japanese Exceptionalism: Japan and the Coordination of North Korea Policy
Authors: Hagström Linus 
Published: July 2008

AbstractThe idea that Japan is playing an 'alternative role' in its foreign policy—that it is keeping a 'conspicuously low profile' and that its stance is in some sense 'unique'—has been a recurring theme of analysis of Japanese foreign policy. This article aims to critique this idea of Japanese exceptionalism, epitomised for instance in the 'aikido state' metaphor. By analysing Japan's role in the Six-Party Talks—arguably a suitable case for testing this metaphor—the article concludes that, far from keeping a low profile, Tokyo has exercised obstructive power over other actors involved in the talks. This conclusion is substantiated by comparison with Tokyo's role in other important instances of North Korea policy coordination over the period 1993–2002. By comparing Japanese behaviour with that of the USA, China, Russia and North Korea, the article concludes, furthermore, that the concepts of 'obstructionism' and 'power' facilitate understanding of their behaviour as well—with the implication that Japan's foreign policy is not so unique.
The Continuous Present in Ozu Yasujiro's Late Spring
Authors: Pigott Michael 
Published: July 2008

AbstractOzu Yasujiro's Late Spring uses time in a very distinct and compelling way. It effectively tenses the image as the 'continuous present'. Through the use of unconventional (by Western standards) editing strategies and cinematography, the characteristic durations of objects, places and people are foregrounded, and a peculiarly affecting sense of time is created. This paper constitutes an attempt to understand the way in which this specific sense of time is constructed in the film, by analyzing the editing, mise-en-scène, and sound of two scenes in very close detail.