bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Syncytial Virus Influences NF-κB-Dependent Gene Expression through a Novel Pathway Involving MAP3K14/NIK Expression and Nuclear Complex Formation with NF-κB2
Authors: Choudhary Sanjeev , Boldogh Steve , Garofalo Roberto , Jamaluddin Mohammad , Brasier Allan R. 
Published: July 2005

ABSTRACT

A member of the
Paramyxoviridae
family of RNA viruses, respiratory syncytial virus (RSV), is a leading cause of epidemic respiratory tract infection in children. In children, RSV primarily replicates in the airway mucosa, a process that alters epithelial cell chemokine expression, thereby inducing airway inflammation. We investigated the role of the mitogen-activated protein kinase kinase kinase 14/NF-κB-inducing kinase (NIK) in the activation of NF-κB-dependent genes in alveolus-like A549 cells. RSV infection induces a time dependent increase of NIK mRNA and protein expression that peaks 12 to 24 h after viral exposure. Immunoprecipitation kinase assays indicate that NIK kinase activity is activated even more rapidly (within 6 h of RSV adsorption) associated with an endogenous ∼50-kDa NF-κB2 substrate. Because NIK associates with IKKα to mediate processing of the 100-kDa NF-κB2 precursor into its 52-kDa DNA binding isoform (“p52”), the effects of RSV on NIK complex formation with IKKα and NF-κB2 were determined by coimmunoprecipitation assay. We find that NIK, IKKα, and both 100 kDa- and 52-kDa NF-κB2 isoforms strongly complex 15 h after exposure to RSV at times subsequent to NIK kinase activation. Western immunoblot and microaffinity DNA pull-down assays showed a parallel increase in nuclear translocation and DNA binding of the NF-κB2-Rel B complex. Interestingly, we make the novel observations that NIK also transiently translocates into the nucleus complexed with 52-kDa NF-κB2. Small interfering RNA-mediated NIK “knock-down” blocked RSV-inducible 52-kDa NF-κB2 processing and interfered with the early activation of a subset of NF-κB-dependent genes, indicating the importance of this activation pathway in the genomic NF-κB response to RSV. Together, these data indicate that RSV infection rapidly activates the noncanonical NF-κB activation pathway prior to the more potent canonical pathway activation. This appears to be through a novel mechanism involving induction of NIK kinase activity, expression, and nuclear translocation of a ternary complex with IKKα and processed NF-κB2.
Novel Human Monoclonal Antibody Combination Effectively Neutralizing Natural Rabies Virus Variants and Individual In Vitro Escape Mutants
Authors: Bakker Alexander B. H. , Marissen Wilfred E. , Kramer R. Arjen , Rice Amy B. , Weldon William C. , Niezgoda Michael , Hanlon Cathleen A. , Thijsse Sandra , Backus Harold H. J. , de Kruif John , Dietzschold Bernhard , Rupprecht Charles E. , Goudsmit Jaap 
Published: July 2005

ABSTRACT
The need to replace rabies immune globulin (RIG) as an essential component of rabies postexposure prophylaxis is widely acknowledged. We set out to discover a unique combination of human monoclonal antibodies (MAbs) able to replace RIG. Stringent criteria concerning neutralizing potency, affinity, breadth of neutralization, and coverage of natural rabies virus (RV) isolates and in vitro escape mutants were set for each individual antibody, and the complementarities of the two MAbs were defined at the onset. First, we identified and characterized one human MAb (CR57) with high in vitro and in vivo neutralizing potency and a broad neutralization spectrum. The linear antibody binding site was mapped on the RV glycoprotein as antigenic site I by characterizing CR57 escape mutants. Secondly, we selected using phage display a complementing antibody (CR4098) that recognized a distinct, nonoverlapping epitope (antigenic site III), showed similar neutralizing potency and breadth as CR57, and neutralized CR57 escape mutants. Reciprocally, CR57 neutralized RV variants escaping CR4098. Analysis of glycoprotein sequences of natural RV isolates revealed that the majority of strains contain both intact epitopes, and the few remaining strains contain at least one of the two. In vitro exposure of RV to the combination of CR57 and CR4098 yielded no escape mutants. In conclusion, a novel combination of human MAbs was discovered suitable to replace RIG.
Contributions of the Viral Genetic Background and a Single Amino Acid Substitution in an Immunodominant CD8+T-Cell Epitope to Murine Coronavirus Neurovirulence
Authors: MacNamara Katherine C. , Chua Ming Ming , Phillips Joanna J. , Weiss Susan R. 
Published: July 2005

ABSTRACTThe immunodominant CD8+T-cell epitope of a highly neurovirulent strain of mouse hepatitis virus (MHV), JHM, is thought to be essential for protection against virus persistence within the central nervous system. To test whether abrogation of this H-2Db-restricted epitope, located within the spike glycoprotein at residues S510 to 518 (S510), resulted in delayed virus clearance and/or virus persistence we selected isogenic recombinants which express either the wild-type JHM spike protein (RJHM) or spike containing the N514S mutation (RJHMN514S), which abrogates the response to S510. In contrast to observations in suckling mice in which viruses encoding inactivating mutations within the S510 epitope (epitope escape mutants) were associated with persistent virus and increased neurovirulence (Pewe et al., J Virol. 72:5912-5918, 1998), RJHMN514Swas not more virulent than the parental, RJHM, in 4-week-old C57BL/6 (H-2b) mice after intracranial injection. Recombinant viruses expressing the JHM spike, wild type or encoding the N514S substitution, were also selected in which background genes were derived from the neuroattenuated A59 strain of MHV. Whereas recombinants expressing the wild-type JHM spike (SJHM/RA59) were highly neurovirulent, A59 recombinants containing the N514S mutation (SJHMN514S/RA59) were attenuated, replicated less efficiently, and exhibited reduced virus spread in the brain at 5 days postinfection (peak of infectious virus titers in the central nervous system) compared to parental virus encoding wild-type spike. Virulence assays in BALB/c mice (H-2d), which do not recognize the S510 epitope, revealed that attenuation of the epitope escape mutants was not due to the loss of a pathogenic immune response directed against the S510 epitope. Thus, an intact immunodominant S510 epitope is not essential for virus clearance from the CNS, the S510 inactivating mutation results in decreased virulence in weanling mice but not in suckling mice, suggesting that specific host conditions are required for epitope escape mutants to display increased virulence, and the N514S mutation causes increased attenuation in the context of A59 background genes, demonstrating that genes other than that for the spike are also important in determining neurovirulence.
Suppressors of a Host Range Mutation in the Rabbitpox Virus Serpin SPI-1 Map to Proteins Essential for Viral DNA Replication
Authors: Luttge Benjamin G. , Moyer Richard W. 
Published: July 2005

ABSTRACT

The orthopoxvirus serpin SPI-1 is an intracellular serine protease inhibitor that is active against cathepsin G in vitro. Rabbitpox virus (RPV) mutants with deletions of the SPI-1 gene grow on monkey kidney cells (CV-1) but do not plaque on normally permissive human lung carcinoma cells (A549). This reduced-host-range (
hr
) phenotype suggests that SPI-1 may interact with cellular and/or other viral proteins. We devised a genetic screen for suppressors of SPI-1
hr
mutations by first introducing a mutation into SPI-1 (T309R) at residue P14 of the serpin reactive center loop. The SPI-1 T309R serpin is inactive as a protease inhibitor in vitro. Introduction of the mutation into RPV leads to the same restricted
hr
phenotype as deletion of the SPI-1 gene. Second-site suppressors were selected by restoration of growth of the RPV SPI-1 T309R
hr
mutant on A549 cells. Both intragenic and extragenic suppressors of the T309R mutation were identified. One novel intragenic suppressor mutation, T309C, restored protease inhibition by SPI-1 in vitro. Extragenic suppressor mutations were mapped by a new procedure utilizing overlapping PCR products encompassing the entire genome in conjunction with marker rescue. One suppressor mutation, which also rendered the virus temperature sensitive for growth, mapped to the DNA polymerase gene (E9L). Several other suppressors mapped to gene D5R, an NTPase required for DNA replication. These results unexpectedly suggest that the host range function of SPI-1 may be associated with viral DNA replication by an as yet unknown mechanism.
ERV3 and Related Sequences in Humans: Structure and RNA Expression
Authors: Andersson Ann-Catrin , Yun Zhihong , Sperber Göran O. , Larsson Erik , Blomberg Jonas 
Published: July 2005

ABSTRACT

The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral (HERV) sequence, owing to an
env
open reading frame (ORF) and placental RNA and protein expression. An analysis of the human genome demonstrated that ERV3 is one of a group of 41 highly related elements (ERV3-like HERVs) which use proline, isoleucine, or arginine tRNA in their primer binding sites. In addition to elements closely related to ERV3, the group included the previously known retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was separate from the related HERV-E elements. The ERV3-like elements are defective. The only element with an ORF among
gag
,
pro
,
pol
, and
env
genes was the
env
ORF of the original ERV3 locus. A search in dbEST revealed ERV3 RNA expression in placenta, skin, carcinoid tumor, and adrenal glands. Expression was also studied with newly developed real-time quantitative PCRs (QPCR) of ERV3 and HERV-E(4-1)
env
sequences. Results from a novel histone 3.3 RNA QPCR result served as the expression control. QPCR results for ERV3 were compatible with previously published results, with a stronger expression in adrenal gland and placenta than in 15 other human tissues. The expression of the envelope (
env
) of ERV3 at chromosome 7q11 was also studied by using stringent in situ hybridization. Expression was found in corpus luteum, testis, adrenal gland, Hassal's bodies in thymus, brown fat, pituitary gland, and epithelium of the lung. We conclude that ERV3
env
is most strongly expressed in adrenal and sebaceous glands as well as in placenta.
Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness
Authors: Lo Mindy S. , Brazas Robert M. , Holtzman Michael J. 
Published: July 2005

ABSTRACTRespiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion.
Comparison of the Genetic Recombination Rates of Human Immunodeficiency Virus Type 1 in Macrophages and T Cells
Authors: Chen Jianbo , Rhodes Terence D. , Hu Wei-Shau 
Published: July 2005

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) exhibits a high level of genetic variation generated by frequent mutation and genetic recombination during reverse transcription. We have measured HIV-1 recombination rates in T cells in one round of virus replication. It was recently proposed that HIV-1 recombines far more frequently in macrophages than in T cells. In an attempt to delineate the mechanisms that elevate recombination, we measured HIV-1 recombination rates in macrophages at three different marker distances. Surprisingly, the recombination rates were comparable in macrophages and in T cells. In addition, we observed similar recombination rates in two monocytic cell lines regardless of the differentiation status. These results indicate that HIV-1 undergoes similar numbers of recombination events when infecting macrophages and T cells.
Herpes Simplex Virus Type 1 Single-Strand DNA Binding Protein ICP8 Enhances the Nuclease Activity of the UL12 Alkaline Nuclease by Increasing Its Processivity
Authors: Reuven Nina Bacher , Weller Sandra K. 
Published: July 2005

ABSTRACT

UL12 is a 5′- to 3′-exonuclease encoded by herpes simplex virus type 1 (HSV-1) which degrades single- and double-stranded DNA. UL12 and the single-strand DNA binding protein ICP8 mediate a strand exchange reaction. We found that ICP8 inhibited UL12 digestion of single-stranded DNA but stimulated digestion of double-stranded DNA threefold. The stimulatory effect of ICP8 was independent of a strand exchange reaction; furthermore, the effect was specific to ICP8, as it could not be reproduced by
Escherichia coli
single-stranded DNA binding protein. The effect of ICP8 on the rate of UL12 double-stranded DNA digestion is attributable to an increase in processivity in the presence of ICP8.
Informed consent, participation in, and withdrawal from a population based cohort study involving genetic analysis
Authors: Matsui K , Kita Y , Ueshima H 
Published: July 2005

Objective:Population based cohort studies involving genetic research have been initiated in several countries. However, research published to date provides little information on the willingness of the general population to participate in such studies. Furthermore, there is a need to discover the optimal methods for acquiring fully informed consent from the general population. We therefore examined the results of a population based genetic cohort study to identify the factors affecting the participation rate by members of the general public and also specifically to examine the impact of different consent procedures on the rate of participation by prospective candidates and their subsequent withdrawal rate from the study.Design:Descriptive analyses.Setting and participants:The study evaluated two non-genetic subcohorts comprising 3166 people attending for a health checkup during 2002, and two genetic subcohorts comprising 2195 people who underwent a checkup during 2003.Main outcome measurements:Analysis endpoints were differences in participation rates between the non-genetic and genetic subcohorts, differences between providing non-extensive and extensive preliminary information, and changes in participation status between baseline and at 6 months.Results:Participation rates in the genetic subcohorts were 4·7–9·3% lower than those in the non-genetic subcohorts. The odds ratios (OR) of participation in genetic research were between 0·60 and 0·77, and the OR for withdrawal from the research was over 7·70; providing preliminary extensive information about genetic research reduced the withdrawal risks (OR 0·15 for all dependent variables) but worsened participation rates (OR 0·63–0·74).Conclusions:The general population responded sceptically towards genetic research. It is crucial that genetic researchers utilise an informative and educational consent process worthy of public trust.
Common Visions: In fluences of the Nisga'a Final Agreement on Lheidli T'enneh Negotiations in the BC Treaty Process
Authors: Krehbiel Richard 
Published: July 2005

AbstractRati fication of the Nisga'a Final Agreement has had an inevitable effect on the conduct of negotiations for First Nations in the British Columbia treaty process. These effects include a general sense of encouragement set against British Columbia's historical denial of First Nation interests, direct support of negotiations, litigation and coping with special interest group resistance to aboriginal progress. This article examines these in fluences in the context of negotiations being conducted by the Lheidli T'enneh First Nation in the Northern interior of British Columbia.
Our Treaty, Our Inherent Right to Self-Government: An Overview of the Nisga'a Final Agreement
Authors: Allen Edward 
Published: July 2005

AbstractThis article provides an overview of the Nisga'a Final Agreement (the Treaty), the first comprehensive claims agreement to include recognition of the inherent right of self-government and constitutional protection of this right. This right is of long history to the Nisga'a people (as evidenced by a brief review of the 1913 Petition), to the Nisga'a Final Agreement, and, ultimately, to our defence of the Treaty against the legal challenge to the self-government provisions by Gordon Campbell (then leader of the opposition in the British Columbia legislature, now Premier of BC). It is this consistent thread in respect of the importance of self-government which has defined the Nisga'a approach to treaty making with the federal and provincial governments. Moreover, the Treaty also represents a unique example of legal pluralism whereby a distinct system of law making and governance successfully and peacefully operates within and in accordance with the constitutional framework of the Canadian State.
Networked Acoustic Modems for Real-Time Data Telemetry from Distributed Subsurface Instruments in the Coastal Ocean: Application to Array of Bottom-Mounted ADCPs
Authors: Codiga Daniel L. , Rice Joseph A. , Baxley Paul A. , Hebert David 
Published: July 2005

AbstractThrough the winter and spring of 2002, networked acoustic modems demonstrated real-time wireless data telemetry from an array of bottom-mounted acoustic Doppler current profilers (ADCPs) on the inner continental shelf 20–60 m deep off of Montauk Point, New York. To achieve typical temporal and spatial sampling needs for data assimilative numerical modeling, the array spanned 10 km × 10 km and transmitted data each ∼2 h. Network nodes included five sensors, each an ADCP with acoustic modem housed in a trawl-resistant bottom frame; five repeaters that are individual acoustic modems on near-bottom taut-wire moorings; and two gateways, each a buoy with a subsurface acoustic modem and topside cellular modem allowing for two-way communication with the shore. Deliveries from an ADCP adjacent to the gateway buoy were more than 97% successful through both winter and spring. Deliveries from ADCPs 5 km from the gateway averaged 25% (86%) reliability in winter (spring). Winter performance degrades because of upward-refracting sound speed profiles that limit direct acoustic paths, and strong winds that disrupt sea surface reflectivity and increase ambient noise. Reliability improved up to 36% due to the receive-all gateway mode, and more than doubled for certain node pairs due to a handshake protocol incorporating an automatic repeat request. Shore-based network control demonstrated adaptive sampling by changing ADCP vertical and temporal resolution, and network data path rerouting in response to unplanned events, such as trawling impacts. Networked acoustic modems are well suited for coastal ocean-observing systems, particularly at sites such as this where seafloor cables and surface buoys are vulnerable to fishing and shipping activities.
Chinese concepts of mental health
Authors: Yip Kam-shing 
Published: July 2005

English In terms of the traditional Chinese medical, Confucian and Taoist schools of thought, Chinese concepts of mental health have a strong impact. All these have significant implications for culturally sensitive or culturally competent social work practice in Chinese communities. French Les concepts chinois de santé mentale, issus des écoles de pensée médicale chinoise traditionnelle, confucianiste et taoiste, ont un fort impact sur la santé mentale de la population chinoise. Ces écoles de pensée ont une implication significative pour le travail social compétent et culturellement sensible dans les communautés chinoises. Spanish De acuerdo a la medicina tradicional china y a las escuelas de pensamiento Confucianas y Taoi¨stas, los conceptos chinos sobre salud mental tienen un fuerte impacto en la salud mental de la población. Ello tiene implicaciones significativas sobre la cultura de sensibilidad o la cultura competente de la práctica del trabajo social con las comunidades chinas.
Task-centered groupwork
Authors: Lo T. Wing 
Published: July 2005

English This article describes the transferability of task-centered casework to group-work in Hong Kong. While task-centered casework helps individual clients to solve their personal problems, its short intervention period may limit the development of intensive social support and treatment in groups. The article summarizes social workers’ experiences in reconciling this conflict. French Cet article décrit le processus de transfert, à Hong Kong, de cas individuels de travail orienté vers la tache en travail de groupe. Si l'intervention individuelle orientée vers la tâche aide les clients à solutionner leurs problèmes personnels, son intervention de courte durée risque de limiter le développement de traitement et de soutien social intensif de groupe. Le texte résume les expériences de travailleurs sociaux dans un effort de réconciliation de ce conflit. Spanish Este artículo describe la transferibilidad del trabajo de caso centrado en la tarea al trabajo con grupos en Hong Kong. Mientras que el trabajo de caso centrado en la tarea ayuda a los clientes individuales a resolver sus problemas personales, su corto período de intervención puede limitar el desarrollo del apoyo social intensivo y el tratamiento en grupos. El artículo resume las experiencias de trabajadores sociales para resolver este conflicto.
Mental Health Social Work and the Troubles in Northern Ireland
Authors: Campbell Jim , Mccrystal Patrick 
Published: July 2005

Summary: During the last decade increasing attention has been paid to the impact of the Troubles1 on social work in Northern Ireland. In this paper, the authors describe the first survey used to test some of the assumptions which exist in the literature. An 87-item questionnaire was applied to a range of social work staff currently working in, or associated with, mental health settings. One hundred and one questionnaires were returned: it is estimated that this represented over 70 per cent of mental health social workers in Northern Ireland. Findings: The design of the questionnaire elicited both qualitative and quantitative data. The findings reveal a workforce with complex religious and national identities and many of the respondents have experienced relatively high levels of Troubles-related incidents whilst carrying out their duties in a variety of organizational and geographical settings. High proportions of respondents received minimal agency support and training to equip them to deal with Troubles-related problems faced by them during this period. Applications: The authors conclude that the profession and employing agencies should pay greater attention to past and present effects of the Troubles on social work practice and develop appropriate strategies for supporting, training and resourcing staff in this neglected area.