bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐1‐induced neurotoxicity is mediated by glia and requires caspase activation and free radical release
Authors: Thornton Peter , Pinteaux Emmanuel , Gibson Rosemary M. , Allan Stuart M. , Rothwell Nancy J. 
Published: May 2006

AbstractInterleukin (IL)‐1 expression is induced rapidly in response to diverse CNS insults and is a key mediator of experimentally induced neuronal injury. However, the mechanisms of IL‐1‐induced neurotoxicity are unknown. The aim of the present study was to examine the toxic effects of IL‐1 on rat cortical cell cultures. Treatment with IL‐1β did not affect the viability of pure cortical neurones. However, IL‐1 treatment of cocultures of neurones with glia or purified astrocytes induced caspase activation resulting in neuronal death. Neuronal cell death induced by IL‐1 was prevented by pre‐treatment with the IL‐1 receptor antagonist, the broad spectrum caspase inhibitor Boc‐Asp‐(OMe)‐CH2F or the antioxidant α‐tocopherol. The NMDA receptor antagonist dizolcipine (MK‐801) attenuated cell death induced by low doses of IL‐1β but the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid receptor antagonist 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(F)quinoxaline (NBQX) had no effect. Inhibition of inducible nitric oxide synthase with N(ω)‐nitro‐l‐arginine methyl ester had no effect on neuronal cell death induced by IL‐1β. Thus, IL‐1 activates the IL‐1 type 1 receptor in astrocytes to induce caspase‐dependent neuronal death, which is dependent on the release of free radicals and may contribute to neuronal cell death in CNS diseases.
Regulation of ApC/EBP mRNA by the Aplysia AU‐rich element‐binding protein, ApELAV, and its effects on 5‐hydroxytryptamine‐induced long‐term facilitation
Authors: Yim Se‐Jeong , Lee Yong‐Seok , Lee Jin‐A , Chang Deok‐Jin , Han Jin‐Hee , Kim Hyoung , Park Hyungju , Jun Heejung , Kim V. Narry , Kaang Bong‐Kiun 
Published: May 2006

Abstract Aplysia CCAAT enhancer‐binding protein (ApC/EBP), a key molecular switch in 5‐hydroxytryptamine (5‐HT)‐induced long‐term facilitation of Aplysia, is quickly and transiently expressed in response to a 5‐HT stimulus, but the mechanism underlying this dynamic expression profile remains obscure. Here, we report that the dynamic expression of ApC/EBP during long‐term facilitation is regulated at the post‐transcriptional level by AU‐rich element (ARE)‐binding proteins. We found that the 3′UTR of ApC/EBP mRNA contains putative sequences for ARE, which is a representative post‐transcriptional cis‐acting regulatory element that modulates the stability and/or the translatability of a distinct subset of labile mRNAs. We cloned the Aplysia homologue of embryonic lethal abnormal visual system homologue (ELAV/Hu) protein, one of the best‐studied RNA‐binding proteins that associate with ARE, and elucidated the involvement of Aplysia ELAV/Hu protein in ApC/EBP gene expressional regulation. Cloned Aplysia ELAV/Hu protein, Aplysia embryonic lethal abnormal visual system (ApELAV), bound to an AU‐rich region within the 3′UTR of ApC/EBP mRNA. Additionally, ApELAV controlled the expression of ApC/EBP 3′UTR‐containing reporter gene by functioning as a stability‐enhancing factor. In particular, 5‐HT‐induced long‐term facilitation was impaired when the AU‐rich region within the 3′UTR of ApC/EBP was over‐expressed, which suggests the significance of this region in 5‐HT‐induced ApC/EBP expression, and in the resultant formation of long‐term facilitation. Our results imply that the Aplysia ARE‐binding protein, ApELAV, can regulate ApC/EBP gene expression at the mRNA level, and accordingly, ARE‐mediated post‐transcriptional mechanism may serve a crucial function in regulating the expression of ApC/EBP in response to a 5‐HT stimulus.
Ethics, Policy, and Educational Issues in Genetic Testing
Authors: Williams Janet K. , Skirton Heather , Masny Agnes 
Published: May 2006

Purpose: Analyze ethics, public policy, and education issues that arise in the United States (US) and the United Kingdom (UK) when genomic information acquired as a result of genetic testing is introduced into healthcare services.
Organizing Construct: Priorities in the Ethical, Legal, and Social Issues Research Program include privacy, integration of genetic services into clinical health care, and educational preparation of the nursing workforce. These constructs are used to examine health policies in the US and UK, and professional interactions of individuals and families with healthcare providers.
Findings: Individual, family, and societal goals may conflict with current healthcare practices and policies when genetic testing is done. Current health policies do not fully address these concerns. Unresolved issues include protection of privacy of individuals while considering genetic information needs of family members, determination of appropriate monitoring of genetic tests, addressing genetic healthcare discrepancies, and assuring appropriate nursing workforce preparation.
Conclusions: Introduction of genetic testing into health care requires that providers are knowledgeable regarding ethical, policy, and practice issues in order to minimize risk for harm, protect the rights of individuals and families, and consider societal context in the management of genetic test results. Understanding of these issues is a component of genetic nursing competency that must be addressed at all levels of nursing education.
Concept Analysis of Good Death in the Japanese Community
Authors: Hattori Keiko , McCubbin Marilyn A. , Ishida Dianne N. 
Published: May 2006

Purpose: To describe the meaning of a good death in the Japanese community.
Organizing Framework: Rogers's (2000) concept analysis strategy.
Methods: A review of the literature was done in March 2004, with a focus on older adults' experiences of good death in the Japanese community; “good death” was the subject heading or key words; and literature was published in English or Japanese.
Findings: Attributes of a good death include sociocultural norms, personal experiences, and continuous process. The person's experience of dying, the social context, the patient's autonomy and control over the dying process, and quality of end‐of‐life health care are the consequences of the concept. When good death occurs, it leads to family satisfaction, positive bereavement process, and work satisfaction for healthcare professionals.
Conclusions: Integration of findings from the concept analysis and field research results in more accurate understanding of good death. Knowing the individual concept of good death enables nurses to provide culturally competent care to achieve an optimum death experience for both patients and families.
Prejudice and schizophrenia: a review of the ‘mental illness is an illness like any other’ approach
Authors: Read J. , Haslam N. , Sayce L. , Davies E. 
Published: May 2006

Objective:  Many anti‐stigma programmes use the ‘mental illness is an illness like any other’ approach. This review evaluates the effectiveness of this approach in relation to schizophrenia.Method:  The academic literature was searched, via PsycINFO and MEDLINE, to identify peer‐reviewed studies addressing whether public espousal of a biogenetic paradigm has increased over time, and whether biogenetic causal beliefs and diagnostic labelling are associated with less negative attitudes.Results:  The public, internationally, continues to prefer psychosocial to biogenetic explanations and treatments for schizophrenia. Biogenetic causal theories and diagnostic labelling as ‘illness’, are both positively related to perceptions of dangerousness and unpredictability, and to fear and desire for social distance.Conclusion:  An evidence‐based approach to reducing discrimination would seek a range of alternatives to the ‘mental illness is an illness like any other’ approach, based on enhanced understanding, from multi‐disciplinary research, of the causes of prejudice.
Jane Austen and the Public Sphere
Authors: Jones Chris 
Published: May 2006

AbstractWithout renouncing his speculations on the historical emergence of the idea of the public sphere, Habermas’s later writings explore the potential of language itself, when oriented towards reaching understanding, to sustain public sphere values. Stressing transformation rather than structure, he sees such intersubjective understandings as the means by which social norms are maintained and critiqued. The works of Austen and her family show a similar eighteenth‐century faith that society can be reformed by social means. Austen’s novels criticise restricted views of who constitutes society, use a common language, go beyond politeness in robust argumentation, and mediate between private and public in ways that answer to Habermas’s ideas. While the values of the public sphere are used to satirically critique society’s values and practices, Austen resists polarised antagonisms and Romantic pessimism, granting authority neither to unexamined traditions, professionalised ‘reason’ nor one class. Conversation is allowed to frame problems and, in the ‘utopian’ conclusions granted to principal characters, suggest solutions. Habermas might not deal adequately with non‐verbal communication, but his concept of communicative rationality can be usefully applied to major aspects of Austen’s work.
The Herpesvirus Capsid Surface Protein, VP26, and the Majority of the Tegument Proteins Are Dispensable for Capsid Transport toward the Nucleus
Authors: Antinone Sarah E. , Shubeita George T. , Coller Kelly E. , Lee Joy I. , Haverlock-Moyns Sarah , Gross Steven P. , Smith Gregory A. 
Published: May 2006

ABSTRACT
Upon entering a cell, alphaherpesvirus capsids are transported toward the minus ends of microtubules and ultimately deposit virus DNA within the host nucleus. The virus proteins that mediate this centripetal transport are unknown but are expected to be either viral tegument proteins, which are a group of capsid-associated proteins, or a surface component of the capsid itself. Starting with derivatives of pseudorabies virus that encode a fluorescent protein fused to a structural component of the virus, we have made a collection of 12 mutant viruses that lack either the VP26 capsid protein or an individual tegument protein. Using live-cell fluorescence microscopy, we tracked individual virus particles in axons following infection of primary sensory neurons. Quantitative analysis of the VP26-null virus indicates that this protein plays no observable role in capsid transport. Furthermore, viruses lacking tegument proteins that are nonessential for virus propagation in cell culture were also competent for axonal transport. These results indicate that a protein essential for viral propagation mediates transport of the capsid to the nucleus.
The Cytoplasmic Tail of the Influenza A Virus M2 Protein Plays a Role in Viral Assembly
Authors: Iwatsuki-Horimoto Kiyoko , Horimoto Taisuke , Noda Takeshi , Kiso Maki , Maeda Junko , Watanabe Shinji , Muramoto Yukiko , Fujii Ken , Kawaoka Yoshihiro 
Published: May 2006

ABSTRACT
The viral replication cycle concludes with the assembly of viral components to form progeny virions. For influenza A viruses, the matrix M1 protein and two membrane integral glycoproteins, hemagglutinin and neuraminidase, function cooperatively in this process. Here, we asked whether another membrane protein, the M2 protein, plays a role in virus assembly. The M2 protein, comprising 97 amino acids, possesses the longest cytoplasmic tail (54 residues) of the three transmembrane proteins of influenza A viruses. We therefore generated a series of deletion mutants of the M2 cytoplasmic tail by reverse genetics. We found that mutants in which more than 22 amino acids were deleted from the carboxyl terminus of the M2 tail were viable but grew less efficiently than did the wild-type virus. An analysis of the virions suggested that viruses with M2 tail deletions of more than 22 carboxy-terminal residues apparently contained less viral ribonucleoprotein complex than did the wild-type virus. These M2 tail mutants also differ from the wild-type virus in their morphology: while the wild-type virus is spherical, some of the mutants were filamentous. Alanine-scanning experiments further indicated that amino acids at positions 74 to 79 of the M2 tail play a role in virion morphogenesis and affect viral infectivity. We conclude that the M2 cytoplasmic domain of influenza A viruses plays an important role in viral assembly and morphogenesis.
Human Cytomegalovirus Attenuates Interleukin-1β and Tumor Necrosis Factor Alpha Proinflammatory Signaling by Inhibition of NF-κB Activation
Authors: Jarvis Michael A. , Borton Jamie A. , Keech Amy M. , Wong John , Britt William J. , Magun Bruce E. , Nelson Jay A. 
Published: May 2006

ABSTRACTViral infection is associated with a vigorous inflammatory response characterized by cellular infiltration and release of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). In the present study, we identified a novel function of human cytomegalovirus (HCMV) that results in inhibition of IL-1 and TNF-α signaling pathways. The effect on these pathways was limited to cells infected with the virus, occurred at late times of infection, and was independent of cell type or virus strain. IL-1 and TNF-α signaling pathways converge at a point upstream of NF-κB activation and involve phosphorylation and degradation of the NF-κB inhibitory molecule IκBα. The HCMV inhibition of IL-1 and TNF-α pathways corresponded to a suppression of NF-κB activation. Analysis of IκBα phosphorylation and degradation suggested that HCMV induced two independent blocks in NF-κB activation, which occurred upstream from the point of convergence of the IL-1 and TNF-α pathways. We believe that the ability of HCMV to inhibit these two major proinflammatory pathways reveals a critical aspect of HCMV biology, with possible importance for immune evasion, as well as establishment of infection in cell types persistently infected by this virus.
Rapid Upregulation of Interferon-Regulated and Chemokine mRNAs upon Injection of 108International Units, but Not Lower Doses, of Adenoviral Vectors into the Brain
Authors: Zirger Jeffrey M. , Barcia Carlos , Liu Chunyan , Puntel Mariana , Mitchell Ngan , Campbell Iain , Castro Maria , Lowenstein Pedro R. 
Published: May 2006

ABSTRACTThe innate immune response, characterized by the rapid induction of proinflammatory genes, plays an important role in immune responses to viral vectors utilized in gene therapy. We demonstrate that several innate proinflammatory mRNAs, i.e., those coding for the interferon (IFN)-regulated proteins interferon regulatory factor 1, 2′,5′-oligoadenylate synthetase, and double-stranded-RNA-dependent protein kinase as well as those coding for the chemokines RANTES, IFN-γ-inducible protein 10, and monocyte chemoattractant protein 1, were all increased in a statistically significant manner in response to 1 × 108IU, but not lower doses, of a first-generation adenovirus injected into the naïve brain. This indicates the presence of a threshold dosage of adenovirus needed to elicit an acute innate inflammatory response.
Prediction and Identification of Herpes Simplex Virus 1-Encoded MicroRNAs
Authors: Cui Can , Griffiths Anthony , Li Guanglin , Silva Lindsey M. , Kramer Martha F. , Gaasterland Terry , Wang Xiu-Jie , Coen Donald M. 
Published: May 2006

ABSTRACT

MicroRNAs (miRNAs) are key regulators of gene expression in higher eukaryotes. Recently, miRNAs have been identified from viruses with double-stranded DNA genomes. To attempt to identify miRNAs encoded by herpes simplex virus 1 (HSV-1), we applied a computational method to screen the complete genome of HSV-1 for sequences that adopt an extended stem-loop structure and display a pattern of nucleotide divergence characteristic of known miRNAs. Using this method, we identified 11 HSV-1 genomic loci predicted to encode 13 miRNA precursors and 24 miRNA candidates. Eight of the HSV-1 miRNA candidates were predicted to be conserved in HSV-2. The precursor and the mature form of one HSV-1 miRNA candidate, which is encoded ∼450 bp upstream of the transcription start site of the latency-associated transcript (LAT), were detected during infection of Vero cells by Northern blot hybridization. These RNAs, which behave as late gene products, are not predicted to be conserved in HSV-2. Additionally, small RNAs, including some that are roughly the expected size of precursor miRNAs, were detected using probes for miRNA candidates derived from sequences encoding the 8.3-kilobase LAT, from sequences complementary to

U
L

15
mRNA, and from the region between
ICP4
and

U
S

1
. However, no species the size of typical mature miRNAs were detected using these probes. Three of these latter miRNA candidates were predicted to be conserved in HSV-2. Thus, HSV-1 encodes at least one miRNA. We hypothesize that HSV-1 miRNAs regulate viral and host gene expression.
High-Efficiency System for the Construction of Adenovirus Vectors and Its Application to the Generation of Representative Adenovirus-Based cDNA Expression Libraries
Authors: Hillgenberg Moritz , Hofmann Christian , Stadler Herbert , Löser Peter 
Published: May 2006

ABSTRACT

We here describe a convenient system for the production of recombinant
adenovirus vectors and its use for the construction of a representative
adenovirus-based cDNA expression library. The system is based on direct
site-specific insertion of transgene cassettes into a replicating donor
virus. The transgene is inserted into a donor plasmid containing the
viral 5′ inverted terminal repeat, the complete viral packaging
signal, and a single
loxP
site. The plasmid is then
transfected into a Cre recombinase-expressing packaging cell line that
has been infected with a donor virus containing a partially deleted
packaging signal flanked by
loxP
sites. Cre recombinase, by
two steps of action, sequentially catalyzes the generation of a
nonpackageable donor virus acceptor substrate and the generation of the
desired recombinant adenovirus vector. Due to its growth impairment,
residual donor virus can efficiently be counterselected during
amplification of the recombinant adenovirus vector. By using this
adenovirus construction system, a plasmid-based human liver cDNA
library was converted by a single step into an adenovirus-based cDNA
expression library with about 10
6
independent adenovirus
clones. The high-titer purified library was shown to contain about 44%
of full-length cDNAs with an average insert size of 1.3 kb. cDNAs of a
gene expressed at a high level (human α
1
-antitrypsin) and a gene expressed at a relatively
low level (human coagulation factor IX) in human liver were isolated
from the adenovirus-based library using an enzyme-linked immunosorbent
assay-based screening procedure.
Gag Regulates Association of Human Immunodeficiency Virus Type 1 Envelope with Detergent-Resistant Membranes
Authors: Bhattacharya Jayanta , Repik Alexander , Clapham Paul R. 
Published: May 2006

ABSTRACT
Assembly of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein on budding virus particles is important for efficient infection of target cells. In infected cells, lipid rafts have been proposed to form platforms for virus assembly and budding. Gag precursors partly associate with detergent-resistant membranes (DRMs) that are believed to represent lipid rafts. The cytoplasmic domain of the envelope gp41 usually carries palmitate groups that were also reported to confer DRM association. Gag precursors confer budding and carry envelope glycoproteins onto virions via specific Gag-envelope interactions. Thus, specific mutations in both the matrix domain of the Gag precursor and gp41 cytoplasmic domain abrogate envelope incorporation onto virions. Here, we show that HIV-1 envelope association with DRMs is directly influenced by its interaction with Gag. Thus, in the absence of Gag, envelope fails to associate with DRMs. A mutation in the p17 matrix (L30E) domain in Gag (Gag L30E) that abrogates envelope incorporation onto virions also eliminated envelope association with DRMs in 293T cells and in the T-cell line, MOLT 4. These observations are consistent with a requirement for an Env-Gag interaction for raft association and subsequent assembly onto virions. In addition to this observation, we found that mutations in the gp41 cytoplasmic domain that abrogated envelope incorporation onto virions and impaired infectivity of cell-free virus also eliminated envelope association with DRMs. On the basis of these observations, we propose that Gag-envelope interaction is essential for efficient envelope association with DRMs, which in turn is essential for envelope budding and assembly onto virus particles.
Inhibition of DNA Replication of Human Papillomavirus by Artificial Zinc Finger Proteins
Authors: Mino Takashi , Hatono Takeaki , Matsumoto Naoki , Mori Tomoaki , Mineta Yusuke , Aoyama Yasuhiro , Sera Takashi 
Published: May 2006

ABSTRACT

Recently,
we demonstrated that plant DNA virus replication was inhibited in
planta by using an artificial zinc finger protein (AZP) and created
AZP-based transgenic plants resistant to DNA virus infection. Here we
apply the AZP technology to the inhibition of replication of a
mammalian DNA virus, human papillomavirus type 18 (HPV-18). Two AZPs,
designated AZP
HPV
-1 and AZP
HPV
-2, were designed
by using our nondegenerate recognition code table and were constructed
to block binding of the HPV-18 E2 replication protein to the
replication origin. Both of the newly designed AZPs had much higher
affinities towards the replication origin than did the E2 protein, and
they efficiently blocked E2 binding in vitro. In transient replication
assays, both AZPs inhibited viral DNA replication, especially
AZP
HPV
-2, which reduced the replication level to
approximately 10%. We also demonstrated in transient replication
assays, using plasmids with mutant replication origins, that
AZP
HPV
-2 could precisely recognize the replication origin in
mammalian cells. Thus, it was demonstrated that the AZP technology
could be applied not only to plant DNA viruses but also to mammalian
DNA
viruses.
Inhibition of the NF-κB Pathway by Varicella-Zoster Virus In Vitro and in Human Epidermal Cells In Vivo
Authors: Jones Jeremy O. , Arvin Ann M. 
Published: May 2006

ABSTRACTVaricella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. Using human cellular DNA microarrays, we found that many nuclear factor kappa B (NF-κB)-responsive genes were down-regulated in VZV-infected fibroblasts, suggesting that VZV infection inhibited the NF-κB pathway. The activation of this pathway causes a cellular antiviral response, including the production of alpha/beta interferon, cytokines, and other proteins that restrict viral infection. In these experiments, we demonstrated that VZV interferes with NF-κB activation in cultured fibroblasts and in differentiated epidermal cells in skin xenografts of SCIDhu mice infected in vivo. VZV infection of fibroblasts caused a transient nuclear translocation of p50 and p65, the canonical NF-κB family members. In a process that was dependent upon the presence of infectious VZV, these proteins rapidly became sequestered in the cytoplasm of VZV-infected cells. Exclusion of NF-κB proteins from nuclei was associated with the continued presence of IκBα, which binds p50 and p65 and prevents their nuclear accumulation. IκBα levels did not diminish even though the protein became phosphorylated and ubiquitinated, as determined based on detection of the characteristic high-molecular-weight form of the protein, and the 26S proteasome remained functional in VZV-infected cells. VZV infection also inhibited the characteristic degradation of IκBα that is induced by exposure of fibroblasts to tumor necrosis factor alpha. As expected, herpes simplex virus 1 caused the persistent nuclear translocation of NF-κB proteins, which has been shown to facilitate its replication, whereas VZV infection progressed without persistent NF-κB nuclear localization. We suggest that VZV has evolved a mechanism to limit host cell antiviral defenses by sequestering NF-κB proteins in the cytoplasm, a strategy that appears to be unique among the herpesviruses.