bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction pathways
Authors: Ravni Aurélia , Bourgault Steve , Lebon Alexis , Chan Philippe , Galas Ludovic , Fournier Alain , Vaudry Hubert , Gonzalez Bruno , Eiden Lee E. , Vaudry David 
Published: May 2006

AbstractPituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are closely related members of the secretin superfamily of neuropeptides expressed in both the brain and peripheral nervous system, and they exhibit neurotrophic and neurodevelopmental effectsin vivo. Like the index member of the Trk receptor ligand family, nerve growth factor (NGF), PACAP promotes the differentiation of PC12 cells, a well‐established cell culture model, to investigate neuronal differentiation, survival and function. Stimulation of catecholamine secretion and enhanced neuropeptide biosynthesis are effects exerted by PACAP at the adrenomedullary synapsein vivoand on PC12 cellsin vitrothrough stimulation of the specific PAC1 receptor. Induction of neuritogenesis, growth arrest, and promotion of cell survival are effects of PACAP that occur in developing cerebellar, hippocampal and cortical neurons, as well as in the more tractable PC12 cell model. Study of the mechanisms through which PACAP exerts its various effects on cell growth, morphology, gene expression and survival, i.e. its actions as a neurotrophin, in PC12 cells is the subject of this review. The study of neurotrophic signalling by PACAP in PC12 cells reveals that multiple independent pathways are coordinated in the PACAP response, some activated by classical and some by novel or combinatorial signalling mechanisms.
Comparison of the binding pockets of two chemically unrelated allosteric antagonists of the mGlu5 receptor and identification of crucial residues involved in the inverse agonism of MPEP
Authors: Malherbe Pari , Kratochwil Nicole , Mühlemann Andreas , Zenner Marie‐Thérèse , Fischer Christophe , Stahl Martin , Gerber Paul R. , Jaeschke Georg , Porter Richard H. P. 
Published: May 2006

AbstractFenobam [N‐(3‐chlorophenyl)‐N′‐(4,5‐dihydro‐1‐methyl‐4‐oxo‐1H‐imidazole‐2‐yl)urea], a clinically validated non‐benzodiazepine anxiolytic, has been shown to be a potent and non‐competitive metabotropic glutamate (mGlu)‐5 receptor antagonist. In the present study, we have used the site‐directed mutagenesis coupled with three‐dimensional receptor‐based pharmacophore modelling to elucidate the interacting mode of fenobam within the seven‐transmembrane domain (7TMD) of mGlu5 receptor and its comparison with that of 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP), the prototype antagonist. The common residues involved in the recognition of MPEP and fenobam include Pro6543.36, Tyr6583.40, Thr7806.44, Trp7846.48, Phe7876.51, Tyr7916.55and Ala8097.47. The differentiating residues between both modulators' interacting modes are Arg6473.29, Ser6573.39and Leu7435.47. Our data suggest that these chemically unrelated mGlu5 antagonists act similarly, probing a functionally unique region of the 7TMD. Using [3H]inositol phosphates accumulation assay, we have also identified the critical residues involved in the inverse agonist effect of MPEP. The mutation W7846.48A completely blocked the inverse agonist activity of MPEP; two mutations F7876.51A and Y7916.55A, caused a drastic decrease in the MPEP inverse agonism. Furthermore, these three mutations led to an increased efficacy of quisqualate without having any effect on its potency. The fact that the residues Trp7846.48and Phe7876.51are essential equally in antagonism and inverse agonism effects emphasizes again the key role of these residues and the involvement of a common transmembrane network in receptor inactivation by MPEP.
Two Methods for Predicting Limited Life Expectancy in Nursing Homes
Authors: Wallace J. Brandon , Prevost Suzanne S. 
Published: May 2006

Purpose: To compare two methods of identifying nursing home residents with a life expectancy of 6 months or less.
Design: Secondary analysis of Minimum Data Set (MDS) assessment data from 111 U.S. nursing homes was used in two approaches to compare the prognostic value of each approach. MDS assessment data were collected during 2003 and 2004, and secondary analyses were completed during 2004 and 2005.
Methods: A bivariate analysis was used to identify variables associated with death within 6 months and a summative index was produced. Second, logistic regression was performed to develop a formula for calculating a Probability of Death score.
Findings: Both methods were reasonably sensitive in identifying dying residents. In the total sample of 21,852 residents, 17.5% died within 6 months. When the bivariate analysis and summative index were used, 51.1% of residents who had a score of 4 or higher died within 6 months, and residents who scored 10 or higher had an 80% mortality rate. With use of the logistic regression and Probability of Death scores, 52% of residents who had scores of 0.4 or higher died within 6 months, and residents who scored 0.9 or higher had an 80% mortality rate.
Conclusions: MDS assessment data, collected in all U.S. nursing homes, can be useful to increase the specificity of identifying terminal residents. These statistical methods have high and similar prognostic values, but the summative index is easier to understand. It also is more user‐friendly and could be incorporated into the nursing home assessment process with minimal additional training, and with no additional hardware or changes in software programming.
Sexual Assault Nurse Examiner (SANE) Program Goals and Patient Care Practices
Authors: Patterson Debra , Campbell Rebecca , Townsend Stephanie M. 
Published: May 2006

Purpose: To examine Sexual Assault Nurse Examiners (SANE) programs' goals and guiding philosophies and how they influence patient care practices for sexual assault victims.
Design: Data were collected from a national random sample of SANE to examine whether programs differed significantly in their goals and patient care practices.
Methods: Iterative cluster analysis was used to identify types of programs distinct in their stated goals.
Findings: Three types of emphasis in SANE programs were identified: (a) prosecution of cases as a primary goal; (b) attending to patients' emotional needs, supporting feminist values, empowering patients, and changing the community response to rape; and (c) least importance on prosecution of cases and average importance on the other goals. Programs that were more focused on prosecution goals provided less comprehensive patient services.
Conclusions: Programs focused on prosecution as a primary goal were less likely to provide comprehensive services, especially those involving patient education. Such information is important for patients because their health concerns (e.g., pregnancy, STIs) have long‐term implications for their well‐being. Historical and structural differences among SANE programs might explain these different patient care practices. Researchers should examine the underlying processes in SANE programs that shape both their goals and patient care approaches.
Replication and Examination of Research Data on Job Stress and Coworker Social Support With Internet and Traditional Samples
Authors: AbuAlRub Raeda Fawzi 
Published: May 2006

Purpose: To replicate previous results about job stress and coworkers' support that were obtained from a Web‐based American sample with a sample of Jordanian nurses using traditional methods.
Design and Methods: The convenience sample of 300 Jordanian staff nurses completed the pencil‐and‐paper version of a questionnaire that included the Nursing Stress Scale, the McCain and Marklin Social Integration Scale, and the demographic form. The sample of the replicated study consisted of 263 American staff nurses who were accessible over the Internet and completed the Web‐based version of the questionnaire. Descriptive statistics, chi‐square, t test, and Pearson product‐moment correlations were used to analyze the data.
Results: The American and Jordanian samples differed significantly on all demographic variables. However, they had similar patterns of responses in regard to the association between job stress and social support from coworkers.
Conclusions: The predicted comparability of findings with different methods and samples lends credence to the reliability and validity of Internet‐based research.
Psychoanalytic Criticism of Shakespeare
Authors: Mikics David 
Published: May 2006

AbstractWhy has Shakespeare proved such profitable ground for psychoanalytic study? Part of the answer lies in the affinity between theatre, not just Shakespeare’s, and psychoanalytic practice, an affinity recognized by Freud when he adapted Aristotle’s idea of catharsis to his own “talking cure.” This essay traces psychoanalytic criticism of Shakespeare from its origins in the work of Freud and Ernest Jones through studies by Jung, Rank, Lacan, Norman Holland, and others. In conclusion, the author presents a practical example of psychoanalytic Shakespeare criticism: a reading ofThe Tempestdrawing on the object relations school of D. W. Winnicott.
Varicella-Zoster Virus Infection of Human Foreskin Fibroblast Cells Results in Atypical Cyclin Expression and Cyclin-Dependent Kinase Activity
Authors: Leisenfelder Stacey A. , Moffat Jennifer F. 
Published: May 2006

ABSTRACT

In its course of human infection, varicella-zoster virus (VZV) infects rarely dividing cells such as dermal fibroblasts, differentiated keratinocytes, mature T cells, and neurons, none of which are actively synthesizing DNA; however, VZV is able to productively infect them and use their machinery to replicate the viral genome. We hypothesized that VZV alters the intracellular environment to favor viral replication by dysregulating cell cycle proteins and kinases. Cyclin-dependent kinases (CDKs) and cyclins displayed a highly unusual profile in VZV-infected confluent fibroblasts: total amounts of CDK1, CDK2, cyclin B1, cyclin D3, and cyclin A protein increased, and kinase activities of CDK2, CDK4, and cyclin B1 were strongly and simultaneously induced. Cyclins B1 and D3 increased as early as 24 h after infection, concurrent with VZV protein synthesis. Confocal microscopy indicated that cyclin D3 overexpression was limited to areas of IE62 production, whereas cyclin B1 expression was irregular across the VZV plaque. Downstream substrates of CDKs, including pRb, p107, and GM130, did not show phosphorylation by immunoblotting, and p21 and p27 protein levels were increased following infection. Finally, although the complement of cyclin expression and high CDK activity indicated a progression through the S and G
2
phases of the cell cycle, DNA staining and flow cytometry indicated a possible G
1
/S blockade in infected cells. These data support earlier studies showing that pharmacological CDK inhibitors can inhibit VZV replication in cultured cells.
Role of the Stable Signal Peptide and Cytoplasmic Domain of G2 in Regulating Intracellular Transport of the Junín Virus Envelope Glycoprotein Complex
Authors: Agnihothram Sudhakar S. , York Joanne , Nunberg Jack H. 
Published: May 2006

ABSTRACT

Enveloped viruses utilize the membranous compartments of the host cell for the assembly and budding of new virion particles. In this report, we have investigated the biogenesis and trafficking of the envelope glycoprotein (GP-C) of the Junín arenavirus. The mature GP-C complex is unusual in that it retains a stable signal peptide (SSP) as an essential component in association with the typical receptor-binding (G1) and transmembrane fusion (G2) subunits. We demonstrate that, in the absence of SSP, the G1-G2 precursor is restricted to the endoplasmic reticulum (ER). This constraint is relieved by coexpression of SSP in
trans
, allowing transit of the assembled GP-C complex through the Golgi and to the cell surface, the site of arenavirus budding. Transport of a chimeric CD4 glycoprotein bearing the transmembrane and cytoplasmic domains of G2 is similarly regulated by SSP association. Truncations to the cytoplasmic domain of G2 abrogate SSP association yet now permit transport of the G1-G2 precursor to the cell surface. Thus, the cytoplasmic domain of G2 is an important determinant for both ER localization and its control through SSP binding. Alanine mutations to either of two dibasic amino acid motifs in the G2 cytoplasmic domain can also mobilize the G1-G2 precursor for transit through the Golgi. Taken together, our results suggest that SSP binding masks endogenous ER localization signals in the cytoplasmic domain of G2 to ensure that only the fully assembled, tripartite GP-C complex is transported for virion assembly. This quality control process points to an important role of SSP in the structure and function of the arenavirus envelope glycoprotein.
Characterization of a Permissive Epitope Insertion Site in Adenovirus Hexon
Authors: McConnell Michael J. , Danthinne Xavier , Imperiale Michael J. 
Published: May 2006

ABSTRACTA robust immune response is generated against components of the adenovirus capsid. In particular, a potent and long-lived humoral response is elicited against the hexon protein. This is due to the efficient presentation of adenovirus capsid proteins to CD4+T cells by antigen-presenting cells, in addition to the highly repetitive structure of the adenovirus capsids, which can efficiently stimulate B-cell proliferation. In the present study, we take advantage of this immune response by inserting epitopes against which an antibody response is desired into the adenovirus hexon. We use a B-cell epitope fromBacillus anthracisprotective antigen (PA) as a model antigen to characterize hypervariable region 5 (HVR5) of hexon as a site for peptide insertion. We demonstrate that HVR5 can accommodate a peptide of up to 36 amino acids without adversely affecting virus infectivity, growth, or stability. Viruses containing chimeric hexons elicited antibodies against PA in mice, with total immunoglobulin G (IgG) titers reaching approximately 1 × 103after two injections. The antibody response contained both IgG1 and IgG2a subtypes, suggesting that Th1 and Th2 immunity had been stimulated. Coinjection of wild-type adenovirus and a synthetic peptide from PA produced no detectable antibodies, indicating that incorporation of the epitope into the capsid was crucial for immune stimulation. Together, these results indicate that the adenovirus capsid is an efficient vehicle for presenting B-cell epitopes to the immune system, making this a useful approach for the design of epitope-based vaccines.
Ebola Virus VP35-VP40 Interaction Is Sufficient for Packaging 3E-5E Minigenome RNA into Virus-Like Particles
Authors: Johnson Reed F. , McCarthy Sarah E. , Godlewski Peter J. , Harty Ronald N. 
Published: May 2006

ABSTRACT
The packaging of viral genomic RNA into nucleocapsids and subsequently into virions is not completely understood. Phosphoprotein (P) and nucleoprotein (NP) interactions link NP-RNA complexes with P-L (polymerase) complexes to form viral nucleocapsids. The nucleocapsid then interacts with the viral matrix protein, leading to specific packaging of the nucleocapsid into the virion. A mammalian two-hybrid assay and confocal microscopy were used to demonstrate that Ebola virus VP35 and VP40 interact and colocalize in transfected cells. VP35 was packaged into budding virus-like particles (VLPs) as observed by protease protection assays. Moreover, VP40 and VP35 were sufficient for packaging an Ebola virus minignome RNA into VLPs. Results from immunoprecipitation-reverse transcriptase PCR experiments suggest that VP35 confers specificity of the nucleocapsid for viral genomic RNA by direct VP35-RNA interactions.
Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection
Authors: Eda Yasuyuki , Murakami Toshio , Ami Yasushi , Nakasone Tadashi , Takizawa Mari , Someya Kenji , Kaizu Masahiko , Izumi Yasuyuki , Yoshino Naoto , Matsushita Shuzo , Higuchi Hirofumi , Matsui Hajime , Shinohara Katsuaki , Takeuchi Hiroaki , Koyanagi Yoshio , Yamamoto Naoki , Honda Mitsuo 
Published: May 2006

ABSTRACTIn an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B′ with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.
Influence of Pseudorabies Virus Proteins on Neuroinvasion and Neurovirulence in Mice
Authors: Klopfleisch Robert , Klupp Barbara G. , Fuchs Walter , Kopp Martina , Teifke Jens P. , Mettenleiter Thomas C. 
Published: May 2006

ABSTRACT

Neurotropism is a distinctive feature of members of the
Alphaherpesvirinae
. However, its molecular basis remains enigmatic. In the past, research has been focused mainly on the role of viral envelope proteins in modulating herpesvirus neuroinvasion and neurovirulence (T. C. Mettenleiter, Virus Res. 92:192-206, 2003). To further analyze the molecular requirements for neuroinvasion of the alphaherpesvirus pseudorabies virus (PrV), adult mice were infected intranasally with a set of single- or multiple-deletion mutants lacking the UL3, UL4, UL7, UL11, UL13, UL16, UL17, UL21, UL31, UL34, UL37, UL41, UL43, UL46, UL47, UL48, UL51, US3, US9, glycoprotein E (gE), gM, UL11/US9, UL11/UL16, UL16/UL21, UL11/UL16/UL21, UL11/gE, UL11/gM, UL43/gK, UL43/gM, or UL43/gK/gM genes. Neurovirulence was evaluated by measuring mean survival times compared to that after wild-type virus infection. Furthermore, by immunohistochemical detection of infected neurons, the kinetics of viral spread in the murine central nervous system was investigated.
LC16m8, a Highly Attenuated Vaccinia Virus Vaccine Lacking Expression of the Membrane Protein B5R, Protects Monkeys from Monkeypox
Authors: Saijo Masayuki , Ami Yasushi , Suzaki Yuriko , Nagata Noriyo , Iwata Naoko , Hasegawa Hideki , Ogata Momoko , Fukushi Shuetsu , Mizutani Tetsuya , Sata Tetsutaro , Kurata Takeshi , Kurane Ichiro , Morikawa Shigeru 
Published: May 2006

ABSTRACT
The potential threat of smallpox as a bioweapon has led to the production
and stockpiling of smallpox vaccine in some countries. Human monkeypox,
a rare but important viral zoonosis endemic to central and western
Africa, has recently emerged in the United States. Thus, even though
smallpox has been eradicated, a vaccinia virus vaccine that can induce
protective immunity against smallpox and monkeypox is still invaluable.
The ability of the highly attenuated vaccinia virus vaccine strain
LC16m8, with a mutation in the important immunogenic membrane protein
B5R, to induce protective immunity against monkeypox in nonhuman
primates was evaluated in comparison with the parental Lister strain.
Monkeys were immunized with LC16m8 or Lister and then infected
intranasally or subcutaneously with monkeypox virus strain Liberia or
Zr-599, respectively. Immunized monkeys showed no symptoms of monkeypox
in the intranasal-inoculation model, while nonimmunized controls showed
typical symptoms. In the subcutaneous-inoculation model, monkeys
immunized with LC16m8 showed no symptoms of monkeypox except for a mild
ulcer at the site of monkeypox virus inoculation, and those immunized
with Lister showed no symptoms of monkeypox, while nonimmunized
controls showed lethal and typical symptoms. These results
indicate that LC16m8 prevents lethal monkeypox in monkeys, and they
suggest that LC16m8 may induce protective immunity against
smallpox.
Diversity of the CD8+T-Cell Response to Herpes Simplex Virus Type 2 Proteins among Persons with Genital Herpes
Authors: Hosken Nancy , McGowan Patrick , Meier Amalia , Koelle David M. , Sleath Paul , Wagener Felecia , Elliott Mark , Grabstein Ken , Posavad Christine , Corey Lawrence 
Published: May 2006

ABSTRACTCytolytic T cells play a major role in controlling herpes simplex virus type 2 (HSV-2) infections in humans. In an effort to more thoroughly evaluate the response to HSV-2 directly, ex vivo, we developed an enzyme-linked immunospot (ELISPOT) assay that utilized pools of overlapping synthetic peptides presented by autologous dendritic cells to purified CD8+T cells. Donor response rates to individual open reading frames (ORFs) ranged from fewer than 5% responding to as many as 70% responding, with the greatest frequency of responses (by ORF) being directed against UL39, UL25, UL27, ICP0, UL46, and UL47 in descending order of frequency. HSV-2-seropositive subjects responded to as few as 3 or as many as 46 of the 48 ORFs tested, with a median of 11 ORFs recognized. HLA-B*07 expression correlated with stronger responses overall that were directed primarily against UL49 and UL46. Cumulative precursor frequencies in the blood ranged from 500 to almost 6,000 HSV-2 spot-forming units/106CD8+T cells. The magnitude and breadth of the response in the infected population were greater than previously appreciated. Whether this variability in the CD8+T-cell response within individuals is associated with the frequency of viral reactivation warrants further study.
Evidence for Functional Protein Interactions Required for Poliovirus RNA Replication
Authors: Teterina Natalya L. , Levenson Eric , Rinaudo Mario S. , Egger Denise , Bienz Kurt , Gorbalenya Alexander E. , Ehrenfeld Ellie 
Published: May 2006

ABSTRACT
Poliovirus protein 2C contains a predicted N-terminal amphipathic helix that mediates association of the protein with the membranes of the viral RNA replication complex. A chimeric virus that contains sequences encoding the 18-residue core from the orthologous amphipathic helix from human rhinovirus type 14 (HRV14) was constructed. The chimeric virus exhibited defects in viral RNA replication and produced minute plaques on HeLa cell monolayers. Large plaque variants that contained mutations within the 2C-encoding region were generated upon subsequent passage. However, the majority of viruses that emerged with improved growth properties contained no changes in the region encoding 2C. Sequence analysis and reconstruction of genomes with individual mutations revealed changes in 3A or 2B sequences that compensated for the HRV14 amphipathic helix in the polio 2C-containing proteins, implying functional interactions among these proteins during the replication process. Direct binding between these viral proteins was confirmed by mammalian cell two-hybrid analysis.