bluuebunny/crossref_metadata_2025_split huggingface dataset:
Samson’s “Rousing Motions”: What They Are, How They Work, and Why They Matter
Authors: DuRocher Richard 
Published: May 2006

AbstractBefore going to the Temple of Dagon with the Philistian Officer near the climax of Milton’s Samson Agonistes, Samson tells the uncomprehending Chorus to “Be of good courage.” For, he assures them, “I begin to feel / Some rousing motions in me which dispose / To something extraordinary my thoughts” (1381–3). Samson’s motivation for his decision to enter the temple, together with his catastrophic act of pulling down the temple upon the Philistian nobility, and “inevitably” upon himself, has become the flashpoint of voluminous debate about Samson Agonistes in recent Milton criticism. This essay aims to contribute to this critical conversation by exploring precisely what Milton and his readers would have understood by the “rousing motions” that Samson reports feeling at this pivotal moment. Seventeenth‐century readers would have recognized Samson’s “motions” as the part of the so‐called system of “faculty psychology” responsible for the feelings. Beyond scrutinizing Milton’s text, I examine contextual support from ancient and early modern sources toward understanding Samson’s “motions” and their workings. As well as reviewing the theory of emotions expounded by Aristotle in the Rhetoric and Nicomachean Ethics, I describe the modifications to that theory propounded by the Protestant reformer Philip Melanchthon, as well as the nuanced approach to dealing with affective volatility developed by the Cambridge theologian William Fenner. Milton and these Protestant writers share three essential convictions: they locate the emotions within a comprehensive model of the mental faculties; they assert the power of the human agent, typically through the will, to control – in Milton’s phrase, “to temper and reduce to just measure”– their potentially overwhelming power; and, most significant of all, they regard the emotions as the specific point of interaction between God, typically in the form of the Spirit, and the aspiring spirits of the human being. This last claim in particular addresses a question raised by several recent commentators on Samson Agonistes, namely, whether Samson’s impulse to act comes from himself or from God.
Women Writers in World War II
Authors: Maslen Elizabeth 
Published: May 2006

AbstractThis article covers the period 1939 to 1945, looking at women writers and their work throughout the Second World War. It explores their writing in the context of the jobs they were, in many cases, called upon to do over that time, and also examines the subjects they chose to write about. It attempts to answer certain central questions, as, for instance, was there a difference between generations in the way women wrote and the issues that concerned them; did they look outside the war situation for their subject matter or did they engage? Readers are pointed to leading research on women’s writing in the war years, to biographies, and to primary texts.
Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA
Authors: Burgos Javier S. , Ramirez Carlos , Sastre Isabel , Valdivieso Fernando 
Published: May 2006

ABSTRACT
Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.
Evidence for Potent Autologous Neutralizing Antibody Titers and Compact Envelopes in Early Infection with Subtype C Human Immunodeficiency Virus Type 1
Authors: Li Bing , Decker Julie M. , Johnson Roy W. , Bibollet-Ruche Frederic , Wei Xiping , Mulenga Joseph , Allen Susan , Hunter Eric , Hahn Beatrice H. , Shaw George M. , Blackwell Jerry L. , Derdeyn Cynthia A. 
Published: May 2006

ABSTRACT

Information about neutralizing antibody responses in subtype C-infected individuals is limited, even though this viral subtype causes the majority of AIDS cases worldwide. Here we compared the course and magnitude of the autologous neutralizing antibody (NAb) response against viral envelope (Env) glycoproteins present during acute and early infection with subtypes B and C human immunodeficiency virus type 1 (HIV-1). NAb responses were evaluated in 6 subtype B-infected and 11 subtype C-infected subjects over a mean evaluation period of 25 months using a pseudovirus reporter gene assay. All subjects in the C cohort were infected through heterosexual contact, while five of the six subjects in the B cohort were infected via male-to-male contact. The kinetics and magnitude of the NAb responses varied among subjects in the B and C cohorts; however, the median 50% inhibitory concentration (IC
50
titer) reached by antibody in the plasma of subtype C-infected subjects, overall, was 3.5-fold higher than in the subtype B-infected subjects (
P
= 0.06). The higher titers of NAbs in the C cohort were associated with viruses having significantly shorter amino acid length (
P
= 0.002) in the V1 to V4 region of the surface Env glycoprotein, gp120, compared to the B cohort. Despite the potency of the autologous subtype C NAb response, it was not directed against cross-neutralizing epitopes. These data demonstrate that subtype C Envs elicit a potent yet restricted NAb response early in infection that frequently reaches IC
50
titers in excess of 1:1,000 and suggest that clade-specific differences may exist in Env immunogenicity or susceptibility to neutralization.
Molecular Determinants of Substrate Specificity for Semliki Forest Virus Nonstructural Protease
Authors: Lulla Aleksei , Lulla Valeria , Tints Kairit , Ahola Tero , Merits Andres 
Published: May 2006

ABSTRACTThe C-terminal cysteine protease domain of Semliki Forest virus nonstructural protein 2 (nsP2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein P1234. The site between nsP3 and nsP4 (the 3/4 site) is cleaved most efficiently. Analysis of Semliki Forest virus-specific cleavage sites with shuffled N-terminal and C-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region preceding the cleavage site. Random mutagenesis analysis revealed that amino acid residues in positions P4, P3, P2, and P1 of the 3/4 cleavage site cannot tolerate much variation, whereas in the P5 position most residues were permitted. When mutations affecting cleavage efficiency were introduced into the 2/3 and 3/4 cleavage sites, the resulting viruses remained viable but had similar defects in P1234 processing as observed in the in vitro assay. Complete blockage of the 3/4 cleavage was found to be lethal. The amino acid in position P1′ had a significant effect on cleavage efficiency, and in this regard the protease markedly preferred a glycine residue over the tyrosine natively present in the 3/4 site. Therefore, the cleavage sites represent a compromise between protease recognition and other requirements of the virus life cycle. The protease recognizes at least residues P4 to P1′, and the P4 arginine residue plays an important role in the fast cleavage of the 3/4 site.
Lepidopteran Ortholog of
Drosophila
Breathless Is a Receptor for the Baculovirus Fibroblast Growth Factor
Authors: Katsuma Susumu , Daimon Takaaki , Mita Kazuei , Shimada Toru 
Published: May 2006

ABSTRACT

The
Bombyx mori
nucleopolyhedrovirus (BmNPV) encodes a gene homologous to the mammalian fibroblast growth factor (FGF) family. We report the cloning of
B. mori
and
Spodoptera frugiperda
orthologous genes (
Bmbtl
and
Sfbtl
, respectively) of
Drosophila melanogaster breathless
(
btl
) encoding a receptor for Branchless/FGF and show that these genes encode the receptor for a baculovirus-encoded FGF (vFGF). Sequence analysis showed that BmBtl is composed of 856 amino acid residues, which potentially encodes a 97.3-kDa polypeptide and shares structural features and sequence similarities with the FGF receptor family. Reverse transcription-PCR experiments showed that
Bmbtl
was abundantly expressed in the trachea and midgut in
B. mori
larvae, with moderate expression observed in the hemocytes and the
B. mori
cultured cell line BmN. We generated Sf-9 cells that stably expressed His-tagged BmBtl. Western blot analysis revealed that BmBtl was an ∼110-kDa protein. Immunoprecipitation experiments showed that BmNPV vFGF markedly phosphorylated BmBtl in Sf-9 cells. In addition, we found that BmBtl overexpression enhanced the migration activity for BmNPV vFGF. Furthermore, we generated Sf-9 cells in which
Sfbtl
was knocked down by transfection with double-strand RNA-expressing plasmids. In these cells, cell motility triggered by vFGF was markedly reduced. These results strongly suggest that the Btl orthologs, BmBtl and SfBtl, are the receptors for vFGF, which mediate vFGF-induced host cell chemotaxis.
Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection
Authors: Shrestha Bimmi , Wang Tian , Samuel Melanie A. , Whitby Kevin , Craft Joe , Fikrig Erol , Diamond Michael S. 
Published: May 2006

ABSTRACT

West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (IFN-α/β), immunoglobulin M, γδ T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-γ production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-γ
−/−
or IFN-γR
−/−
mice) and a decrease in the average survival time. This survival pattern in IFN-γ
−/−
and IFN-γR
−/−
mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-γ
−/−
or IFN-γR
−/−
mice. Bone marrow reconstitution experiments showed that γδ T cells require IFN-γ to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-γ reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-γ against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.
Modulation of Kaposi's Sarcoma-Associated Herpesvirus Infection and Replication by MEK/ERK, JNK, and p38 Multiple Mitogen-Activated Protein Kinase Pathways during Primary Infection
Authors: Pan Hongyi , Xie Jianping , Ye Fengchun , Gao Shou-Jiang 
Published: May 2006

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma, a dominant AIDS-related tumor of endothelial cells, and several other lymphoproliferative malignancies. While activation of the phosphatidylinositol 3-kinase-protein kinase C-MEK-ERK pathway is essential for KSHV infection, we have recently shown that KSHV also activates JNK and p38 mitogen-activated protein kinase (MAPK) pathways during primary infection (J. Xie, H. Y. Pan, S. Yoo, and S.-J. Gao, J. Virol. 79:15027-15037, 2005). Here, we found that activation of both JNK and p38 pathways was also essential for KSHV infection. Inhibitors of all three MAPK pathways reduced KSHV infectivity in both human umbilical vein endothelial cells (HUVEC) and 293 cells. These inhibitory effects were dose dependent and occurred at the virus entry stage of infection. Consistently, inhibition of all three MAPK pathways with dominant-negative constructs reduced KSHV infectivity whereas activation of the ERK pathway but not the JNK and p38 pathways enhanced KSHV infectivity. Importantly, inhibition of all three MAPK pathways also reduced the yield of infectious virions during KSHV productive infection of HUVEC. While the reduction of infectious virions was in part due to the reduced infectivity, it was also the result of direct modulation of KSHV lytic replication by the MAPK pathways. Accordingly, KSHV upregulated the expression of RTA (Orf50), a master transactivator of KSHV lytic replication, and activated its promoter during primary infection. Furthermore, KSHV activation of RTA promoter during primary infection was modulated by all three MAPK pathways, predominantly through their downstream target AP-1. Together, these results indicate that, by modulating multiple MAPK pathways, KSHV manipulates the host cells to facilitate its entry into the cells and postentry productive lytic replication during primary infection.
Lipid-Mediated Introduction of Hepatitis B Virus Capsids into Nonsusceptible Cells Allows Highly Efficient Replication and Facilitates the Study of Early Infection Events
Authors: Rabe Birgit , Glebe Dieter , Kann Michael 
Published: May 2006

ABSTRACTThe hepatitis B virus (HBV) is an enveloped DNA virus which is highly infectious in vivo. In vitro, only primary hepatocytes of humans andTupaia belangerior the novel HepaRG cell line are susceptible to HBV, but infection is inefficient and study of early infection events in single cells is unsatisfactory. Since hepatoma cells replicate the virus efficiently after transfection, this limited infection efficiency must be related to the initial entry phase. Here, we describe the lipid-based delivery of HBV capsids into nonsusceptible cells, circumventing the natural entry pathway. Successful infection was monitored by observing the emergence of the nuclear viral covalently closed circular DNA and the production of progeny virus and subviral particles. Lipid-mediated transfer initiated productive infection that was at least 100-fold more effective than infection of permissive cell cultures. High-dose capsid transfer showed that the uptake was not receptor limited and allowed the intracellular transport of capsids and genomes to be examined microscopically. The addition of inhibitors confirmed an entry pathway by fusion of the lipid with the plasma membrane. By indirect immune fluorescence and native fluorescence in situ hybridization, we followed the pathway of capsids and viral genomes in individual cells. We observed an active microtubule-dependent capsid transfer to the nucleus and a subsequent release of the viral genomes exclusively into the karyoplasm. Lipid-mediated transfer of viral capsids thus appears to allow efficient introduction of genetic information into target cells, facilitating studies of early infection events which are otherwise impeded by the small number of viruses entering the cell.
Ebola Virus VP24 Binds Karyopherin α1 and Blocks STAT1 Nuclear Accumulation
Authors: Reid St. Patrick , Leung Lawrence W. , Hartman Amy L. , Martinez Osvaldo , Shaw Megan L. , Carbonnelle Caroline , Volchkov Viktor E. , Nichol Stuart T. , Basler Christopher F. 
Published: May 2006

ABSTRACTEbola virus (EBOV) infection blocks cellular production of alpha/beta interferon (IFN-α/β) and the ability of cells to respond to IFN-α/β or IFN-γ. The EBOV VP35 protein has previously been identified as an EBOV-encoded inhibitor of IFN-α/β production. However, the mechanism by which EBOV infection inhibits responses to IFNs has not previously been defined. Here we demonstrate that the EBOV VP24 protein functions as an inhibitor of IFN-α/β and IFN-γ signaling. Expression of VP24 results in an inhibition of IFN-induced gene expression and an inability of IFNs to induce an antiviral state. The VP24-mediated inhibition of cellular responses to IFNs correlates with the impaired nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1), a key step in both IFN-α/β and IFN-γ signaling. Consistent with this proposed function for VP24, infection of cells with EBOV also confers a block to the IFN-induced nuclear accumulation of PY-STAT1. Further, VP24 is found to specifically interact with karyopherin α1, the nuclear localization signal receptor for PY-STAT1, but not with karyopherin α2, α3, or α4. Overexpression of VP24 results in a loss of karyopherin α1-PY-STAT1 interaction, indicating that the VP24-karyopherin α1 interaction contributes to the block to IFN signaling. These data suggest that VP24 is likely to be an important virulence determinant that allows EBOV to evade the antiviral effects of IFNs.
Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency
Authors: Kanno Toru , Kim Kisoon , Kono Ken , Drescher Kristen M. , Chapman Nora M. , Tracy Steven 
Published: May 2006

ABSTRACT
Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5′-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.
Measles Virus V Protein Inhibits p53 Family Member p73
Authors: Cruz Cristian D. , Palosaari Heidi , Parisien Jean-Patrick , Devaux Patricia , Cattaneo Roberto , Ouchi Toru , Horvath Curt M. 
Published: May 2006

ABSTRACTParamyxovirus V proteins function as host interference factors that inactivate antiviral responses, including interferon. Characterization of cellular proteins that copurify with ectopically expressed measles virus V protein has revealed interactions with DNA binding domains of p53 family proteins, p53 and p73. Specific transcriptional assays reveal that expression of measles virus V cDNA inhibits p73, but not p53. Expression of measles virus V cDNA can delay cell death induced by genotoxic stress and also can decrease the abundance of the proapoptotic factor PUMA, a p73 target. Recombinant measles virus with an engineered deficiency in V protein is capable of inducing more severe cytopathic effects than the wild type, implicating measles virus V protein as an inhibitor of cell death. These findings also suggest that p73-PUMA signaling may be a previously unrecognized arm of cellular innate antiviral immunity.
Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines
Authors: Krishnamurthy Sateesh , Takimoto Toru , Scroggs Ruth Ann , Portner Allen 
Published: May 2006

ABSTRACT
Newcastle disease virus (NDV) is a negative-strand RNA virus with oncolytic activity against human tumors. Its effectiveness against tumors and safety in normal tissue have been demonstrated in several clinical studies. Here we show that the spread of NDV infection is drastically different in normal cell lines than in tumor cell lines and that the two cell types respond differently to beta interferon (IFN-β) treatment. NDV rapidly replicated and killed HT-1080 human fibrosarcoma cells but spread poorly in CCD-1122Sk human skin fibroblast cells. Pretreatment with endogenous or exogenous IFN-β completely inhibited NDV replication in normal cells but had little or no effect in tumor cells. Thus, the outcome of NDV infection appeared to depend on the response of uninfected cells to IFN-β. To investigate their differences in IFN responsiveness, we analyzed and compared the expression and activation of components of the IFN signal transduction pathway in these two types of cells. The levels of phosphorylated STAT1 and STAT2 and that of the ISGF3 complex were markedly reduced in IFN-β-treated tumor cells. Moreover, cDNA microarray analysis revealed significantly fewer IFN-regulated genes in the HT-1080 cells than in the CDD-1122Sk cells. This finding suggests that tumor cells demonstrate a less-than-optimum antiviral response because of a lesion in their IFN signal transduction pathway. The rapid spread of NDV in HT-1080 cells appears to be caused by their deficient expression of anti-NDV proteins upon exposure to IFN-β.
Epstein-Barr Virus Protein Kinase BGLF4 Is a Virion Tegument Protein That Dissociates from Virions in a Phosphorylation-Dependent Process and Phosphorylates the Viral Immediate-Early Protein BZLF1
Authors: Asai Risa , Kato Ai , Kato Kentaro , Kanamori-Koyama Mikiko , Sugimoto Ken , Sairenji Takeshi , Nishiyama Yukihiro , Kawaguchi Yasushi 
Published: May 2006

ABSTRACT

Epstein-Barr virus (EBV) BGLF4 is a viral protein kinase that is expressed in the lytic phase of infection and is packaged in virions. We report here that BGLF4 is a tegument protein that dissociates from the virion in a phosphorylation-dependent process. We also present evidence that BGLF4 interacts with and phosphorylates BZLF1, a key viral regulator of lytic infection. These conclusions are based on the following observations. (i) In in vitro tegument release assays, a significant fraction of BGLF4 was released from virions in the presence of physiological NaCl concentrations. (ii) Addition of physiological concentrations of ATP and MgCl
2
to virions enhanced BGLF4 release, but phosphatase treatment of virions significantly reduced BGLF4 release. (iii) A recombinant protein containing a domain of BZLF1 was specifically phosphorylated by purified recombinant BGLF4 in vitro, and BGLF4 altered BZLF1 posttranslational modification in vivo. (iv) BZLF1 was specifically coimmunoprecipitated with BGLF4 in 12-
O
-tetradecanoylphorbol-13-acetate-treated B95-8 cells and in COS-1 cells transiently expressing both of these viral proteins. (v) BGLF4 and BZLF1 were colocalized in intranuclear globular structures, resembling the viral replication compartment, in Akata cells treated with anti-human immunoglobulin G. Our results suggest that BGLF4 functions not only in lytically infected cells by phosphorylating viral and cellular targets but also immediately after viral penetration like other herpesvirus tegument proteins.