bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Characterization of Dominant Helper T-Cell Epitopes in the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus
Authors: Zhao Jincun , Huang Qianrong , Wang Wei , Zhang Yan , Lv Ping , Gao Xiao-Ming 
Published: March 2007

ABSTRACTBy using a series of overlapping synthetic peptides covering 98% of the amino acid sequence of the nucleocapsid protein (NP) of severe acute respiratory syndrome coronavirus (SARS-CoV), four helper T-cell (Th) epitopes (NP11, residues 11 to 25; NP51, residues 51 to 65; NP61, residues 61 to 75; and NP111, residues 111 to 125) in C57BL mice (H-2b), four (NP21, residues 21 to 35; NP91, residues 91 to 105; NP331, residues 331 to 345; and NP351, residues 351 to 365) in C3H mice (H-2k), and two (NP81, residues 81 to 95; and NP351, residues 351 to 365) in BALB/c mice (H-2d) have been identified. All of these peptides were able to stimulate the proliferation of NP-specific T-cell lines or freshly isolated lymph node cells from mice immunized with recombinant NP. Immunization of mice with synthetic peptides containing appropriate Th epitopes elicited strong cellular immunity in vivo, as evidenced by delayed-type hypersensitivity. Priming with the helper peptides (e.g., NP111 and NP351) significantly accelerated the immune response induced by recombinant NP, as determined by the production of NP-specific antibodies. When fused with a conserved neutralizing epitope (SP1143-1157) from the spike protein of SARS-CoV, NP111 and NP351 assisted in the production of high-titer neutralizing antibodies in vivo. These data provide useful insights regarding immunity against SARS-CoV and have the potential to help guide the design of peptide-based vaccines.
Suppression of Viral Gene Expression in Bovine Leukemia Virus-Associated B-Cell Malignancy: Interplay of Epigenetic Modifications Leading to Chromatin with a Repressive Histone Code
Authors: Merimi Makram , Klener Pavel , Szynal Maud , Cleuter Yvette , Kerkhofs Pierre , Burny Arsène , Martiat Philippe , Van den Broeke Anne 
Published: March 2007

ABSTRACT
Ovine leukemia/lymphoma resulting from bovine leukemia virus infection of sheep offers a large animal model for studying mechanisms underlying leukemogenesis. Silencing of viral information including Tax, the major contributor to the oncogenic potential of the virus, is critical if not mandatory for tumor progression. In this study, we have identified epigenetic mechanisms that govern the complete suppression of viral expression, using a lymphoma-derived B-cell clone carrying a silent provirus. Silencing was not relieved by injection of the malignant B cells into sheep. However, exogenous expression of Tax or treatment with either the DNA methyltransferase inhibitor 5′azacytidine or the histone deacetylase (HDAC) inhibitor trichostatin A rescued viral expression, as demonstrated by in vivo infectivity trials. Comparing silent and reactivated provirus, we found mechanistic connections between chromatin conformation and tumor-associated transcriptional repression. Silencing is associated with DNA methylation and decreased accessibility of promoter sequences. HDAC1 and the transcriptional corepressor mSin3A are associated with the inactive but not the reactivated promoter. Silencing correlates with a repressed chromatin structure marked by histone H3 and H4 hypoacetylation, a loss of methylation at H3 lysine 4, and an increase of H3 lysine 9 methylation. These observations point to the critical role of epigenetic mechanisms in tumor-specific virus/oncogene silencing, a potential strategy to evade immune response and favor the propagation of the transformed cell.
Selective and Nonselective Packaging of Cellular RNAs in Retrovirus Particles
Authors: Rulli Samuel J. , Hibbert Catherine S. , Mirro Jane , Pederson Thoru , Biswal Shyam , Rein Alan 
Published: March 2007

ABSTRACT

Assembly of retrovirus particles normally entails the selective encapsidation of viral genomic RNA. However, in the absence of packageable viral RNA, assembly is still efficient, and the released virus-like particles (termed “Ψ
−
” particles) still contain roughly normal amounts of RNA. We have proposed that cellular mRNAs replace the genome in Ψ
−
particles. We have now analyzed the mRNA content of Ψ
−
and Ψ
+
murine leukemia virus (MLV) particles using both microarray analysis and real-time reverse transcription-PCR. The majority of mRNA species present in the virus-producing cells were also detected in Ψ
−
particles. Remarkably, nearly all of them were packaged nonselectively; that is, their representation in the particles was simply proportional to their representation in the cells. However, a small number of low-abundance mRNAs were greatly enriched in the particles. In fact, one mRNA species was enriched to the same degree as Ψ
+
genomic RNA. Similar results were obtained with particles formed from the human immunodeficiency virus type 1 (HIV-1) Gag protein, and the same mRNAs were enriched in MLV and HIV-1 particles. The levels of individual cellular mRNAs were ∼5- to 10-fold higher in Ψ
−
than in Ψ
+
MLV particles, in agreement with the idea that they are replacing viral RNA in the former. In contrast, signal recognition particle RNA was present at the same level in Ψ
−
and Ψ
+
particles; a minor fraction of this RNA was weakly associated with genomic RNA in Ψ
+
MLV particles.
Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus
Authors: Brandsma Janet L. , Shylankevich Mark , Su Yuhua , Roberts Anjeanette , Rose John K. , Zelterman Daniel , Buonocore Linda 
Published: March 2007

ABSTRACT
Persistent human papillomavirus (HPV)-associated benign and malignant lesions are a major cause of morbidity and mortality worldwide. Vaccination against HPV early proteins could provide an effective means of treating individuals with established infections. Recombinant vesicular stomatitis virus (VSV) vectors have been used previously to elicit strong humoral and cellular immune responses and develop prophylactic vaccines. We have shown that VSV vectors also can be used to elicit therapeutic immunity in the cottontail rabbit papillomavirus (CRPV)-rabbit model of high-risk HPV infection. In the present study, three new VSV vectors expressing the CRPV E1, E2, or E7 protein were produced and compared to the previously generated VSV-E6 vector for therapeutic efficacy. To determine whether vaccine efficacy could be augmented by simultaneous vaccination against two CRPV proteins, the four vaccines were delivered individually and in all possible pairings to rabbits 1 week after CRPV infection. Control rabbits received the recombinant wild-type VSV vector or medium only. Cumulative papilloma volumes were computed for analysis of the data. The analyses showed that VSV-based vaccination against the E1, E2, E6, or E7 protein significantly reduced papilloma volumes relative to those of the controls. Furthermore, VSV-based CRPV vaccination cured all of the papillomas in 5 of 30 rabbits. Of the individual vaccines, VSV-E7 was the most effective. The VSV-E7 vaccine alone was the most effective, as it reduced cumulative papilloma volumes by 96.9% overall, relative to those of the controls, and ultimately eliminated all of the disease in all of the vaccinees. Vaccine pairing was not, however, found to be beneficial, suggesting antigenic competition between the coexpressed CRPV proteins. These preclinical results, obtained in a physiologically relevant animal model of HPV infection, demonstrate that VSV vectors deserve serious consideration for further development as therapeutic antitumor vaccines.
Cytoplasmic Envelopment of Human Cytomegalovirus Requires the Postlocalization Function of Tegument Protein pp28 within the Assembly Compartment
Authors: Seo Jun-Young , Britt William J. 
Published: March 2007

ABSTRACT
The assembly of herpesvirus remains incompletely defined due to the structural complexity of these viruses. Although the assembly of the capsid of these large DNA viruses is well studied and reasonably well conserved for all members of this diverse family of viruses, the cytoplasmic processes of tegumentation and envelopment are not well understood. The virion of the largest human herpesvirus, human cytomegalovirus (HCMV), contains over 70 virus-encoded proteins that are incorporated during a nuclear and cytoplasmic phase of assembly. Envelopment of this virus requires the function of at least one tegument protein, pp28, the product of the UL99 open reading frame. However, the role of pp28 in the envelopment of HCMV remains undefined. We have generated a pp28 mutant virus that encodes only the first 50 amino acids (aa) of this 190-aa virion protein. This virus is replication impaired and is defective in virus assembly. Characterization of both intracellular and extracellular virions from cells infected with this viral mutant indicated that the decrease in production of infectious virus was secondary to a defect in envelopment and the accumulation of tegumented, noninfectious intracellular particles. Image analysis using fluorescence recovery after photobleaching indicated that the pp28 mutant protein encoded by this virus failed to efficiently accumulate in the virus assembly compartment (AC). Our results suggest that pp28 must accumulate in the AC for efficient envelopment of the particle and provide evidence for a direct role of this tegument protein in the late stages of assembly, such as envelopment.
Tsunami, Text and Trauma: Hermeneutics after the Asian Tsunami
Authors: Sugirtharajah  
Published: March 2007

AbstractThis essay is about the political and hermeneutical ramifications of the 2004 Boxing Day tsunami which had such a devastating effect upon millions of people. The first section deals with how a national disaster like a tsunami becomes a vehicle for both decolonization and recolonization. In Dutch colonial Indonesia, an earlier tsunami became in the hands of nationalists an ideal gift to whip up anti-colonial sentiments. The current humanitarian reconstruction, with all its good intentions, lends itself to economic, cultural and spiritual neo-colonialism. The second section looks at how the biblical flood story was utilized for the justification of colonial projects such as the invasion of South America and also used as a benchmark to evaluate and judge other peoples' history and chronology, and how in the process the authenticity of the biblical account was established. The third section addresses the theological reactions of different faith communities, which tend either to blame an angry God for the misfortune, or attribute the disaster to the misbehavior of the people. The last section advances the idea that a possible place to look for an answer to the theological conundrum produced by the tsunami is in secular stories which, in contemporary society, act as surrogate sacred texts. The essay analyses two novels—José Saramago's The Gospel According to Jesus Christ, and Vicente Leñero's The Gospel of Lucas Gavilán, which shed new light on old stories and offer a complex picture of God.
Heroism in 1 and 2 Maccabees
Authors: Tomes Roger 
Published: March 2007

AbstractThree types of heroism can be identified in 1 and 2 Maccabees: those of the warrior, the martyr and the suicide. While these concepts derive in part from the histories in the Hebrew Bible, they also display affinities with Greek ideas. Greek influence may be traced in vocabulary, in the manner of writing history, and in the emphasis on the motivation of the heroes. Greek history writing however occasionally appeals to universal values, whereas the Maccabaean literature does not look directly beyond the defence of the Jewish way of life. The martyrs were honoured by both Christians and Jews in times of persecution; and, although they never directly appealed to the suicide of Razis, Jews embraced suicide under the threat of torture or forced conversion as a legitimate way of 'sanctifying the name'. The example of Judas and his brothers may have been used to justify the Crusades: it has certainly helped to inspire Zionism and Israeli aspirations.
Legal and Cultural Aspects of Ignominious Parading (Tashhir) in Islam
Authors: Lange Christian 
Published: March 2007

AbstractIgnominious parading (tashhīr) was a crucial element of Islamic punitive practice well into the 19th century CE. In the context of a cultural-legal tradition for which the distinction between private and public was all-important, a punishment consisting, literally, in "making someone public" had a fundamental role to play. However, tashhīr has gone largely unnoticed by historians of Islamic law, despite the fact that it features prominently in legal discussions as the penalty for perjury (shahādat al-zūr). This essay, based for the most part on sources from the late-classical period (5th/11th and 6th/12th centuries), not only analyzes the place of tashhīr in fiqh, but it also takes into account instances of tashhīr in Islamic historiography and in the eschatological literature, thus uncovering the symbolic structure that underlies the tashhīr ritual.
Vessel Volumetrics and the Myth of the Cyclopean Bronze Age Ship
Authors: Monroe Christopher 
Published: March 2007

AbstractThe largest seagoing sailed merchantmen in the Mediterranean and Gulf during the Bronze Age (c. 3000-1150 BC) were probably not much larger than the ship that wrecked at Uluburun—about 20 tons capacity and 16 meters long. A 13th c. letter from Ugarit, long interpreted as indicative of much larger ships, is reinterpreted in the context of available texts, archaeology, and iconography. Available iconographical evidence points toward a 20 meter maximum length, and the evidence of the Uluburun shipwreck only nominally exceeds the maximum size of seagoing ships appearing in Mesopotamian records. Storage jars from shipwrecks, including those found at Uluburun, are used to address problematical aspects of the textual evidence, wherein the capacity of ships is given in volumetric units. Though problematic, all available evidence suggests that reconstructions of Bronze Age trade networks should assume smaller ship capacities. On se doute que les navires de commerce les plus larges – il s'agit des voiliers – naviguant sur la Méditerranée et le Golfe à l'Âge du Bronze (vers 3000-1150 av. J.-C.) ne furent pas plus grands que le vaisseau qui coula au large d'Uluburun (côte méridionale de la Turquie). Ce bateau-là a dû avoir une contenance d'environ 20 tonnes et une longueur de 16 mètres. Un passage se trouvant dans une lettre d'Ugarit datant du XIIIe s. av. J.-C. longuement interprété comme reflétant l'existence des vaisseaux beaucoup plus larges à cette époque-là, a été réinterprété dans le contexte des témoignages textuels, archéologiques et iconographiques disponibles. Tandisque l'iconographie suggère une longueur maximale de 20 mètres, l'épave d'Uluburun par contre correspond à peu près à la largeur maximale des navires de mer tels qu'ils figurent dans les documents Mésopotamiens. Les amphores sorties des épaves, y inclus celles d'Uluburun, servent à aborder des aspects problématiques des textes donnant la capacité des vaisseaux sous forme d'unités volumétriques. Or, en admettant que les l'interprétation des sources disponibles posent des difficultés, tout se porte à croire que la reconstruction des réseaux de commerce de l'Â ge de Bronze devrait être fait à base des capacités plus modestes.
"The Doctor Quarrels with Some Pictures": Exegesis and Animals in Thomas Browne's Pseudodoxia epidemica
Authors: Killeen Kevin 
Published: March 2007

AbstractThis essay explores Thomas Browne's Pseudodoxia epidemica (1646), with its lengthy book on 'errors' in animal lore. In the limited critical literature on Browne's natural history, this author is generally seen as stumbling towards a zoological idiom and clearing away the emblematic 'clutter' of earlier writers on natural history—Gesner, Aldrovandi, Topsell or Franzius. This essay proposes that Browne is working with a more complex set of co-ordinates in his thought, beyond his experimental inclinations and his Aristotelian assumptions. It will explore the extent to which his studies of animals emerge from, and duplicate, the presumptions of his biblical hermeneutics, and it will suggest that Browne regularly exports terms from scriptural exegesis—the categories of the literal, the figurative, and the emblematic—into his investigations of the natural world.
Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A
Authors: Zhang Wei , Colman Robert W. 
Published: March 2007

AbstractThrombin-induced cyclic AMP (cAMP) reduction potentates several steps in platelet activation, including Ca++ mobilization, cytoskeletal reorganization, and fibrinogen receptor conformation. We now reinvestigate the signaling pathways by which intracellular cAMP content is controlled after platelet activation by thrombin. When washed human platelets were stimulated with thrombin, cAMP-dependent phosphodiesterase (PDE3A) activity was significantly increased. A nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX), and the PDE3 selective inhibitors milrinone and cilostazol each suppressed thrombin-induced cAMP-dependent PDE responses, but not 2 different PDE2 inhibitors. Selective inhibition of PDE3A resulted in reversal of thrombin-induced cAMP reduction, indicating that thrombin activated PDE3A. In synergy with inhibition of adenylate cyclase by thrombin, activated PDE3A accelerates cAMP hydrolysis and maximally reduces the cAMP content. Thrombin-induced PDE3A activation was diminished concomitantly with dephosphorylation of PDE3A by protein phosphatase 1 (PP1). An Akt inhibitor blocked PDE3A activation and constrained thrombin-induced cAMP reduction. A P2Y12 inhibitor also reduced thrombin-induced cAMP reduction. The combination of both reversed cAMP decrease by thrombin. Thrombin-mediated phosphorylated PDE3A was isolated by liquid chromatography, detected by a monoclonal antibody against Akt-phosphorylated substrate, and verified by immunoprecipitation study. The predominant isoform phosphorylated by Akt was the 136-kDa species. We suggest that activation/phosphorylation of PDE3A via Akt signaling pathway participates in regulating cAMP during thrombin activation of platelets.
Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse
Authors: Reichardt Peter , Dornbach Bastian , Rong Song , Beissert Stefan , Gueler Faikah , Loser Karin , Gunzer Matthias 
Published: March 2007

AbstractNaive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell–dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell–primed regulatory T cells, “bTregs,” as a useful approach for therapeutic intervention in adverse adaptive immune responses.
Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis
Authors: Marty Francisco M. , Bryar Julie , Browne Sarah K. , Schwarzberg Talya , Ho Vincent T. , Bassett Ingrid V. , Koreth John , Alyea Edwin P. , Soiffer Robert J. , Cutler Corey S. , Antin Joseph H. , Baden Lindsey R. 
Published: March 2007

AbstractSirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (CMV) disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for graft-versus-host disease (GVHD) prophylaxis; the rest received non–sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% confidence interval [CI], 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus–based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI, 0.27-0.78; P = .004). The adjusted HR was 0.22 (95% CI, 0.09-0.55; P = .001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P = .14 and P = .35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.
ABO phenotypes and inflammation-related predictors of lung cancer mortality: the Copenhagen Male Study – a 16-year follow-up
Authors: Suadicani P. , Hein H. O. , Gyntelberg F. 
Published: March 2007

Inflammation and genetic susceptibility influence the risk of lung cancer. Previous studies suggest that the inflammatory response may depend upon ABO phenotype.The hypothesis that the association with lung cancer mortality risk of lifestyle and occupational factors previously linked to inflammation would depend upon ABO phenotype was tested in a long-term follow-up of 3,346 male subjects aged 53–74 yrs.During a 16-yr period, 170 (5.1%) of the male subjects died due to lung cancer; 84 (5.9%) of phenotype O, 70 (4.9%) of phenotype A and 16 (3.2%) of phenotype B/AB. In addition to cumulative tobacco consumption, high salt intake long-term occupational dust exposure, high fat intake and consumption of alcohol were significantly predictive of lung cancer mortality for phenotype O subjects. After multivariable adjustment, the hazard ratios associated with the first three of these factors were 2.31, 2.08 and 1.67, respectively. Compared with abstainers, the hazard ratios for males drinking 1–10 wine drinks·week−1and males drinking >10 wine drinks·week−1were 1.65 and 2.02, respectively. Among phenotype A subjects, only cumulative tobacco consumption was associated with lung cancer mortality risk.The predictive role of inflammation-related risk factors for lung cancer mortality was significantly stronger among males of phenotype O than A.