bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Cell Turnover in Bovine LeukemiaVirus-Infected, Persistently LymphocytoticCattle
Authors: Debacq Christophe , Asquith Becca , Reichert Michal , Burny Arsène , Kettmann Richard , Willems Luc 
Published: November 2003

ABSTRACT

Although
nucleotide analogs like bromodeoxyuridine have been extensively used to
estimate cell proliferation in vivo, precise dynamic parameters are
scarce essentially because of the lack of adequate mathematical models.
Besides recent developments on T cell dynamics, the turnover rates of B
lymphocytes are largely unknown particularly in the context of a
virally induced pathological disorder. Here, we aim to resolve this
issue by determining the rates of cell proliferation and death during
the chronic stage of the bovine leukemia virus (BLV) infection, called
bovine persistent lymphocytosis (PL). Our methodology is based on
direct intravenous injection of bromodeoxyuridine in association with
subsequent flow cytometry. By this in vivo approach, we show that the
death rate of PL B lymphocytes is significantly reduced (average death
rate, 0.057 day
−1
versus 0.156
day
−1
in the asymptomatic controls). Concomitantly,
proliferation of the PL cells is also significantly restricted compared
to the controls (average proliferation rate, 0.0046
day
−1
versus 0.0085 day
−1
). We
conclude that bovine PL is characterized by a decreased cell turnover
resulting both from a reduction of cell death and an overall impairment
of proliferation. The cell dynamic parameters differ from those
measured in sheep, an experimental model for BLV infection. Finally,
cells expressing p24 major capsid protein ex vivo were not BrdU
positive, suggesting an immune selection against proliferating
virus-positive lymphocytes. Based on a comparative leukemia approach,
these observations might help to understand cell dynamics during other
lymphoproliferative disease such as chronic lymphocytic leukemia or
human T-cell lymphotropic virus-induced adult T-cell leukemia in
humans.
HumanImmunodeficiency Virus Type 1 Fitness Is a Determining Factor in ViralRebound and Set Point in ChronicInfection
Authors: Trkola Alexandra , Kuster Herbert , Leemann Christine , Ruprecht Claudia , Joos Beda , Telenti Amalio , Hirschel Bernhard , Weber Rainer , Bonhoeffer Sebastian , Günthard Huldrych F. 
Published: November 2003

ABSTRACT
Human
immunodeficiency virus type 1 (HIV-1) isolates from 20
chronically infected patients who participated in a structured
treatment interruption (STI) trial were studied to determine whether
viral fitness influences reestablishment of viremia. Viruses derived
from individuals who spontaneously controlled viremia had significantly
lower in vitro replication capacities than viruses derived from
individuals that did not control viremia after interruption of
antiretroviral therapy (ART), and replication capacities
correlated with pre-ART and post-STI viral set points. Of
note, no clinically relevant improvement of viral loads upon STI
occurred. Virus isolates from controlling and noncontrolling patients
were indistinguishable in terms of coreceptor usage, genetic subtype,
and sensitivity to neutralizing antibodies. In contrast, viruses from
controlling patients exhibited increased sensitivity to inhibition by
chemokines. Sensitivity to inhibition by RANTES correlated strongly
with slower replication kinetics of the virus isolates, suggesting a
marked dependency of these virus isolates on high coreceptor densities
on the target cells. In summary, our data indicate that viral fitness
is a driving factor in determining the magnitude of viral rebound and
viral set point in chronic HIV-1 infection, and thus fitness should be
considered as a parameter influencing the outcome of therapeutic
intervention in chronic
infection.
Immunoprotective Activity and Safety of a RespiratorySyncytial Virus Vaccine: Mucosal Delivery of Fusion Glycoprotein with aCpG OligodeoxynucleotideAdjuvant
Authors: Prince Gregory A. , Mond James J. , Porter David D. , Yim Kevin C. , Lan Steve J. , Klinman Dennis M. 
Published: November 2003

ABSTRACTCpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin production and cell proliferation in cotton rat cells in vitro. Three of these ODN were used as a mucosal adjuvant in the noses of cotton rats immunized via this route with respiratory syncytial virus fusion (F) protein. The CpG ODN markedly increased the cotton rat humoral neutralizing-antibody response to respiratory syncytial virus. Such immunized animals had a marked reduction in the production of infectious virus after a live-virus challenge. Animals immunized with the combination of F protein and CpG developed enhanced pulmonary pathology consisting of alveolitis and interstitial pneumonitis after a live-virus challenge. Similar enhanced disease has been seen in cotton rats and children immunized with formalin-inactivated respiratory syncytial virus.
Sequestration of p53 in the Cytoplasm by AdenovirusType 12 E1B 55-Kilodalton Oncoprotein Is Required for Inhibition ofp53-MediatedApoptosis
Authors: Zhao Lisa Y. , Liao Daiqing 
Published: November 2003

ABSTRACT
The
adenovirus E1B 55-kDa protein is a potent inhibitor of p53-mediated
transactivation and apoptosis. The proposed mechanisms include
tethering the E1B repression domain to p53-responsive promoters via
direct E1B-p53 interaction. Cytoplasmic sequestration of p53 by the
55-kDa protein would impose additional inhibition on p53-mediated
effects. To investigate further the role of cytoplasmic sequestration
of p53 in its inhibition by the E1B 55-kDa protein we systematically
examined domains in both the Ad12 55-kDa protein and p53 that underpin
their colocalization in the cytoplasmic body and show that the
N-terminal transactivation domain (TAD) of p53 is essential for
retaining p53 in the cytoplasmic body. Deletion of amino acids 11 to 27
or even point mutation L22Q/W23S abolished the localization of p53 to
the cytoplasmic body, whereas other parts of TAD and the C-terminal
domain of p53 are dispensable. This cytoplasmic body is distinct from
aggresome associated with overexpression of some proteins, since it
neither altered vimentin intermediate filaments nor associated with
centrosome or ubiquitin. Formation of this structure is sensitive to
mutation of the Ad12 55-kDa protein. Strikingly, mutation S476/477A
near the C terminus of the Ad12 55-kDa protein eliminated the formation
of the cytoplasmic body. The equivalent residues in the Ad5 55-kDa
protein were shown to be critical for its ability to inhibit p53.
Indeed, Ad12 55-kDa mutants that cannot form a cytoplasmic body can no
longer inhibit p53-mediated effects. Conversely, the Ad12 55-kDa
protein does not suppress p53 mutant L22Q/W23S-mediated apoptosis.
Finally, we show that E1B can still sequester p53 that contains the
mitochondrial import sequence, thereby potentially preventing the
localization of p53 to mitochondria. Thus, cytoplasmic sequestration of
p53 by the E1B 55-kDa protein plays an important role in restricting
p53
activities.
A Recombinant Influenza A Virus Expressing anRNA-Binding-Defective NS1 Protein Induces High Levels of BetaInterferon and Is Attenuated inMice
Authors: Donelan Nicola R. , Basler Christopher F. , García-Sastre Adolfo 
Published: November 2003

ABSTRACT
Previously
we found that the amino-terminal region of the NS1 protein of influenza
A virus plays a key role in preventing the induction of beta interferon
(IFN-β) in virus-infected cells. This region is characterized
by its ability to bind to different RNA species, including
double-stranded RNA (dsRNA), a known potent inducer of IFNs. In order
to investigate whether the NS1 RNA-binding activity is required for its
IFN antagonist properties, we have generated a recombinant influenza A
virus which expresses a mutant NS1 protein defective in dsRNA binding.
For this purpose, we substituted alanines for two basic amino acids
within NS1 (R38 and K41) that were previously found to be required for
RNA binding. Cells infected with the resulting recombinant virus showed
increased IFN-β production, demonstrating that these two amino
acids play a critical role in the inhibition of IFN production by the
NS1 protein during viral infection. In addition, this virus grew to
lower titers than wild-type virus in MDCK cells, and it was attenuated
in mice. Interestingly, passaging in MDCK cells resulted in the
selection of a mutant virus containing a third mutation at amino acid
residue 42 of the NS1 protein (S42G). This mutation did not result in a
gain in dsRNA-binding activity by the NS1 protein, as measured by an in
vitro assay. Nevertheless, the NS1 R38AK41AS42G mutant virus was able
to replicate in MDCK cells to titers close to those of wild-type virus.
This mutant virus had intermediate virulence in mice, between those of
the wild-type and parental NS1 R38AK41A viruses. These results suggest
not only that the IFN antagonist properties of the NS1 protein depend
on its ability to bind dsRNA but also that they can be modulated by
amino acid residues not involved in RNA
binding.
Human Cytomegalovirus Transmission from the Uterus tothe Placenta Correlates with the Presence of Pathogenic Bacteria andMaternalImmunity
Authors: Pereira Lenore , Maidji Ekaterina , McDonagh Susan , Genbacev Olga , Fisher Susan 
Published: November 2003

ABSTRACTPrenatal cytomegalovirus infection may cause pregnancy complications such as intrauterine growth restriction and birth defects. How virus from the mother traverses the placenta is unknown. PCR analysis of biopsy specimens of the maternal-fetal interface revealed that DNA sequences from cytomegalovirus were commonly found with those of herpes simplex viruses and pathogenic bacteria. Cytomegalovirus DNA and infected cell proteins were found more often in the decidua than in the placenta, suggesting that the uterus functions as a reservoir for infection. In women with low neutralizing titers, cytomegalovirus replicated in diverse decidual cells and placental trophoblasts and capillaries. In women with intermediate to high neutralizing titers, decidual infection was suppressed and the placenta was spared. Overall, cytomegalovirus virions and maternal immunoglobulin G were detected in syncytiotrophoblasts, villus core macrophages, and dendritic cells. These results suggest that the outcome of cytomegalovirus infection depends on the presence of other pathogens and coordinated immune responses to viral replication at the maternal-fetal interface.
CD8+T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis
Authors: Wang Yang , Lobigs Mario , Lee Eva , Müllbacher Arno 
Published: November 2003

ABSTRACTC57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+T-cell-deficient mice infected with 103PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+T cells are involved in both recovery and immunopathology in WNV infection.
The δ Region of Outer-Capsid Proteinμ1 Undergoes Conformational Change and Release from ReovirusParticles during CellEntry
Authors: Chandran Kartik , Parker John S. L. , Ehrlich Marcelo , Kirchhausen Tomas , Nibert Max L. 
Published: November 2003

ABSTRACT
Cell
entry by reoviruses requires a large, transcriptionally active
subvirion particle to gain access to the cytoplasm. The features of
this particle have been the subject of debate, but three primary
candidates—the infectious subvirion particle (ISVP), ISVP*, and
core particle forms—that differ in whether putative membrane
penetration protein μ1 and adhesin σ1 remain particle
bound have been identified. Experiments with antibody reagents in this
study yielded new information about the steps in particle disassembly
during cell entry. Monoclonal antibodies specific for the δ
region of μ1 provided evidence for a conformational change inμ
1 and for release of the δ proteolytic fragment from
entering particles. Antiserum raised against cores provided evidence
for entry-related changes in particle structure and identified entering
particles that largely lack the δ fragment inside cells.
Antibodies specific for σ1 showed that it is also largely shed
from entering particles. Limited coimmunostaining with markers for late
endosomes and lysosomes indicated the particles lacking δ andσ
1 did not localize to those subcellular compartments, and
other observations suggested that both the particles and free δ
were released into the cytoplasm. Essentially equivalent findings were
obtained with native ISVPs and highly infectious recoated particles
containing wild-type proteins. Poorly infectious recoated particles
containing a hyperstable mutant form of μ1, however, showed no
evidence for the in vitro and intracellular changes in particle
structure normally detected by antibodies, and these particles instead
accumulated in late endosomes or lysosomes. Recoated particles with
hyperstable μ1 were also ineffective at mediating erythrocyte
lysis in vitro and promoting α-sarcin coentry and intoxication
of cells in cultures. Based on these and other findings, we propose
that ISVP* is a transient intermediate in cell entry which mediates
membrane penetration and is then further uncoated in the cytoplasm to
yield particles, resembling cores, that largely lack the δ
fragment ofμ
1.
DetailedAnalysis of the CD8
+
T-Cell Response followingAdenovirusVaccination
Authors: Yang Teng Chih , Dayball Kelley , Wan Yong Hong , Bramson Jonathan 
Published: November 2003

ABSTRACT

We
examined CD8
+
T-cell expansion and function
following intramuscular immunization with a recombinant adenovirus.
This study has identified a number of properties which may explain the
strong immunogenicity of adenovirus vectors: (i) the ability to deliver
large amounts of antigen into the lymphoid tissues, (ii) the ability to
induce rapid expansion and migration of CD8
+
T cells
throughout the lymphatics, and (iii) the ability to produce a
sustained, high-level CD8
+
T-cell
response.
Identificationof Proteins Associated with Murine Gammaherpesvirus68Virions
Authors: Bortz Eric , Whitelegge Julian P. , Jia Qingmei , Zhou Z. Hong , Stewart James P. , Wu Ting-Ting , Sun Ren 
Published: November 2003

ABSTRACT
Murine
gammaherpesvirus 68 (MHV68 [also known asγ
HV-68]) is distinguished by its ability to
replicate to high titers in cultured cells, making it an excellent
candidate for studying gammaherpesvirus virion composition.
Extracellular MHV68 virions were isolated, and abundant
virion-associated proteins were identified by mass spectrometry. Five
nucleocapsid protein homologues, the tegument protein homologue encoded
by open reading frame (ORF) 75c, and envelope glycoproteins B and H
were detected. In addition, gene products from MHV68 ORF20,
ORF24, ORF28, ORF45, ORF48, and ORF52 were identified in
association with virions, suggesting that these gammaherpesvirus genes
are involved in the early phase of infection or virion assembly and
egress.
A Prophet Tested: Elisha, the Great Woman of Shunem, and the Story's Double Message
Authors: Amit Yairah 
Published: November 2003

AbstractOn casual reading, the story of Elisha and the Shunammite appears to belong to the genre of prophetic legends in praise of the prophets. A closer look, however, reveals marked differences between this story and the usual laudatory tales from the lives of the prophets, and places it in quite a different category. Though Elisha performs miracles—showing that he possessed super-human powers—the story exposes his limitations and human errors. It is, therefore, not so much a laudatory story as one of development. In a development story the miracles are meant not only to impress the prophet's surroundings and the readers of the story, but also to teach the prophet a lesson and to imply to the readers that although he possesses super-human powers, the prophet is only a human being with the failings of his kind. In other words, the prophetic stories of development have a double ambivalent message, and this article attempts to answer the question; what is the purpose and the importance of this complicated message, or of this elaboration of the story.
Israel's Indigenous Origins: Cultural Hybridity and the Formation of Israelite Ethnicity
Authors: Brett Mark 
Published: November 2003

AbstractThis paper addresses the question of whether Iron I settlements in the central Levantine hill country can properly be termed 'Israelite'. Drawing on anthropological theory to interpret the recent archaeological debates, the argument suggests that an Israelite ethnic 'network' arose in the early Iron Age—albeit with a low degree of incorporation—by a process of social fission. In contrast to the Philistine incursion of the same period, there was no imposition of a foreign cultural system. The historical evidence implies that in the course of time the worship of Yhwh, an exodus story, and a 'pig taboo', were added to the indigenous culture in the making of Israelite identity. Yhwh worship was probably not originally seen as a separate religion, but in the Iron II period, it came to be interpreted by some as antagonistic to other gods.
Ezra-Nehemiah as a Narrative of (Re-Invented) Israelite Identity
Authors: Esler Philip 
Published: November 2003

AbstractThis article applies notions of ethnic identity deriving from the work of Fredrik Barth to Ezra-Nehemiah that highlight the processes of boundary formation and maintenance. In particular, it focuses on one of the common indicia of ethnic boundaries, a shared history, here in the form of a 'narrative of ethnic identity' as explained by Stephen Cornell. Such a narrative is a story with a subject (the ethnic group in question), with action, normally in the past, and a value attached to it which bears upon the group's sense of its own worth. It covers the selection, plotting and interpretation of events. The post-exilic return of the Israelites to the land beginning under Cyrus, the erection of the Temple and the re-construction of the walls of Jerusalem described in Ezra-Nehemiah are usefully illuminated and explained when set within such a perspective. A central element of the Barthian understanding of ethnic boundaries, that they are patterns of prescription and proscription, is graphically illustrated in the account of the newly re-installed gates of the city being closed during the sabbath to keep out non-Israelite traders. A model focusing on the creation of a narrative of ethnic identity sheds considerable light on the re-invention of Israelite identity that is arguably the dominant theme in Ezra-Nehemiah.
Evil at Odds with Itself (Matthew 12:22-29): Demonising Rhetoric and Deconstructive Potential in the Matthean Narrative
Authors: Longenecker Bruce 
Published: November 2003

AbstractDeconstructive analysis assumes that every text inevitably contains within itself the seeds of its own rhetorical self-destruction. The Matthean Gospel threatens to undermine its own rhetorical legitimisation in its depiction of evil, the cohorts of evil and evil's strategic incoherence. In Matt. 12:22-29 the story's central protagonist (Jesus) and his main antagonists (the Pharisees) are shown to hold different views on the character of evil. Within the course of the Matthean narrative, the view of the antagonists proves itself to be accurate, with the protagonist's view proving itself to be deficient. The reliability of the protagonist's discernment of things central to his own career and identity is thereby undermined. Comparison of the Matthean narrative with that of Mark suggests that this deconstructive tendency is to be credited to the Matthean evangelist in his efforts to demonise the synagogue of his contemporaries by means of a rhetoric of evil.
Biblical Scholarship in Public Discourse
Authors: Gottwald Norman 
Published: November 2003

AbstractWhile various scholarly strategies for engaging in or avoiding public discourse are recognized as valid, several factors conspire to induce, even compel, biblical scholars to speak their minds in public. This essay examines the various forums in which biblical scholars enter public discourse and the issues they typically address, both in biblical studies and current affairs. It further assesses the net effect of biblical scholars in shaping public policy. Finally, it focuses on the special challenges and dilemmas biblical scholars face when they engage in public discourse, or decline to do so.
"Ja, bin denn ich an Gottes Stelle?" (Genesis 50:19): Beobachtungen und Überlegungen zu einem Schlüsselsatz der Josefsgeschichte und den vielfachen Konsequenzen aus einer rhetorischen Frage
Authors: Ebach Jürgen 
Published: November 2003

AbstractDie Passage Gen. 50:15-21 (fast) am Ende der Josefsgeschichte ist lesbar als Schlüsseltext der gesamten Genesis 37–50 in all ihren Teilen umfassenden Erzählung. Hier kommen die großen Themen der in der Josefsgeschichte fokussierten "Familiengeschichte Jakobs" zusammen. Der zentrale Satz in dieser Passage ist aber nicht die oft hervorgehobene Formulierung in V. 20 (in der Luther-Bibel: "Ihr gedachtet es böse mit mir zu machen, aber Gott gedachte es gut zu machen"), sondern die Frage Josefs in V. 19: "Ja, bin denn ich an Gottes Stelle?" Als rhetorische Frage zielt sie nicht auf die naheliegende Antwort, sondern auf die Konsequenzen, die aus dieser Antwort zu ziehen sind. Der Satz markiert die Grenzen der Herrschaft Josefs, indem sich der Traum aus Genesis 37 ebenso erfüllt wie er korrigiert wird, er markiert aber auch die Grenzen der Vergebung. Brüder sollen einander nicht Knechte sein—das ist das eine. Josefs Rechnung kann nicht Gottes Rechnung sein—das ist das andere. Ob die Geschichte gut ausgeht, ist stets eine Frage der Lektüre und ihrer Perspektive. Josef kann Familie und werdendes Volk retten, weil er in gewisser Weise zum Ägypter geworden ist. Das Rettende wird aber auch zum Trennenden. In dieser Dialektik scheint über Genesis 50 und die Jakob-Josef-Geschichten hinaus ein Dauerthema jüdischer Existenz auf. Diesen Aspekten geht der Aufsatz exegetisch, systematisch-theologisch und geschichtsphilosophisch nach.