bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host-Selected Amino Acid Changes at the Sialic Acid Binding Pocket of the Parvovirus Capsid Modulate Cell Binding Affinity and Determine Virulence
Authors: López-Bueno Alberto , Rubio Mari-Paz , Bryant Nathan , McKenna Robert , Agbandje-McKenna Mavis , Almendral José M. 
Published: January 2006

ABSTRACT

The role of receptor recognition in the emergence of virulent viruses was investigated in the infection of severe combined immunodeficient (SCID) mice by the apathogenic prototype strain of the parvovirus minute virus of mice (MVMp). Genetic analysis of isolated MVMp viral clones (
n
= 48) emerging in mice, including lethal variants, showed only one of three single changes (V325M, I362S, or K368R) in the common sequence of the two capsid proteins. As was found for the parental isolates, the constructed recombinant viruses harboring the I362S or the K368R single substitutions in the capsid sequence, or mutations at both sites, showed a large-plaque phenotype and lower avidity than the wild type for cells in the cytotoxic interaction with two permissive fibroblast cell lines in vitro and caused a lethal disease in SCID mice when inoculated by the natural oronasal route. Significantly, the productive adsorption of MVMp variants carrying any of the three mutations selected through parallel evolution in mice showed higher sensitivity to the treatment of cells by neuraminidase than that of the wild type, indicating a lower affinity of the viral particle for the sialic acid component of the receptor. Consistent with this, the X-ray crystal structure of the MVMp capsids soaked with sialic acid (
N
-acetyl neuraminic acid) showed the sugar allocated in the depression at the twofold axis of symmetry (termed the dimple), immediately adjacent to residues I362 and K368, which are located on the wall of the dimple, and approximately 22 Å away from V325 in a threefold-related monomer. This is the first reported crystal structure identifying an infectious receptor attachment site on a parvovirus capsid. We conclude that the affinity of the interactions of sialic-acid-containing receptors with residues at or surrounding the dimple can evolutionarily regulate parvovirus pathogenicity and adaptation to new hosts.
Mass Spectrometric Analyses of Purified Rhesus Monkey Rhadinovirus Reveal 33 Virion-Associated Proteins
Authors: O'Connor Christine M. , Kedes Dean H. 
Published: January 2006

ABSTRACT
The repertoire of proteins that comprise intact gammaherpesviruses, including the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), is likely to have critical functions not only in viral structure and assembly but also in the early stages of infection and evasion of the host's rapidly deployed antiviral defenses. To develop a better understanding of these proteins, we analyzed the composition of rhesus monkey rhadinovirus (RRV), a close phylogenetic relative of KSHV. Unlike KSHV, RRV replicates to high titer in cell culture and thus serves as an effective model for studying primate gammaherpesvirus structure and virion proteomics. We employed two complementary mass spectrometric approaches and found that RRV contains at least 33 distinct virally encoded proteins. We have assigned 7 of these proteins to the capsid, 17 to the tegument, and 9 to the envelope. Of the five gammaherpesvirus-specific tegument proteins, three have no known function. We also found three proteins not previously associated with a purified herpesvirus and an additional seven that represent new findings for a member of the gamma-2 herpesviruses. Detergent extraction resulted in particles that contained six distinct tegument proteins in addition to the expected capsid structural proteins, suggesting that this subset of tegument components may interact more directly with or with higher affinity for the underlying capsid and, in turn, may play a role in assembly or transport of viral or subviral particles during entry or egress.
Papillomavirus E1 Protein Binds to and Stimulates Human Topoisomerase I
Authors: Clower Randolph V. , Fisk John C. , Melendy Thomas 
Published: January 2006

ABSTRACT
The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular DNA replication factors, such as replication protein A or polymerase α-primase, to replicate PV genomes. Here, E1 is shown to bind to human topoisomerase I and stimulate its relaxation activity up to sevenfold. The interaction between E1 and topoisomerase I was mapped to the E1 DNA binding domain and C terminus. These findings imply a mechanism for the recruitment of topoisomerase I to PV DNA replication forks and for stimulating topoisomerase I to allow for efficient relaxation of the torsional stress induced by replication fork progression.
Direct Stimulation of Translation by the Multifunctional Herpesvirus ICP27 Protein
Authors: Larralde Osmany , Smith Richard W. P. , Wilkie Gavin S. , Malik Poonam , Gray Nicola K. , Clements J. Barklie 
Published: January 2006

ABSTRACT
Herpes simplex virus type 1 (HSV-1) ICP27 protein is an essential regulator of viral gene expression with roles at various levels of RNA metabolism in the nucleus. Using the tethered function assay, we showed a cytoplasmic activity for ICP27 in directly enhancing mRNA translation in vivo in the absence of other viral factors. The region of ICP27 required for translational stimulation maps to the C terminus. Furthermore, in infected cells, ICP27 is associated with polyribosomes, indicating a function in translation during the lytic cycle.
A Gammaherpesvirus 68 Gene 50 Null Mutant Establishes Long-Term Latency in the Lung but Fails To Vaccinate against a Wild-Type Virus Challenge
Authors: Moser Janice M. , Farrell Michael L. , Krug Laurie T. , Upton Jason W. , Speck Samuel H. 
Published: January 2006

ABSTRACT
The gammaherpesvirus immediate-early genes are critical regulators of virus replication and reactivation from latency. Rta, encoded by gene 50, serves as the major transactivator of the lytic program and is highly conserved among all the gammaherpesviruses, including Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and murine gammaherpesvirus 68 (γHV68). Introduction of a translation stop codon in γHV68 gene 50 (gene 50.stop γHV68) demonstrated that Rta is essential for virus replication in vitro. To investigate the role that virus replication plays in the establishment and maintenance of latency, we infected mice with gene 50.stop γHV68. Notably, the gene 50.stop virus established a long-term infection in lung B cells following intranasal infection of mice but was unable to establish latency in the spleen. This complete block in the establishment of latency in the spleen was also seen when lytic virus production was inhibited by treating mice infected with wild-type virus with the antiviral drug cidofovir, implicating virus replication and not an independent function of Rta in the establishment of splenic latency. Furthermore, we showed that gene 50.stop γHV68 was unable to prime the immune system and was unable to protect against a challenge with wild-type γHV68, despite its ability to chronically infect lung B cells. These data indicate gammaherpesviruses that are unable to undergo lytic replication in vivo may not be viable vaccine candidates despite the detection of cells harboring viral genome at late times postinfection.
Rapid Expression of Human Immunodeficiency Virus following Activation of Latently Infected Cells
Authors: Arlen Philip A. , Brooks David G. , Gao Lian Y. , Vatakis Dimitrios , Brown Helen J. , Zack Jerome A. 
Published: January 2006

ABSTRACTThe host cell activation state impacts the nature of human immunodeficiency virus infection. Activated cells facilitate productive infections; quiescent cells enable the virus to enter a latent state, the major obstacle to viral clearance. We wanted to understand how these differences affected viral gene expression. In quiescent cells activated prior to infection, viral RNA was seen 12 h postinfection; when cells were stimulated postinfection, viral RNA was not seen until 36 h postinfection. Up-regulation of viral RNA in latently infected cells occurred within 2 h poststimulation. This hierarchy also held true for viral protein production. These results may explain the rapid reemergence of viremia following termination of therapy.
Identification and Characterization of Two Internal Cleavage and Polyadenylation Sites of Parvovirus B19 RNA
Authors: Yoto Yuko , Qiu Jianming , Pintel David J. 
Published: January 2006

ABSTRACT

Polyadenylation of B19 pre-mRNAs at the major internal site, (pA)p1, is programmed by the nonconsensus core cleavage and polyadenylation specificity factor-binding hexanucleotide AUUAAA. Efficient use of this element requires both downstream and upstream
cis
-acting elements and is further influenced by an adjacent AAUAAC motif. The primary hexanucleotide element must be nonconsensus to allow efficient readthrough of P6-generated pre-mRNAs into the capsid-coding region. An additional cleavage and polyadenylation site, (pA)p2, 296 nucleotides downstream of (pA)p1 was shown to be used following both B19 infection and transfection of a genomic clone. RNAs polyadenylated at (pA)p2 comprise approximately 10% of B19 RNAs that are polyadenylated internally.
Tetrapeptide AcSDKP Induces Postischemic Neovascularization Through Monocyte Chemoattractant Protein-1 Signaling
Authors: Waeckel Ludovic , Bignon Jérôme , Liu Jian-Miao , Markovits Delphine , Ebrahimian Téni G. , Vilar José , Mees Barend , Blanc-Brude Olivier , Barateau Véronique , Le ricousse-Roussanne Sophie , Duriez Micheline , Tobelem Gérard , Wdzieczak-Bakala Joanna , Lévy Bernard I , Silvestre Jean-Sébastien 
Published: January 2006

Background—We investigated the putative proangiogenic activity and molecular pathway(s) of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in a model of surgically induced hindlimb ischemia.Methods and Results—Hindlimb ischemia was induced by femoral artery ligature and an osmotic minipump was implanted subcutaneously to deliver low (0.12 mg/kg per day) or high (1.2 mg/kg per day) doses of AcSDKP, for 7 or 21 days. Angiography scores, arteriole density, capillary number, and foot perfusion were increased at day 21 in the high-dose AcSDKP-treated mice (by 1.9-, 1.8-, 1.3-, and 1.6-fold, respectively) compared with control animals (P<0.05,P<0.01,P<0.01, respectively). AcSDKP treatment for 24 hours upregulated the monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels by 1.5-fold in cultured endothelial cells (P<0.01). In the ischemic hindlimb model, administration of AcSDKP also enhanced MCP-1 mRNA levels by 90-fold in ischemic leg (P<0.001) and MCP-1 plasma levels by 3-fold (P<0.001 versus untreated ischemic control mice). MCP-1 levels upregulation were associated with a 2.3-fold increase in the number of Mac3-positive cells in ischemic area of AcSDKP-treated mice (P<0.001 versus untreated animals). Interestingly, AcSDKP-induced monocyte/macrophage infiltration and postischemic neovascularization was fully blunted in MCP-1-deficient animals.Conclusion—AcSDKP stimulates postischemic neovascularization through activation of a proinflammatory MCP-1-related pathway.
Educational Change Over Time? The Sustainability and Nonsustainability of Three Decades of Secondary School Change and Continuity
Authors: Hargreaves Andy , Goodson Ivor 
Published: January 2006

Purpose: This article presents the conceptual framework, methodological design, and key research findings from a Spencer Foundation-funded project of long-term educational change over time. Research Design: Based on more than 200 interviews, supplementary observations, and extensive archival data, it examines perceptions and experiences of educational change in eight high schools in the United States and Canada among teachers and administrators who worked in the schools in the 1970s, 1980s, and 1990s. Findings: The article indicates that most mainstream educational change theory and practice in the field of educational administration neglects the political, historical, and longitudinal aspects of change to their detriment. Educational change, it finds, is shaped by the convergence of large-scale economic and demographic shifts that produce five change forces (waves of reform, changing student demographics, teacher generations, leadership succession, and school interrelations) that have defined three distinct periods of educational change during the past 30 years. Conclusions: These forces and their convergence have ultimately reaffirmed the traditional identities and practices of conventional high schools and pulled innovative ones back toward the traditional norm in an age of standardization (though to a lesser extent where the schools are professional learning communities or have anactivist orientation). Conclusions are drawn in the form of a strategic theory of sustainable change.
Teacher Nostalgia and the Sustainability of Reform: The Generation and Degeneration of Teachers’ Missions, Memory, and Meaning
Authors: Goodson Ivor , Moore Shawn , Hargreaves Andy 
Published: January 2006

Purpose : This article focuses on the sustainability of reform through the lens of teachers’ nostalgia—the major form of memory among a demographically dominant cohort of experienced older teachers. Unwanted change evokes senses of nostalgia for these lost missions that take two forms: social and political. As teachers age, their responses to change are influenced not only by processes of degeneration (loss of commitment, energy, enthusiasm, etc.) but also by the agendas of the generation—historically situated missions formed decades ago that teachers have carried with them throughout their careers. Findings: Findings indicate that the effects of cumulative demographic and educational change and the resulting nostalgias have left teachers feeling resistant to mandated reform, insecure about their own professional capacity, disenchanted with their students, and pessimistic about their schools’ future. The results of this research have practical implications for policy makers, administrators, and classroom teachers.
School Leadership Succession and the Challenges of Change
Authors: Fink Dean , Brayman Carol 
Published: January 2006

Background: Throughout the Western world, the fallout from the standards/standardization agenda has resulted in potential leaders questioning educational leadership as a career path. Moreover, the aging of the baby boom generation has created a shortage of qualified principals in many educational jurisdictions. Policy makers have responded to these twin pressures by initiating major programs to identify, recruit, and prepare future leaders. Leadership succession, whether planned or unplanned, has become an accelerated and cumulative process that is including people of increasing levels of inexperience. Succession is now a chronic process rather than an episodic crisis. Purpose: This article argues that succession is not the key issue. What is crucial is the degree of autonomy that principals can exercise on behalf of their school community. Findings: During the 30 years of the Change Over Time? study (described elsewhere), we have seen this autonomy eroded to the point that leaders have become managers of systems’ agendas rather than serving their schools and students. Staff members have become cynical about both leaders and leadership succession in the face of cumulative and accelerated succession and perceived changes in their principals’ roles and obligations—increasing the degree of resistance to change. Only when young people begin to see that leadership roles in schools once again make a difference to students learning not just test scores, then quality leaders will emerge and effective succession planning policies developed.
Changing Spaces: Urban School Interrelationships and the Impact of Standards-Based Reform
Authors: Baker Michael , Foote Martha 
Published: January 2006

Background: This article is an historical sociospatial analysis of change during the past three decades within and between three high schools in a deindustrialized city in the northeastern United States. Sociospatial relations are the everyday spatial practices, perceptions, and representations that constitute social worlds. Interrelated with the continued economic decline and spatial segregation in many U.S. cities, state standards-based reform policies are reinforcing and furthering a more hierarchical, homogeneous, and fragmented educational space, increasing the marginalization of some urban schools, teachers, and students. Purpose: This historical sociospatial analysis of urban secondary schools will describe the conjunction of demographic and policy changes contributing to patterns of uneven development that raise questions about the consequences and sustainability of the current state and federal standards-based reform initiatives.
The Sustainability of Innovative Schools as Learning Organizations and Professional Learning Communities During Standardized Reform
Authors: Giles Corrie , Hargreaves Andy 
Published: January 2006

Background: Implicitly, innovative schools have historically contained some (but not usually all) of the properties of learning organizations and professional learning communities but have a weak record of sustaining success over time. Can innovative schools that self-consciously establish themselves as learning organizations and professional learning communities sustain their early promise of success in the face of the predictable cycle of the “attrition of change”; of pressure and envy in the surrounding district, profession, and community; and of the historically specific and recent pressure of standardized reform? Purpose : This article explores the impact of these influences on three innovative schools and their sustainability over time. It concentrates in particular on the promise and viability of one of these schools, which has been consciously modeled as a learning organization and professional learning community. Conclusions: Although further research is required, the article concludes that the learning organization and professional learning community model may provide a more robust resistance to conventional processes of the attrition of change and of surrounding change forces, but much like other innovative schools, it also shows signs of defaulting to conventional patterns of schooling in the face of standardized reform.
Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML
Authors: Reindl Carola , Bagrintseva Ksenia , Vempati Sridhar , Schnittger Susanne , Ellwart Joachim W. , Wenig Katja , Hopfner Karl-Peter , Hiddemann Wolfgang , Spiekermann Karsten 
Published: January 2006

In acute myeloid leukemia (AML), two clusters of activating mutations are known in the FMS-like tyrosine kinase-3 (FLT3) gene: FLT3-internal tandem duplications (FLT3-ITDs) in the juxtamembrane (JM) domain in 20% to 25% of patients, and FLT3 point mutations in the tyrosine-kinase domain (FLT3-TKD) in 7% to 10% of patients, respectively. Here, we have characterized a new class of activating point mutations (PMs) that cluster in a 16-amino acid stretch of the juxtamembrane domain of FLT3 (FLT3-JM-PMs). Expression of 4 FLT3-JM-PMs in interleukin-3 (IL-3)-dependent Ba/F3 cells led to factor-independent growth, hyperresponsiveness to FLT3 ligand, and resistance to apoptotic cell death. FLT3-JM-PM receptors were autophosphorylated and showed a higher constitutive dimerization rate compared with the FLT3-wild-type (WT) receptor. As a molecular mechanism, we could show activation of STAT5 and up-regulation of Bcl-x(L) by all FLT3-JM-PMs. The FLT3 inhibitor PKC412 abrogated the factor-independent growth of FLT3-JM-PM-expressing cells. Compared with FLT3-ITD and FLT3-TKD mutants, the FLT3-JM-PMs showed a weaker transforming potential related to lower autophosphorylation of the receptor and its downstream target STAT5.Mapping of the FLT3-JM-PMs on the crystal structure of FLT3 showed that these mutations reduce the stability of the autoinhibitory JM domain, and provides a structural basis for the transforming capacity of this new class of gain-of-function mutations of FLT3.
Interference with 3′,5′-Cyclic Adenosine Monophosphate Response Element Binding Protein Stimulates Apoptosis through Aberrant Cell Cycle Progression and Checkpoint Activation
Authors: Dworet Jessica H. , Meinkoth Judy L. 
Published: January 2006

Abstract
We previously reported that protein kinase A activity is an important determinant of thyroid cell survival. Given the important role of cAMP response element binding protein (CREB) in mediating the transcriptional effects of protein kinase A, we explored whether interference with CREB family members impaired thyroid cell survival. Expression of A-CREB, a dominant-negative CREB mutant that inhibits CREB DNA binding activity, induced apoptosis in rat thyroid cells. A-CREB inhibited CRE-regulated gene expression but failed to alter the expression of bcl-2 family members or of well-characterized inhibitors of apoptosis. To elucidate the mechanism through which impaired CREB function triggered apoptosis, its effects on cell proliferation were examined. Expression of A-CREB inhibited cell number increases, in part due to delayed cell cycle transit. Protracted S-phase progression in A-CREB-expressing cells was sufficient to activate a checkpoint response characterized by Chk-1, histone H2A.X, and p53 phosphorylation. To determine whether cell cycle progression was required for apoptosis, the effects of p27 overexpression were investigated. Overexpression of p27 prevented cell cycle progression, checkpoint activation, and apoptosis in A-CREB-expressing cells. These data reveal a novel mechanism through which interference with CREB abrogates cell survival, through checkpoint activation secondary to cell cycle delay. This study may explain how interference with CREB induces apoptosis in cells where alterations in the expression of pro- and anti-survival genes are not detected.
Function Cultivation of Transparent Oxides Utilizing Built-In Nanostructure
Authors: Hosono Hideo , Kamiya Toshio , Hirano Masahiro 
Published: January 2006

Abstract
This review article describes recent progress in our research on cultivation of functionality in crystalline and amorphous transparent oxides utilizing nanostructures embedded in the material itself. It includes the background of our research and approach. Subjects included are material exploration and device application of transparent oxide semiconductors for transparent electronics, function emergence in nano-porous crystal 12CaO·7Al2O3 utilizing active anion species stabilized by sub-nanometer-sized cages, and modified silica glass for vacuum/deep ultraviolet lasers. Our description of each subject include: background and approach, material design concept, fabrication or modification method, properties, and device fabrication. Emphasis is placed on the importance of a variety of built-in nanostructures in transparent oxides for novel function realization and the high potential of transparent oxides as ingredients for an ubiquitous element strategy of material research in this century.