bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotavirus Nonstructural Protein NSP3 Is Not Required for Viral Protein Synthesis
Authors: Montero Hilda , Arias Carlos F. , Lopez Susana 
Published: August 2006

ABSTRACT
Initiation is the rate-limiting step in protein synthesis and therefore an important target for regulation. For the initiation of translation of most cellular mRNAs, the cap structure at the 5′ end is bound by the translation factor eukaryotic initiation factor 4E (eIF4E), while the poly(A) tail, at the 3′ end, is recognized by the poly(A)-binding protein (PABP). eIF4G is a scaffold protein that brings together eIF4E and PABP, causing the circularization of the mRNA that is thought to be important for an efficient initiation of translation. Early in infection, rotaviruses take over the host translation machinery, causing a severe shutoff of cell protein synthesis. Rotavirus mRNAs lack a poly(A) tail but have instead a consensus sequence at their 3′ ends that is bound by the viral nonstructural protein NSP3, which also interacts with eIF4GI, using the same region employed by PABP. It is widely believed that these interactions lead to the translation of rotaviral mRNAs, impairing at the same time the translation of cellular mRNAs. In this work, the expression of NSP3 in infected cells was knocked down using RNA interference. Unexpectedly, under these conditions the synthesis of viral proteins was not decreased, while the cellular protein synthesis was restored. Also, the yield of viral progeny increased, which correlated with an increased synthesis of viral RNA. Silencing the expression of eIF4GI further confirmed that the interaction between eIF4GI and NSP3 is not required for viral protein synthesis. These results indicate that NSP3 is neither required for the translation of viral mRNAs nor essential for virus replication in cell culture.
Novel Function of Prothymosin Alpha as a Potent Inhibitor of Human Immunodeficiency Virus Type 1 Gene Expression in Primary Macrophages
Authors: Mosoian Arevik , Teixeira Avelino , High Anthony A. , Christian Robert E. , Hunt Donald F. , Shabanowitz Jeffrey , Liu Xinyan , Klotman Mary 
Published: August 2006

ABSTRACT

CD8
+
T lymphocytes control human immunodeficiency virus type 1 (HIV-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. Several components of CD8
+
cell supernatants have been identified that contribute to the latter activity. In this study we report that prothymosin alpha (ProTα), a protein found in the cell culture medium of the herpesvirus saimiri-transformed CD8
+
T-cell line, K#1 50K, has potent HIV-1-inhibitory activity. Depletion of native ProTα from an HIV-1-inhibitory fraction of CD8
+
cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProTα is an abundant, acidic peptide that has been reported to be localized in the nucleus and associated with cell proliferation and activation of transcription. In this report we demonstrate that ProTα suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProTα protein potently inhibit HIV-1 long terminal repeat (LTR)-driven gene expression in macrophages. Furthermore studies using different promoters in lentiviral vectors (cytomegalovirus and phosphoglycerate kinase) revealed that suppression of viral replication by ProTα is not HIV LTR specific.
High-Throughput, Library-Based Selection of a Murine Leukemia Virus Variant To Infect Nondividing Cells
Authors: Yu Julie H. , Schaffer David V. 
Published: August 2006

ABSTRACT

Gammaretroviruses, such as murine leukemia virus (MLV), are functionally distinguished from lentiviruses, such as human immunodeficiency virus, by their inability to infect nondividing cells. Attempts to engineer this property into MLV have been hindered by an incomplete understanding of early events in the viral life cycle. We utilized a transposon-based method to generate saturated peptide insertion libraries of MLV
gag-pol
variants with nuclear localization signals randomly incorporated throughout these overlapping genes. High-throughput selection of the libraries via iterative retroviral infection of nondividing cells led to the identification of a novel variant that successfully transduced growth-arrested cells. Vector packaging by cotransfection of the
gag-pol
.
NLS
variant with wild-type
gag-pol
produced high-titer virions capable of infecting neurons in vitro and in vivo. The capacity of mutant virions to transduce nondividing cells could help to elucidate incompletely understood mechanisms of the viral life cycle and greatly broaden the gene therapy applications of retroviral vectors. Furthermore, the ability to engineer key intracellular viral infection steps has potential implications for the understanding, design, and control of other postentry events. Finally, this method of library generation and selection for a desired phenotype directly in a mammalian system can be readily expanded to address other challenges in protein engineering.
Alphavirus Capsid Protein Helix I Controls a Checkpoint in Nucleocapsid Core Assembly
Authors: Hong Eunmee M. , Perera Rushika , Kuhn Richard J. 
Published: August 2006

ABSTRACT
The assembly of the alphavirus nucleocapsid core has been investigated using an in vitro assembly system. The C-terminal two-thirds of capsid protein (CP), residues 81 to 264 in Sindbis virus (SINV), have been previously shown to have all the RNA-CP and CP-CP contacts required for core assembly in vitro. Helix I, which is located in the N-terminal dispensable region of the CP, has been proposed to stabilize the core by forming a coiled coil in the CP dimer formed by the interaction of residues 81 to 264. We examined the ability of heterologous alphavirus CPs to dimerize and form phenotypically mixed core-like particles (CLPs) using an in vitro assembly system. The CPs of SINV and Ross River virus (RRV) do not form phenotypically mixed CLPs, but SINV and Western equine encephalitis virus CPs do form mixed cores. In addition, CP dimers do not form between SINV and RRV in these assembly reactions. In contrast, an N-terminal truncated SINV CP (residues 81 to 264) forms phenotypically mixed CLPs when it is assembled with full-length heterologous CPs, suggesting that the region that controls the mixing is present in the N-terminal 80 residues. Furthermore, this result suggests that the dimeric interaction, which was absent between SINV and RRV CPs, can be restored by the removal of the N-terminal 80 residues of the SINV CP. We mapped the determinant that is responsible for phenotypic mixing onto helix I by using domain swapping experiments. Thus, discrimination of the CP partner in alphavirus core assembly appears to be dependent on helix I sequence compatibility. These results suggest that helix I provides one of the important interactions during nucleocapsid core formation and may play a regulatory role during the early steps of the assembly process.
Keratinocyte-Secreted Laminin 5 Can Function as a Transient Receptor for Human Papillomaviruses by Binding Virions and Transferring Them to Adjacent Cells
Authors: Culp Timothy D. , Budgeon Lynn R. , Marinkovich M. Peter , Meneguzzi Guerrino , Christensen Neil D. 
Published: August 2006

ABSTRACT
Human papillomaviruses (HPVs) replicate only in the terminally differentiating epithelium of the skin and mucosa. While infection of basal keratinocytes is considered a requirement for permissive infection, it remains unclear whether virions can specifically target basal cells for adsorption and uptake following epithelial wounding. We present evidence that HPV binds specifically to laminin 5 (LN5), a component of the extracellular matrix (ECM) secreted by migrating and basal keratinocytes. HPV type 11 capsids colocalized with LN5 in the ECM secreted by vaginal keratinocytes. Binding of both virions and virus-like particles to purified LN5 and to the LN5-rich ECM secreted by cultured keratinocytes was effectively blocked by pretreatment with anti-LN5 antibodies. HPV capsid binding to human cervical mucosa sections included the basement membrane which contains LN5. Cultured keratinocytes expressing α6 integrin, a transmembrane protein known to bind LN5, were readily infected by virions preadsorbed to LN5-containing substrates, whereas mutant keratinocytes lacking α6 integrin were relatively resistant to infection via this route. These findings suggest a model of natural HPV infection in which proliferating keratinocytes expressing α6 integrin at the site of epithelial wounding might be targeted by virions adsorbed transiently to LN5 secreted by migrating keratinocytes.
Envelope Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Induce Similar Bronchioalveolar Tumors in Lungs of Mice
Authors: Wootton Sarah K. , Halbert Christine L. , Miller A. Dusty 
Published: August 2006

ABSTRACT
Jaagsiekte sheep retrovirus (JSRV) induces bronchioalveolar tumors in sheep and goats. Expression of the JSRV envelope (Env) protein in mouse airway epithelial cells induces similar tumors, indicating that Env expression is sufficient for tissue-specific tumor formation. Enzootic nasal tumor virus (ENTV) is related to JSRV but induces tumors in the nasal epithelium of sheep and goats. Here we found that ENTV Env can also induce tumors in mice but, unexpectedly, with a phenotype identical to that of tumors induced by the JSRV Env, indicating that factors other than Env mediate the tissue specificity of tumor induction by ENTV.
Vaginal Protection and Immunity after Oral Immunization of Mice with a Novel Vaccine Strain ofListeria monocytogenesExpressing Human Immunodeficiency Virus Type 1gag
Authors: Zhao Xinyan , Zhang Manxin , Li Zhongxia , Frankel Fred R. 
Published: August 2006

ABSTRACTNatural transmission of human immunodeficiency virus (HIV) occurs at mucosal surfaces. During acute infection, intestinal and other mucosae are preferential sites of virus replication and rapidly become depleted of CD4+T cells. Therefore, mucosal immunity may be critical to control both initial infection and the massive early spread of virus. An attenuatedd-alanine-requiring strain of the oral intracellular microorganismListeria monocytogenesexpressing HIV type 1gagwas shown to induce protective cell-mediated immunity in mice against viruses that express HIVgagwhen immunization occurs in the presence of a transient supply ofd-alanine. In this study, we examined the efficacy of new attenuated strains that are able to synthesized-alanine from a heterologousdalgene tightly regulated by anactA-promoted resolvase recombination system. In the absence ofd-alanine, Gag-specific cytotoxic T lymphocytes (CTLs) were induced systemically after intravenous immunization, and one strain, Lmdd-gag/pARS, induced strong dose-dependent Gag-specific CTLs after oral immunization. A significant level of Gag-specific CD8+T cells was induced in the mucosal-associated lymphoid tissues (MALTs). Upon intravaginal challenge of these orally immunized mice with recombinant vaccinia virus (rVV) expressing HIVgag, gamma interferon- and tumor necrosis factor alpha-secreting Gag-specific CD8+T cells were dramatically increased in the spleen and MALTs. Oral immunization with Lmdd-gag/pARS led to complete protection against vaginal challenge by a homologous clade Bgag-expressing rVV. In addition, strong cross-clade protection was seen against clades A and C and partial protection against clade Ggag-expressing rVV. These results suggest that Lmdd-gag/pARS may be considered as a novel vaccine candidate for use against HIV/AIDS.
α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6
Authors: Wu Zhijian , Miller Edward , Agbandje-McKenna Mavis , Samulski Richard Jude 
Published: August 2006

ABSTRACT

Recombinant adeno-associated viruses (AAVs) are promising vectors in the field of gene therapy. Different AAV serotypes display distinct tissue tropism, believed to be related to the distribution of their receptors on target cells. Of the 11 well-characterized AAV serotypes, heparan sulfate proteoglycan and sialic acid have been suggested to be the attachment receptors for AAV type 2 and types 4 and 5, respectively. In this report, we identify the receptor for the two closely related serotypes, AAV1 and AAV6. First, we demonstrate using coinfection experiments and luciferase reporter analysis that AAV1 and AAV6 compete for similar receptors. Unlike heparin sulfate, enzymatic or genetic removal of sialic acid markedly reduced AAV1 and AAV6 binding and transduction. Further analysis using lectin staining and lectin competition assays identified that AAV1 and AAV6 use either α2,3-linked or α2,6-linked sialic acid when transducing numerous cell types (HepG2, Pro-5, and Cos-7). Treatment of cells with proteinase K but not glycolipid inhibitor reduced AAV1 and AAV6 infection, supporting the hypothesis that the sialic acid that facilitates infection is associated with glycoproteins rather than glycolipids. In addition, we determined by inhibitor (
N
-benzyl GalNAc)- and cell line-specific (Lec-1) studies that AAV1 and AAV6 require N-linked and not O-linked sialic acid. Furthermore, a resialylation experiment on a deficient Lec-2 cell line confirmed a 2,3 and 2,6 N-linked sialic acid requirement, while studies of mucin with O-linked sialic acid showed no inhibition effect for AAV1 and AAV6 transduction on Cos-7 cells. Finally, using a glycan array binding assay we determined that AAV1 efficiently binds to NeuAcα2-3GalNAcβ1-4GlcNAc, as well as two glycoproteins with α2,3 and α2,6 N-linked sialic acids. Taken together, competition, genetic, inhibitor, enzymatic reconstitution, and glycan array experiments support α2,3 and α2,6 sialic acids that are present on N-linked glycoproteins as primary receptors for efficient AAV1 and AAV6 viral infection.
Temporal Transcription Program of Recombinant
Autographa californica
Multiple Nucleopolyhedrosis Virus
Authors: Jiang Shih Sheng , Chang I-Shou , Huang Lin-Wei , Chen Po-Cheng , Wen Chi-Chung , Liu Shu-Chen , Chien Li-Chu , Lin Chung-Yen , Hsiung Chao A. , Juang Jyh-Lyh 
Published: August 2006

ABSTRACT

Baculoviruses, a family of large, rod-shaped viruses that mainly infect lepidopteran insects, have been widely used to transduce various cells for exogenous gene expression. Nonetheless, how a virus controls its transcription program in cells is poorly understood. With a custom-made baculovirus DNA microarray, we investigated the recombinant
Autographa californica
multiple nucleopolyhedrosis virus (Ac
M
NPV) gene expression program in lepidopteran Sf21 cells over the time course of infection. Our analysis of transcription kinetics in the cells uncovered sequential viral gene expression patterns possibly regulated by different mechanisms during different phases of infection. To gain further insight into the regulatory network, we investigated the transcription program of a mutant virus deficient in an early transactivator (
pe38
) and uncovered several
pe38
-dependent and
pe38
-independent genes. This study of baculovirus dynamic transcription programs in different virus genetic backgrounds provides new molecular insights into how gene expression in viruses is regulated.
Inhibiting Hypoxia-Inducible Factor 1 for Cancer Therapy
Authors: Melillo Giovanni 
Published: August 2006

AbstractHypoxia has long been recognized as a common feature of solid tumors and a negative prognostic factor for response to treatment and survival of cancer patients. The discovery of hypoxia-inducible factor 1 (HIF-1), a molecular determinant of the response of mammalian cells to hypoxia, has led to the identification of a “molecular target” of hypoxia suitable for the development of cancer therapeutics. Early controversy about whether or not HIF-1 is a good target for therapy has not discouraged academic groups and pharmaceutical companies from actively engaging in the discovery of small-molecule inhibitors of HIF. However, what is the best strategy to inhibit HIF and how HIF inhibitors should be developed for treatment of human cancers is still poorly defined. In this review, aspects related to the identification and early development of novel HIF inhibitors are discussed. Identification and validation of pharmacodynamic end points relevant to the HIF-1 pathway is essential for a rational development of HIF inhibitors. Integration of these biomarkers in early clinical trials may provide valuable information to determine the contribution of HIF inhibitors to response to therapy. Finally, HIF inhibitors should be incorporated in combination strategies to effectively target multiple cellular components of the tumor microenvironment and redundant signaling pathways frequently deregulated in human cancer. (Mol Cancer Res 2006;4(9):601–5)
Late Judeo-Aramaic: The Language of Theosophic Kabbalah
Authors: Mopsik Charles 
Published: August 2006

AbstractFrom Antiquity to the modern era, Aramaic co-existed with Hebrew as a language of Jewish literary production, and for certain types of writing, especially on topics associated with a degree of esotericism such as magic, prophetic revelation and mystical speculation, it often asserted itself as the preferred language long after Aramaic had ceased to function as a spoken vernacular. This article considers the possible reasons for this preference. It focuses on the Zohar, which established Aramaic as the language of theosophical mysticism in thirteenth-century Castile, and traces the linguistic impact of this work on subsequent schools of Kabbalah.
Hebrew and Aramaic as Languages of the Zohar
Authors: Liebes Yehuda 
Published: August 2006

AbstractApart from a few Hebrew sections, most of the Zohar is written in a unique language: an idiosyncratic Aramaic that cannot be classified within the standard division of Aramaic dialects and which was never a spoken language. On these grounds the scholarly literature has labelled it 'artificial'. The present article challenges this label, arguing that the Aramaic of the Zohar is completely natural. Aramaic was traditionally used for mystical purposes, and the Zohar's preference for this language as the best vehicle for advancing its own mystical purpose has been vindicated by the work's quality and lasting effect.
Observations on the Verbless Clause in the Language of Neophyti I
Authors: Butts Aaron Michael 
Published: August 2006

AbstractThe present study provides a description of the syntax of the verbless clause in Targum Neophyti I. It begins with several introductory remarks before proceeding to the main portion of the paper, which consists of a description of the two primary patterns for the verbless clause in Neophyti, each of which may be expanded via extraposition of the subject. The study concludes with a brief discussion of the translation technique of Neophyti, arguing that at least in the case of the verbless clause, Targum Neophyti should be considered idiomatic Aramaic syntax and not a calque of the Hebrew Vorlage.
?q(n) 'wood' in the Aramaic Ostraca from Idumea: A Note on the Reflex of Proto-Semitic/*s/in Imperial Aramaic
Authors: Notarius Tania 
Published: August 2006

AbstractA new spelling of the Aramaic lexeme 'wood' has been revealed. The note deals with the paleographic, orthographic, phonetic and phonemic implications of this spelling. It is claimed that in Idumean Aramaic of the fourth century BCE the reflex of the Proto-Semitic lateral fricative emphatic was realized as pharyngeal approximant ayin, what brought to the dissimilation of the first of two pharyngeals in this lexeme.
Multicenter Phase II Clinical Study of Iodine-131–Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma
Authors: Leahy Michael F. , Seymour John F. , Hicks Rodney J. , Turner J. Harvey 
Published: August 2006

Purpose To evaluate efficacy and safety of iodine-131 (131I) –rituximab chimeric anti-CD20 antibody radioimmunotherapy in patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL). Patients and Methods After a standard loading dose of rituximab 375 mg/m2, individualized dosimetry was performed by whole-body gamma imaging of a tracer activity of 131I-rituximab followed by administration of a therapeutic activity of 131I-rituximab to deliver an estimated whole-body radiation absorbed dose of 0.75 Gy. Results Ninety-one patients were entered onto the trial: 78 patients (86%) had follicular lymphoma, six patients (7%) had mucosa-associated lymphoid tissue/marginal zone lymphoma, and seven patients (8%) had small lymphocytic lymphoma. The objective overall response rate (ORR) was 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Median duration of response for patients achieving CR/CRu was 20 v 7 months for those with a partial response (P = .0121). Median progression-free survival for the entire cohort was 13 months, with 14% remaining relapse free beyond 4 years. Median follow-up was 23 months, with a 4-year actuarial survival rate of 59% ± 10%. Toxicity was principally hematologic; grade 4 thrombocytopenia occurred in 4% and neutropenia occurred in 16% of patients, with nadirs at 6 to 7 weeks after treatment. Conclusion 131I-rituximab radioimmunotherapy of relapsed or refractory indolent NHL achieves high ORR and CR rates with minimal toxicity.
An Easy Approach to Fabrication of Silica Nanofibers/Nanotubes via Wrapping Sacrificial Cd(OH)2 Nanostrands
Authors: He Junhui , Li Chengzhang 
Published: August 2006

Abstract
An easy approach to synthesis of silica nanofibers and nanotubes via wrapping sacrificial Cd(OH)2 nanostrands was developed, and a plausible formation mechanism was proposed.
Direct α-Hydroxylation of Ketones Catalyzed by Organic–Inorganic Hybrid Polymer
Authors: Arai Takayoshi , Sato Toru , Noguchi Hiroshi , Kanoh Hirofumi , Kaneko Katsumi , Yanagisawa Akira 
Published: August 2006

Abstract
Direct α-hydroxylation of ketones using molecular oxygen was accomplished by organic–inorganic hybrid polymers. A newly prepared Cu-piperazine hybrid polymer was tolerant to the basic conditions, and with employment of lithium hydroxide smoothly catalyzed the α-hydroxylation of ketones. In the present catalytic process not only tetralone derivatives, but also acyclic ketones were converted to the α-hydroxy ketones in good yield.
Dye Adsorption as a Method of Identifying Clays
Authors: Dodd Charles G. 
Published: August 2006

Abstract
Dyestuffs and other reagents which exhibit characteristic colors when
adsorbed on clay granules frequently have been employed as aids in clay
identification. The colors generally are believed to result from pleochroic
effects and acid-base or oxidation-reduction reaction mechanisms. Certain
aniline dyes, solutions of which vary in color according to their hydrogen
ion content, may be used to indicate the relative acidity of clay.surfaces
as well as to heighten the natural pleochroism of kaolin minerals. When n
clay sample has been pretreated with acid, the colors assumed by the
adsorbed dye depend on the characteristic base exchange capacities of the
various clay mineral groups present.
Aromatic diamines, amino phenols, and other compounds which can be
oxidized to colored semiquinone cations permit particularly sensitive and
positive identification of members of the montmorillonoid family and certain
other three-layer clay minerals. Theories concerning the nature of this
apparently catalytic oxidation on clay surfaces are inadequate to explain
the reactions. New concepts and additional experimental information are
needed.