bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Immunodeficiency Virus Type 1 Escape Is Restricted When Conserved Genome Sequences Are Targeted by RNA Interference
Authors: von Eije Karin Jasmijn , Brake Olivier ter , Berkhout Ben 
Published: December 2007

ABSTRACT

RNA interference (RNAi) is a cellular mechanism in which small interfering RNAs (siRNAs) mediate sequence-specific gene silencing by cleaving the targeted mRNA. RNAi can be used as an antiviral approach to silence the human immunodeficiency virus type 1 (HIV-1) through stable expression of short-hairpin RNAs (shRNAs). We previously reported efficient HIV-1 inhibition by an shRNA against the nonessential
nef
gene but also described viral escape by mutation or deletion of the
nef
target sequence. The objective of this study was to obtain insight in the viral escape routes when essential and highly conserved sequences are targeted in the Gag, protease, integrase, and Tat-Rev regions of HIV-1. Target sequences were analyzed of more than 500 escape viruses that were selected in T cells expressing individual shRNAs. Viruses acquired single point mutations, occasionally secondary mutations, but—in contrast to what is observed with
nef
—no deletions were detected. Mutations occurred predominantly at target positions 6, 8, 9, 14, and 15, whereas none were selected at positions 1, 2, 5, 18, and 19. We also analyzed the type of mismatch in the siRNA-target RNA duplex, and G-U base pairs were frequently selected. These results provide insight into the sequence requirements for optimal RNAi inhibition. This knowledge on RNAi escape may guide the design and selection of shRNAs for the development of an effective RNAi therapy for HIV-1 infections.
Identification of Three Interferon-Inducible Cellular Enzymes That Inhibit the Replication of Hepatitis C Virus
Authors: Jiang Dong , Guo Haitao , Xu Chunxiao , Chang Jinhong , Gu Baohua , Wang Lijuan , Block Timothy M. , Guo Ju-Tao 
Published: December 2007

ABSTRACTHepatitis C virus (HCV) infection is a common cause of chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. However, the underlying mechanism of IFN-α therapy remains to be elucidated. To identify the cellular proteins that mediate the antiviral effects of IFN-α, we created a HEK293-based cell culture system to inducibly express individual interferon-stimulated genes (ISGs) and determined their antiviral effects against HCV. By screening 29 ISGs that are induced in Huh7 cells by IFN-α and/or up-regulated in HCV-infected livers, we discovered that viperin, ISG20, and double-stranded RNA-dependent protein kinase (PKR) noncytolytically inhibited the replication of HCV replicons. Mechanistically, inhibition of HCV replication by ISG20 and PKR depends on their 3′-5′ exonuclease and protein kinase activities, respectively. Moreover, our work, for the first time, provides strong evidence suggesting that viperin is a putative radicalS-adenosyl-l-methionine (SAM) enzyme. In addition to demonstrating that the antiviral activity of viperin depends on its radical SAM domain, which contains conserved motifs to coordinate [4Fe-4S] cluster and cofactor SAM and is essential for its enzymatic activity, mutagenesis studies also revealed that viperin requires an aromatic amino acid residue at its C terminus for proper antiviral function. Furthermore, although the N-terminal 70 amino acid residues of viperin are not absolutely required, deletion of this region significantly compromises its antiviral activity against HCV. Our findings suggest that viperin represents a novel antiviral pathway that works together with other antiviral proteins, such as ISG20 and PKR, to mediate the IFN response against HCV infection.
CCL3 and Viral Chemokine-Binding Protein gG Modulate Pulmonary Inflammation and Virus Replication during Equine Herpesvirus 1 Infection
Authors: Van de Walle Gerlinde R. , Sakamoto Kaori , Osterrieder Nikolaus 
Published: December 2007

ABSTRACTCCL3 is a proinflammatory chemokine that mediates many of the cellular changes occurring in pulmonary disease. Here, CCL3−/−mice were used to investigate the role of this chemokine during respiratory herpesvirus infection. Compared to wild-type mice, CCL3−/−mice infected with the alphaherpesvirus equine herpesvirus 1 (EHV-1) displayed reduced body weight loss but had higher pulmonary viral loads. Lungs from infected CCL3−/−mice suffered a milder interstitial pneumonia, and fewer immune cells were recovered from the pulmonary airways after infection. We could also demonstrate that herpesvirus-encoded chemokine-binding glycoprotein G (gG) was capable of inhibiting the chemotactic functions of CCL3. This CCL3-mediated chemotaxis, however, was restored in the presence of gG-specific antibodies, which puts into question the advertised use of gG deletion mutants as marker vaccines. In summary, we concluded that CCL3 is a major player in controlling herpesvirus replication in the target organ, the lung, and does so by evoking a strong inflammatory response. The immunomodulatory activity of CCL3 is balanced by the expression of viral gG, whose chemokine-binding activity is mitigated in secondary infections by the production of anti-gG antibodies.
Autorepression of Epstein-Barr Virus Nuclear Antigen 1 Expression by Inhibition of Pre-mRNA Processing
Authors: Yoshioka Mikio , Crum Michelle M. , Sample Jeffery T. 
Published: December 2007

ABSTRACT
Epstein-Barr virus (EBV) latent infection, and its associated oncogenic potential, is dependent on genome maintenance functions of EBV nuclear antigen 1 (EBNA-1), one of six EBNAs expressed from a common promoter (Wp and then Cp) upon infection of naive B cells. Subsequent host-mediated silencing, however, necessitates the expression of EBNA-1 from the EBNA-1-specific promoter Qp to ensure against genome loss during cell division, including EBV-associated malignancy. Here we addressed the mechanism by which EBNA-1 represses Qp through binding downstream of the transcription start site and the role of this autoregulatory function in EBV latency. Our results revealed that EBNA-1 does not inhibit transcription from Qp, as previously predicted, but acts post- or cotranscriptionally to block the processing of primary transcripts. This does not, however, require the RGG motifs responsible for strong but nonspecific RNA binding by EBNA-1. Within isogenic B-cell lines using either Cp/Wp or Qp, EBNA-1 occupancy of Qp is equivalent, suggesting that autoregulation occurs, albeit to different degrees, during full and restricted EBV latency programs. Finally, in cell lines using Cp or Wp for EBNA expression, unprocessed transcripts from Qp are detectable in the absence of corresponding mRNAs, providing further evidence that this novel mechanism of EBNA-1 action functions during latency. This posttranscriptional mechanism of regulation would provide an efficient means to monitor and regulate EBNA-1 expression from Qp, ensuring levels adequate for genome maintenance but, perhaps more importantly, below an immunogenic threshold above which latently infected cells may be at risk for elimination by EBNA-1-specific cytotoxic T cells.
Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007
Authors: Wu Wai Lan , Chen Yixin , Wang Pui , Song Wenjun , Lau Siu-Ying , Rayner Jane M. , Smith Gavin J. D. , Webster Robert G. , Peiris J. S. Malik , Lin Tianwei , Xia Ningshao , Guan Yi , Chen Honglin 
Published: December 2007

ABSTRACT
Antigenic profiles of post-2002 H5N1 viruses representing major genetic clades and various geographic sources were investigated using a panel of 17 monoclonal antibodies raised from five H5N1 strains. Four antigenic groups from seven clades of H5N1 virus were distinguished and characterized based on their cross-reactivity to the monoclonal antibodies in hemagglutination inhibition and cell-based neutralization assays. Genetic polymorphisms associated with the variation of antigenicity of H5N1 strains were identified and further verified in antigenic analysis with recombinant H5N1 viruses carrying specific mutations in the hemagglutinin protein. Modification of some of these genetic variations produced marked improvement to the immunogenicity and cross-reactivity of H5N1 strains in assays utilizing monoclonal antibodies and ferret antisera raised against clade 1 and 2 H5N1 viruses, suggesting that these sites represent antigenically significant amino acids. These results provide a comprehensive antigenic profile for H5N1 virus strains circulating in recent years and will facilitate the recognition of emerging antigenic variants of H5N1 virus and aid in the selection of vaccine strains.
SIAH-1 Interacts with the Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF45 Protein and Promotes Its Ubiquitylation and Proteasomal Degradation
Authors: Abada Rinat , Dreyfuss-Grossman Tsofia , Herman-Bachinsky Yifat , Geva Haim , Masa Shiri-Rivka , Sarid Ronit 
Published: December 2007

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8, is a potentially tumorigenic virus implicated in the etiology of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The open reading frame 45 (ORF45) protein, encoded by the KSHV genome, is capable of inhibiting virus-dependent interferon induction and appears to be essential for both early and late stages of infection. In the present study, we show, both in yeast two-hybrid assays and in mammalian cells, that the ORF45 protein interacts with the cellular ubiquitin E3 ligase family designated seven in absentia homologue (SIAH). We provide evidence that SIAH-1 promotes the degradation of KSHV ORF45 through a RING domain-dependent mechanism and via the ubiquitin-proteasome system. Furthermore, our data indicate the involvement of SIAH-1 in the regulation of the expression of ORF45 in KSHV-infected cells. Since the availability of KSHV ORF45 is expected to influence the course of KSHV infection, our findings identify a novel biological role for SIAH proteins as modulators of virus infection.
Expression of Murine Leukemia Virus Envelope Protein Is Sufficient for the Induction of Apoptosis
Authors: Zhao Xiaoqing , Yoshimura Fayth K. 
Published: December 2007

ABSTRACT

The generation of cytopathic effects by murine leukemia viruses (MLVs) in different cell types correlates with the ability of the virus to induce thymic lymphoma. We showed that the induction of apoptosis in mink epithelial cells by mink cell focus-forming (MCF) MLV infection results in the accumulation of high levels of both unintegrated viral DNA and the envelope precursor polyprotein (gPr80

env

). Comparisons of envelope protein expression levels of plasmid clones of the
env
gene of the MCF13 and noncytopathic NZB-9 MLV strains demonstrated that the accumulation of MCF13 gPr80

env

results in endoplasmic reticulum stress and is sufficient for the induction of apoptosis.
A Biophysical Consideration on Radiation Mutagenesis
Authors: Kondo Sohei 
Published: December 2007

AbstractA perspective picture of radiation mutagenesis, the sequence of events which leads from the absorption of radiation to the eventual recovery of mutants, is presented. A model of the mechanism of mutational events in microorganisms modifiable by postirradiation treatments is proposed and applied to the interpretation of the differences in mutation rate at various stages of germ cells of a higher organism, the silkworm.
Ciliated protozoans from the Precambrian Doushantuo Formation, Wengan, South China
Authors: Li C.-W. , Chen J.-Y. , Lipps J. H. , Gao F. , Chi H.-M. , Wu H.-J. 
Published: December 2007

Abstract
Ciliates, a major eukaryotic crown-group lineage with thousands of living species, are poorly represented in the fossil record. Ciliate biomarkers are known from the Precambrian, but only one group, the tintinnids, have an extensive fossil record dating back to the Ordovician. Thus, the occurrence of probable ciliate body fossils in Neoproterozoic rocks confirms their earlier appearance, so far inferred only from molecular sequence data and biomarkers. In this paper, we describe those fossils from the 580 million year old Precambrian Doushantuo phosphates, Guizhou, South China. Three new monospecific genera (100 µm to 200 µm in size) are represented by three-dimensional specimens with exceptionally well-preserved cell bodies including cilia, cytostome and tentacles. Two possess loricas and are referred to the tintinnids. The third has numerous tentacles, an apical cytostome and somatic cilia; it is interpreted as an ancestral early suctorian ciliate. These fossils indicate that the origin and evolutionary differentiation and specialization of ciliates took place before or along with the radiation of other crown-group eukaryotes, including metazoans.
A brief review of the fossil record of the Ediacaran–Cambrian transition in the area of Montes de Toledo–Guadalupe, Spain
Authors: Jensen S. , Palacios T. , Martí Mus M. 
Published: December 2007

Abstract

The area of western Montes de Toledo to Guadalupe boasts a thick succession of mainly siliciclastic sediment spanning terminal Ediacaran to lower Cambrian strata as indicated by a relatively sparse but diverse palaeontological record. A terminal Ediacaran age is based on the occurrence of
Cloudina
in platform carbonates of the lower part of the Ibor group and in correlative levels of olistostromes at the base of the Río Huso group. Higher in the Río Huso group are found trace fossils which indicate a Cambrian age, notably
Treptichnus bifurcus
, which overlaps the local stratigraphic range of macroscopic carbonaceous disc-shaped fossils identified as
Beltanelliformis
. Strata underlying the Río Huso group contain treptichnids. The fossil record of the terminal Ediacaran–Lower Cambrian of this area is in part comparable to
Cloudina
-bearing sediments from other regions, in particular Namibia, where treptichnid trace fossils also overlap the range of
Cloudina
. The possibility of a wider biostratigraphic significance of this should be further tested, including its relation to the base of the Cambrian.
Discoidal fossils of the Ediacaran biota: a review of current understanding
Authors: MacGabhann B. A. 
Published: December 2007

Abstract
Discoidal fossils, despite being the oldest, youngest, and most common elements of the Ediacaran biota, have not received their fair share of attention. Taxonomy of discoidal fossils is currently dubious, and some forms have not been properly re-examined since the initial incorrect descriptions as medusae. Attachment discs of benthic stalked forms, which adhere to microbial mats at the sediment–water interface, are unequivocally present without stalks or other upper parts in most discoidal Ediacaran assemblages. However, many discoidal assemblages are likely to have represented a heterogeneous mixture of benthic discoidal organisms, including bacterial colonies, fungi, actinian-grade cnidarians, and perhaps poriferans. Such organisms probably account for the vast majority of fossils in the Fermeuse Formation of Newfoundland and similar assemblages from Norway, England, and Wales. Discs in the underlying complex Mistaken Point assemblages, however, likely mostly represent holdfasts. Other complex assemblages, such as those of South Australia and the White Sea of Russia, unequivocally contain more than one biological construction responsible for the discoidal structures, but holdfasts likely represent a significant proportion. The disc-dominated Fermeuse assemblages and the nearby rangeomorph-dominated Mistaken Point assemblages are unlikely to merely represent different taphonomic windows on identical communities, as previously suggested, but rather reflect environmental control on both biotic composition and taphonomy.
Biota in the terminal Proterozoic successions on the Indian subcontinent: a review
Authors: Maithy P. K. , Kumar G. 
Published: December 2007

AbstractOn the Indian subcontinent, Late Proterozoic rocks form part of a continuous sequence grading into Cambrian, postdating the Sturtian glaciation (Cryogenian) and terminated by the Xingkaian/Pan African Orogeny (Late Cambrian). These sequences are restricted to the northwestern part of the Indian Shield, are overlain by Cenozoic sediments of the Indo-Gangetic Plain, and rest unconformably on the oldest platform sequences (Meso—Cryogenian) in many parts of the Lesser and Tethys/Higher Himalaya. Of these, the succession in the Krol Belt, Lesser Himalaya, divided into Baliana, Krol and Tal Groups, is fossiliferous. Changes in faunal composition of acritarchs and cyanobacteria are recorded in the upper part of the Baliana Group, as is the appearance and extinction of forms assigned to the Ediacara fauna in the overlying Krol. Such biotic change is accompanied by a significant depletion in δ13C values in the ‘cap carbonates’. Another δ13C depletion is recorded in the upper part of the Krol Group along with appearance of spiny acanthomorphic acritarchs, scaphomorphs and hercomorphs, small shelly fossils, a variety of Early Cambrian trace fossils and trilobites in the overlying Tal Group. A review of biota reported from the oldest platform sediments (Vindhyan Supergroup, Karnool, Bhima Groups) suggests a Meso-Cryogenian (pre-Sturtian glaciation) age.
Siliceous microfossils and biosiliceous sedimentation in the lowermost Cambrian of China
Authors: Braun A. , Chen J.-Y. , Waloszek D. , Maas A. 
Published: December 2007

Abstract
Clay-rich and siliceous sedimentary rocks of earliest Cambrian age on the Yangtze Platform, China, contain abundant siliceous microfossils. The black cherts and black shales in this sequence, of earliest Cambrian age, contain sponge spicules (both macroscleres and microscleres), derived from lithistid demosponges and hexactinellids. These spicule associations are useful for biostratigraphic correlation, and indicate that Porifera played an important role in the geochemical cycling of silica at the beginning of the Phanerozoic. Phosphatic microfossils also contributed to the deep-sea ecology of this region during the earliest Cambrian.
Molecular Mechanisms of Resveratrol Action in Lung Cancer Cells Using Dual Protein and Microarray Analyses
Authors: Whyte Lorna , Huang Yuan-Yen , Torres Karen , Mehta Rajendra G. 
Published: December 2007

Abstract
Resveratrol, a natural phytoestrogen found in red wine and a variety of plants, is reported to have protective effects against lung cancer; however, there is little work directed toward the understanding of the mechanism of its action in this disease. In this study, we used a combination of experimental approaches to understand the biological activity and molecular mechanisms of resveratrol. Microarray gene expression profiling and high-throughput immunoblotting (PowerBlot) methodologies were employed to gain insights into the molecular mechanisms of resveratrol action in human lung cancer cells. In this report, we confirm the up-regulation of p53 and p21 and the induction of apoptosis by the activation of the caspases and the disruption of the mitochondrial membrane complex. We show the arrest of A549 cells in the G1 phase of cell cycle in the presence of resveratrol and also report alterations in both gene and protein expressions of cyclin A, chk1, CDC27, and Eg5. Furthermore, the results indicated that resveratrol action is mediated via the transforming growth factor-β pathway, particularly through the Smad proteins. Results showed the down-regulation of the Smad activators 2 and 4 and the up-regulation of the repressor Smad 7 as a result of resveratrol treatment. Resveratrol is a potent inhibitor of A549 lung cancer cell growth, and our results suggest that resveratrol may be a promising chemopreventive or chemotherapeutic agent for lung cancer. [Cancer Res 2007;67(24):12007–17]
Predicting Response to Radioimmunotherapy from the Tumor Microenvironment of Colorectal Carcinomas
Authors: El Emir Ethaar , Qureshi Uzma , Dearling Jason L.J. , Boxer Geoffrey M. , Clatworthy Innes , Folarin Amos A. , Robson Mathew P. , Nagl Sylvia , Konerding Moritz A. , Pedley R. Barbara 
Published: December 2007

AbstractSolid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled antibodies (A5B7 anti–carcinoembryonic antigen antibody and a nonspecific control) after i.v. injection in two contrasting human colorectal xenografts in MF1 nude mice. The LS174T is moderately/poorly differentiated, whereas SW1222 has a well-differentiated glandular structure. Biodistribution studies (1.8 MBq 131I-labeled A5B7, four mice per group) showed similar gross tumor uptake at 48 h in the two models (25.1% and 24.0% injected dose per gram, respectively). However, in therapy studies (six mice per group), LS174T required a 3-fold increase in dose (18 versus 6 MBq) to equal SW1222 growth inhibition (∼55 versus ∼60 days, respectively). To investigate the basis of this discrepancy, high-resolution multifluorescence microscopy was used to study antibody localization in relation to tumor parameters (5 min, 1 and 24 h, four mice per time point). Three-dimensional microvascular corrosion casting and transmission electron microscopy showed further structural differences between xenografts. Vascular supply, overall antigen distribution, and tumor structure varied greatly between models, and were principally responsible for major differences in antibody localization and subsequent therapeutic efficacy. The study shows that multiparameter, high-resolution imaging of both therapeutic and tumor microenvironment is required to comprehend complex antibody-tumor interactions, and to determine which tumor regions are being successfully treated. This will inform the design of optimized clinical trials of single and combined agents, and aid individual patient selection for antibody-targeted therapies. [Cancer Res 2007;67(24):11896–905]
Galectin-3 Cleavage: A Novel Surrogate Marker for Matrix Metalloproteinase Activity in Growing Breast Cancers
Authors: Nangia-Makker Pratima , Raz Tirza , Tait Larry , Hogan Victor , Fridman Rafael , Raz Avraham 
Published: December 2007

Abstract
Failed therapies directed against matrix metalloproteinases (MMP) in cancer patients may be attributed, in part, to lack of diagnostic tools to differentiate between pro-MMPs and active MMPs, which indicate whether a treatment is efficacious or not. Because galectin-3 is cleavable in vitro by MMPs, we have developed differential antibodies recognizing its cleaved and noncleaved forms and tested their clinical utilization as a surrogate diagnostic marker for the presence of active MMPs in growing breast cancers. Wild-type and cleavage-resistant galectin-3 were constructed and expressed in galectin-3–null human breast carcinoma cells (BT-549). Tumorigenic and angiogenic potential of the clones was studied by injections into nude mice. MMP-2, MMP-9, full-length, and cleaved galectin-3 were localized in the xenografts by immunohistochemical analysis of paraffin-embedded sections using specific antibodies. Activities of MMP-2/9 were corroborated by in situ zymography on frozen tissue sections. Galectin-3 cleavage was shown in vivo by differential antibody staining and colocalized with predicted active MMPs both in mouse xenografts and human breast cancer specimens. In situ zymography validated these results. In addition, BT-549 cells harboring noncleavable galectin-3 showed reduced tumor growth and angiogenesis compared with the wild-type. We conclude that galectin-3 cleavage is an active process during tumor progression and could be used as a simple, rapid, and reliable surrogate marker for the activities of MMPs in growing breast cancers. [Cancer Res 2007;67(24):11760–8]