bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a Polymer-Based DNA Chip Platform in Detection and Genotyping of Human Papillomavirus in Clinical Samples
Authors: Schenk T. , Brandstetter T. , zur Hausen A. , Alt-Mörbe J. , Huzly D. , Rühe J. 
Published: March 2009

ABSTRACT
Human papillomavirus (HPV) plays a key role in the development of cervical and laryngeal cancers. The aim of our study was to compare the performance of a new hydrogel-based HPV genotyping biochip assay (Biochip) to a commercially available and CE-marked conventional PCR followed by reverse hybridization (GenID-PCR). One hundred twenty-three samples were available for the study. Of these samples, 101/123 were gynecological swabs, 8/123 were swabs or biopsy samples of genital warts, 7/123 were biopsy samples of otorhinolaryngeal lesions, 5/123 were samples of skin warts, and 2/123 were samples of orolabial abnormalities. These molecular methods for HPV genotyping showed comparable sensitivity and specificity. However, 19/123 of the results were discrepant. Specifically, Biochip showed better performance in the detection of multiple infections, especially when more than one high-risk genotype was present. Due to the different probe configurations used in the two assays, GenID-PCR achieves only group-specific detection of many HPV genotypes, whereas Biochip allows for specific identification. Overall, the newly developed HPV chip system (Biochip) proved to be a suitable tool for HPV detection and genotyping; it also proved to be superior for establishing HPV genotyping methods.
Improvement in Mycobacterial Yield and Reduced Time to Detection in Pediatric Samples by Use of a Nutrient Broth Growth Supplement
Authors: Brittle W. , Marais B. J. , Hesseling A. C. , Schaaf H. S. , Kidd M. , Wasserman E. , Botha T. 
Published: March 2009

ABSTRACT

There is an urgent need to improve the methods used for the bacteriological diagnosis of childhood mycobacterial disease. This study compared the mycobacterial yields and the times to detection (in days) of mycobacteria in pediatric clinical specimens by using Mycobacterial Growth Indicator Tubes (MGITs) and solid Löwenstein-Jensen (LJ) slants with and without a nutrient broth supplement. A total of 801 specimens from 493 patients were processed: 82.8% were gastric aspirate specimens, 15.6% were sputum specimens, and 1.6% were fine-needle-aspiration biopsy specimens. The mycobacterial yield obtained with MGITs (with and without nutrient broth) was 11.0%, and that obtained with LJ slants was 1.6% (
P
< 0.001). Of the 88 positive cultures, 62 were detected in MGITs and 73 were detected in MGITs supplemented with nutrient broth (
P
= 0.11). The mean time to detection in MGITs (without nutrient broth) was 18.5 days, whereas it was 12.4 days in MGITs with nutrient broth (
P
< 0.001). Supplementation of standard MGITs improved the mycobacterial yield and significantly reduced the time to detection of mycobacteria in pediatric samples.
Cervid Herpesvirus 2 Causes Respiratory and Fetal Infections in Semidomesticated Reindeer
Authors: das Neves Carlos G. , Rimstad Espen , Tryland Morten 
Published: March 2009

ABSTRACTMembers of the viral subfamilyAlphaherpesvirinaeestablish latency from which they can be reactivated. Bovine herpesvirus 1 causes infectious bovine rhinotracheitis and infectious pustular vulvovaginitis in cattle, as well as abortion and weak calves. Serological evidence of alphaherpesvirus infection has been reported for wild and semidomesticated reindeer (Rangifer tarandus tarandus) in Norway. To address the possibility that reindeer alphaherpesvirus (cervid herpesvirus 2 [CvHV-2]) infection might affect the respiratory system and in part explain the relatively high mortality of reindeer calves during their first year, tissue samples were obtained from reindeer and reindeer fetuses at slaughterhouses in Finnmark County, Norway. A nested pan-alphaherpesvirus PCR amplification targeting the highly conserved UL27 gene (encoding glycoprotein B) was used. Sequencing of amplicons revealed the presence of CvHV-2 DNA. The detection of CvHV-2 DNA in trigeminal ganglia (27 of 143 samples), nasal swabs (5 of 75 samples), and fetal tissues (12 of 48 samples) indicates that CvHV-2 infection is endemic in this reindeer population. Moreover, the virus is transmitted horizontally by the respiratory route, establishing latency in the trigeminal ganglion, and vertically to the fetus through the placenta. Further studies should focus on the reproductive impact of CvHV-2 infection in reindeer.
The LMP1 Promoter Can Be Transactivated Directly by NF-κB
Authors: Demetriades Constantinos , Mosialos George 
Published: March 2009

ABSTRACT

A bioinformatic analysis identified two putative NF-κB binding sites in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promoter. The ability of p65RelA to interact with the LMP1 promoter was shown by in vitro and in vivo assays. Using an EBV-transformed lymphoblastoid cell line as a reporter system for the activity of the +40/−328 LMP1 promoter region, the functional importance of NF-κB and other transcription factor binding sites was demonstrated. p65RelA could also induce LMP1 expression from the EBV genome in Daudi and P3HR1 Burkitt's lymphoma cell lines. Finally, it was shown that p65RelA could cooperate with EBNA2 or the aryl hydrocarbon receptor in the transactivation of the LMP1 promoter. Our study established the importance of NF-κB and several
cis
-acting elements in the regulation of the LMP1 promoter in a latency III environment and highlighted a complex interplay between NF-κB and other transcription factors in this process.
Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope
Authors: Arnold Gail Ferstandig , Velasco Paola K. , Holmes Andrew K. , Wrin Terri , Geisler Sheila C. , Phung Pham , Tian Yu , Resnick Dawn A. , Ma Xuejun , Mariano Thomas M. , Petropoulos Christos J. , Taylor John W. , Katinger Hermann , Arnold Eddy 
Published: March 2009

ABSTRACTIn efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.
Myxoma Virus Expressing Interleukin-15 Fails To Cause Lethal Myxomatosis in European Rabbits
Authors: Liu Jia , Wennier Sonia , Reinhard Mary , Roy Edward , MacNeill Amy , McFadden Grant 
Published: March 2009

ABSTRACT
Myxoma virus (MYXV) is a poxvirus pathogenic only for European rabbits, but its permissiveness in human cancer cells gives it potential as an oncolytic virus. A recombinant MYXV expressing both the tdTomato red fluorescent protein and interleukin-15 (IL-15) (vMyx-IL-15-tdTr) was constructed. Cells infected with vMyx-IL-15-tdTr secreted bioactive IL-15 and had in vitro replication kinetics similar to that of wild-type MYXV. To determine the safety of this virus for future oncolytic studies, we tested its pathogenesis in European rabbits. In vivo, vMyx-IL-15-tdTr no longer causes lethal myxomatosis. Thus, ectopic IL-15 functions as an antiviral cytokine in vivo, and vMyx-IL-15-tdTr is a safe candidate for animal studies of oncolytic virotherapy.
Effect of Preexisting Immunity on an Adenovirus Vaccine Vector: In Vitro Neutralization Assays Fail To Predict Inhibition by Antiviral Antibody In Vivo
Authors: Pichla-Gollon Susan L. , Lin Shih-Wen , Hensley Scott E. , Lasaro Marcio O. , Herkenhoff-Haut Larissa , Drinker Mark , Tatsis Nia , Gao Guang-Ping , Wilson James M. , Ertl Hildegund C. J. , Bergelson Jeffrey M. 
Published: March 2009

ABSTRACT

A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8
+
T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8
+
T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
Nonreplicating Vaccinia Virus Vectors Expressing the H5 Influenza Virus Hemagglutinin Produced in Modified Vero Cells Induce Robust Protection
Authors: Mayrhofer Josef , Coulibaly Sogue , Hessel Annett , Holzer Georg W. , Schwendinger Michael , Brühl Peter , Gerencer Marijan , Crowe Brian A. , Shuo Shen , Hong Wanjing , Tan Yee Joo , Dietrich Barbara , Sabarth Nicolas , Savidis-Dacho Helga , Kistner Otfried , Barrett P. Noel , Falkner Falko G. 
Published: March 2009

ABSTRACT
The timely development of safe and effective vaccines against avian influenza virus of the H5N1 subtype will be of the utmost importance in the event of a pandemic. Our aim was first to develop a safe live vaccine which induces both humoral and cell-mediated immune responses against human H5N1 influenza viruses and second, since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic, an egg-independent production procedure based on a permanent cell line. In the present article, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia virus vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain. This experimental vaccine was compared with a formalin-inactivated whole-virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high-dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain. A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole-virus vaccine, the dVV-HA5 vaccine induced substantial amounts of gamma interferon-secreting CD8 T cells. Thus, the nonreplicating recombinant vaccinia virus vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.
Differential Functions of Interferon-Upregulated Sp100 Isoforms: Herpes Simplex Virus Type 1 Promoter-Based Immediate-Early Gene Suppression and PML Protection from ICP0-Mediated Degradation
Authors: Negorev Dmitri G. , Vladimirova Olga V. , Maul Gerd G. 
Published: March 2009

ABSTRACT

Cells have intrinsic defenses against virus infection, acting before the innate or the adaptive immune response. Preexisting antiviral proteins such as PML, Daxx, and Sp100 are stored in specific nuclear domains (ND10). In herpes simplex virus type 1 (HSV-1), the immediate-early protein ICP0 serves as a counterdefense through degradation of the detrimental protein PML. We asked whether interferon (IFN)-upregulated Sp100 is similarly antagonized by ICP0 in normal human fibroblasts by using a selective-knockdown approach. We find that of the four Sp100 isoforms, the three containing a SAND domain block the transcription of HSV-1 proteins ICP0 and ICP4 at the promoter level and that IFN changes the differential splicing of the
Sp100
transcript in favor of the inhibitor Sp100C. At the protein level, ICP0 activity does not lead to the hydrolysis of any of the Sp100 isoforms. The SAND domain-containing isoforms are not general inhibitors of viral promoters, as the activity of the major immediate-early cytomegalovirus promoter is not diminished, whereas the long terminal repeat of a retrovirus, like the ICP0 promoter, is strongly inhibited. Since we could not find a specific promoter region in the ICP0 gene that responds to the SAND domain-containing isoforms, we questioned whether Sp100 could act through other antiviral proteins such as PML. We find that all four Sp100 isoforms stabilize ND10 and protect PML from ICP0-based hydrolysis. Loss of either all PML isoforms or all Sp100 isoforms reduces the opposite constituent ND10 protein, suggesting that various interdependent mechanisms of ND10-based proteins inhibit virus infection at the immediate-early level.
NS5 of Dengue Virus Mediates STAT2 Binding and Degradation
Authors: Ashour Joseph , Laurent-Rolle Maudry , Shi Pei-Yong , García-Sastre Adolfo 
Published: March 2009

ABSTRACT
The mammalian interferon (IFN) signaling pathway is a primary component of the innate antiviral response. As such, viral pathogens have devised multiple mechanisms to antagonize this pathway and thus facilitate infection. Dengue virus (DENV) encodes several proteins (NS2a, NS4a, and NS4b) that have been shown individually to inhibit the IFN response. In addition, DENV infection results in reduced levels of expression of STAT2, which is required for IFN signaling (M. Jones, A. Davidson, L. Hibbert, P. Gruenwald, J. Schlaak, S. Ball, G. R. Foster, and M. Jacobs, J. Virol. 79:5414-5420, 2005). Translation of the DENV genome results in a single polypeptide, which is processed by viral and host proteases into at least 10 separate proteins. To date, no single DENV protein has been implicated in the targeting of STAT2 for decreased levels of expression. We demonstrate here that the polymerase of the virus, NS5, binds to STAT2 and is necessary and sufficient for its reduced level of expression. The decrease in protein level observed requires ubiquitination and proteasome activity, strongly suggesting an active degradation process. Furthermore, we show that the degradation of but not binding to STAT2 is dependent on the expression of the polymerase in the context of a polyprotein that undergoes proteolytic processing for NS5 maturation. Thus, the mature form of NS5, when not expressed as a precursor, was able to bind to STAT2 but was unable to target it for degradation, establishing a unique role for viral polyprotein processing in providing an additional function to a viral polypeptide. Therefore, we have identified both a novel mechanism by which DENV evades the innate immune response and a potential target for antiviral therapeutics.
Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia
Authors: Li Xiujie , Hanson Charlotte , Cmarik Joan L. , Ruscetti Sandra 
Published: March 2009

ABSTRACT
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic retrovirus that has undergone genetic changes from its nonneuropathogenic parent, Friend MuLV, that allow it to efficiently infect rat brain capillary endothelial cells (BCEC). To clarify the mechanism by which PVC-211 MuLV expression in BCEC induces neurological disease, we examined virus-infected rats at various times during neurological disease progression for vascular and inflammatory changes. As early as 2 weeks after virus infection and before any marked appearance of spongiform neurodegeneration, we detected vessel leakage and an increase in size and number of vessels in the areas of the brain that eventually become diseased. Consistent with these findings, the amount of vascular endothelial growth factor (VEGF) increased in the brain as early as 1 to 2 weeks postinfection. Also detected at this early disease stage was an increased level of macrophage inflammatory protein 1α (MIP-1α), a cytokine involved in recruitment of microglia to the brain. This was followed at 3 weeks postinfection by a marked accumulation of activated microglia in the spongiform areas of the brain accompanied by an increase in tissue plasminogen activator, a product of microglia implicated in neurodegeneration. Pathological observations at the end stage of the disease included loss of neurons, decreased myelination, and mild muscle atrophy. Treatment of PVC-211 MuLV-infected rats with clodronate-containing liposomes, which specifically kill microglia, significantly blocked neurodegeneration. Together, these results suggest that PVC-211 MuLV infection of BCEC results in the production of VEGF and MIP-1α, leading to the vascular changes and microglial activation necessary to cause neurodegeneration.
Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection
Authors: Beckham J. David , Tuttle Kathryn , Tyler Kenneth L. 
Published: March 2009

ABSTRACT
Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.
Nyamanini and Midway Viruses Define a Novel Taxon of RNA Viruses in the Order
Mononegavirales
Authors: Mihindukulasuriya Kathie A. , Nguyen Nang L. , Wu Guang , Huang Henry V. , Travassos da Rosa Amelia P. A. , Popov Vsevolod L. , Tesh Robert B. , Wang David 
Published: March 2009

ABSTRACT

Here, we report the sequencing and classification of Nyamanini virus (NYMV) and Midway virus (MIDWV), two antigenically related viruses that were first isolated in 1957 and 1966, respectively. Although these viruses have been cultured multiple times from cattle egrets, seabirds, and their ticks, efforts to classify them taxonomically using conventional serological and electron microscopic approaches have failed completely. We used a random shotgun sequencing strategy to define the genomes of NYMV and MIDWV. Contigs of 11,631 and 11,752 nucleotides, representing the complete genome of NYMV and the near-complete genome of MIDWV, respectively, were assembled. Each virus genome was predicted to carry six open reading frames (ORFs). BLAST analysis indicated that only two of the ORF proteins of each virus, the putative nucleocapsid and polymerase, had detectable sequence similarity to known viral proteins. Phylogenetic analysis of these ORF proteins demonstrated that the closest relatives of NYNV and MIDWV are negative-stranded-RNA viruses in the order
Mononegavirales
. On the basis of their very limited sequence similarity to known viruses, we propose that NYMV and MIDWV define a novel genus,
Nyavirus
, in this order.
STRING THEORY, THE CRISIS IN PARTICLE PHYSICS AND THE ASCENT OF METAPHORIC ARGUMENTS
Authors: SCHROER BERT 
Published: March 2009

This essay presents a critical evaluation of the concepts of string theory and its impact on particle physics. The point of departure is a historical review of four decades of string theory within the broader context of six decades of failed attempts at an autonomous S matrix approach to particle theory. The central message, contained in Secs. 5 and 6, is that string theory is not what its name suggests, namely a theory of objects in space–time whose localization is string-instead of pointlike. Contrary to popular opinion, the oscillators corresponding to the Fourier models of a quantum-mechanical string do not become embedded in space–time and neither does the "range space" of a chiral conformal QFT acquire the interpretation of stringlike-localized quantum matter. Rather, string theory represents a solution to a problem which enjoyed some popularity in the 1960s: find a principle which, similar to the SO (4,2) group in the case of the hydrogen spectrum, determines an infinite component wave function with a (realistic) mass/spin spectrum. Instead of the group theory used in the old failed attempts, it creates this mass/spin spectrum by combining an internal oscillator quantum mechanics with a pointlike-localized quantum-field-theoretic object, i.e. the mass/spin tower "sits" over one point and does not arise from a wiggling string in space–time. The widespread acceptance of a theory whose interpretation has been based on metaphoric reasoning had a corroding influence on particle theory, a point which will be illustrated in the last section with some remarks of a more sociological nature. These remarks also lend additional support to observations on connections between the discourse in particle physics and the present Zeitgeist of the post–Cold War period that are made in the introduction.
A MEDICAL KNOWLEDGE SERVICE SYSTEM FOR CROSS-ORGANIZATIONAL HEALTHCARE COLLABORATION
Authors: CHEN YUH-JEN 
Published: March 2009

Collaboration among healthcare organizations depends on coordination, communication and control among healthcare organizations and effective sharing of medical information and knowledge. Medical services are knowledge-intensive activities. All information, knowledge, techniques and experience should be integrated, managed and shared using the Internet and information technology. Overall medical service quality and efficiency would be improved markedly if medical professionals and staff at different healthcare organizations could use and share medical knowledge resources. Therefore, a collaborative medical knowledge service would promote medical service quality. This study presents a novel medical knowledge service system for cross-organizational healthcare collaboration such that all medical professionals and staff at different healthcare organizations could capture, store, manage, integrate and share medical knowledge. This system should improve medical service quality and efficiency, and promote competition in the healthcare industry. Thus, this study (i) proposes a collaborative medical knowledge service model, (ii) designs a collaborative medical knowledge service system framework, (iii) develops this proposed system, and (iv) evaluates the developed system based on user satisfaction.