bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lethal Mutagenesis of Poliovirus Mediated by a Mutagenic Pyrimidine Analogue
Authors: Graci Jason D. , Harki Daniel A. , Korneeva Victoria S. , Edathil Jocelyn P. , Too Kathleen , Franco David , Smidansky Eric D. , Paul Aniko V. , Peterson Blake R. , Brown Daniel M. , Loakes David , Cameron Craig E. 
Published: August 2007

ABSTRACT
Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase-mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension, and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous base-pairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture, owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses.
Torque Teno Virus (SANBAN Isolate) ORF2 Protein Suppresses NF-κB Pathways via Interaction with IκB Kinases
Authors: Zheng Hong , Ye Linbai , Fang Xiaonan , Li Baozong , Wang Yuhua , Xiang Xiaoxiao , Kong Lingbao , Wang Wei , Zeng Yinchun , Ye Li , Wu Zhenghui , She Yinglong , Zhou Xiaolin 
Published: August 2007

ABSTRACTSince the first discovery of Torque teno virus (TTV) in 1997, many researchers focused on its epidemiology and transcriptional regulation, but the function of TTV-encoded proteins remained unknown. The function of the TTV open reading frame (ORF) in the nuclear factor κB (NF-κB) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-κB activity in a dose-dependent manner in the canonical NF-κB pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-κB expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IκBα protein degradation. Further immunoprecipitation assays showed that the TTV ORF2 protein could physically interact with IKKβ as well as IKKα, but not IKKγ. Luciferase assays and Western blot experiments showed that the TTV ORF2 protein could also suppress NF-κB activity in the noncanonical NF-κB pathway and block the activation and translocation of p52. Finally, we found that the TTV ORF2 protein inhibited the transcription of NF-κB-mediated downstream genes (interleukin 6 [IL-6], IL-8, and COX-2) through down-regulation of NF-κB. Together, these data indicate that the TTV ORF2 protein suppresses the canonical and noncanonical NF-κB pathways, suggesting that the TTV ORF2 protein may be involved in regulating the innate and adaptive immunity of organisms, contributing to TTV pathogenesis, and even be related to some diseases.
Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans
Authors: Belser Jessica A. , Lu Xuihua , Maines Taronna R. , Smith Catherine , Li Yan , Donis Ruben O. , Katz Jacqueline M. , Tumpey Terrence M. 
Published: August 2007

ABSTRACTBefore 2003, only occasional case reports of human H7 influenza virus infections occurred as a result of direct animal-to-human transmission or laboratory accidents; most of these infections resulted in conjunctivitis. An increase in isolation of avian influenza A H7 viruses from poultry outbreaks and humans has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. To better understand the pathogenesis of H7 viruses, we have investigated their ability to cause disease in mouse and ferret models. Mice were infected intranasally with H7 viruses of high and low pathogenicity isolated from The Netherlands in 2003 (Netherlands/03), the northeastern United States in 2002-2003, and Canada in 2004 and were monitored for morbidity, mortality, viral replication, and proinflammatory cytokine production in respiratory organs. All H7 viruses replicated efficiently in the respiratory tracts of mice, but only Netherlands/03 isolates replicated in systemic organs, including the brain. Only A/NL/219/03 (NL/219), an H7N7 virus isolated from a single fatal human case, was highly lethal for mice and caused severe disease in ferrets. Supporting the apparent ocular tropism observed in humans following infection with viruses of the H7 subtype, both Eurasian and North American lineage H7 viruses were detected in the mouse eye following ocular inoculation, whereas an H7N2 virus isolated from the human respiratory tract was not. Therefore, in general, the relative virulence and cell tropism of the H7 viruses in these animal models correlated with the observed virulence in humans.
Fusion Induced by a Class II Viral Fusion Protein, Semliki Forest Virus E1, Is Dependent on the Voltage of the Target Cell
Authors: Markosyan Ruben M. , Kielian Margaret , Cohen Fredric S. 
Published: August 2007

ABSTRACT
Cells expressing the low pH-triggered class II viral fusion protein E1 of Semliki Forest virus (SFV) were fused to target cells. Fusion was monitored by electrical capacitance and aqueous dye measurements. Electrical voltage-clamp measurements showed that SFV E1-induced cell-cell fusion occurred quickly after acidification for a trans-negative potential across the target membrane (i.e., negative potential inside the target cell) but that a trans-positive potential eliminated all fusion. Use of an ionophore to control potentials for a large population of cells confirmed the dependence of fusion on voltage polarity. In contrast, fusion induced by the class I fusion proteins of human immunodeficiency virus, avian sarcoma leukosis virus, and influenza virus was independent of the voltage polarity across the target cell. Initial pore size and pore growth were also independent of voltage polarity for the class I proteins. An intermediate of SFV E1-induced fusion was created by transient acidification at low temperature. Membranes were hemifused at this intermediate state, and raising the temperature at neutral pH allowed full fusion to occur. Capacitance measurements showed that maintaining a trans-positive potential definitely blocked fusion at steps following the creation of the hemifusion intermediate and may have inhibited fusion at prior steps. It is proposed that the trans-negative voltage across the endosomal membrane facilitates fusion after low-pH-induced conformational changes of SFV E1 have occurred.
Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis
Authors: Schaecher Scott R. , Touchette Erin , Schriewer Jill , Buller R. Mark , Pekosz Andrew 
Published: August 2007

ABSTRACT
The proteins encoded by gene 7 of the severe acute respiratory syndrome coronavirus (SARS-CoV) have been demonstrated to have proapoptotic activity when expressed from cDNA but appear to be dispensable for virus replication. Recombinant SARS-CoVs bearing deletions in gene 7 were used to assess the contribution of gene 7 to virus replication and apoptosis in several transformed cell lines, as well as to replication and pathogenesis in golden Syrian hamsters. Deletion of gene 7 had no effect on SARS-CoV replication in transformed cell lines, nor did it alter the induction of early apoptosis markers such as annexin V binding and activation of caspase 3. However, viruses with gene 7 disruptions were not as efficient as wild-type virus in inducing DNA fragmentation, as judged by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, indicating that the gene 7 products do contribute to virus-induced apoptosis. Disruption of gene 7 did not affect virus replication or morbidity in golden Syrian hamsters, suggesting that the gene 7 products are not required for acute infection in vivo. The data indicate that open reading frames 7a and 7b contribute to but are not solely responsible for the apoptosis seen in SARS-CoV-infected cells.
Critical Role for Arginine Methylation in Adenovirus-Infected Cells
Authors: Iacovides Demetris C. , O'Shea Clodagh C. , Oses-Prieto Juan , Burlingame Alma , McCormick Frank 
Published: August 2007

ABSTRACT
During the late stages of adenovirus infection, the 100K protein (100K) inhibits the translation of cellular messages in the cytoplasm and regulates hexon trimerization and assembly in the nucleus. However, it is not known how it switches between these two functions. Here we show that 100K is methylated on arginine residues at its C terminus during infection and that this region is necessary for binding PRMT1 methylase. Methylated 100K is exclusively nuclear. Mutation of the third RGG motif (amino acids 741 to 743) prevents localization to the nucleus during infection, suggesting that methylation of that sequence is important for 100K shuttling. Treatment of infected cells with methylation inhibitors inhibits expression of late structural proteins. These data suggest that arginine methylation of 100K is necessary for its localization to the nucleus and is a critical cellular function necessary for productive adenovirus infection.
Neonatal volume guarantee ventilation: effects of spontaneous breathing, triggered and untriggered inflations
Authors: McCallion N , Lau R , Morley C J , Dargaville P A 
Published: August 2007

Background:During volume guarantee (VG) ventilation the peak inflating pressure (PIP) for each ventilator inflation is adjusted to ensure the expired tidal volume (VTe) is close to the set VTe. Differences in the PIP between inflations triggered by the infant’s inspirations and untriggered inflations are seen.Aim:To investigate the effects of triggered and untriggered inflations on PIP and VTe.Methods:Neonates were ventilated with the Dräger Babylog 8000 using assist control (synchronous intermittent positive pressure ventilation) and VG modes. Continuous recordings of ventilator pressures and tidal volumes were made at 200 Hz for 10 minutes.Results:In 10 infants, 6540 inflations were analysed, of which 4052 (62%) were triggered. Triggered inflations had a significantly lower mean (SD) PIP than untriggered inflations: 12.9 (4.9) vs 17.0 (3.3) cm H2O, (p<0.001). Despite this, there was no significant difference in the VTe of each type of inflation (103% and 101% of the set VTe, respectively). When a triggered inflation was immediately preceded or followed by an untriggered inflation the PIP changed by about 5 cm H2O. Between adjacent inflations of the same type, the change in PIP was less than 3 cm H2O: for triggered inflations it was 0.11 (1.50) cm H2O and for untriggered inflations 0.06 (1.53) cm H2O.Conclusion:During VG ventilation with the Dräger Babylog 8000 the PIP was 4 cm H2O lower during triggered inflations than untriggered inflations, although the expired tidal volumes were similar.
Geochronology and the geological record
Authors: Snelling N.J. 
Published: August 2007

Abstract
Some history

By about the middle of the nineteeth century natural scientists had come to the conclusion that geological time was to be measured in hundreds of millions of years. Darwin in the first edition of
The Origin of Species
published in 1859 estimated that 300 million years had elapsed since the end of the Mesozoic Era; Lyell concluded in 1867 that about 240 million years had elapsed since the beginning of the Ordovician Period. Despite the temptation to point out the obvious discrepancy in these particular estimates and to suggest that they were no more than educated guesses it must be remembered that they reflected the most careful marshalling of a vast number of verifiable observations. Indeed they can now be seen to be remarkably realistic and in marked contrast to the estimates based on more theoretical considerations such as ocean salinity, sediment thickness, the cooling of the Earth or the Sun's energy source.

Towards the end of the nineteenth century the geologists' views regarding the age of the Earth came under particularly strong attack from W. Thomson (later Lord Kelvin) whose arguments were based on the energy source of the Sun and the cooling history of the Earth, and who concluded that the Earth was probably younger than about 100 million years. That geologists found Thomson's estimates thoroughly unpalatable is very clear from the literature of the time but his calculations were apparently irrefutable. However, the impasse was soon to be resolved following the discovery of the phenomenon of radioactivity
Precambrian geochronology and the geological record
Authors: Moorbath S. , Taylor P. N. 
Published: August 2007

Summary
Rb-Sr, Sm-Nd and Pb/Pb whole-rock isochron methods and the U-Pb zircon method have been widely applied to dating Precambrian igneous and meta-igneous rocks. Application of these methods in regional geochronological studies provides reliable constraints on the age and temporal evolution of rock units, even when some parent-daughter systems have suffered disturbance in metamorphic and/or metasomatic events which significantly post-date primary rock formation. Initial isotopic compositions of Sr, Nd and Pb aid geological interpretation of isochron age data, constrain crustal residence time of the protoliths and can be used to assess the relative contributions of mantle and crust in magma genesis.

Precambrian sediments can be indirectly dated by reference to age data on interbedded volcanics, or by age-bracketing between dated basement rocks and dated cross-cutting intrusives. Significant progress has also been made in the direct dating of sedimentary rocks. Published isotopic age determinations on early Precambrian sediments containing biogenic remains are briefly reviewed. Provided that stratigraphical and geochronological correlations are correct, it appears that stromatohtic limestones were being deposited by
c.
3400 - 3300 Ma ago, and that true microfossils occur in rocks dated at
c.
3200 - 3000 Ma. Evidence relating to possible biogenic markers in sediments reliably dated at
c.
3800 - 3700 Ma is not yet definitive.
The Ordovician, Silurian and Devonian periods
Authors: McKerrow W. S. , Lambert R. St. J. , Cocks L. R. M. 
Published: August 2007

Summary

A reassessment of published age determinations, including some recent dates on Middle Devonian, Late Silurian, basal Caradoc and middle Arenig rocks, enables the construction of a more precise time-scale. The most accurate points on our scale are: basal Frasnian, 368 ± 8 Ma; early Ludlow, 421 ± 2 Ma; end of early Llandovery, 431 ± 6 Ma; early Caradoc, 450 ± 7; middle Arenig, 482 ± 5 Ma. Interpolations from these data indicate that the base of the Devonian is 412 ± 5 Ma, and the base of the Silurian is 435 ± 7 Ma. The end of the Devonian is less precise, we estimated it to be at 354 + 10, -5 Ma (depending on stratigraphic and sedimentological estimates for the duration of the Frasnian and Famennian stages). The base of the Tremadoc is perhaps 513 ± 10 Ma. Dating by K/Ar,
40
Ar/
39
Ar, U/Pb and Sm/Nd all show good agreement, but some Rb/Sr isochrons on acid volcanic rocks lie off our time-scale line. Most fission track dates on zircons from bentonites have very large errors; a few with the smallest errors are shown on our graph, but none of them have been precise enough to use in the construction of the time-scale.
Geochronology of the Carboniferous, Permian and Triassic
Authors: Forster S. C. , Warrington G. 
Published: August 2007

Abstract
Criteria concerning sample and analytical data and stratigraphic control have been used in a critical assessment of the suitability, for use in construction of a Phancrozoic time-scale, of radiometric data relevant to the Carboniferous, Permian and Triassic periods. Few of the age determinations available in 1982 satisfy these criteria and many of those used previously as a basis for time-scales for this part of the Phanerozoic are considred unacceptable by present standards. On the basis of this review, ages of 365 ± 5 Ma, 290 ± Ma and 250 © 5 Ma. respectively, are proposed for the beginning of the Carboniferous. Permain and Triassic periods, and 205 © 5 Ma for the end of the Triassic. Radiometric ages are related. where possible, to the principal chronostratigraphic divisions of the rock successions representing those periods.
Jurassic to Paleogene: Part 2 Paleogene geochronology and chronostratigraphy
Authors: Berggren W. A. , Kent Dennis V. , Flynn John J. 
Published: August 2007

Summary
We present a revised Paleogene geochronology based upon a best fit to selected high temperature radiometric dates on a number of identified magnetic polarity chrons (within the late Cretaceous, Paleogene and Neogene) which minimizes apparent accelerations in sea-floor spreading. An assessment of first order correlations of calcareous plankton biostratigraphic datum events to magnetic polarity stratigraphy yields the following estimated magnetobiochronology of major chronostratigraphic boundaries: Cretaceous-Tertiary boundary (Chron C29R), 66.4 Ma; Paleocene-Eocene (Chron C24R), 57.8 Ma; Eocene-Oligocene (Chron C13R), 36.6 Ma; Oligocene-Miocene (Chron C6CN), 23.7 Ma.
The Eocene is seen to have expanded chronologically (~ 21 m.y.) at the expense of the Paleocene (~ 9 m.y.) and is indeed the longest of the Cenozoic epochs. In addition, magnetobiostratigraphic correlations require adjustments in apparent correlations with standard marine stage boundaries in some cases (particularly in the Oligocene). Finally, we present a correlation between standard Paleogene marine and terrestrial stratigraphies.
The Neogene: Part 1
Authors: Jenkins D. G. , Bowen D. Q. , Adams C. G. , Shackleton N. J. , Brassell S. C. 
Published: August 2007

Summary
The Neogene is taken to include the Miocene, Pliocene, Pleistocene and Holocene, and a well established sequence of marine stages now exists from the early Miocene Aquitanian to the Calabrian in the early Pleistocene. Up-to-date reviews are provided for the classification of continental Pleistocene deposits, oxygen and carbon isotope stratigraphy, organic geochemical stratigraphy and the letter classification of the East Indies Neogene. Major boundaries of the Miocene have been narrowed down to durations of about 1 Ma or less and to progressively shorter durations for the Pleistocene to Holocene boundaries. Future work will have to identify and date these boundaries in stratotype sections. Authors contributions are identified by initials at the end of each section.
B7-H3 Ligand Expression by Prostate Cancer: A Novel Marker of Prognosis and Potential Target for Therapy
Authors: Roth Timothy J. , Sheinin Yuri , Lohse Christine M. , Kuntz Susan M. , Frigola Xavier , Inman Brant A. , Krambeck Amy E. , Mckenney Maureen E. , Karnes R. Jeffrey , Blute Michael L. , Cheville John C. , Sebo Thomas J. , Kwon Eugene D. 
Published: August 2007

Abstract
B7 coregulatory ligands can be aberrantly expressed in human disease. In the context of cancer, these ligands may act as antigen-specific inhibitors of T-cell–mediated antitumoral immunity. We recently reported that B7-H1 expression by carcinomas of the kidney and bladder portends aggressive disease and diminished survival. The expression of these proteins in prostate cancer, however, has not been investigated. We evaluated B7-H3 and B7-H1 protein expression in the pathologic specimens of 338 men treated for clinically localized prostate cancer between 1995 and 1998 with radical retropubic prostatectomy. Expression levels of B7-H3 in prostate cancer were correlated with pathologic indicators of aggressive cancer as well as clinical outcome. We report that B7-H3 is uniformly and aberrantly expressed by adenocarcinomas of the prostate, high-grade prostatic intraepithelial neoplasia, and four prostate cancer cell lines, whereas B7-H1 is rarely expressed. B7-H3 is expressed by benign prostatic epithelia, although at a more reduced level relative to neoplastic tissue. Increasing levels of B7-H3 intensity correlate with worsening clinicopathologic features of prostate cancer. Marked B7-H3 intensity, present in 67 (19.8%) specimens, confers a &gt;4-fold increased risk of cancer progression after surgery (risk ratio, 4.42; P &lt; 0.001). A survey of normal tissues revealed that B7-H3 is expressed within the liver, urothelium, and fetal kidney. In summary, B7-H3 is aberrantly expressed in all prostate cancers and represents an independent predictor of cancer progression following surgery. Moreover, B7-H3 encompasses a novel diagnostic and potential therapeutic target for the clinical management of prostate cancer and, perhaps, other malignancies as well. [Cancer Res 2007;67(16):7893–900]
3D volume and SUV analysis of oncological PET studies
Authors: Kaiser H.-J. , Gagel B. , Boy C. , Schaefer W. M. , Buell U. , Zimny M. , Krohn T. 
Published: August 2007

Summary
Aim: The standardized uptake value (SUV) of 18FDG-PET is an important parameter for therapy monitoring and prognosis of malignant lesions. SUV determination requires delineating the respective volume of interest against surrounding tissue. The present study proposes an automatic image segmentation algorithm for lesion volume and FDG uptake quantitation. Methods: A region growing-based algorithm was developed, which goes through the following steps: 1. Definition of a starting point by the user. 2. Automatic determination of maximum uptake within the lesion. 3. Calculating a threshold value as percentage of maximum. 4. Automatic 3D lesion segmentation. 5. Quantitation of lesion volume and SUV. The procedure was developed using CTI CAPP and ECAT 7.2 software. Validation was done by phatom studies (Jaszczak phantom, various “lesion” sizes and contrasts) and on studies of NSCLC patients, who underwent clinical CT and FDG-PET scanning. Results: Phantom studies demonstrated a mean error of 3.5% for volume quantification using a threshold of 41% for contrast ratios ≥5 : 1 and sphere volumes >5 ml. Comparison between CT- and PET-based volumetry showed a high correlation of both methods (r = 0.98) for lesions with homogeneous FDG uptake. Radioactivity concentrations were underestimated by on average .41%. Employing an empirical threshold of 50% for SUV determination, the underestimation decreased to on average .34%. Conclusions: The algorithm facilitates an easy and reproducible SUV quantification and volume assessment of PET lesions in clinical practice. It was validated using NSCLC patient data and should also be applicable to other tumour entities.