bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Domain 10 Components Promyelocytic Leukemia Protein and hDaxx Independently Contribute to an Intrinsic Antiviral Defense against Human Cytomegalovirus Infection
Authors: Tavalai Nina , Papior Peer , Rechter Sabine , Stamminger Thomas 
Published: October 2007

ABSTRACTInfection with DNA viruses commonly results in the association of viral genomes with a cellular subnuclear structure known as nuclear domain 10 (ND10). Recent studies demonstrated that individual ND10 components, like hDaxx or promyelocytic leukemia protein (PML), mediate an intrinsic immune response against human cytomegalovirus (HCMV) infection, strengthening the assumption that ND10 components are part of a cellular antiviral defense mechanism. In order to further define the role of hDaxx and PML for HCMV replication, we generated either primary human fibroblasts with a stable, individual knockdown of PML or hDaxx (PML-kd and hDaxx-kd, respectively) or cells exhibiting a double knockdown. Comparative analysis of HCMV replication in PML-kd or hDaxx-kd cells revealed that immediate-early (IE) gene expression increased to a similar extent, regardless of which ND10 constituent was depleted. Since a loss of PML, the defining component of ND10, results in a dispersal of the entire nuclear substructure, the increased replication efficacy of HCMV in PML-kd cells could be a consequence of the dissociation of the repressor protein hDaxx from its optimal subnuclear localization. However, experiments using three different recombinant HCMVs revealed a differential growth complementation in PML-kd versus hDaxx-kd cells, strongly arguing for an independent involvement in suppressing HCMV replication. Furthermore, infection experiments using double-knockdown cells devoid of both PML and hDaxx illustrated an additional enhancement in the replication efficacy of HCMV compared to the single-knockdown cells. Taken together, our data indicate that both proteins, PML and hDaxx, mediate an intrinsic immune response against HCMV infection by contributing independently to the silencing of HCMV IE gene expression.
Accelerated Evolution of Maribavir Resistance in a Cytomegalovirus Exonuclease Domain II Mutant
Authors: Chou Sunwen , Marousek Gail I. 
Published: October 2007

ABSTRACT

A human cytomegalovirus (CMV) UL54
pol
exonuclease domain II mutation, D413A, found in a clinical specimen, conferred ganciclovir (GCV) and cidofovir resistance but not foscarnet resistance when incorporated into laboratory strain T2294. After several passages without drug, mutation was observed in five of eight plaques of T2294, and its plating efficiency under foscarnet was increased ∼30-fold over that of a control strain. When T2294 was serially passed under maribavir (MBV), phenotypic changes and viral UL97 mutations were detected by passage 5, much earlier than previously reported for other CMV strains. By passage 15, mutations included two cases of H411Y, one each of H411L and H411N, three of T409M, five of V353A, and one of L397R. Five instances of codon 409 or 411 mutations evolved into double mutations including V353A. Marker transfer experiments showed H411N/Y/L to confer 9- to 70-fold-increased MBV resistance and combinations of H411L/Y and V353A to confer >150-fold-increased MBV resistance, but no GCV resistance. These findings are consistent with defective exonuclease activity of the
pol
D413A mutant T2294, leading to the accelerated evolution of UL97 mutations under MBV. This recapitulated the known resistance mutations V353A, L397R, and T409M; suggested their relative frequency; and identified new ones at codon 411. These UL97 mutations predict an MBV binding region overlapping the kinase ATP binding site and located upstream of known GCV resistance mutations. The existence of viable
pol
D413A mutants may facilitate the selection of additional drug resistance mutations in vivo and the study of these mutations in vitro.
3′ RNA Elements in Hepatitis C Virus Replication: Kissing Partners and Long Poly(U)
Authors: You Shihyun , Rice Charles M. 
Published: October 2007

ABSTRACT

The hepatitis C virus (HCV) genomic RNA possesses conserved structural elements that are essential for its replication. The 3′ nontranslated region (NTR) contains several of these elements: a variable region, the poly(U/UC) tract, and a highly conserved 3′ X tail, consisting of stem-loop 1 (SL1), SL2, and SL3. Studies of drug-selected, cell culture-adapted subgenomic replicons have indicated that an RNA element within the NS5B coding region, 5BSL3.2, forms a functional kissing-loop tertiary structure with part of the 3′ NTR, 3′ SL2. Recent advances now allow the efficient propagation of unadapted HCV genomes in the context of a complete infectious life cycle (HCV cell culture [HCVcc]). Using this system, we determine that the kissing-loop interaction between 5BSL3.2 and 3′ SL2 is required for replication in the genotype 2a HCVcc context. Remarkably, the overall integrity of the 5BSL3 cruciform is not an absolute requirement for the kissing-loop interaction, suggesting a model in which
trans
-acting factor(s) that stabilize this interaction may interact initially with the 3′ X tail rather than 5BSL3. The length and composition of the poly(U/UC) tract were also critical determinants of HCVcc replication, with a length of 33 consecutive U residues required for maximal RNA amplification. Interrupting the U homopolymer with C residues was deleterious, implicating a
trans
-acting factor with a preference for U over mixed pyrimidine nucleotides. Finally, we show that both the poly(U) and kissing-loop RNA elements can function outside of their normal genome contexts. This suggests that the poly(U/UC) tract does not function simply as an unstructured spacer to position the kissing-loop elements.
Human Cytomegalovirus Specifically Controls the Levels of the Endoplasmic Reticulum Chaperone BiP/GRP78, Which Is Required for Virion Assembly
Authors: Buchkovich Nicholas J. , Maguire Tobi G. , Yu Yongjun , Paton Adrienne W. , Paton James C. , Alwine James C. 
Published: October 2007

ABSTRACT
The endoplasmic reticulum (ER) chaperone BiP/GRP78 regulates ER function and the unfolded protein response (UPR). Human cytomegalovirus infection of human fibroblasts induces the UPR but modifies it to benefit viral replication. BiP/GRP78 protein levels are tightly regulated during infection, rising after 36 h postinfection (hpi), peaking at 60 hpi, and decreasing thereafter. To determine the effects of this regulation on viral replication, BiP/GRP78 was depleted using the SubAB subtilase cytotoxin, which rapidly and specifically cleaves BiP/GRP78. Toxin treatment of infected cells for 12-h periods beginning at 36, 48, 60, and 84 hpi caused complete loss of BiP but had little effect on viral protein synthesis. However, progeny virion formation was significantly inhibited, suggesting that BiP/GRP78 is important for virion formation. Electron microscopic analysis showed that infected cells were resistant to the toxin and showed none of the cytotoxic effects seen in uninfected cells. However, all viral activity in the cytoplasm ceased, with nucleocapsids remaining in the nucleus or concentrated in the cytoplasmic space just outside of the outer nuclear membrane. These data suggest that one effect of the controlled expression of BiP/GRP78 in infected cells is to aid in cytoplasmic virion assembly and egress.
Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield
Authors: Halasz Peter , Holloway Gavan , Turner Stephen J. , Coulson Barbara S. 
Published: October 2007

ABSTRACT
Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface integrins with the extracellular matrix. In this study, we detected alterations in cellular integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of α2β1 and β2 integrins was up-regulated, whereas that of αVβ3, αVβ5, and α5β1 integrins, if present, was down-regulated. This differential regulation of integrins was reflected at the transcriptional level. It was unrelated to the use of integrins as rotavirus receptors, as both integrin-using and integrin-independent viruses induced integrin regulation. Using pharmacological agents that inhibit kinase activity, integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of α2β1 expression. Blockade of integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.
Accumulation of Substrates of the Anaphase-Promoting Complex (APC) during Human Cytomegalovirus Infection Is Associated with the Phosphorylation of Cdh1 and the Dissociation and Relocalization of APC Subunits
Authors: Tran Karen , Mahr Jeffrey A. , Choi Jiwon , Teodoro Jose G. , Green Michael R. , Spector Deborah H. 
Published: October 2007

ABSTRACT
Cell cycle dysregulation upon human cytomegalovirus (HCMV) infection of human fibroblasts is associated with the inactivation of the anaphase-promoting complex (APC), a multisubunit E3 ubiquitin ligase, and accumulation of its substrates. Here, we have further elucidated the mechanism(s) by which HCMV-induced inactivation of the APC occurs. Our results show that Cdh1 accumulates in a phosphorylated form that may prevent its association with and activation of the APC. The accumulation of Cdh1, but not its phosphorylation, appears to be cyclin-dependent kinase dependent. The lack of an association of exogenously added Cdh1 with the APC from infected cells indicates that the core APC also may be impaired. This is further supported by an examination of the localization and composition of the APC. Coimmunoprecipitation studies show that both Cdh1 and the subunit APC1 become dissociated from the complex. In addition, immunofluorescence analysis demonstrates that as the infection progresses, several subunits redistribute to the cytoplasm, while APC1 remains nuclear. Dissociation of the core complex itself would account for not only the observed inactivity but also its inability to bind to Cdh1. Taken together, these results illustrate that HCMV has adopted multiple mechanisms to inactivate the APC, which underscores its importance for a productive infection.
Friend Virus Utilizes the BMP4-Dependent Stress Erythropoiesis Pathway To Induce Erythroleukemia
Authors: Subramanian Aparna , Hegde Shailaja , Porayette Prashanth , Yon Michele , Hankey Pamela , Paulson Robert F. 
Published: October 2007

ABSTRACT

More than 50 years of genetic analysis has identified a number of host genes that are required for the expansion of infected cells during the progression of Friend-virus-induced erythroleukemia. In this report, we show that Friend virus induces the bone morphogenetic protein 4 (BMP4)-dependent stress erythropoiesis pathway in the spleen, which rapidly amplifies target cells, propagating their infection and resulting in acute splenomegaly. This mechanism mimics the response to acute anemia, in which BMP4 expressed in the spleen drives the expansion of a specialized population of stress erythroid progenitors. Previously we demonstrated that these progenitors, termed stress BFU-E, are targets for Friend virus in the spleen (A. Subramanian, H. E. Teal, P. H. Correll, and R. F. Paulson, J. Virol.
79:
14586-14594, 2005). Here, we extend those findings by showing that Friend virus infects two distinct populations of bone marrow cells. One population, when infected, differentiates into mature erythrocytes in an Epo-independent manner, while a second population migrates to the spleen after infection, where it induces BMP4 expression and acts as a reservoir of virus. The activation of the stress erythropoiesis pathway in the spleen by Friend virus results in the rapid expansion of stress BFU-E, providing abundant target cells for viral infection. These observations suggest a novel mechanism by which a virus induces a stress response pathway that amplifies target cells for the virus, leading to acute expansion of infected cells.
EMITTANCE DEGRADATION DUE TO WAKE FIELDS IN A HIGH BRIGHTNESS PHOTOINJECTOR
Authors: FERRARIO M. , FUSCO V. , MIGLIORATI M. , PALUMBO L. 
Published: October 2007

Wake fields effects in addition to space charge forces may have an important impact during the emittance compensation process in a high brightness photo-injector. To study this effect we developed an upgraded version of the Homdyn code including off axis beam dynamics and wake fields. Homdyn describes a bunch as a uniformly charged cylinder, divided in cylindrical slices; in the upgraded version each slice's centroid can be transversally displaced from the nominal axis thus inducing wake fields. When the bunch is short as compared to the beam pipe radius, wake fields for a single cavity are calculated using methods of diffraction theory; instead we use, for a periodic collection of cavities, an asymptotic wake field obtained numerically at SLAC and then fitted to a simple function. As a first application we studied and verified a correction scheme for the SPARC photo-injector to control the bunch trajectory and angle at the entrance of the undulator. The correction scheme consists of a number of steering magnets and beam position monitors placed along the photo-injector. Two different steering approaches are analyzed and the emittance degradation is studied. The code demonstrates the steering positions and number do correct the bunch's orbit and angle and gives good results concerning the emittance degradation. The emittance and energy spread degradation due to wake fields in the emittance meter experiment is also discussed.
Coal and coal-bearing strata: recent advances and future prospects
Authors: Scott Andrew C. 
Published: October 2007

Abstract
Recent advances in coal geology are highlighted. The increase in our knowledge of peat formation is emphasized and the application of hydrological models of mire systems to coal-bearing strata is advocated. The importance of coalification studies to the geological community as a whole should not be underestimated. Consideration of the original peat-forming vegetation by coal geologists is advocated. Both conceptual and technical advances in coal geology are reviewed. Integration of different disciplines is likely to yield further insights into the study of coal and coal-bearing strata.
Sulphur in peat and coal
Authors: Casagrande D. J. 
Published: October 2007

Abstract
Coal sulphur content is a major consideration in coal marketing. To predict sulphur content and distribution in a coal basin, a sulphur geochemical model needs to be developed. A series of questions are posed regarding coal sulphur distribution, forms and origins. Salient aspects of literature on coal sulphur content and distribution are reviewed to establish a framework for developing a sulphur geochemical model.
Some coal sulphur originates from peat-forming processes. Sulphate, ferrous iron, and microorganisms are key ingredients for the origins of coal pyrite and organic sulphur. Hydrogen sulphide is an important intermediate for pyrite and organic sulphur formation in peats. Sulphur isotope values for peat sulphate, plant sulphur, peat pyrite and peat organic sulphur corroborate the hypothesis that microorganisms reduce sulphate to hydrogen sulphide, which in turn reacts with available ferrous iron or organic matter to produce pyrite and organic sulphur respectively.
Interpreting the characteristics of coal seams from chemical, physical and petrographic studies of peat deposits
Authors: Cohen Arthur D. , Spackman William , Raymond Robert 
Published: October 2007

Abstract
The purpose of this paper is to illustrate some of the kinds of information about coals that are at present being generated from studies of peat deposits and also to point out some possible new areas of research that might be undertaken in the future.
Some notable examples of new ideas about coal seam composition or formation that have been generated from studies of modern peat deposits include: (1) discovery of the probable progenitors of certain coal macerals and elucidation of the processes by which they may have formed; (2) evidence that some types of mineral matter may be dissolved out of peat deposits; (3) verification of the role of marine waters in emplacement of sulphur in peat; (4) discovery of the importance of ‘doming’ in peat deposit development; (5) discovery of a new way to form a split in a coal seam, i.e. development of a ‘fire splay’; (6) elucidation of the mechanisms responsible for producing stratification in coal seams; (7) recognition of the world-wide importance of ‘back-barrier’ coal-forming environments.
These kinds of discoveries are important in themselves; however, they can also be shown to have many additional practical applications, especially if woven into models to predict the economic characteristics of coal seams.
Recent advances in coalification studies and their application to geology
Authors: Teichmüller Marlies 
Published: October 2007

Abstract
Recent advances in coalification studies since 1970 are reported, concerning microscopic methods, causes of coalification, the coalification process as such and application to geology. The degree of coalification (‘rank’) is mostly determined on the basis of vitrinite reflectance measured on finely dispersed material in rocks. For rocks bare of vitrinite other microscopic methods are used, such as fluorescence properties of liptinites and graptolite reflectance under incident light or coloration of microfossils like palynomorphs and conodonts in transmitted light. The validity of the various methods is discussed.
Maximum rock temperature and its duration are the main causes of chemical coalification reactions. Heating rates during subsidence influence the attainment of rank equilibrium. Contact-metamorphic coals and natural cokes formed from bituminous coals are characterized by a relatively high reflectance and anisotropy. Strong frictional heat may cause local increase of rank adjacent to thrust planes. Graphitization is thermodynamically not possible in nature without pressure and shearing. Confining pressure retards the chemical coalification reactions. Tectonic stress, especially shearing, promotes the increase of maximum reflectance and of anisotropy. It commonly leads to bi-axial optical properties instead of the more typical uni-axial negative geometry of vitrinite in undisturbed coal seams. Bi-axial optical properties are common for vitrinite inclusions in clastic rocks.

On the basis of combined fluorescence microscopical and geochemical studies, ‘bituminization’ has been recognized as
the
characteristic part of coalification in the range between sub-bituminous and bituminous coal. It is characterized by the generation of petroleum-like substances which enable the coal to soften and to agglomerate during carbonization. Hydrogenation properties are favoured by the bituminization process. The different liptinite macerals behave differently during coalification and pass coalification ‘jumps’ at different rank stages. A considerable part of total inertinites is formed during early coalification (brown coal to sub-bituminous coal stage) as ‘rank inertinite’. This new knowledge appears to become important in relation to hydrocarbon exploration (‘diagenetic methane’).

Some examples for the application of coalification studies to geology refer to vitrinite reflectance as an indicator of rock diagenesis and metamorphism, palaeogeographical and structural history, palaeogeothermics and hydrocarbon exploration. Large-scale areal coalification studies in foredeeps and backdeeps of ancient and recent orogens suggest estimations of crustal thicknesses and relations to plate tectonics.
Oil-prone coals of the Walloon Coal Measures, Surat Basin, Australia
Authors: Khorasani Ganjavar Khavari 
Published: October 2007

Abstract
Studies of autochthonous coals from the Walloon Coal Measures, Surat Basin, Australia, suggest that the process of liptinite enrichment and the formation of perhydrous vitrinites have given rise to oil-prone coals. These processes were essentially controlled by the type of flora contributing to the peat accumulation and the biochemical transformation of the flora under dysaerobic conditions. These processes lead to the coals being hydrogen-rich and oil prone, and contrast with the process described by other authors for Indonesian source rocks. The mature phase of oil generation from hydrogen-rich coals such as those of the Walloon Coal Measures may be preceded by several earlier phases, during which hydrocarbons are likely to be generated from subereous components and terpene resinites in low rank lignites and sub-bituminous coals.
The Rexinoid LG100268 Prevents the Development of Preinvasive and Invasive Estrogen Receptor–Negative Tumors in MMTV-erbB2 Mice
Authors: Li Yuxin , Zhang Yun , Hill Jamal , Shen Qiang , Kim Hee-Tae , Xu Xiaochun , Hilsenbeck Susan G. , Bissonnette Reid P. , Lamph William W. , Brown Powel H. 
Published: October 2007

Abstract
Purpose: To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor–negative mammary tumorigenesis in MMTV-erbB2 mice.
Experimental Design: For invasive breast cancer prevention, MMTV-erbB2 mice were treated with daily gastric gavage of vehicle, LG100268 (10 mg/kg), or LG100268 (100 mg/kg) for long term starting at 3 months of age. For preinvasive lesion study, mice were treated with daily gastric gavage of vehicle or LG100268 (100 mg/kg) for 4 months.
Results: Long-term treatment with LG100268 significantly prevented invasive mammary tumor development. Median time (age) to tumor development was delayed from 217 days in vehicle group to 357 days in low-dose group. In high-dose group, only 2 of 20 mice developed tumors after 430 days of treatment. Short-term treatment of LG100268 significantly prevented the development of preinvasive mammary lesions including hyperplasia and ductal carcinoma in situ. The cancer prevention effect was associated with reduced expression of Ki67 and cyclin D1 in mammary glands by &gt;80%.
Conclusion: Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.