bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Premature Termination Codon Mutation at the C Terminus of Foamy Virus Gag Downregulates the Levels of Spliced
pol
mRNA
Authors: Lee Eun-Gyung , Kuppers Daniel , Horn Megan , Roy Jacqueline , May Cynthia , Linial Maxine L. 
Published: December 2007

ABSTRACT

Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of Gag. FV
pol
splicing uses a 3′ splice site located at the 3′ end of
gag
, resulting in a shared exon between
gag
and
pol
. Previously, our laboratory showed that C-terminal Gag premature termination codon (PTC) mutations in the 3′ shared exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L. Linial, J. Virol.
78
:9423-9430, 2004). To further characterize these mutants, we quantitated the levels of unspliced
gag
and spliced
pol
mRNAs using a real-time PCR assay. In some of the PTC mutants, the levels of spliced
pol
mRNA were reduced as much as 30-fold, whereas levels of unspliced
gag
RNA were not affected. Substitutions of a missense codon in place of a PTC restored normal levels of spliced
pol
mRNA. Disrupting Upf proteins involved in nonsense-mediated mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic splicing enhancer downstream of the PTC mutation restored
pol
splicing to the wild-type level. Taken together, our results show that the PTC mutation itself is responsible for decreased levels of
pol
mRNA but that mechanisms other than NMD might be involved in downregulating Pol expression. The results also suggest that normal
pol
splicing utilizes a suboptimal splice site seen for other spliced mRNAs in most retroviruses, in that introduced exonic enhancer elements can increase splicing efficiency.
Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts
Authors: Peng Tao , Zhu Jia , Hwangbo Yon , Corey Lawrence , Bumgarner Roger E. 
Published: December 2007

ABSTRACT
Type I and type II interferons (IFNs) act in synergy to inhibit the replication of a variety of viruses, including herpes simplex virus (HSV). To understand the mechanism of this effect, we have analyzed the transcriptional profiles of primary human fibroblast cells that were first treated with IFN-β1, IFN-γ, or a combination of both and then subsequently infected with HSV-1. We have identified two types of synergistic activities in the gene expression patterns induced by IFN-β1 and IFN-γ that may contribute to inhibition of HSV-1 replication. The first is defined as “synergy by independent action,” in which IFN-β1 and IFN-γ induce distinct gene categories. The second, “synergy by cooperative action,” is a term that describes the positive interaction between IFN-β1 and IFN-γ as defined by a two-way analysis of variance. This form of synergy leads to a much higher level of expression for a subset of genes than is seen with either interferon alone. The cooperatively induced genes by IFN-β1 and IFN-γ include those involved in apoptosis, RNA degradation, and the inflammatory response. Furthermore, the combination of IFN-β1 and IFN-γ induces significantly more apoptosis and inhibits HSV-1 gene expression and DNA replication significantly more than treatment with either interferon alone. Taken together, these data suggest that IFN-β1 and IFN-γ work both independently and cooperatively to create an antiviral state that synergistically inhibits HSV-1 replication in primary human fibroblasts and that cooperatively induced apoptosis may play a role in the synergistic effect on viral replication.
Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation
Authors: Kim Min-Jung , Hwang Sun-Young , Imaizumi Tadaatsu , Yoo Joo-Yeon 
Published: December 2007

ABSTRACT

RIG-I senses intracellular virus-specific nucleic acid structures and initiates an antiviral response that induces interferon (IFN) production, which, in turn, activates the transcription of RIG-I to increase RIG-I protein levels. Upon intracellular poly(I:C) stimulation, however, the levels of RIG-I protein did not correlate with the expression patterns of
RIG-I
transcripts. When the ISG15 conjugation system was overexpressed, ISG15 was conjugated to RIG-I and cellular levels of the unconjugated form of RIG-I decreased. The ISGylation of RIG-I reduced levels of both basal and virus-induced IFN promoter activity. Levels of unconjugated RIG-I also decreased when 26S proteasome activity was blocked by treatment with MG132, ALLN, or Lactacystin. In the presence of MG132, ISG15 conjugation to RIG-I increased, and hence, the unconjugated form of RIG-I was reduced. In Ube1L
−/−
cells, which lack the ability to conjugate ISG15, basal levels of both RIG-I protein and transcripts were increased compared to those in wild-type cells. As a result, enhanced production of ISGs and enhanced IFN promoter activity in Ube1L
−/−
cells were observed, and the phenotype was restored to that of wild-type cells by the overexpression of Ube1L. Based on these results, we propose a novel negative feedback loop which adjusts the strength of the RIG-I-mediated antiviral response and IFN production through the regulation of RIG-I protein by IFN-induced ISG15 conjugation.
Replication of Coxsackievirus B3 in Primary Cell Cultures Generates Novel Viral Genome Deletions
Authors: Kim K.-S. , Chapman N. M. , Tracy S. 
Published: December 2007

ABSTRACT
Coxsackievirus B3 (CVB3) generates 5′-terminally deleted genomes (TDs) during replication in murine hearts. We show here that CVB3 populations with TDs can also be generated within two to three passages of CVB3 in primary, but not immortalized, cell cultures. Deletions of less than 49 nucleotides increase in size during passage, while 5′ TDs of 49 nucleotides appear to be the maximum deletion size. The cellular environment of contact-inhibited primary cell cultures or the myocardium in vivo is sufficient for the selection of 5′ TDs over undeleted genomes.
Evidence of the Recombinant Origin of a Bat Severe Acute Respiratory Syndrome (SARS)-Like Coronavirus and Its Implications on the Direct Ancestor of SARS Coronavirus
Authors: Hon Chung-Chau , Lam Tsan-Yuk , Shi Zheng-Li , Drummond Alexei J. , Yip Chi-Wai , Zeng Fanya , Lam Pui-Yi , Leung Frederick Chi-Ching 
Published: December 2007

ABSTRACTBats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.
Complete In Vitro Reconstitution of Adeno-Associated Virus DNA Replication Requires the Minichromosome Maintenance Complex Proteins
Authors: Nash Kevin , Chen Weijun , Muzyczka Nicholas 
Published: December 2007

ABSTRACT
Adeno-associated virus (AAV) replicates its DNA exclusively by a leading-strand DNA replication mechanism and requires coinfection with a helper virus, such as adenovirus, to achieve a productive infection. In previous work, we described an in vitro AAV replication assay that required the AAV terminal repeats (the origins for DNA replication), the AAV Rep protein (the origin binding protein), and an adenovirus-infected crude extract. Fractionation of these crude extracts identified replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and polymerase δ as cellular enzymes that were essential for AAV DNA replication in vitro. Here we identify the remaining factor that is necessary as the minichromosome maintenance (MCM) complex, a cellular helicase complex that is believed to be the replicative helicase for eukaryotic chromosomes. Thus, polymerase δ, RFC, PCNA, and the MCM complex, along with the virally encoded Rep protein, constitute the minimal protein complexes required to reconstitute efficient AAV DNA replication in vitro. Interfering RNAs targeted to MCM and polymerase δ inhibited AAV DNA replication in vivo, suggesting that one or more components of the MCM complex and polymerase δ play an essential role in AAV DNA replication in vivo as well as in vitro. Our reconstituted in vitro DNA replication system is consistent with the current genetic information about AAV DNA replication. The use of highly conserved cellular replication enzymes may explain why AAV is capable of productive infection in a wide variety of species with several different families of helper viruses.
Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways
Authors: Cameron Jennifer E. , Yin Qinyan , Fewell Claire , Lacey Michelle , McBride Jane , Wang Xia , Lin Zhen , Schaefer Brian C. , Flemington Erik K. 
Published: December 2007

ABSTRACTThe Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor κB (NF-κB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-κB binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.
Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens
Authors: Brumell John H. , Scidmore Marci A. 
Published: December 2007

SUMMARY
Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.
Interspecies Interactions within Oral Microbial Communities
Authors: Kuramitsu Howard K. , He Xuesong , Lux Renate , Anderson Maxwell H. , Shi Wenyuan 
Published: December 2007

SUMMARYWhile reductionism has greatly advanced microbiology in the past 400 years, assembly of smaller pieces just could not explain the whole! Modern microbiologists are learning “system thinking” and “holism.” Such an approach is changing our understanding of microbial physiology and our ability to diagnose/treat microbial infections. This review uses oral microbial communities as a focal point to describe this new trend. With the common name “dental plaque,” oral microbial communities are some of the most complex microbial floras in the human body, consisting of more than 700 different bacterial species. For a very long time, oral microbiologists endeavored to use reductionism to identify the key genes or key pathogens responsible for oral microbial pathogenesis. The limitations of reductionism forced scientists to begin adopting new strategies using emerging concepts such as interspecies interaction, microbial community, biofilms, polymicrobial disease, etc. These new research directions indicate that the whole is much more than the simple sum of its parts, since the interactions between different parts resulted in many new physiological functions which cannot be observed with individual components. This review describes some of these interesting interspecies-interaction scenarios.
Structural and stratigraphic controls on fold-related fracturing in the Zagros Mountains, Iran: implications for reservoir development
Authors: Stephenson Ben J. , Koopman Anton , Hillgartner Heiko , McQuillan Harry , Bourne Stephen , Noad Jon J. , Rawnsley Keith 
Published: December 2007

Abstract
New observations of fracture corridors > 150 m tall and planes of bedding-parallel slip are integrated with sedimentological descriptions of the Asmari Formation to understand the main controls on the development of fractures in the Zagros Mountains of Iran. In the Kuh-e Pahn, fold-related fracture corridors are axis-parallel (NW-SE) and occur in the crest of the anticline. They form by neutral surface folding, but at a critical dip of the beds (c. 15°), bedding-parallel slip by flexural slip folding is the predominant mechanism. This relationship is substantiated by curvature calculations. Crestal fractures have a large vertical extent in mechanical unit B (> 150 m), primarily due to the lithological homogeneity of massive packstones within the Asmari Formation. Northerly and easterly trending fracture corridors, interpreted from satellite imagery, are spatially unrelated to the detachment folding of the cover series, but represent the distributed effect of deep-seated basement reactivation related to fault movement. These trends define high production zones in the nearby Gachsaran super giant oilfield. Observations from an adjacent eroded box fold, the Kuh-e Mish, with steeper dipping limbs (60°), revealed a contrast in the style of deformation, and we interpret these folds to represent different stages in box fold evolution.
Laboratory measurements of acoustic emissions and wave velocities associated with the formation of fractures in sandstones
Authors: Pettitt W. S. , King M. S. 
Published: December 2007

Abstract
Acoustic emission (AE), ultrasonic velocity and petrophysical property measurements are increasingly being used as tools to investigate mechanical, thermal and hydraulic changes in rock masses around underground excavations and in the exploration of oil and gas. In order to develop these measurements into an effective tool it is necessary to understand how they relate to changes in the fracture and fluid content under controlled laboratory conditions. A polyaxial (true triaxial) test system has been developed to perform high-resolution measurements of AE, ultrasonic velocities and fluid permeability characteristics in a cubic specimen under true-triaxial stress. The polyaxial system also allows the measurement of AEs using an array of small-diameter, high-frequency transducers. The measurements allow the AE source locations and mechanisms to be calculated, thus providing an analysis of the distribution, orientation and type of fracture growth in the specimens. Example results are given from an experiment, showing that AE mechanisms during crack initiation describe a dominant failure mode with a significant tensile component.
Combining diagenesis and mechanics to quantify fracture aperture distributions and fracture pattern permeability
Authors: Olson Jon E. , Laubach Stephen E. , Lander Robert H. 
Published: December 2007

Abstract
Diagenesis and fracture are often linked processes in deformed rock. Empirical observations show that quartz-lined natural fractures are very common in sandstones that have been exposed to temperatures in excess of 90°C. These fractures exhibit crack-seal textures as well as cement bridges propping the fractures open and preserving fracture porosity. These diagenetic effects are examined in the context of detailed fracture characterizations generated by geomechanical modelling. Aperture, length and fracture network geometry are examined in the context of subcritical crack growth and various biaxial loading boundary conditions of varying initial anisotropy. An isotropic initial state results in more polygonal fracture patterns. A small initial anisotropy creates preferential through-going fractures that are later connected by cross-fractures. A larger initial anisotropy results in only one parallel set. The flow connectivity of isotropic and small strain anisotropic patterns appears high based on trace pattern geometry, but when the effects of diagenesis are added, preferentially filling smaller aperture fracture segments, connectivity can be significantly reduced. Finite difference, steady-state flow simulations demonstrate the permeability effects of heterogeneous fracture aperture distributions predicted by the mechanical model and permeability reduction caused by systematic diagenetic fracture sealing.
Understanding the Earth scientist's role in the pre-restoration research of monuments: an overview
Authors: Přikryl R. 
Published: December 2007

Abstract
To understand the role of the earth scientist in the pre-restoration research of stone monuments, it is necessary to summarize the tasks that he/she can fulfil. Pre-restoration research into building materials is generally conducted to provide information on types of material, their damage and repair. Although the technologist and restorer must manage the practical aspects of repair, the earth scientist can make a significant contribution in terms of material research. First, he or she can answer questions on the nature of the stone(s) used, their provenance (location of the quarry), and their weathering characteristics in terms of the deterioration of physical and mechanical properties and destruction of rock fabric. Second, the earth scientist can research the physical and mechanical properties of new stone proposed for as a replacement for decayed stonework, including recommendations for alternative materials where stone from the original quarry is no longer available.
Characterization of serpentinites to define their appropriate use as dimension stone
Authors: Pereira D. , Yenes M. , Blanco J. A. , Peinado M. 
Published: December 2007

Abstract
Many questions arise when considering the appropriate use of building stones such as serpentinites. The commercial names of these rocks, collectively grouped as ‘Green marbles’, have no correspondence to their actual mineralogy, geochemistry and/or physical characteristics. Serpentinite being the hydrated product of an ultramafic parent rock and not a metamorphic product of limestone as implied by the term ‘marble’. However, the serpentinites most widely used for ornamental purposes come from India (e.g. Rajasthan Green, Emerald Green) and in these the original mineralogy has been almost completely converted into carbonates. By contrast, serpentinites from elsewhere (e.g. Vermont Verde Antique from the USA and Verde Pirineos from Spain) do preserve some of their original mineralogy. The different physical and chemical behaviour of carbonates and serpentine minerals can result in significantly different behaviour of commercial building stones. Thus, carbonates are resistant to weathering but suffer from acidic cleaning agents in interior use; whereas serpentinites, with a high content of talc, used on external faces undergo an increase in volume and a consequent rapid degradation.
Accurate and precise characterization of serpentinites, including information on their mineralogy and geochemistry (including major, trace and volatile elements together with oxygen isotopes), in conjunction with their physical properties, would enable architects to select the appropriate interior or exterior use of these handsome building stones.
Stone properties and weathering induced by salt crystallization of Maltese Globigerina Limestone
Authors: Rothert E. , Eggers T. , Cassar J. , Ruedrich J. , Fitzner B. , Siegesmund S. 
Published: December 2007

Abstract
Most monuments and buildings in the Maltese Islands are constructed of the local Globigerina Limestone. Today, this Globigerina Limestone shows considerable damage in many buildings, particularly through alveolar weathering, which is frequently very intense. Owing to Malta's marine environment, salt crystallization in the stone's pore spaces has been recognized as the main weathering process responsible for the deterioration of the country's monuments. In order to obtain more information on the fabric-dependent weathering processes of Globigerina Limestone, detailed analyses were carried out. Globigerina Limestone samples obtained from stone types with two different known qualities were characterized according to petrographical, geochemical and physical properties. These included porosity, pore radii distribution and tensile strength, as well as water and humidity transport properties. Investigations by means of salt crystallization tests on quarry samples of both stone types reinforced the idea that the extent of salt weathering depends on salt type and concentration and pore-space properties. Visible weathering damage was recorded and evaluated for a representative monument (the Church of Santa Marija Ta' Cwerra in Siggiewi) by means of a monument mapping method, which was carried out twice over a period of 9 years (1995 and 2004). The identified weathering forms were also correlated with a previously developed weathering model for Globigerina Limestone. According to the results of the mapping, salt analyses carried out on samples from the church and salt-loading tests on quarry samples, there exists a significant correlation between visible damage and salt load. The zoning of weathering damage is obviously related to different salt concentrations. The zone with severe weathering damage is characterized by a high concentration of halite. Consequently, salt weathering represents the main damage process for the Globigerina Limestone of Malta.