bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evaluation of Three Commercial Quantitative Cytomegalovirus Standards by Use of Digital and Real-Time PCR
Authors: Hayden R. T. , Gu Z. , Sam S. S. , Sun Y. , Tang L. , Pounds S. , Caliendo A. M. 
Published: February 2015

ABSTRACT

The recent development of the 1st WHO International Standard for human cytomegalovirus (CMV) and the introduction of commercially produced secondary standards have raised hopes of improved agreement among laboratories performing quantitative PCR for CMV. However, data to evaluate the trueness and uniformity of secondary standards and the consistency of results achieved when these materials are run on various assays are lacking. Three concentrations of each of the three commercially prepared secondary CMV standards were tested in quadruplicate by three real-time and two digital PCR methods. The mean results were compared in a pairwise fashion with nominal values provided by each manufacturer. The agreement of results among all methods for each sample and for like concentrations of each standard was also assessed. The relationship between the nominal values of standards and the measured values varied, depending upon the assay used and the manufacturer of the standards, with the degree of bias ranging from +0.6 to −1.0 log
10
IU/ml. The mean digital PCR result differed significantly among the secondary standards, as did the results of the real-time PCRs, particularly when plotted against nominal log
10
IU values. Commercially available quantitative secondary CMV standards produce variable results when tested by different real-time and digital PCR assays, with various magnitudes of bias compared to nominal values. These findings suggest that the use of such materials may not achieve the intended uniformity among laboratories measuring CMV viral load, as envisioned by adaptation of the WHO standard.
CCCTC-Binding Factor Recruitment to the Early Region of the Human Papillomavirus 18 Genome Regulates Viral Oncogene Expression
Authors: Paris Christian , Pentland Ieisha , Groves Ian , Roberts David C. , Powis Simon J. , Coleman Nicholas , Roberts Sally , Parish Joanna L. 
Published: February 2015

ABSTRACT
Host cell differentiation-dependent regulation of human papillomavirus (HPV) gene expression is required for productive infection. The host cell CCCTC-binding factor (CTCF) functions in genome-wide chromatin organization and gene regulation. We have identified a conserved CTCF binding site in the E2 open reading frame of high-risk HPV types. Using organotypic raft cultures of primary human keratinocytes containing high-risk HPV18 genomes, we show that CTCF recruitment to this conserved site regulates viral gene expression in differentiating epithelia. Mutation of the CTCF binding site increases the expression of the viral oncoproteins E6 and E7 and promotes host cell proliferation. Loss of CTCF binding results in a reduction of a specific alternatively spliced transcript expressed from the early gene region concomitant with an increase in the abundance of unspliced early transcripts. We conclude that high-risk HPV types have evolved to recruit CTCF to the early gene region to control the balance and complexity of splicing events that regulate viral oncoprotein expression.

IMPORTANCE
The establishment and maintenance of HPV infection in undifferentiated basal cells of the squamous epithelia requires the activation of a subset of viral genes, termed early genes. The differentiation of infected cells initiates the expression of the late viral transcripts, allowing completion of the virus life cycle. This tightly controlled balance of differentiation-dependent viral gene expression allows the virus to stimulate cellular proliferation to support viral genome replication with minimal activation of the host immune response, promoting virus productivity. Alternative splicing of viral mRNAs further increases the complexity of viral gene expression. In this study, we show that the essential host cell protein CTCF, which functions in genome-wide chromatin organization and gene regulation, is recruited to the HPV genome and plays an essential role in the regulation of early viral gene expression and transcript processing. These data highlight a novel virus-host interaction important for HPV pathogenicity.
Herpes Simplex Virus 1 Upregulates p35, Alters CDK-5 Localization, and Stimulates CDK-5 Kinase Activity during Acute Infection in Neurons
Authors: Mostafa Heba H. , van Loben Sels Jessica M. , Davido David J. 
Published: February 2015

ABSTRACT
The cyclin-dependent kinase 5 (CDK-5) activating protein, p35, is important for acute herpes simplex virus 1 (HSV-1) replication in mice. This report shows that HSV-1 increases p35 levels, changes the primary localization of CDK-5 from the nucleus to the cytoplasm, and enhances CDK-5 activity during lytic or acute infection. Infected neurons also stained positive for the DNA damage response (DDR) marker γH2AX. We propose that CDK-5 is activated by the DDR to protect infected neurons from apoptosis.
Evidence Supporting a Role for TopBP1 and Brd4 in the Initiation but Not Continuation of Human Papillomavirus 16 E1/E2-Mediated DNA Replication
Authors: Gauson Elaine J. , Donaldson Mary M. , Dornan Edward S. , Wang Xu , Bristol Molly , Bodily Jason M. , Morgan Iain M. 
Published: February 2015

ABSTRACT
To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination.

IMPORTANCE
Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease burden on the current, and future, generations. Targeting viral DNA replication that is mediated by two viral proteins, E1 and E2, in association with cellular proteins such as TopBP1 and Brd4 would have therapeutic benefits. This report suggests a role for these cellular proteins in the initiation of viral DNA replication by HPV16 E1-E2 but not for continuing replication. This is important if viral replication is to be effectively targeted; we need to understand the viral and cellular proteins required at each phase of viral DNA replication so that it can be effectively disrupted.
Viral DNA Replication-Dependent DNA Damage Response Activation during BK Polyomavirus Infection
Authors: Verhalen Brandy , Justice Joshua L. , Imperiale Michael J. , Jiang Mengxi 
Published: February 2015

ABSTRACT
BK polyomavirus (BKPyV) reactivation is associated with severe human disease in kidney and bone marrow transplant patients. The interplay between viral and host factors that regulates the productive infection process remains poorly understood. We have previously reported that the cellular DNA damage response (DDR) is activated upon lytic BKPyV infection and that its activation is required for optimal viral replication in primary kidney epithelial cells. In this report, we set out to determine what viral components are responsible for activating the two major phosphatidylinositol 3-kinase-like kinases (PI3KKs) involved in the DDR: ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3-related (ATR) kinase. Using a combination of UV treatment, lentivirus transduction, and mutant virus infection experiments, our results demonstrate that neither the input virus nor the expression of large T antigen (TAg) alone is sufficient to trigger the activation of ATM or ATR in our primary culture model. Instead, our data suggest that the activation of both the ATM- and ATR-mediated DDR pathways is linked to viral DNA replication. Intriguingly, a TAg mutant virus that is unable to activate the DDR causes substantial host DNA damage. Our study provides insight into how DDRs are activated by polyomaviruses in primary cells with intact cell cycle checkpoints and how the activation might be linked to the maintenance of host genome stability.

IMPORTANCE
Polyomaviruses are opportunistic pathogens that are associated with several human diseases under immunosuppressed conditions. BK polyomavirus (BKPyV) affects mostly kidney and bone marrow transplant patients. The detailed replication mechanism of these viruses remains to be determined. We have previously reported that BKPyV activates the host DNA damage response (DDR), a response normally used by the host cell to combat genotoxic stress, to aid its own replication. In this study, we identified that the trigger for DDR activation is viral replication. Furthermore, we show that the virus is able to cause host DNA damage in the absence of viral replication and DDR activation. These results suggest an intricate relationship between viral replication, DDR activation, and host genome instability.
Core Principles of Bacterial Autoinducer Systems
Authors: Hense Burkhard A. , Schuster Martin 
Published: February 2015

SUMMARY
Autoinduction (AI), the response to self-produced chemical signals, is widespread in the bacterial world. This process controls vastly different target functions, such as luminescence, nutrient acquisition, and biofilm formation, in different ways and integrates additional environmental and physiological cues. This diversity raises questions about unifying principles that underlie all AI systems. Here, we suggest that such core principles exist. We argue that the general purpose of AI systems is the homeostatic control of costly cooperative behaviors, including, but not limited to, secreted public goods. First, costly behaviors require preassessment of their efficiency by cheaper AI signals, which we encapsulate in a hybrid “push-pull” model. The “push” factors cell density, diffusion, and spatial clustering determine when a behavior becomes effective. The relative importance of each factor depends on each species' individual ecological context and life history. In turn, “pull” factors, often stress cues that reduce the activation threshold, determine the cellular demand for the target behavior. Second, control is homeostatic because AI systems, either themselves or through accessory mechanisms, not only initiate but also maintain the efficiency of target behaviors. Third, AI-controlled behaviors, even seemingly noncooperative ones, are generally cooperative in nature, when interpreted in the appropriate ecological context. The escape of individual cells from biofilms, for example, may be viewed as an altruistic behavior that increases the fitness of the resident population by reducing starvation stress. The framework proposed here helps appropriately categorize AI-controlled behaviors and allows for a deeper understanding of their ecological and evolutionary functions.
Tracking a big Miocene river across the Continental Divide at Monida Pass, Montana/Idaho
Authors: Sears James W. 
Published: February 2015

Abstract
Exotic Miocene and Pliocene river gravel lies on top of the Continental Divide along the Idaho-Montana border near Monida Pass. The gravel is interlayered with tuffs and basalt flows of the Heise volcanic field, which erupted from the site of the Yellowstone hotspot between 6.62 and 4.45 Ma. The gravel includes pebbles that may have been derived from bedrock outcrops in Nevada and Utah, implying a paleo-river with headwaters to the south of the modern Continental Divide and Snake River Plain. The river may have been a tributary of the pre–ice age Bell River of Canada.
The field trip examines evidence for the tectonic evolution of the Monida Pass area. The course of the Miocene river appears to have been diverted around growing mountain ranges, and then pinched off at Monida Pass on the northern shoulder of the Yellowstone hotspot track.
A slice through time
Authors: Sugden J.C. , Hartshorn A.S. , Dixon J.L. , Montagne C. 
Published: February 2015

Abstract
On this field trip, participants will get their hands dirty while characterizing soils formed on five different rock types: Archean Gneiss, Flathead Sandstone, Wolsey Shale, Meagher Limestone, and Absaroka Volcanics (a basaltic andesite rock). We first recap prior soil survey efforts across the Gallatin National Forest in southwestern Montana and introduce a state factor approach to understanding soils. For over 50 years, Montana State University faculty have explored parts of this lithosequence, using it as a natural laboratory for thousands of students. We continue this tradition with this field guide, emphasizing how the combination of field and laboratory data can enrich our understanding of soil processes. We will observe and measure striking differences in soils; these differences in physical and chemical properties, from textures and colors to pH and elemental composition, are discussed in the context of quantifying the influence of the underlying rock on soil properties. We use these differences to ask whether heterogeneity in soil properties justifies the inference that soil properties are dominated by the underlying lithology. We conclude that the underlying rock strongly influences soil properties, but in variable ways across this lithosequence. This influence is both direct and indirect: chemical weathering of the rock leads to compositional changes in overlying soil, but rock weathering also leads to coarse fragments in the soil profile, which alters soil hydrology.
Polyphase collapse of the Cordilleran hinterland
Authors: Kalakay Thomas J. , Foster David A. , Lonn Jeffrey D. 
Published: February 2015

Abstract
The Anaconda and Bitterroot metamorphic core complexes are located in western Montana, along the eastern edge of the Cordilleran hinterland. This multi-tiered extensional terrain contains exceptional exposures that collectively exhibit a crustal cross section through orogenic continental crust (i.e., middle through upper crust). The core complex footwall rocks consist of Late Cretaceous arc-related plutons and Eocene granitic plutons intruded into deformed and metamorphosed Midproterozoic Belt Supergroup and Paleozoic to Cretaceous shelf-platform strata. Late Cretaceous shear zones and folds dominate footwall structure, representing significant thinning of the stratigraphic section. Eocene detachments, mylonites, and plutonic suites distinctly overprint the Late Cretaceous structures. A stark example of this Eocene overprint is the Anaconda detachment, which resulted in eastward translation of the Late Cretaceous, arc-related Boulder batholith. This field trip will cover a transect through the Anaconda core complex from the Philipsburg valley to Butte, Montana. Field trip participants will examine key locations that clarify the distinction between the timing and structural style of Late Cretaceous crustal thickening and/or collapse features versus those related to Eocene core complex development.
Glacial and Quaternary geology of the northern Yellowstone area, Montana and Wyoming
Authors: Pierce Kenneth L. , Licciardi Joseph M. , Krause Teresa R. , Whitlock Cathy 
Published: February 2015

Abstract
This field guide focuses on the glacial geology and paleoecology beginning in the Paradise Valley and progressing southward into northern Yellowstone National Park. During the last (Pinedale) glaciation, the northern Yellowstone outlet glacier flowed out of Yellowstone Park and down the Yellowstone River Valley into the Paradise Valley. The field trip will traverse the following Pinedale glacial sequence: (1) deposition of the Eightmile terminal moraines and outwash 16.5 ± 1.4 10Be ka in the Paradise Valley; (2) glacial recession of ~8 km and deposition of the Chico moraines and outwash 16.1 ± 1.7 10Be ka; (3) glacial recession of 45 km to near the northern Yellowstone boundary and moraine deposition during the Deckard Flats readjustment 14.2 ± 1.2 10Be ka; and (4) glacial recession of ~37 km and deposition of the Junction Butte moraines 15.2 ± 1.3 10Be ka (this age is a little too old based on the stratigraphic sequence). Yellowstone's northern range of sagebrush-grasslands and bison, elk, wolf, and bear inhabitants is founded on glacial moraines, sub-glacial till, and outwash deposited during the last glaciation. Floods released from glacially dammed lakes and a landslide-dammed lake punctuate this record.
The glacial geologic reconstruction was evaluated by calculation of basal shear stress, and yielded the following values for flow pattern in plan view: strongly converging—1.21 ± 0.12 bars (n = 15); nearly uniform—1.04 ± 0.16 bars (n = 11); and strongly diverging—0.84 ± 0.14 bars (n = 16). Reconstructed mass balance yielded accumulation and ablation each of ~3 km3/yr, with glacial movement near the equilibrium line altitude dominated by basal sliding.
Pollen and charcoal records from three lakes in northern Yellowstone provide information on the postglacial vegetation and fire history. Following glacial retreat, sparsely vegetated landscapes were colonized first by spruce parkland and then by closed subalpine forests. Regional fire activity increased significantly with the development of closed subalpine forests as a result of increased fuel biomass and warmer summers. Warm dry conditions prevailed at low elevations during the early Holocene, as indicated by the presence of steppe and open mixed conifer forest. At the same time, closed subalpine forests with low fire frequency were present at higher elevations, suggesting relatively wet summer conditions. Douglas fir populations expanded throughout northern Yellowstone in the middle Holocene as a result of effectively drier conditions than before, and a decline of mesophytic plant taxa during the late Holocene imply continued drying, even though fire frequency decreased in recent millennia.
A systematic review of the effects of upper body warm-up on performance and injury
Authors: McCrary J Matt , Ackermann Bronwen J , Halaki Mark 
Published: February 2015

PurposeThis systematic review was conducted to identify the impact of upper body warm-up on performance and injury prevention outcomes.MethodsWeb of Science, MEDLINE, SPORTDiscus, PsycINFO and Cochrane databases were searched using terms related to upper extremity warm-up. Inclusion criteria were English language randomised controlled trials from peer-reviewed journals in which investigation of upper body warm-up on performance and injury prevention outcomes was a primary aim. Included studies were assessed for methodological quality using the PEDro scale. A wide variety of warm-up modes and outcomes precluded meta-analysis except for one group of studies. The majority of warm-ups were assessed as having ‘positive’, ‘neutral’, ‘negative’ or ‘specific’ effects on outcomes.ResultsThirty-one studies met the inclusion criteria with 21 rated as having ‘good’ methodological quality. The studies investigated a total of 25 warm-up modes and 43 outcome factors that could be grouped into eight mode and performance outcome categories. No studies of upper body warm-up effects on injury prevention were discovered.ConclusionsStrong research-based evidence was found for the following: high-load dynamic warm-ups enhance power and strength performance; warm-up swings with a standard weight baseball bat are most effective for enhancing bat speed; short-duration static stretching warm-up has no effect on power outcomes; and passive heating/cooling is a largely ineffective warm-up mode. A clear knowledge gap in upper body warm-up literature is the lack of investigation of injury prevention outcomes.
Bibliometrics of NIHR HTA monographs and their related journal articles
Authors: Royle Pamela , Waugh Norman 
Published: February 2015

ObjectivesA bibliometric analysis of the UK National Institute for Health Research (NIHR)Health Technology Assessment(HTA) monographs and their related journal articles by: (1) exploring the differences in citations to the HTA monographs in Google Scholar (GS), Scopus and Web of Science (WoS), and (2) comparing Scopus citations to the monographs with their related journal articles.SettingA study of 111 HTA monographs published in 2010 and 2011, and their external journal articles.Main outcome measuresCitations to the monographs in GS, Scopus and WoS, and to their external journal articles in Scopus.ResultsThe number of citations varied among the three databases, with GS having the highest and WoS the lowest; however, the citation-based rankings among the databases were highly correlated. Overall, 56% of monographs had a related publication, with the highest proportion for primary research (76%) and lowest for evidence syntheses (43%). There was a large variation in how the monographs were cited, compared to journal articles, resulting in more frequent problems, with unlinked citations in Scopus and WoS. When comparing differences in the number of citations between monograph publications with their related journal articles from the same project, we found that monographs received more citations than their journal articles for evidence syntheses and methodology projects; by contrast, journal articles related to primary research monographs were more highly cited than their monograph.ConclusionsThe numbers of citations to the HTA monographs differed considerably between the databases, but were highly correlated. When a HTA monograph had a journal article from the same study, there were more citations to the journal article for primary research, but more to the monographs for evidence syntheses. Citations to the related journal articles were more reliably recorded than citations to the HTA monographs.