bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Bad People Can't be Good Friends
Authors: Elder Alexis 
Published: July 2013

AbstractMust the best friends necessarily be good people? On the one hand, as Aristotle puts it, ‘people think that the same people are good and also friends’. But on the other hand, friendship sometimes seems to require that one behave badly. For example, a normally honest person might lie to corroborate a friend's story. What I will call closeness, which I take to include sensitivity to friends' subjective values and concerns as well as an inclination to take their subjective interests as reasons for action, is characteristic of friendship. But this seems to require that good friends should be morally flexible, more so than is compatible with a virtuous character. This would imply tension between ideals of friendship and ideals of character. But there is an important connection between virtue and friendship which arises precisely from friends' closeness, when concern for wellbeing, another important feature of friendship, is also taken into account. This helps mitigate the tension and shows how friendship and virtue are interconnected. The connection in turn provides friendship‐based reason to think the best friends must be good people, even though concerns of friendship may occasionally clash with other moral concerns.
Doa PosterioriPhysicalists Get Our Phenomenal Concepts Wrong?
Authors: Diaz‐Leon E. 
Published: July 2013

AbstractA posterioriphysicalism is the combination of two appealing views: physicalism (i.e. the view that all facts are either physical or entailed by the physical), and conceptual dualism (i.e. the view that phenomenal truths are not entaileda prioriby physical truths). Recently, some philosophers such as Goff (2011), Levine (2007) and Nida‐Rümelin (2007), among others, have suggested thata posterioriphysicalism cannot explain how phenomenal concepts can reveal the nature of phenomenal properties. In this paper, I wish to defenda posterioriphysicalism from this new and interesting challenge, by arguing thata posterioriphysicalists have the resources to explain how phenomenal concepts can reveal at least something of what it would take for the corresponding phenomenal property to be instantiated.
Relation between soil P test values and mobilization of dissolved and particulate P from the plough layer of typical Danish soils from a long‐term field experiment with applied P fertilizers
Authors: Glæsner N. , Kjaergaard C. , Rubæk G. H. , Magid J. 
Published: July 2013

AbstractAccumulation of phosphorus (P) in agricultural topsoils can contribute to leaching of P which may cause eutrophication of surface waters. An understanding of P mobilization processes in the plough layer is needed to improve agricultural management strategies. We compare leaching of total dissolved and particulate P through the plough layer of a typical Danish sandy loam soil subjected to three different P fertilizer regimes in a long‐term field experiment established in 1975. The leaching experiment used intact soil columns (20 cm diameter, 20 cm high) during unsaturated conditions. The three soils had small to moderate labile P contents, expressed by water‐extractable P (3.6–10.7 mg/kg), Olsen P (11–28 mg/kg) and degree of P saturation (DPS) (25–34%). Mobilization of total dissolved P (TDP) increased significantly (P < 0.05) from the intact soil columns with increasing labile P, whereas the increase in particulate P (PP) with increasing labile P content was modest and statistically insignificant. We found concentrations up to 1.5 mg TP/L for the plough layer of this typical Danish sandy loam soil. This highlights that even a moderate labile P content can be a potential source of TDP from the plough layer, and that a lower concentration margin of optimum agronomic P levels should be considered.
Teaching with Complicating Views: Beyond the Survey, Behind the Pro and Con
Authors: Locklin Reid B. 
Published: July 2013

AbstractIn this article I propose a method of selecting and assigning readings in the religious studies or theology classroom, such that these readings complicate one another, rather than standing in opposition or as simple alternatives. Such a strategy emulates key pedagogical insights of twelfth‐century sentence collection, an activity at the very heart of the earliest universities in Europe. It also draws support from the theories of intellectual development advanced by William G. Perry, Jr. and the Women's Ways of Knowing Collaborative. Both precedents suggest a principle of “complicating views” that can be flexibly employed in a variety of ways and diverse pedagogical contexts, as illustrated by examples from several classes. Such strategies aim to avoid reinforcing intellectual patterns of dualism or undifferentiated relativism; instead, they attempt to promote students' ability to integrate discordant voices and to appreciate diverse points of view, while also staking their own claims relative to them.
Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection
Authors: Min Joo-Won , Lee Ha-Youn , Lee Ji Sun , Lee Jinwoo , Chung Jae Ho , Han Sung Koo , Yim Jae-Joon 
Published: July 2013

ABSTRACT
Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.
Rapid Antifungal Susceptibility Testing by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Analysis
Authors: Vella Antonietta , De Carolis Elena , Vaccaro Luisa , Posteraro Patrizia , Perlin David S. , Kostrzewa Markus , Posteraro Brunella , Sanguinetti Maurizio 
Published: July 2013

ABSTRACT

The widespread use of antifungal agents, which is likely to expand with their enhanced availability, has promoted the emergence of drug-resistant strains. Antifungal susceptibility testing (AFST) is now an essential procedure for guiding appropriate antifungal therapy. Recently, we developed a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS)-based method that enables the detection of fungal isolates with reduced echinocandin susceptibility, relying on the proteome changes that are detectable after a 15-h exposure of fungal cells to serial drug concentrations. Here, we describe a simplified version of this approach that facilitates discrimination of the susceptible and resistant isolates of
Candida albicans
after a 3-h incubation in the presence of “breakpoint” level drug concentrations of the echinocandin caspofungin (CSF). Spectra at concentrations of 0 (null), 0.03 (intermediate), and 32 (maximal) μg/ml of CSF were used to create individual composite correlation index (CCI) matrices for 65
C. albicans
isolates, including 13
fks1
mutants. Isolates are then classified as susceptible or resistant to CSF if the CCI values of spectra at 0.03 and 32 μg/ml are higher or lower, respectively, than the CCI values of spectra at 0.03 and 0 μg/ml. In this way, the drug resistance of
C. albicans
isolates to echinocandin antifungals can be quickly assessed. Furthermore, the isolate categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant
FKS1
genotypes and the AFST reference methodology. The ms-AFST approach may provide a rapid and reliable means of detecting emerging antifungal resistance and accelerating the initiation of appropriate antifungal treatment.
Identification of Salmonella enterica Serovar Typhi Genotypes by Use of Rapid Multiplex Ligation-Dependent Probe Amplification
Authors: Pham Thanh Duy , Tran Vu Thieu Nga , Tran Thuy Chau , Lodén Martin , Tuin Kiki , Campbell James I. , Van Minh Hoang Nguyen , Voong Vinh Phat , Farrar Jeremy J. , Holt Kathryn E. , Dougan Gordon , Baker Stephen 
Published: July 2013

ABSTRACT

Salmonella enterica
serovar Typhi, the causative agent of typhoid fever, is highly clonal and genetically conserved, making isolate subtyping difficult. We describe a standardized multiplex ligation-dependent probe amplification (MLPA) genotyping scheme targeting 11 key phylogenetic markers of the
S
. Typhi genome. The MLPA method demonstrated 90% concordance with single nucleotide polymorphism (SNP) typing, the gold standard for
S
. Typhi genotyping, and had the ability to identify isolates of the H58 haplotype, which is associated with resistance to multiple antimicrobials. Additionally, the assay permitted the detection of fluoroquinolone resistance-associated mutations in the DNA gyrase-encoding gene
gyrA
and the topoisomerase gene
parC
with a sensitivity of 100%. The MLPA methodology is simple and reliable, providing phylogenetically and phenotypically relevant genotyping information. This MLPA scheme offers a more-sensitive and interpretable alternative to the nonphylogenetic subgrouping methodologies that are currently used in reference and research laboratories in areas where typhoid is endemic.
Caspase Activation as a Versatile Assay Platform for Detection of Cytotoxic Bacterial Toxins
Authors: Payne Angela M. , Zorman Julie , Horton Melanie , Dubey Sheri , ter Meulen Jan , Vora Kalpit A. 
Published: July 2013

ABSTRACTPathogenic bacteria produce several virulence factors that help them establish infection in permissive hosts. Bacterial toxins are a major class of virulence factors and hence are attractive therapeutic targets for vaccine development. Here, we describe the development of a rapid, sensitive, and high-throughput assay that can be used as a versatile platform to measure the activities of bacterial toxins. We have exploited the ability of these toxins to cause cell death via apoptosis of sensitive cultured cell lines as a readout for measuring toxin activity. Caspases (cysteine-aspartic proteases) are induced early in the apoptotic pathway, and so we used their induction to measure the activities ofClostridium difficiletoxins A (TcdA) and B (TcdB) and binary toxin (CDTa-CDTb),Corynebacterium diphtheriaetoxin (DT), andPseudomonas aeruginosaexotoxin A (PEA). Caspase induction in the cell lines, upon exposure to toxins, was optimized by toxin concentration and intoxication time, and the specificity of caspase activity was established using a genetically mutated toxin and a pan-caspase inhibitor. In addition, we demonstrate the utility of the caspase assay for measuring toxin potency, as well as neutralizing antibody (NAb) activity againstC. difficiletoxins. Furthermore, the caspase assay showed excellent correlation with the filamentous actin (F-actin) polymerization assay for measuring TcdA and TcdB neutralization titers upon vaccination of hamsters. These results demonstrate that the detection of caspase induction due to toxin exposure using a chemiluminescence readout can support potency and clinical immunogenicity testing for bacterial toxin vaccine candidates in development.
Rapid Differentiation of Cryptic Species within Cryptococcus gattii by a Duplex PCR Assay
Authors: Feng Xiaobo , Fu Xiaohua , Ling Bo , Wang Lei , Liao Wanqing , Pan Weihua , Yao Zhirong 
Published: July 2013

ABSTRACT

Cryptococcus gattii
consists of four cryptic species, VGI, VGII, VGIII, and VGIV. Herein, a duplex PCR assay using two primer pairs targeting the vacuolar membrane gene and the intergenic spacer region was developed. It successfully distinguished the cryptic species according to the distinct size of the amplicons.
Expanded Cocirculation of Stable Subtypes, Emerging Lineages, and New Sporadic Reassortants of Porcine Influenza Viruses in Swine Populations in Northwest Germany
Authors: Harder Timm C. , grosse Beilage Elisabeth , Lange Elke , Meiners Carolin , Döhring Stefanie , Pesch Stefan , Noé Thomas , Grund Christian , Beer Martin , Starick Elke 
Published: July 2013

ABSTRACT
The emergence of the human 2009 pandemic H1N1 (H1N1pdm) virus from swine populations refocused public and scientific attention on swine as an important source of influenza A viruses bearing zoonotic potential. Widespread and year-round circulation of at least four stable lineages of porcine influenza viruses between 2009 and 2012 in a region of Germany with a high-density swine population is documented here. European avian influenza virus-derived H1N1 (H1N1av) viruses dominated the epidemiology, followed by human-derived subtypes H1N2 and H3N2. H1N1pdm viruses and, in particular, recently emerging reassortants between H1N1pdm and porcine HxN2 viruses (H1pdmN2) were detected in about 8% of cases. Further reassortants between these main lineages were diagnosed sporadically. Ongoing diversification both at the phylogenetic and at the antigenic level was evident for the H1N1av lineage and for some of its reassortants. The H1avN2 reassortant R1931/11 displayed conspicuously distinct genetic and antigenic features and was easily transmitted from pig to pig in an experimental infection. Continuing diverging evolution was also observed in the H1pdmN2 lineage. These viruses carry seven genome segments of the H1N1pdm virus, including a hemagglutinin gene that encodes a markedly antigenically altered protein. The zoonotic potential of this lineage remains to be determined. The results highlight the relevance of surveillance and control of porcine influenza virus infections. This is important for the health status of swine herds. In addition, a more exhaustive tracing of the formation, transmission, and spread of new reassortant influenza A viruses with unknown zoonotic potential is urgently required.
Identification of a Suppressor Mutation That Improves the Yields of Hexon-Modified Adenovirus Vectors
Authors: Bruder Joseph T. , Chen Ping , Semenova Elena , Thomas Charlie A. , Konovalova Svetlana , Ekberg Greg , Ettyreddy Damodar , McVey Duncan , Gall Jason G. , King C. Richter , Brough Douglas E. 
Published: July 2013

ABSTRACTWe have generated hexon-modified adenovirus serotype 5 (Ad5) vectors that are not neutralized by Ad5-specific neutralizing antibodies in mice. These vectors are attractive for the advancement of vaccine products because of their potential for inducing robust antigen-specific immune responses in people with prior exposure to Ad5. However, hexon-modified Ad5 vectors displayed an approximate 10-fold growth defect in complementing cells, making potential vaccine costs unacceptably high. Replacing hypervariable regions (HVRs) 1, 2, 4, and 5 with the equivalent HVRs from Ad43 was sufficient to avoid Ad5 preexisting immunity and retain full vaccine potential. However, the resulting vector displayed the same growth defect as the hexon-modified vector carrying all 9 HVRs from Ad43. The growth defect is likely due to a defect in capsid assembly, since DNA replication and late protein accumulation were normal in these vectors. We determined that the hexon-modified vectors have a 32°C cold-sensitive phenotype and selected revertants that restored vector productivity. Genome sequencing identified a single base change resulting in a threonine-to-methionine amino acid substitution at the position equivalent to residue 342 of the wild-type protein. This mutation has a suppressor phenotype (SP), since cloning it into our Ad5 vector containing all nine hypervariable regions from Ad43, Ad5.H(43m-43), increased yields over the version without the SP mutation. This growth improvement was also shown for an Ad5-based hexon-modified vector that carried the hexon hypervariable regions of Ad48, indicating that the SP mutation may have broad applicability for improving the productivity of different hexon-modified vectors.
Mutational Analysis of the Binding Pockets of the Diketo Acid Inhibitor L-742,001 in the Influenza Virus PA Endonuclease
Authors: Stevaert Annelies , Dallocchio Roberto , Dessì Alessandro , Pala Nicolino , Rogolino Dominga , Sechi Mario , Naesens Lieve 
Published: July 2013

ABSTRACT
The influenza virus PA endonuclease, which cleaves capped host pre-mRNAs to initiate synthesis of viral mRNA, is a prime target for antiviral therapy. The diketo acid compound L-742,001 was previously identified as a potent inhibitor of the influenza virus endonuclease reaction, but information on its precise binding mode to PA or potential resistance profile is limited. Computer-assisted docking of L-742,001 into the crystal structure of inhibitor-free N-terminal PA (PA-Nter) indicated a binding orientation distinct from that seen in a recent crystallographic study with L-742,001-bound PA-Nter (R. M. DuBois et al., PLoS Pathog. 8:e1002830, 2012). A comprehensive mutational analysis was performed to determine which amino acid changes within the catalytic center of PA or its surrounding hydrophobic pockets alter the antiviral sensitivity to L-742,001 in cell culture. Marked (up to 20-fold) resistance to L-742,001 was observed for the H41A, I120T, and G81F/V/T mutant forms of PA. Two- to 3-fold resistance was seen for the T20A, L42T, and V122T mutants, and the R124Q and Y130A mutants were 3-fold more sensitive to L-742,001. Several mutations situated at noncatalytic sites in PA had no or only marginal impact on the enzymatic functionality of viral ribonucleoprotein complexes reconstituted in cell culture, consistent with the less conserved nature of these PA residues. Our data provide relevant insights into the binding mode of L-742,001 in the PA endonuclease active site. In addition, we predict some potential resistance sites that should be taken into account during optimization of PA endonuclease inhibitors toward tight binding in any of the hydrophobic pockets surrounding the catalytic center of the enzyme.
Cell Susceptibility to Baculovirus Transduction and Echovirus Infection Is Modified by Protein Kinase C Phosphorylation and Vimentin Organization
Authors: Turkki Paula , Makkonen Kaisa-Emilia , Huttunen Moona , Laakkonen Johanna P. , Ylä-Herttuala Seppo , Airenne Kari J. , Marjomäki Varpu 
Published: July 2013

ABSTRACTSome cell types are more susceptible to viral gene transfer or virus infection than others, irrespective of the number of viral receptors or virus binding efficacy on their surfaces. In order to characterize the cell-line-specific features contributing to efficient virus entry, we studied two cell lines (Ea.hy926 and MG-63) that are nearly nonpermissive to insect-specific baculovirus (BV) and the human enterovirus echovirus 1 (EV1) and compared their characteristics with those of a highly permissive (HepG2) cell line. All the cell lines contained high levels of viral receptors on their surfaces, and virus binding was shown to be efficient. However, in nonpermissive cells, BV and its receptor, syndecan 1, were unable to internalize in the cells and formed large aggregates near the cell surface. Accordingly, EV1 had a low infection rate in nonpermissive cells but was still able to internalize the cells, suggesting that the postinternalization step of the virus was impaired. The nonpermissive and permissive cell lines showed differential expression of syntenin, filamentous actin, vimentin, and phosphorylated protein kinase C subtype α (pPKCα). The nonpermissive nature of the cells could be modulated by the choice of culture medium. RPMI medium could partially rescue infection/transduction and concomitantly showed lower syntenin expression, a modified vimentin network, and altered activities of PKC subtypes PKCα and PKCε. The observed changes in PKCα and PKCε activation caused alterations in the vimentin organization, leading to efficient BV transduction and EV1 infection. This study identifies PKCα, PKCε, and vimentin as key factors affecting efficient infection and transduction by EV1 and BV, respectively.
Alphacoronavirus Protein 7 Modulates Host Innate Immune Response
Authors: Cruz Jazmina L. G. , Becares Martina , Sola Isabel , Oliveros Juan Carlos , Enjuanes Luis , Zúñiga Sonia 
Published: July 2013

ABSTRACTInnate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to subvert host defense mechanisms and increase their survival. In the transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts the host antiviral response by associating with the catalytic subunit of protein phosphatase 1 (PP1c). In the present work, the effect of the absence of gene 7 on the host cell, during infection, was further analyzed by transcriptomic analysis. The pattern of gene expression of cells infected with a recombinant mutant TGEV, lacking gene 7 expression (rTGEV-Δ7), was compared to that of cells infected with the parental virus (rTGEV-wt). Genes involved in the immune response, the interferon response, and inflammation were upregulated during TGEV infection in the absence of gene 7. An exacerbated innate immune response during infection with rTGEV-Δ7 virus was observed bothin vitroandin vivo. An increase in macrophage recruitment and activation in lung tissues infected with rTGEV-Δ7 virus was observed compared to cells infected with the parental virus. In summary, the absence of protein 7 bothin vitroandin vivoled to increased proinflammatory responses and acute tissue damage after infection. In a porcine animal model, which is immunologically similar to humans, we present a novel example of how viral proteins counteract host antiviral pathways to determine the infection outcome and pathogenesis.
Involvement of the Reparative DNA Polymerase Pol X of African Swine Fever Virus in the Maintenance of Viral Genome Stability
In Vivo
Authors: Redrejo-Rodríguez Modesto , Rodríguez Javier M. , Suárez Cristina , Salas José , Salas María L. 
Published: July 2013

ABSTRACT
The function of the African swine fever virus (ASFV) reparative DNA polymerase, Pol X, was investigated in the context of virus infection. Pol X is a late structural protein that localizes at cytoplasmic viral factories during DNA replication. Using an ASFV deletion mutant lacking the Pol X gene, we have shown that Pol X is not required for virus growth in Vero cells or swine macrophages under one-step growth conditions. However, at a low multiplicity of infection, when multiple rounds of replication occur, the growth of the mutant virus is impaired in swine macrophages but not in Vero cells, suggesting that Pol X is needed to repair the accumulated DNA damage. The replication of the mutant virus in Vero cells presents sensitivity to oxidative damage, and mutational analysis of viral DNA shows that deletion of Pol X results in an increase in the mutation frequency in macrophages. Therefore, our data reveal a biological role for ASFV Pol X in the context of the infected cell in the preservation of viral genetic information.