bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tinkering with Technology and Religion in the Digital Age: The Effects of Internet Use on Religious Belief, Behavior, and Belonging
Authors: McClure Paul K. 
Published: December 2017

AbstractInternet technology presents a new conceptual reality, one that could potentially challenge religion in subtle but distinct ways. Few sociologists of religion, however, have attempted to evaluate whether using the Internet impacts the way people think about and practice religion. This article elaborates on the concept of “tinkering” discussed by Berger, Berger, and Kellner (1974), Turkle (1997), and Wuthnow (2010) to argue that Internet use affects how people think about and affiliate with religious traditions. Using data from Wave III of the Baylor Religion Survey (2010), I find that Internet use is associated with increases in being religiously unaffiliated and decreases in religious exclusivism. At the same time, I find that television viewing is linked to decreases in religious attendance and other time‐related religious activities, but these outcomes are not impacted by Internet use. To explain these disparate findings, I argue that the Internet is fundamentally different from previous technologies like television and thus impacts religious beliefs and belonging but not time‐related religious activities.
Molecular phylogenetics and microsatellite analysis reveal a new pathogenic Ceratocystis species in the Asian‐Australian clade
Authors: Liu F. F. , Barnes I. , Roux J. , Wingfield M. J. , Chen S. F. 
Published: December 2017

The ascomycete genus Ceratocystis has a broad geographic distribution and includes pathogens of a wide range of mostly woody hosts. Black rot of Colocasia esculenta (taro), a popular cultivated root crop in China, is caused by a species of Ceratocystis broadly treated as C. fimbriata sensu lato. Recently, isolates of Ceratocystis were obtained from black rot lesions on C. esculenta corms in two Chinese provinces. Sequence comparison of the ITS, partial β‐tubulin, TEF‐1α, MS204 and RPBII gene regions were used to identify these isolates and compare them to other Ceratocystis species. Furthermore, the diversity of Ceratocystis species in the Asian‐Australian clade (AAC) was investigated using 23 microsatellite markers. Results showed that the isolates from C. esculenta represent a novel species, which is morphologically and phylogenetically different to closely related species in the AAC, and is described here as Ceratocystis changhui sp. nov. In microsatellite analyses, this new species also emerged as distinct from others in the AAC. Inoculation tests showed that C. changhui sp. nov. is a virulent pathogen of C. esculenta corms, but produces only small lesions on Eucalyptus grandis and Eriobotrya japonica.
Community-Acquired Pneumonia in Children: the Challenges of Microbiological Diagnosis
Authors: Rodrigues C. M. C. , Groves H. 
Published: December 2017

ABSTRACT
Community-acquired pneumonia (CAP) is the leading cause of mortality in children under 5 years of age globally. To improve the management of CAP, we must distinguish CAP from other common pediatric conditions and develop better diagnostic methods to detect the causative organism, so as to best direct appropriate resources in both industrialized and developing countries. Here, we review the diagnostic modalities available for identifying viruses and bacteria in the upper and lower respiratory tract of children, with a discussion of their utility and limitations in diagnosing CAP in children.
Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan
Authors: Fedeli Chiara , Torriani Giulia , Galan-Navarro Clara , Moraz Marie-Laurence , Moreno Hector , Gerold Gisa , Kunz Stefan 
Published: December 2017

ABSTRACT

Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan. Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed
in vivo
. The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates. However, their role in LASV entry is not entirely understood. Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG. To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model. We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using “apoptotic mimicry” in a way similar to that of other enveloped viruses. We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis. Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor. In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry. In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.

IMPORTANCE
The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa. Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism. The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear. Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification. We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry. Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1. In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry. In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
Herpes Simplex Virus 1 DNA Polymerase RNase H Activity Acts in a 3′-to-5′ Direction and Is Dependent on the 3′-to-5′ Exonuclease Active Site
Authors: Lawler Jessica L. , Mukherjee Purba , Coen Donald M. 
Published: December 2017

ABSTRACT

The catalytic subunit (Pol) of herpes simplex virus 1 (HSV-1) DNA polymerase has been extensively studied both as a model for other family B DNA polymerases and for its differences from these enzymes as an antiviral target. Among the activities of HSV-1 Pol is an intrinsic RNase H activity that cleaves RNA from RNA-DNA hybrids. There has long been a controversy regarding whether this activity is due to the 3′-to-5′ exonuclease of Pol or whether it is a separate activity, possibly acting on 5′ RNA termini. To investigate this issue, we compared wild-type HSV-1 Pol and a 3′-to-5′ exonuclease-deficient mutant, D368A Pol, for DNA polymerase activity, 3′-to-5′ exonuclease activity, and RNase H activity
in vitro
. Additionally, we assessed the RNase H activity using differentially end-labeled templates with 5′ or 3′ RNA termini. The mutant enzyme was at most modestly impaired for DNA polymerase activity but was drastically impaired for 3′-to-5′ exonuclease activity, with no activity detected even at high enzyme-to-DNA substrate ratios. Importantly, the mutant showed no detectable ability to excise RNA with either a 3′ or 5′ terminus, while the wild-type HSV-1 Pol was able to cleave RNA from the annealed RNA-DNA hairpin template, but only detectably with a 3′ RNA terminus in a 3′-to-5′ direction and at a rate lower than that of the exonuclease activity. These results suggest that HSV-1 Pol does not have an RNase H separable from its 3′-to-5′ exonuclease activity and that this activity prefers DNA degradation over degradation of RNA from RNA-DNA hybrids.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) is a member of the
Herpesviridae
family of DNA viruses, several of which cause morbidity and mortality in humans. Although the HSV-1 DNA polymerase has been studied for decades and is a crucial target for antivirals against HSV-1 infection, several of its functions remain to be elucidated. A hypothesis suggesting the existence of a 5′-to-3′ RNase H activity intrinsic to this enzyme that could remove RNA primers from Okazaki fragments has been particularly controversial. In this study, we were unable to identify RNase H activity of HSV-1 DNA polymerase on RNA-DNA hybrids with 5′ RNA termini. We detected RNase H activity on hybrids with 3′ termini, but this was due to the 3′-to-5′ exonuclease. Thus, HSV-1 is unlikely to use this method to remove RNA primers during DNA replication but may use pathways similar to those used in eukaryotic Okazaki fragment maturation.
Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes
Authors: Steele Margaret I. , Kwong Waldan K. , Whiteley Marvin , Moran Nancy A. 
Published: December 2017

ABSTRACTMicrobial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains ofSnodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared withGilliamella apicola, a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes inEscherichia coli. Using transcriptome sequencing, we demonstrate thatS. alviT6SSs and associated toxins are upregulated in the gut environment. We find thatS. alviRhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effectsin vivo. Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota.IMPORTANCEThe structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)—protein complexes used to deliver toxic proteins into bacterial competitors—within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed inEscherichia coli. Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities.
Retargeting Lentiviruses via SpyCatcher-SpyTag Chemistry for Gene Delivery into Specific Cell Types
Authors: Kasaraneni Nagarjun , Chamoun-Emanuelli Ana M. , Wright Gus , Chen Zhilei 
Published: December 2017

ABSTRACT

We report a simple strategy for the creation of lentiviral vectors specific to any desired target cells. SpyTag is inserted into an engineered Sindbis virus envelope protein and displayed on the lentivirus surface to create Sindbis virus-SpyTag pseudoparticles (Sind-SpyTag-pp). The SpyTag serves as the covalent anchoring site for a target-cell-specific cell-binding protein (CBP) that is fused to a truncated SpyCatcher (SpyCatcherΔ). Target-cell-specific lentiviruses are created by mixing the Sind-SpyTag-pp and CBP-SpyCatcherΔ
in vitro
. We first used a HER2-binding designed ankyrin repeat protein (DARPin.9.26) as the model CBP. The DARPin-conjugated lentivirus transduced HER2
+
SKOV3 cells with an infectious titer of 5.2 × 10
6
IU/ml, >500-fold higher than the unfunctionalized “naked” virions (<10
4
IU/ml). The ability of the DARPin-conjugated lentivirus to transduce HER2
+
cells correlated with the surface expression level of HER2. Furthermore, these lentiviruses preferentially transduced HER2
+
cells in cocultures containing HER2
+
and HER2
−
cells. To enable the use of commercially available monoclonal antibodies (MAbs) as the CBP, we developed a convenient click chemistry-based approach to conjugate MAb-derived Fab fragments to a variant SpyCatcherΔ protein containing a nonnatural amino acid, 4-azido-
l
-phenylalanine (AzF). Using the HER2-binding trastuzumab as a model cell-specific MAb, we created Fab-conjugated lentiviral vectors that transduced HER2
+
SKOV3 cells with an infectious titer of 2.8 × 10
6
IU/ml, on par with the result achieved using the DARPin-SpyCatcherΔ fusion protein. The ability to create cell-specific lentiviral vectors through chemical conjugation of a CBP should make this approach generalizable to any antibody, giving it broad utility for a wide range of research and clinical applications.

IMPORTANCE
Lentiviral vectors hold great potential in gene therapy. However, it remains a major hurdle to robustly engineer cell-specific lentiviral vectors. This article reports a simple and effective strategy to functionalize lentiviral vectors with cell-binding proteins, thus retargeting these viruses to cells expressing the binding partner of the CBP. The CBP is genetically or chemically linked to the SpyCatcher. The SpyTag is displayed on the virion surface as a fusion to an engineered Sindbis virus envelope protein and is used as the anchorage site for SpyCatcher-linked CBP. Using this strategy, we created lentiviral vectors highly infectious toward HER2
+
cancer cells. The ability to rapidly create cell-specific lentiviral vectors targeting a wide range of cell types should accelerate the development of custom lentiviral vectors for many research and clinical applications.
Immune-Mediated Damage Completes the Parabola:
Cryptococcus neoformans
Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response
Authors: Pirofski Liise-anne , Casadevall Arturo 
Published: December 2017

ABSTRACT

Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017,
https://doi.org/10.1128/mBio.01415-17
) that reports that CD4
+
T cells mediate tissue damage in experimental murine cryptococcosis. This finding has fundamental implications for our understanding of the pathogenesis of cryptococcal disease; it helps explain why immunotherapy has been largely unsuccessful in treatment and provides insight into the paradoxical observation that HIV-associated cryptococcosis may have a better prognosis than cryptococcosis in those with no known immune impairment. The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction.
Identity-by-Descent Mapping Identifies Major Locus for Serum Triglycerides in Amerindians Largely Explained by an
APOC3
Founder Mutation
Authors: Hsueh Wen-Chi , Nair Anup K. , Kobes Sayuko , Chen Peng , Göring Harald H.H. , Pollin Toni I. , Malhotra Alka , Knowler William C. , Baier Leslie J. , Hanson Robert L. 
Published: December 2017

Background—
Identity-by-descent mapping using empirical estimates of identity-by-descent allele sharing may be useful for studies of complex traits in founder populations, where hidden relationships may augment the inherent genetic information that can be used for localization.

Methods and Results—

Through identity-by-descent mapping, using ≈400 000 single-nucleotide polymorphisms (SNPs), of serum lipid profiles, we identified a major linkage signal for triglycerides in 1007 Pima Indians (LOD=9.23;
P
=3.5×10
−11
on chromosome 11q). In subsequent fine-mapping and replication association studies in ≈7500 Amerindians, we determined that this signal reflects effects of a loss-of-function Ala43Thr substitution in
APOC3
(rs147210663) and 3 established functional SNPs in
APOA5
. The association with rs147210663 was particularly strong; each copy of the Thr allele conferred 42% lower triglycerides (β=−0.92±0.059 SD unit;
P
=9.6×10
−55
in 4668 Pimas and 2793 Southwest Amerindians combined). The Thr allele is extremely rare in most global populations but has a frequency of 2.5% in Pimas. We further demonstrated that 3
APOA5
SNPs with established functional impact could explain the association with the most well-replicated SNP (rs964184) for triglycerides identified by genome-wide association studies. Collectively, these 4 SNPs account for 6.9% of variation in triglycerides in Pimas (and 4.1% in Southwest Amerindians), and their inclusion in the original linkage model reduced the linkage signal to virtually null.

Conclusions—

APOC3/APOA5
constitutes a major locus for serum triglycerides in Amerindians, especially the Pimas, and these results provide an empirical example for the concept that population-based linkage analysis is a useful strategy to identify complex trait variants.
Mindfulness and Compliance: The Way We Make Requests Influences Compliance With the Foot-in-the-Door Strategy
Authors: Gamian-Wilk Malgorzata , Dolinski Dariusz , Danieluk Barnaba 
Published: December 2017

The foot-in-the-door effect is considered more effective when a time lapse occurs between performing an initial, smaller request and being asked a second request. It has been hypothesized that mindfulness moderates the effectiveness of two versions of the strategy – time-delay and no-delay foot-in-the-door. The greater magnitude of time-delay foot-in-the-door is considered to be connected with increased mindfulness. The aim of this study was to verify the assumption concerning mindfulness as a state triggering time-delay foot-in-the-door. In a field experiment ( N = 249), we manipulated the time lapse and kind of reason (real, placebic, and no reason) accompanying a difficult or less difficult target request. This extended Langer et al. replication indicates that time-delay foot-in-the-door is indeed greater after mindfulness activation.
Indigenous Intellectuals in Contemporary Ecuador: Encounters with “Seven Erroneous Theses about Latin America”
Authors: Fernández Blanca Soledad 
Published: December 2017

The indigenous intellectuals who were part of the foundation of the Ecuadorean indigenous movement of the 1980s contributed to the theoretical and political grounding of the concept of the plurinational state that is now recognized in the country’s new constitution. This concept constitutes a critique of the idea of nationhood that developed in Latin America throughout the twentieth century. A comparative reading of these intellectuals’ work on the occasion of the fiftieth anniversary of the publication of Rodolfo Stavenhagen’s “Seven Erroneous Theses about Latin America” reveals two themes: colonial continuity and historical continuity. Both can be seen as a “settling of scores” with colonialism understood both as a historical period and as an analytical term for understanding the social reality of Latin America. Los intelectuales indígenas que formaron parte de la fundación del movimiento indígena ecuatoriano hacia la década de 1980 contribuyeron a la fundamentación teórica y política de la noción de Estado plurinacional, hoy reconocida por la nueva constitución del Ecuador. Sus principales antecedentes se encuentran en la elaboración de una crítica a la idea de nación tributaria de la corriente de pensamiento que se forjó en Nuestramérica a lo largo del siglo XX. Una lectura comparada de las obras escritas por estos intelectuales indígenas ecuatorianos en el marco de la conmemoración de los cincuenta años de la publicación de las “Siete tesis equivocadas sobre América Latina,” de Rodolfo Stavenhagen, revela dos elementos que aparecen reiteradamente a lo largo de su producción escritural: la idea de “continuidad colonial” y la idea de “continuidad histórica.” Ambas nociones remiten a un tema específico que se relaciona con cierto “ajuste de cuentas” con el colonialismo en tanto hecho histórico y en tanto categoría para el análisis de la realidad social en América Latina.
Metformin Effects on Metabolic Coupling and Tumor Growth in Oral Cavity Squamous Cell Carcinoma Coinjection Xenografts
Authors: Tassone Patrick , Domingo‐Vidal Marina , Whitaker‐Menezes Diana , Lin Zhao , Roche Megan , Tuluc Madalina , Martinez‐Outschoorn Ubaldo , Curry Joseph 
Published: December 2017

ObjectiveMany aggressive head and neck cancers contain 2 metabolically coupled tumor compartments: a glycolytic stromal compartment with low caveolin‐1 (CAV1) and high monocarboxylate transporter 4 (MCT4) expression and a highly proliferative carcinoma cell compartment with high MCT1. Metabolites are shuttled by MCTs from stroma to carcinoma to fuel tumor growth. We studied the effect of carcinoma‐fibroblast coinjection and metformin administration on a mouse model of head and neck squamous cell carcinoma.Study DesignXenograft head and neck squamous cell carcinoma model.SettingBasic science laboratory.Subjects and MethodsOral cavity carcinoma cells were injected alone or as coinjection with human fibroblasts into nude mice to generate xenograft tumors. Tumors were excised and stained with immunohistochemistry for markers of metabolic coupling and apoptosis, including MCT1, MCT4, CAV1, and TUNEL assay (terminal deoxynucleotidyl transferase nick end labeling). Strength of staining was assessed by a pathologist or computer‐assisted pathology software. Metformin was administered orally to mice to test effects on immunohistochemical markers in xenografts.ResultsCoinjection tumors were 2.8‐fold larger (P =. 048) and had 1.4‐fold stronger MCT1 staining (P =. 016) than tumors from homotypic carcinoma cell injection. Metformin decreased the size of coinjection xenograft tumors by 45% (P =. 025). Metformin reduced MCT1 staining by 28% (P =. 05) and increased carcinoma cell apoptosis 1.8‐fold as marked by TUNEL assay (P =. 005). Metformin did not have a significant effect on tumor size when CAV1 knockdown fibroblasts were used in coinjection.ConclusionCoinjection with fibroblasts increases tumor growth and metabolic coupling in oral cavity cancer xenografts. Fibroblast CAV1 expression is required for metformin to disrupt metabolic coupling and decrease xenograft size.