bluuebunny/crossref_metadata_2025_split huggingface dataset:
APORETIC POSSIBILITIES IN CATHERINE KELLER'SCLOUD OF THE IMPOSSIBLE
Authors: White Carol Wayne 
Published: August 2016

AbstractIn stressing the beauty of ignorance, of not knowing in the usual manner, Catherine Keller'sCloud of the Impossibleevokes the death of a metaphysical (A)uthorial presence and the dissolution of closed systems of meaning. In this article, I view her text as part of a crisis of modernity that challenges dominant theological pathways, on which certain problematic views of the human have been constructed. In my reading, Keller'sCloudenriches humanistic thinking in the West and I explore the themes it shares with my own work in religious naturalism: there is no escape from the radical relationality and the irreducible materiality that structure human existence. I also emphasize that textual strategies are mere seductive, disembodied abstractions without acknowledging the force of materiality. Materiality matters; and I explore ways in which religious naturalism demonstrates how it does. In light of Keller's rich analysis, I focus on a “learned ignorance” that accompanies all of our limited interpretations emerging from the shifting, precarious positionalities as we rethink our relationality to each other and to all that it is.
WHY WE SHOULD CARE ABOUT EVOLUTION AND NATURAL HISTORY
Authors: Kjærgaard Peter C. 
Published: August 2016

AbstractHistorians play it safe. Complex issues are dissected while analytical distance keeps stakeholders at bay. But the relevance of historical research may be lost in caution and failure to engage with a wider audience. We can't afford that. We have too much to offer and too much at stake. We need to take the discussion of science and religion beyond our own professional circles. Peter Harrison's The Territories of Science and Religion gives us an opportunity to do so. We can use his book to understand why people consistently get the relation wrong. However, we need to take the next step ourselves, involve historians in the common academic goal, across disciplines, to make sense of the world around us and make that combined knowledge truly useful. Evolution and natural history might help to that effect.
Systemic availability and metabolism of colonic‐derived short‐chain fatty acids in healthy subjects: a stable isotope study
Authors: Boets Eef , Gomand Sara V. , Deroover Lise , Preston Tom , Vermeulen Karen , De Preter Vicky , Hamer Henrike M. , Van den Mooter Guy , De Vuyst Luc , Courtin Christophe M. , Annaert Pieter , Delcour Jan A. , Verbeke Kristin A. 
Published: August 2016

Key points
The short‐chain fatty acids (SCFAs) are bacterial metabolites produced during the colonic fermentation of undigested carbohydrates, such as dietary fibre and prebiotics, and can mediate the interaction between the diet, the microbiota and the host.
We quantified the fraction of colonic administered SCFAs that could be recovered in the systemic circulation, the fraction that was excreted via the breath and urine, and the fraction that was used as a precursor for glucose, cholesterol and fatty acids.
This information is essential for understanding the molecular mechanisms by which SCFAs beneficially affect physiological functions such as glucose and lipid metabolism and immune function.
AbstractThe short‐chain fatty acids (SCFAs), acetate, propionate and butyrate, are bacterial metabolites that mediate the interaction between the diet, the microbiota and the host. In the present study, the systemic availability of SCFAs and their incorporation into biologically relevant molecules was quantified. Known amounts of 13C‐labelled acetate, propionate and butyrate were introduced in the colon of 12 healthy subjects using colon delivery capsules and plasma levels of 13C‐SCFAs 13C‐glucose, 13C‐cholesterol and 13C‐fatty acids were measured. The butyrate‐producing capacity of the intestinal microbiota was also quantified. Systemic availability of colonic‐administered acetate, propionate and butyrate was 36%, 9% and 2%, respectively. Conversion of acetate into butyrate (24%) was the most prevalent interconversion by the colonic microbiota and was not related to the butyrate‐producing capacity in the faecal samples. Less than 1% of administered acetate was incorporated into cholesterol and <15% in fatty acids. On average, 6% of colonic propionate was incorporated into glucose. The SCFAs were mainly excreted via the lungs after oxidation to 13CO2, whereas less than 0.05% of the SCFAs were excreted into urine. These results will allow future evaluation and quantification of SCFA production from 13C‐labelled fibres in the human colon by measurement of 13C‐labelled SCFA concentrations in blood.
Malnutrition Is Associated with Protection from Rotavirus Diarrhea: Evidence from a Longitudinal Birth Cohort Study in Bangladesh
Authors: Verkerke Hans , Sobuz Shihab , Ma Jennie Z. , Petri Sarah E. , Reichman Dan , Qadri Firdausi , Rahman Mustafizur , Haque Rashidul , Petri William A. 
Published: August 2016

ABSTRACT
Rotavirus is a leading cause of dehydrating diarrhea and death among infants and children globally, particularly in communities of the developing world. While numerous studies have described the complex relationships among infectious diarrhea, growth faltering, and poverty, the impact of nutritional status on susceptibility to rotavirus diarrhea is not well understood. In a longitudinal study conducted over the first 3 years of life among 626 slum-dwelling infants enrolled at birth in Dhaka, Bangladesh, we observed that common measures of healthy growth and development were positively associated with a risk of symptomatic rotavirus infection. This finding runs counter to the idea that improving childhood nutrition will implicitly decrease the incidence of symptomatic infection by enteric pathogens. As childhood nutrition improves worldwide, rotavirus infection may remain a public health challenge, making universal vaccination of even greater importance.
Evaluation of Hologic Aptima HIV-1 Quant Dx Assay on the Panther System on HIV Subtypes
Authors: Manak Mark M. , Hack Holly R. , Nair Sangeetha V. , Worlock Andrew , Malia Jennifer A. , Peel Sheila A. , Jagodzinski Linda L. 
Published: August 2016

ABSTRACT

Quantitation of the HIV-1 viral load in plasma is the current standard of care for clinical monitoring of HIV-infected individuals undergoing antiretroviral therapy. This study evaluated the analytical and clinical performances of the Aptima HIV-1 Quant Dx assay (Hologic, San Diego, CA) for monitoring viral load by using 277 well-characterized subtype samples, including 171 cultured virus isolates and 106 plasma samples from 35 countries, representing all major HIV subtypes, recombinants, and circulating recombinant forms (CRFs) currently in circulation worldwide. Linearity of the Aptima assay was tested on each of 6 major HIV-1 subtypes (A, B, C, D, CRF01_AE, and CRF02_AG) and demonstrated an
R
2
value of ≥0.996. The performance of the Aptima assay was also compared to those of the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 v.2 (CAP/CTM) and Abbott m2000 RealTime HIV-1 (RealTime) assays on all subtype samples. The Aptima assay values averaged 0.21 log higher than the CAP/CTM values and 0.30 log higher than the RealTime values, and the values were >0.4 log higher than CAP/CTM values for subtypes F and G and than RealTime values for subtypes C, F, and G and CRF02_AG. Two samples demonstrated results with >1-log differences from RealTime results. When the data were adjusted by the average difference, 94.9% and 87.0% of Aptima results fell within 0.5 log of the CAP/CTM and RealTime results, respectively. The linearity and accuracy of the Aptima assay in correctly quantitating all major HIV-1 subtypes, coupled with the completely automated format and high throughput of the Panther system, make this system well suited for reliable measurement of viral load in the clinical laboratory.
Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication
Authors: Kucharski Thomas J. , Ng Timothy F. , Sharon David M. , Navid-Azarbaijani Pedram , Tavassoli Mahvash , Teodoro Jose G. 
Published: August 2016

ABSTRACT
Chicken anemia virus (CAV) is a single-stranded circular DNA virus that carries 3 genes, the most studied of which is the gene encoding VP3, also known as apoptin. This protein has been demonstrated to specifically kill transformed cells while leaving normal cells unharmed in a manner that is independent of p53 status. Although the mechanistic basis for this differential activity is unclear, it is evident that the subcellular localization of the protein is important for the difference. In normal cells, apoptin exists in filamentous networks in the cytoplasm, whereas in transformed cells, apoptin is present in the nucleus and appears as distinct foci. We have previously demonstrated that DNA damage signaling through the ataxia telangiectasia mutated (ATM) pathway induces the translocation of apoptin from the cytoplasm to the nucleus, where it induces apoptosis. We found that apoptin contains four checkpoint kinase consensus sites and that mutation of either threonine 56 or 61 to alanine restricts apoptin to the cytoplasm. Furthermore, treatment of tumor cells expressing apoptin with inhibitors of checkpoint kinase 1 (Chk1) and Chk2 causes apoptin to localize to the cytoplasm. Importantly, silencing of Chk2 rescues cancer cells from the cytotoxic effects of apoptin. Finally, treatment of virus-producing cells with Chk inhibitor protects them from virus-mediated toxicity and reduces the titer of progeny virus. Taken together, our results indicate that apoptin is a sensor of DNA damage signaling through the ATM-Chk2 pathway, which induces it to migrate to the nucleus during viral replication.

IMPORTANCE
The chicken anemia virus (CAV) protein apoptin is known to induce tumor cell-specific death when expressed. Therefore, understanding its regulation and mechanism of action could provide new insights into tumor cell biology. We have determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy.
Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis
Authors: Ismail Ashrafali M. , Lee Ji Sun , Dyer David W. , Seto Donald , Rajaiya Jaya , Chodosh James 
Published: August 2016

ABSTRACTHuman adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism for some but not all HAdV-Ds are not known. The fiber protein is a major capsid protein; its C-terminal “knob” mediates binding with host cell receptors to facilitate subsequent viral entry. In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene sequences of HAdV-D types associated with EKC formed a unique clade. By proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared. Comparative structural modeling showed no distinct variations in fiber knobs of EKC types but did show variation among HAdV-Ds in a region overlapping with the known CD46 binding site in HAdV-B. We also found signature amino acid positions that distinguish EKC from non-EKC types, and byin vitrostudies we showed that corneal epithelial cell tropism can be predicted by the presence of a lysine or alanine at residue 240. This same amino acid residue in EKC viruses shows evidence for positive selection, suggesting that evolutionary pressure enhances fitness in corneal infection, and may be a molecular determinant in EKC pathogenesis.IMPORTANCEViruses adapt various survival strategies to gain entry into target host cells. Human adenovirus (HAdV) types are associated with distinct disease conditions, yet evidence for connections between genotype and cellular tropism is generally lacking. Here, we provide a structural and evolutionary basis for the association between specific genotypes within HAdV species D and epidemic keratoconjunctivitis, a severe ocular surface infection. We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber knob gene region, share a distinct phylogenetic clade. Deeper analysis of the fiber gene revealed that evolutionary pressure at crucial amino acid sites has a significant impact on its structural conformation, which is likely important in host cell binding and entry. Specific amino acids in hot spot residues provide a link to ocular cell tropism and possibly to corneal pathogenesis.
Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 Family
Authors: Skalsky Rebecca L. , Barr Sarah A. , Jeffery Andrew J. , Blair Tiffany , Estep Ryan , Wong Scott W. 
Published: August 2016

ABSTRACT
Japanese macaque (JM) rhadinovirus (JMRV) is a novel, gamma-2 herpesvirus that was recently isolated from JM with inflammatory demyelinating encephalomyelitis (JME). JME is a spontaneous and chronic disease with clinical characteristics and immunohistopathology comparable to those of multiple sclerosis in humans. Little is known about the molecular biology of JMRV. Here, we sought to identify and characterize the small RNAs expressed during lytic JMRV infection using deep sequencing. Fifteen novel viral microRNAs (miRNAs) were identified in JMRV-infected fibroblasts, all of which were readily detectable by 24 h postinfection and accumulated to high levels by 72 h. Sequence comparisons to human Kaposi's sarcoma-associated herpesvirus (KSHV) miRNAs revealed several viral miRNA homologs. To functionally characterize JMRV miRNAs, we screened for their effects on nuclear factor kappa B (NF-κB) signaling in the presence of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Multiple JMRV miRNAs suppressed cytokine-induced NF-κB activation. One of these miRNAs, miR-J8, has seed sequence homology to members of the cellular miR-17/20/106 and miR-373 families, which are key players in cell cycle regulation as well as inflammation. Using reporters, we show that miR-J8 can target 3′ untranslated regions (UTRs) with miR-17-5p or miR-20a cognate sites. Our studies implicate JMRV miRNAs in the suppression of innate antiviral immune responses, which is an emerging feature of many viral miRNAs.

IMPORTANCE
Gammaherpesviruses are associated with multiple diseases linked to immunosuppression and inflammation, including AIDS-related cancers and autoimmune diseases. JMRV is a recently identified herpesvirus that has been linked to JME, an inflammatory demyelinating disease in Japanese macaques that mimics multiple sclerosis. There are few large-animal models for gammaherpesvirus-associated pathogenesis. Here, we provide the first experimental evidence of JMRV miRNAs
in vitro
and demonstrate that one of these viral miRNAs can mimic the activity of the cellular miR-17/20/106 family. Our work provides unique insight into the roles of viral miRNAs during rhadinovirus infection and provides an important step toward understanding viral miRNA function in a nonhuman primate model system.
Long and Short Isoforms of the Human Cytomegalovirus UL138 Protein Silence IE Transcription and Promote Latency
Authors: Lee Song Hee , Caviness Katie , Albright Emily R. , Lee Jeong-Hee , Gelbmann Christopher B. , Rak Mike , Goodrum Felicia , Kalejta Robert F. 
Published: August 2016

ABSTRACT

The UL133–138 locus present in clinical strains of human cytomegalovirus (HCMV) encodes proteins required for latency and reactivation in CD34
+
hematopoietic progenitor cells and virion maturation in endothelial cells. The encoded proteins form multiple homo- and hetero-interactions and localize within secretory membranes. One of these genes, UL136 gene, is expressed as at least five different protein isoforms with overlapping and unique functions. Here we show that another gene from this locus, the UL138 gene, also generates more than one protein isoform. A long form of UL138 (pUL138-L) initiates translation from codon 1, possesses an amino-terminal signal sequence, and is a type one integral membrane protein. Here we identify a short protein isoform (pUL138-S) initiating from codon 16 that displays a subcellular localization similar to that of pUL138-L. Reporter, short-term transcription, and long-term virus production assays revealed that both pUL138-L and pUL138-S are able to suppress major immediate early (IE) gene transcription and the generation of infectious virions in cells in which HCMV latency is studied. The long form appears to be more potent at silencing IE transcription shortly after infection, while the short form seems more potent at restricting progeny virion production at later times, indicating that both isoforms of UL138 likely cooperate to promote HCMV latency.

IMPORTANCE
Latency allows herpesviruses to persist for the lives of their hosts in the face of effective immune control measures for productively infected cells. Controlling latent reservoirs is an attractive antiviral approach complicated by knowledge deficits for how latently infected cells are established, maintained, and reactivated. This is especially true for betaherpesviruses. The functional consequences of HCMV UL138 protein expression during latency include repression of viral IE1 transcription and suppression of virus replication. Here we show that short and long isoforms of UL138 exist and can themselves support latency but may do so in temporally distinct manners. Understanding the complexity of gene expression and its impact on latency is important for considering potential antivirals targeting latent reservoirs.
Future marginalisation and mortality in young Swedish men with non-psychotic psychiatric disorders and the resilience effect of cognitive ability: a prospective, population-based study
Authors: Löve J , Hensing G , Söderberg M , Torén K , Waern M , Åberg M 
Published: August 2016

ObjectiveLarge-scale studies examining future trajectories of marginalisation and health in adolescents with mental illness are scarce. The aim of this study was to examine if non-psychotic psychiatric disorders (NPDs) were associated with future indicators of marginalisation and mortality. We also aimed to determine whether these associations might be mediated by education level and attenuated by high cognitive ability.DesignThis is a prospective cohort study with baseline data from the Swedish Conscription register.SettingThe study was carried out in Sweden from 1969 to 2005.ParticipantsAll of the participants were 18-year-old men at mandatory conscription in Sweden between 1969 and 2005 (n=1 609 690).MeasuresNPDs were clinically diagnosed at conscription. Cognitive ability was measured by a standardised IQ test at conscription. National register data covered information on welfare support, long-term unemployment, disability pension (DP) and mortality over a period of 1–36 years.ResultsNPD at the age of 18 years was a predictor of future welfare support, OR 3.73 (95% CI 3.65 to 3.80); long-term unemployment, OR 1.97 (95% CI 1.94 to 2.01); DP, HR 2.95 (95% CI 2.89 to 3.02); and mortality, HR 2.45 (2.33–2.52). The adjusted models suggested that these associations were not confounded by fathers’ educational level, cognitive ability had only a minor attenuating effect on most associations and the mediating effect of own educational level was small.ConclusionsThe present study underlines a higher prevalence of future adversities in young men experiencing NPDs at the age of 18 years. It also indicates that higher cognitive ability may work as a potential resilience factor against future marginalisation and mortality.
Study of seven single-nucleotide polymorphisms identified in East Asians for association with obesity in a Taiwanese population
Authors: Huang Wei-Hsin , Hwang Lee-Ching , Chan Hsin-Lung , Lin Hsiang-Yu , Lin Yung-Hsiang 
Published: August 2016

ObjectiveThis study aimed to examine single-nucleotide polymorphisms (SNPs) of seven previously reported obesity genes in East Asians and to analyse their associations and synergistic effects on obesity in the Taiwanese population.DesignCross-sectional study.SettingOne medical centre in northern Taiwan.ParticipantsA total of 323 non-obese and 264 obese participants were recruited. The threshold for obesity in this study was a body mass index of ≥27 kg/m2, as defined by the Ministry of Health and Welfare in Taiwan. The study was performed with the approval of the institutional review board of MacKay Memorial Hospital, Taipei, Taiwan (application number 12MMHIS106).Outcome measuresWe analysed the genotype distributions of seven SNPs localising to thePPARγ2, GNB3, SDC3, ADRB2, FTO, PPARγ and ESR1genes in obese and non-obese groups and then paired obesity-related SNPs to determine if they have synergistic effects on obesity.ResultsAnalysis of the genotype distributions in obese and non-obese groups revealed only a significant positive correlation between an SNP in rs2282440-syndecan 3 (SDC3) and obesity in the Taiwanese population (p=0.006). In addition, the T/T genotype ofSDC3was significantly associated with a larger waist and hip circumference, higher body fat percentage and lower high-density lipoprotein cholesterol. Moreover, the combination of the rs2282440-SDC3T/T genotype with the rs1801282-peroxisome proliferator-activated receptor-gamma2 gene (PPARγ2) G carrier genotype was strongly associated with obesity (OR=6.77).ConclusionsWe found that the rs2282440-SDC3T/T genotype is associated with obesity in the Taiwanese population. Furthermore, there is a synergistic effect of the high-risk alleles of theSDC3andPPARγ2genes on the obese phenotype in the Taiwanese population.Trial registration number12MMHIS106; Results.
Fistulous-type vein of Galen malformation phantom model for endovascular training and research
Authors: Meila Dan , Melber Katharina , Grieb Dominik , Jacobs Collin , Lanfermann Heinrich , Brassel Friedhelm 
Published: August 2016

IntroductionVein of Galen malformation (VGM), a high-flow intracranial arteriovenous shunt, is among the most severe neurovascular diseases in childhood. In many cases untreated children die or survive only severely disabled. Endovascular embolization is the preferred treatment.ObjectiveTo develop a simple fistulous-type VGM phantom model for teaching and training of different endovascular treatment methods and to investigate new treatment options and devices.MethodsAn experimental in vitro pulsatile phantom model was developed imitating a high-flow fistulous-type VGM, which is typical, especially in the neonatal phase. Pressure measurements at different arterial sites were performed before and after closure of the VGM. Closure of the VGM was achieved by coiling using a combined microcatheter-based transvenous and transarterial approach called ‘kissing microcatheter technique’.ResultsThe behaviour of the phantom model in vitro under fluoroscopy and under angiographic runs was extremely similar to that in in vivo conditions in children. The results showed that intra-arterial pressures changed and increased statistically significantly at all measurement sites after embolization, as in human arteriovenous malformation. We also demonstrated different and complementary visualizations of hemodynamics and angioarchitecture by antegrade and retrograde microcatheter injections.ConclusionsOur phantom model behaves like a typical fistulous-type VGM and can be used in vitro for teaching and training and for further research. It offers a new and better understanding of hemodynamics and angioarchitecture in the endovascular management of VGM.