bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish and mussels: Importance of fish for freshwater mussel conservation
Authors: Modesto Vanessa , Ilarri Martina , Souza Allan T , Lopes‐Lima Manuel , Douda Karel , Clavero Miguel , Sousa Ronaldo
Published: November 2017

Co‐extinctions are increasingly recognized as one of the major processes leading to the global biodiversity crisis, but there is still limited scientific evidence on the magnitude of potential impacts and causal mechanisms responsible for the decline of affiliate (dependent) species. Freshwater mussels (Bivalvia, Unionida), one of the most threatened faunal groups on Earth, need to pass through a parasitic larval (glochidia) phase using fishes as hosts to complete their life cycle. Here, we provide a synthesis of published evidence on the fish–mussel relationship to explore possible patterns in co‐extinction risk and discuss the main threats affecting this interaction. We retrieved 205 publications until December 2015, most of which were performed in North America, completed under laboratory conditions and were aimed at characterizing the life cycle and/or determining the suitable fish hosts for freshwater mussels. Mussel species were reported to infest between one and 53 fish species, with some fish families (e.g., Cyprinidae and Percidae) being used more often as hosts than others. No relationship was found between the breadth of host use and the extinction risk of freshwater mussels. Very few studies focused on threats affecting the fish–mussel relationship, a knowledge gap that may impair the application of future conservation measures. Here, we identify a variety of threats that may negatively affect fish species, document and discuss the concomitant impacts on freshwater mussels, and suggest directions for future studies.
The nature and extent of service user involvement in critical care research and quality improvement: A scoping review of the literature
Authors: Bench Suzanne , Eassom Erica , Poursanidou Konstantina
Published: November 2017

The importance of involving patients and the public in health care research is globally recognized, but how best to do this in critical care is unclear. The aim of this first published review was to explore the extent and nature of evidence on service user involvement in critical care research and quality improvement. Using the scoping review framework described by Arksey and O'Malley (), a team of service user and critical care researchers searched eleven online databases, reviewed relevant web sites, conducted forward and backward citation searching and contacted subject experts. Extracted data were subjected to a narrative synthesis based on the objectives of the review. Findings from a broad range of evidence support that involvement is becoming more commonplace and that experiences are generally positive. Data extracted from 34 publications identify that involvement is most commonly reported at the level of consultation or participation in project teams, however, the extent to which involvement impacts on projects output remains unclear. Key barriers and facilitators relate to the challenge of recruiting a diverse group of service users, dealing with power hierarchies, being adaptable and effective consideration of the resource requirements. More research is required to identify the most effective methods to support the opportunity for involvement and more thorough reporting of service user involvement practices is strongly recommended.
Furuncular myiasis for the Western dermatologist: treatment in outpatient consultation
Authors: Blaizot Romain , Vanhecke Christophe , Le Gall Philippe , Duvignaud Alexandre , Receveur Marie‐Catherine , Malvy Denis
Published: November 2017

Background

Furuncular myiasis is likely to be seen by Western dermatologists because of the increasing number of international travelers but remains unfamiliar to most of them, who tend to refer these patients to hospitals. Different treatments have been proposed, but many of them are not achievable in outpatient consultation.

Methods

We reported three typical cases of furuncular myiasis, according to each species involved, and proposed diagnostic and therapeutic guidelines for dermatologists in outpatient consultation.

Results

One patient, complaining of an inflammatory nodule of the leg with a central punctum, was diagnosed with Dermatobia hominis infection, after a forest walk in French Guiana. One woman returned from Senegal with a nodule of the left buttock. She had been infected by a Cordylobia anthropophaga larva after drying her underwear under a mango tree. One woman living in Cameroon presented with scalp nodules, pain, fatigue, and facial edema. She had been infected by more than 40 larvae of Cordylobia rodhaini after drying her sheets under a mango tree. Manual extraction ensured complete healing in the three patients. We used neither doppler ultrasound nor occlusive dressing. Diagnosis was immediately made thanks to the typical clinical stories.

Conclusions

The diagnosis of furuncular myiasis requires only clinical skills and basic knowledge of life cycles. The treatment varies slightly depending on the species involved but is achievable in outpatient consultation and does not require occlusive dressing.
Prospective, pilot evaluation of the performance of nanofractional radiofrequency for improvement of skin texture via skin resurfacing
Authors: Bohnert Krista , Dorizas Andrew , Sadick Neil
Published: November 2017

Background

The latest generation of radiofrequency, nanofractional radiofrequency, allows the heat energy to be delivered through the use of pins or needles as electrodes, facilitating increased efficacy and reduced pain, downtime, and side effects.

Objective

The objective of this prospective pilot clinical study was to evaluate the efficacy of nanofractional radiofrequency in skin resurfacing.

Methods and materials

Seventeen subjects were enrolled in the study, and each received three nanofractional radiofrequency (160‐pin tip) treatments in the facial area at 3‐week intervals. Follow‐up visits were scheduled at 1 and 2 months after the final treatment. Clinical photography, patient, and investigator assessments were conducted during the treatment visits and follow‐up.

Results

All subjects completed the study. At the 1‐ and 2‐month follow‐up, there was a moderate to significant improvement (2.6 and 3.5, respectively,P = .01) according to the investigator global esthetic improvement scale rating. Most subjects reported that they were satisfied or very satisfied with the outcome and level of comfort.

Conclusion

Nanofractional radiofrequency is a safe and effective strategy for improving texture, tone, and skin laxity with high patient satisfaction and tolerable safety profile.
Identification, classification and assessment of dyskinesia in children with cerebral palsy: A survey of clinicians
Authors: Stewart Kirsty , Tavender Emma , Rice James , Harvey Adrienne
Published: November 2017

Aim

The aims of this study were to investigate clinicians’ knowledge, and barriers they perceive exist, relating to the identification and measurement of dyskinesia (dystonia/choreoathetosis) in children with cerebral palsy (CP) and to explore educational needs regarding improving identification and assessment of dyskinesia.

Methods

This was a cross‐sectional online survey of clinicians working with children with CP. Data analysis was descriptive, with qualitative analysis of unstructured questions.

Results

In total, 163 completed surveys from Australian clinicians were analysed. Respondents were allied health (n = 140) followed by medical doctors (n = 18) working mainly in tertiary hospitals and not‐for‐profit organisations. Hypertonia subtypes and movement disorders seen in children with CP appear to be identified by clinicians, although limited knowledge about dyskinesia and access to training were reported as significant barriers to accurate identification. Despite knowledge of available measurement scales, only a small percentage were used clinically and reported to be only somewhat useful or not useful at all. Barriers identified for use of scales included limited training opportunities and knowledge of scales and lack of confidence in their use.

Conclusion

A lack of confidence in identifying and measuring movement disorders in children with CP was reported by Australian clinicians. It was identified that a greater understanding of dyskinetic CP and the tools available to identify and measure it would be valuable in clinical practice. The results of this survey will inform the development of a ‘Toolbox’ to help identify, classify and measure dyskinetic CP and its impact on activity and participation using the framework of the International Classification of Functioning, Disability and Health.
Allergic gastroenteritis hospital admission time trends in Australia and New Zealand
Authors: Mullins Raymond J , Turner Paul J , Barnes Elizabeth H , Campbell Dianne E
Published: November 2017

Aim

Recent epidemiological studies indicate increases in hospital food allergy‐related anaphylaxis admission rates in Australian and New Zealand. The aim of the study was to examine whether non‐IgE‐mediated food allergy might have increased in parallel.

Methods

We analysed childhood hospital admissions rates by ICD 10 codes for allergic gastroenteritis (AG) and infective gastroenteritis in Australia and New Zealand between June 1998 and July 2014.

Results

In Australia, most AG‐related admissions (73%) occurred in those aged <1 year and increased by 7.3%/year (95% confidence interval (CI) 5.5–9.3, P < 0.0001) from 6.8 to 26.5/105 population. Similar trends were observed for New Zealand; 81% of admissions occurred in those aged <1 year and increased by 9.4%/year (95% CI 5.5–9.3, P < 0.0001) from 7.2 to 30.7/105 population. By contrast there were no significant changes in AG‐related admission rates in the older patients and infective gastroenteritis admissions fell in both countries in those aged <1 year; Australia by 4.4%/year (95% CI 4.3–4.6, P < 0.0001) and in New Zealand by 5.8%/year (95% CI 5.4–6.2, P < 0.0001).

Conclusion

We observed a fourfold increase in AG‐related admission rates in two countries with known high rates of IgE‐mediated food allergy/anaphylaxis. If confirmed by other studies, it will be of interest to determine if factors thought to contribute to the increase in IgE‐mediated food allergy might also play a role in non‐IgE‐mediated gastroenterological food allergy syndromes.
Children's perceptions of a ‘self‐explaining road’ intervention to improve neighbourhood safety
Authors: Ryan Rebekah , Hosking Jamie , Wilkinson‐Meyers Laura , Ameratunga Shanthi
Published: November 2017

Aim

Safe neighbourhood environments can provide important spaces for child activity and well‐being. Self‐explaining roads (SERs), which reduce vehicle speeds by changing neighbourhood street design, are an intervention with known safety benefits. However, little is known about children's experiences of SERs.

Methods

We engaged schoolchildren in developing a project to articulate children's perspectives of SERs. Students actively researched the experiences of other children at their school, and then participated in a researcher‐led focus group.

Results

Children emphasised safer spaces for play as an important benefit of SERs. As well as using new designated play spaces adjoining footpaths, children also felt the roadway became safer, and more fun for cycling. In contrast, children reported that parents held mainly negative views of SERs, considering them annoying and inconvenient.

Conclusion

From children's perspective, SERs can provide safe spaces for neighbourhood play, despite limited parental support. Potential benefits for children as well as established safety benefits should inform future implementation of SERs.
Changes and analysis of anti‐HBs titres after primary immunization in 1‐ to 16‐year‐old Chinese children: A hospital‐based study
Authors: Yue X. , Ge C. , Zhuge S. , He H. , Yang H. , Xu H. , Huang A. , Zhao Y.
Published: November 2017

Immunization with the hepatitis B vaccine is the most effective measure to prevent Hepatitis B Virus (HBV) infection. The aim of this study was to investigate the change in antibody levels induced by administration of the hepatitis B vaccine in children aged 1‐16 year old in a large sample sized investigation. HBV markers were determined in 93 326 1‐ to 16‐year‐old hospitalized children who completed primary immunization as infants from south‐west China, Chongqing. Analyses were performed on anti‐HBs titre changes with increasing age, and the revaccination effect was evaluated in children aged 7‐14. The percentage of protective antibody was between 45.29% and 63.33% in all age groups, but was higher in the 1‐, 2‐ and 3‐year‐old groups (90.31%, 83.95% and 71.82%, respectively), and the rate of high‐responder was 5.03%‐10.56%, except in the 1‐year‐old group (23.33%). Additionally, 3.33%‐25.79% of subjects had not seroconverted. There was no significant difference in antibody levels between girls and boys (P > .05). The Geometric Mean Titers in children with confirmed revaccination history were significantly higher than those with unknown or no revaccination history (P < .0001). In conclusion, the overall rate of protective anti‐HBs was 67.10% with consecutive age groups from 1 to 16, it decreased from 90.31% to 45.29% for 1‐ to 8‐year‐old individuals, and interestingly, the rate increased from 45.46% to 63.33% for subjects aged 9‐15. Anti‐HBs titres were significantly improved after revaccination. Booster doses are recommended for those without seroconversion, especially children who live in school with other students or have family members with positive HBsAg.
Recent developments on intramedullary nailing: a biomechanical perspective
Authors: Rosa Natacha , Marta Miguel , Vaz Mário , Tavares S.M.O. , Simoes Ricardo , Magalhães Fernão D. , Marques Antonio Torres
Published: November 2017

Combining contributions from engineering and medicine, we highlight the biomechanical turning points in the historical evolution of the intramedullary nailing stabilization technique and discuss the recent innovations concerning increase in bone–implant system stability. Following the earliest attempts, where stabilization of long bone fractures was purely based on intuition, intramedullary nailing evolved from allowing alignment and translational control through press‐fit fixation to current clinical widespread acceptance marked by the mechanical linkage between nail and bone with interlocking screws that allow alignment, translation, rotation, and length control. In an attempt to achieve an optimum interfragmentary mechanical environment, recent improvements considered the impact of different biomaterials on bone–implant stiffness. Another strategy considered the increase in the structural stability through the reduction of the number of movements between the different components that constitute the bone–implant system. Intramedullary nail improvements will most likely benefit from merging mechanics and fracture‐healing biology by combining surface engineering with sensor tools associated with the innovative progress in wireless technology and with bone‐healing biological active agents. Future research should aim at better understanding the ideal mechanobiological environment for each stage of fracture healing in order to allow for intramedullary nail design that satisfies such requirements.
‘One‐Dimensional Man’
Authors: Badrideen Ahmed
Published: November 2017

Critical accounts of Amis's Money tend to assert that John Self is a representation of postmodernism. This article casts new light on Self by showing that he may be read as an embodiment of positivism. Self's inability to think speculatively and creatively; his eschewal of moral responsibility in his relationships with others, combined with the materiality of his desires and concerns, shows that he is very much a product of positivism – an outlook that is intimately supportive of, and championed by, classical and late capitalism. This article begins with an exploration of the ways in which positivism is fostered in capitalist societies. It then moves on to a consideration of those aspects of Self's personality – namely his intolerance of difference, respect for hierarchy and order, and his trust in the reality of money – that cannot be assimilated into a postmodern reading, and that intimate a positivist outlook. Finally, the article explores the two facets of his personality that are the most conspicuous tokens of his positivism and which he also struggles against – with the aid of Martina Twain – in a bid to recover a stable life: his paucity of emotional feeling for others and his inability to interpret or think speculatively.
(Auto‐)portrait de l'essayiste en esprit universel
Authors: Serpieters Tom , Martens David
Published: November 2017

Bien connu en tant que poète de La Jeune Parque, Paul Valéry (1871–1945) est également un intellectuel de premier ordre, dont la réflexion se situe à la croisée des univers littéraire et scientifique. En tant qu'amateur éclairé des sciences, il a fréquemment écrit au sujet de la science, notamment dans le contexte de ses réflexions littéraires. Ainsi, cette interrogation conjointe de la littérature et de la science constitue un des axes de questionnement centraux de son recueil d'essais Variété (1924–1944). Si cette problématique très valéryenne a déjà fait l'objet d'un certain nombre d’études évaluant la science chez Valéry à la lumière de sa « pensée », le présent article vise à rendre compte de la logique qui sous‐tend les référents scientifiques dans les essais de Variété, en recourant à l'outillage de l'analyse du discours.
“Let no man deceive you by any means”
Authors: Osborne Jeff
Published: November 2017

“‘Let no man deceive you by any means’:Billy Buddand interpretive tragedy” argues that although Vere's dreadful and necessarily tragic decision occupies the central position in the plot, the association of Claggart with the phrasemystery of iniquity –an allusion to 2 Thessalonians – is the culminating moment in the novel's obsession with the madness and tragedy of interpretation. More specifically, the idea of the mystery of iniquity is fundamental to Melville's tragic view of life. In Paul's letter, the mystery of iniquity refers to the radical deceit unleashed by God upon the world before the return of Christ, a force that makes humans particularly susceptible to delusion. Associating Claggart with the mystery of iniquity ironically seduces readers with its explanatory appeal, thereby diverting them from the phrase's implication that textuality, interpretation, and meaning necessarily participate in representational uncertainty.
Cashmere Shawl as Metaphor and Matterfold
Authors: Hsieh Chih‐chien
Published: November 2017

While Mrs. Ramsay's cashmere shawl has been commonly recognized as an organizing trope in Virginia Woolf's To the Lighthouse, this essay calls attention to the “materialities” of the shawl by drawing on a thing‐centered metonymic reading and discourses of new materialism. The first metonymic reading – or what I call a “molar‐form” reading – delves into the historical archive of the cashmere shawl to disclose its role as a material nexus of imperial modernity. But if the shawl is encoded within the molar structure of British Empire in this material archaeology, the second new materialist, “molecular‐force” reading transforms the shawl from a tangible object into an affective body, from a metaphor of imperialism into a “matterfold” of affectivity, to foreground its entangled, vibrant materiality in a dynamic field of forces. Shifting the emphasis from molar aggregates to molecular affects, this essay argues that Lily's “vision” at the end invokes a new aesthetics that replaces the substantialist distinction of subject and object with an affective differentiation of bodies.
Unredemptive Recognition
Authors: Morrison Alastair
Published: November 2017

This essay highlights a distinction within contemporary fiction, and uses it to argue for a parallel distinction within a trend of contemporary criticism. It begins by describing similarities between the so‐called “New Sincerity,” most famously associated with American writers such as Jonathan Safran Foer and Dave Eggers (though I suggest that it has resonances in Europe as well), and the various turns against “critique,” from scholars including Rita Felski, Sharon Marcus, and Stephen Best, among others. My discussion of the correspondence between these movements centers on the dynamic of recognition, the relationship to a depicted character or event that draws the reader into experiences of understanding and solidarity, and which also provides the basis for self‐reflection. An emphasis on recognition links the literary and critical movements; recognition is essential to what the New Sincerity asks of the reader, and the term has also become a central one for critics of critique, who seek to habilitate it as a subject of scholarly interest.

Yet the critical movement has, or should have, a significantly different relationship with recognition than the New Sincerity does. In its most useful iteration, this essay argues, the turn against critique in Anglophone criticism looks (or will look, or should look) less like its cousin in the American novel than like some contemporary fiction from outside the United States – in this case, from Denmark. This essay offers readings of three short stories by Naja Marie Aidt, storiesthat share enough with the New Sincerity to make their departures from it especially salient. Rather than simplyendorsingrecognition – positioning recognitive empathy asdesirable– Aidt's stories offer more measured observations of how recognition works as an already present part of everyday social and political interaction. As well as showing some of the international diversity of recent fiction's interest in intimacy and immediate connection, this distinction may be crucial in establishing the turn against critique as an actionable mode of literary analysis.
How Literature Imagined Television, 1880–1950
Authors: Willaert Tom
Published: November 2017

Television remains one of today's most captivating and popular media. As such, its cultural significance and ties to the literary domain have been well studied. This article aims to further our understanding of television by investigating one of its lesser‐known aspects, namely the role literature had to play in its development prior to its becoming a mass medium in the 1950s and 1960s. Specifically, this paper offers an exploratory overview of how writers from the 1880s onwards contributed to the social construction of television, and how this in turn shaped the ‘medium’ they themselves produced: literature. Based on texts by authors from pioneering television countries France, Germany, the United Kingdom and the United States, this article identifies and discusses three layers of this media‐historical dialectic: the general interplay between television technologies and literary imagination, the more specific interactions between industrialization and authorship, and finally the micro‐level parallels between television's inner workings and the act of writing. Thus, the paper opens up perspectives for a more systematic study of the literary reception of early television.
Primordial Odontogenic Tumor: A case report with histopathological analyses
Authors: Mikami Toshinari , Ohashi Yu , Bologna‐Molina Ronell , Mosqueda‐Taylor Adalberto , Fujiwara Naoki , Tsunoda Naoko , Yamada Hiroyuki , Takeda Yasunori
Published: November 2017

Primordial odontogenic tumor (POT) is a benign mixed epithelial and mesenchymal odontogenic tumor included into the current World Health Organization (WHO) classification of Head and Neck tumours in 2017. As far as the authors have confirmed, only eight cases of this tumor have been reported so far. This paper reports a case of POT that occurred in the right mandible of a 5‐year‐old patient. Panoramic radiograph showed a well‐defined homogeneous radiolucency displacing the unerupted second deciduous molar to the deep part of the mandible. Histopathologically, the tumor was composed of cell‐rich mesenchymal tissue with myxoid areas, surrounded by columnar epithelium and non‐keratinized cuboidal epithelium in the outer layers. The histopathological diagnosis was POT. The expression patterns of cytokeratins (CK) 14, 18, 19, vimentin and CD34 suggested that the grade of differentiation of the POT was approximately equivalent to that of normal primary tooth germ tissues in cap stage to late bell stage.
Newspapers and public grants: A matter of quality
Authors: Battaggion Maria Rosa , Vaglio Alessandro
Published: November 2017

The present paper deals with the issue of newspaper subsidies in a framework of endogenous quality provision. We compare monopoly and duopoly cases in a vertically differentiated model. For monopolies we show that a per‐copy subsidy reduces quality. Conversely, in duopolies in the vertically differentiated model, we show that a state subsidy might increase the quality of the low‐quality newspaper and decrease the quality of the high‐quality newspaper.
Prospective evaluation of surgical management of sliding hiatal hernia and gastroesophageal reflux in dogs
Authors: Mayhew Philipp D. , Marks Stanley L. , Pollard Rachel , Culp William T. N. , Kass Philip H.
Published: November 2017

Objective

To evaluate response to surgical management of sliding hiatal hernia (SHH) and gastroesophageal reflux (GER) in dogs using standardized clinical scoring, videofluoroscopic swallow studies, and impedance planimetry.

Study design

Prospective clinical trial.

Animals

A total of 17 client‐owned dogs.

Methods

Dogs were included if they had clinical signs and videofluoroscopic evidence of SHH and/or GER. Owners were asked to complete a standardized canine dysphagia assessment tool (CDAT) preoperatively and postoperatively. Conscious videofluoroscopic swallowing studies and impedance planimetry (IP) were used to evaluate esophageal function and lower esophageal sphincter location and geometry preoperatively and in a subsection of dogs postoperatively.

Results

Preoperatively, 13/17 dogs included in the study had a history of regurgitation, and 4/17 had radiographic evidence of aspiration pneumonia. Postprandial regurgitation improved in 8/10 dogs with preoperative regurgitation, and for which completed preoperative and postoperative CDAT questionnaires were available (P < .01). The hiatal hernia severity score improved postoperatively (P = .046) in dogs with preoperative and postoperative videofluoroscopic swallowing studies (n = 12). However, hernia frequency score (P = .2) and IP parameters did not differ significantly between time points.

Conclusion

Clinical signs of SHH generally improved with surgery but did not consistently resolve. Videofluoroscopic studies provide evidence that GER and SHH can persist postoperatively in some patients. Based on IP findings, clinical improvement may be attributed to a mechanism independent of lower esophageal sphincter attenuation.
College Soccer Players’ Perceptions of Coach and Team Efficacy
Authors: Atkinson Frazer , Short Sandra E. , Martin Jeffrey
Published: November 2017

The authors examined the relationships among athletes’ perceptions of their coaches’ and their team’s efficacy in a sample of 271 college soccer players (M = 19.84 years,SD = 1.42). Athletes’ perceptions of their coaches’ efficacy were assessed using a modified version of the Coaching Efficacy Scale (CES), and perceptions of team efficacy were assessed using the Collective Efficacy Questionnaire for Sport (CEQS). A canonical correlation analysis between the variants formed by the CES subscales and the CEQS subscales was statistically significant, Wilks’s criterion λ = .440,F(20, 883.17) = 12.40,p < .001. Significant canonical loadings indicated that athletes’ perceptions of their coaches’ being confident in their ability to motivate (β = −.78) and provide successful game strategies (β = −.49) to the team were the most predictive of the athletes’ confidence in their team’s ability to prepare (β = −.58), persist (β = −.13), and unite (β = −.36) during competition. The authors provide practical implications for coaches looking to enhance coaching and team efficacy that are linked directly to their findings.
A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates
Authors: Radtke Stefan , Adair Jennifer E. , Giese Morgan A. , Chan Yan-Yi , Norgaard Zachary K. , Enstrom Mark , Haworth Kevin G. , Schefter Lauren E. , Kiem Hans-Peter
Published: November 2017

A population of hematopoietic stem cells with superior engraftment and repopulating abilities has been identified in nonhuman primates.
Listening with your heart
Authors: Choi Huimahn Alex
Published: November 2017

A subtle change in heart rate variability might indicate ongoing cognitive processing.
Sugar, drugs, and gut bugs
Authors: Shoemaker Ashley H.
Published: November 2017

A high-fat diet in rodents causes changes in gut microbiota and glucose sensing that may be mitigated by treatment with metformin.
Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection
Authors: Weiss Eric R. , Lamers Susanna L. , Henderson Jennifer L. , Melnikov Alexandre , Somasundaran Mohan , Garber Manuel , Selin Liisa , Nusbaum Chad , Luzuriaga Katherine
Published: November 2017

Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time (
P
< 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence (
P
< 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test;
r
= −0.5589,
P
= 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection.

IMPORTANCE
Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients. Overall viral diversity decreased from early to persistent infection, particularly in latently infected B cells, which serve as the viral reservoir. Reduction in B cell-associated viral genome diversity coincided with a convergence toward a reference-like EBV genotype. Greater convergence positively correlated with time after infection, suggesting that the reference-like genome is the result of selection.
Characterization of Elements Regulating the Nuclear-to-Cytoplasmic Translocation of ICP0 in Late Herpes Simplex Virus 1 Infection
Authors: Samrat Subodh Kumar , Ha Binh L. , Zheng Yi , Gu Haidong
Published: November 2017

Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is an immediate early protein containing a RING-type E3 ubiquitin ligase. It targets several host factors for proteasomal degradation and subsequently activates viral expression. ICP0 has a nuclear localization sequence and functions in the nucleus early during infection. However, later in infection, ICP0 is found solely in the cytoplasm. The molecular mechanism and biological function of the ICP0 nuclear-to-cytoplasmic translocation are not well understood. In this study, we sought to characterize elements important for this translocation. We found that (i) in human embryonic lung fibroblast (HEL) cells, ICP0 C-terminal residues 741 to 775 were necessary but not sufficient for the nuclear-to-cytoplasmic translocation; (ii) the loss of ICP0 E3 ubiquitin ligase activity, which led to defective viral replication in nonpermissive cells, also caused mutant ICP0 to be retained in the nucleus of HEL cells; (iii) in permissive U2OS cells, however, ICP0 lacking E3 ligase activity was translocated to the cytoplasm at a pace faster than that of wild-type ICP0, suggesting that nuclear retention of ICP0 occurs in an ICP0 E3 ligase-dependent manner; and (iv) the ICP0 C terminus and late viral proteins cooperate in order to overcome nuclear retention and stimulate ICP0 cytoplasmic translocation. Taken together, less ICP0 nuclear retention may contribute to the permissiveness of U2OS cells to HSV-1 in the absence of functional ICP0.

IMPORTANCE
A distinct characteristic for eukaryotes is the compartmentalization of cell metabolic pathways, which allows greater efficiency and specificity of cellular functions. ICP0 of HSV-1 is a multifunctional viral protein that travels through different compartments as infection progresses. Its main regulatory functions are carried out in the nucleus, but it is translocated to the cytoplasm late during HSV-1 infection. To understand the biological significance of cytoplasmic ICP0 in HSV-1 infection, we investigated the potential players involved in this nuclear-to-cytoplasmic translocation. We found that there is a nuclear retention force in an ICP0 E3 ubiquitin ligase-dependent manner. In addition, we identified the C terminus of ICP0 as a
cis
element cooperating with late viral proteins to overcome the nuclear retention and stimulate the nuclear-to-cytoplasmic translocation of ICP0.
Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells
Authors: Payne Emily H. , Ramalingam Dhivya , Fox Donald T. , Klotman Mary E.
Published: November 2017

Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G
2
cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G
2
-arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G
2
arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G
2
arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells.

IMPORTANCE
Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish between HIV-positive cell survival and death in a known HIV compartment, as well as pharmacological agents that alter these outcomes.
Functional Insights into the Adjacent Stem-Loop in Honey Bee Dicistroviruses That Promotes Internal Ribosome Entry Site-Mediated Translation and Viral Infection
Authors: Au Hilda H. T. , Elspass Valentina M. , Jan Eric
Published: November 2017

All viruses must successfully harness the host translational apparatus and divert it toward viral protein synthesis. Dicistroviruses use an unusual internal ribosome entry site (IRES) mechanism whereby the IRES adopts a three-pseudoknot structure that accesses the ribosome tRNA binding sites to directly recruit the ribosome and initiate translation from a non-AUG start site. A subset of dicistroviruses, including the honey bee Israeli acute paralysis virus (IAPV), encode an extra stem-loop (stem-loop VI [SLVI]) 5′ adjacent to the intergenic region (IGR) IRES. Previously, the function of this additional stem-loop was unknown. Here, we provide mechanistic and functional insights into the role of SLVI in IGR IRES translation and in virus infection. Biochemical analyses of a series of mutant IRESs demonstrated that SLVI does not function in ribosome recruitment but is required for proper ribosome positioning on the IRES to direct translation. Using a chimeric infectious clone derived from the related cricket paralysis virus, we showed that the integrity of SLVI is important for optimal viral translation and viral yield. Based on structural models of ribosome-IGR IRES complexes, SLVI is predicted to be in the vicinity of the ribosome E site. We propose that SLVI of IAPV IGR IRES functionally mimics interactions of an E-site tRNA with the ribosome to direct positioning of the tRNA-like domain of the IRES in the A site.

IMPORTANCE
Viral internal ribosome entry sites are RNA elements and structures that allow some positive-sense monopartite RNA viruses to hijack the host ribosome to start viral protein synthesis. We demonstrate that a unique stem-loop structure is essential for optimal viral protein synthesis and for virus infection. Biochemical evidence shows that this viral stem-loop RNA structure impacts a fundamental property of the ribosome to start protein synthesis.
Klebsiella pneumoniae
Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering
Authors: Barnes Melissa D. , Winkler Marisa L. , Taracila Magdalena A. , Page Malcolm G. , Desarbre Eric , Kreiswirth Barry N. , Shields Ryan K. , Nguyen Minh-Hong , Clancy Cornelius , Spellberg Brad , Papp-Wallace Krisztina M. , Bonomo Robert A.
Published: November 2017

The emergence of
Klebsiella pneumoniae
carbapenemases (KPCs), β-lactamases that inactivate “last-line” antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in
Escherichia coli
and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn “traps” β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases.

IMPORTANCE
Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key mechanism of resistance is the breakdown of β-lactam antibiotics by β-lactamase enzymes. KPC-2 is a β-lactamase that inactivates carbapenems and β-lactamase inhibitors (e.g., clavulanate) and is prevalent around the world, including in the United States. Resistance to the new antibiotic ceftazidime-avibactam, which was designed to overcome KPC resistance, had already emerged within a year. Using protein engineering, we uncovered a mechanism by which resistance to this new drug emerges, which could arm scientists with the ability to forestall such resistance to future drugs.
Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
Authors: Bansal Priyanka , Tripathi Anuj , Thakur Vandana , Mohmmed Asif , Sharma Pushkar
Published: November 2017

Mechanisms by which 3′-phosphorylated phosphoinositides (3′-PIPs) regulate the development of apicomplexan parasites
Plasmodium falciparum
and
Toxoplasma gondii
are poorly understood. The catabolic process of autophagy, which is dependent on autophagy-related proteins (ATGs), is one of the major targets of 3′-PIPs in yeast and mammals. In the present study, we identified autophagy-related protein ATG18 as an effector of 3′-PIPs in these parasites.
P
.
falciparum
ATG18 (PfATG18) and
T
.
gondii
ATG18 (TgATG18) interact with 3′-PIPs but exhibited differences in their specificity of interaction with the ligand PIP. The conditional knockdown of
T
.
gondii
or
P
.
falciparum
ATG18 (Tg/PfATG18) impaired replication of parasites and resulted in their delayed death. Intriguingly, ATG18 depletion resulted in the loss of the apicomplexan parasite-specific nonphotosynthetic plastid-like organelle apicoplast, which harbors the machinery for biosynthesis of key metabolites, and the interaction of ATG18 to phosphatidylinositol 3-phosphate (PI3P) was critical for apicoplast inheritance. Furthermore, ATG18 regulates membrane association and apicoplast localization of ATG8. These findings provide insights into a novel noncanonical role of ATG18 in apicoplast inheritance. This function of ATG18 in organelle biogenesis is unprecedented in any organism and may be conserved across most apicomplexan parasites.

IMPORTANCE
Typically, autophagy is a catabolic process utilized by cells for their survival upon encountering nutrient-limiting conditions. The autophagy machinery is very tightly regulated, and autophagy-related genes (ATGs) play a pivotal role in this process. In the present study, we report a novel noncanonical function of autophagy-related protein ATG18 in inheritance of the nonphotosynthetic plastid-like organelle apicoplast in apicomplexan parasites
Plasmodium
and
Toxoplasma
. ATG18 depletion in these parasites resulted in “delayed death,” which was the result of loss of apicoplast and impaired parasite division. Pf/TgATG18 interact with 3′-phosphorylated PIPs, which guide their cellular localization in the parasite, which is essential for their function.
In Vivo
Behavior of the Tandem Glycine Riboswitch in
Bacillus subtilis
Authors: Babina Arianne M. , Lea Nicholas E. , Meyer Michelle M.
Published: November 2017

In many bacterial species, the glycine riboswitch is composed of two homologous ligand-binding domains (aptamers) that each bind glycine and act together to regulate the expression of glycine metabolic and transport genes. While the structure and molecular dynamics of the tandem glycine riboswitch have been the subject of numerous
in vitro
studies, the
in vivo
behavior of the riboswitch remains largely uncharacterized. To examine the proposed models of tandem glycine riboswitch function in a biologically relevant context, we characterized the regulatory activity of mutations to the riboswitch structure in
Bacillus subtilis
using β-galactosidase assays. To assess the impact disruptions to riboswitch function have on cell fitness, we introduced these mutations into the native locus of the tandem glycine riboswitch within the
B. subtilis
genome. Our results indicate that glycine does not need to bind both aptamers for regulation
in vivo
and mutations perturbing riboswitch tertiary structure have the most severe effect on riboswitch function and gene expression. We also find that in
B. subtilis
, the glycine riboswitch-regulated
gcvT
operon is important for glycine detoxification.

IMPORTANCE
The glycine riboswitch is a unique
cis
-acting mRNA element that contains two tandem homologous glycine-binding domains that act on a single expression platform to regulate gene expression in response to glycine. While many
in vitro
experiments have characterized the tandem architecture of the glycine riboswitch, little work has investigated the behavior of this riboswitch
in vivo
. In this study, we analyzed the proposed models of tandem glycine riboswitch regulation in the context of its native locus within the
Bacillus subtilis
genome and examined how disruptions to glycine riboswitch function impact organismal fitness. Our work offers new insights into riboswitch function
in vivo
and reinforces the potential of riboswitches as novel antimicrobial targets.
Vitamin and Amino Acid Auxotrophy in Anaerobic Consortia Operating under Methanogenic Conditions
Authors: Hubalek Valerie , Buck Moritz , Tan BoonFei , Foght Julia , Wendeberg Annelie , Berry David , Bertilsson Stefan , Eiler Alexander
Published: November 2017

Microbial interactions between
Archaea
and
Bacteria
mediate many important chemical transformations in the biosphere from degrading abundant polymers to synthesis of toxic compounds. Two of the most pressing issues in microbial interactions are how consortia are established and how we can modulate these microbial communities to express desirable functions. Here, we propose that public goods (i.e., metabolites of high energy demand in biosynthesis) facilitate energy conservation for life under energy-limited conditions and determine the assembly and function of the consortia. Our report suggests that an understanding of public good dynamics could result in new ways to improve microbial pollutant degradation in anaerobic systems.