bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of sodium bismuth titanate—barium titanate during solid‐state synthesis
Authors: Hou Dong , Aksel Elena , Fancher Chris M. , Usher Tedi‐Marie , Hoshina Takuya , Takeda Hiroaki , Tsurumi Takaaki , Jones Jacob L.
Published: January 2017

Phase formation of sodium bismuth titanate (Na0.5Bi0.5TiO3 or NBT) and its solid solution with barium titanate (BaTiO3 or BT) during the calcination process is studied using in situ high‐temperature diffraction. The reactant powders were mixed and heated to 1000°C, while X‐ray diffraction patterns were recorded continuously. Phase evolutions from starting materials to final perovskite products are observed, and different transient phases are identified. The formation mechanism of NBT and NBT–xBT perovskite structures is discussed, and a reaction sequence is suggested based on the observations. The in situ study leads to a new processing approach, which is the use of nano‐TiO2, and gives insights to the particle size effect for solid‐state synthesis products. It was found that the use of nano‐TiO2 as reactant powder accelerates the synthesis process, decreases the formation of transient phases, and helps to obtain phase‐pure products using a lower thermal budget.
Assessing the accuracy of the OMRON HEM‐907XL oscillometric blood pressure measurement device in patients with nondialytic chronic kidney disease
Authors: Cohen Jordana B. , Wong Tiffany C. , Alpert Bruce S. , Townsend Raymond R.
Published: January 2017

The OMRON HEM−907XL is a commercial oscillometric blood pressure (BP) monitor that was used in the Systolic Blood Pressure Intervention Trial (SPRINT), in which 28% of participants had chronic kidney disease (CKD). This study examined the accuracy of the monitor in nondialytic patients with CKD. Eighty‐seven patients met inclusion criteria. The authors used a modified Association for the Advancement of Medical Instrumentation (AAMI) protocol, with one observer recording measurements from the monitor and two blinded physicians obtaining simultaneous aneroid values by auscultation. Using AAMI method 1, there was a 2.5±9.5 mm Hg difference in OMRON and aneroid systolic BP, and a −1.6±6.5 mm Hg difference in diastolic BP. Using AAMI method 2, there was a 5.1±7.4 mm Hg difference in systolic BP and a −0.2±5.4 mm Hg difference in diastolic BP. In patients with CKD, the OMRON HEM‐907XL appears to be accurate for measuring diastolic BP, but did not perform as well for systolic BP.
Wilsonosiphonia gen. nov. (Rhodomelaceae, Rhodophyta) based on molecular and morpho‐anatomical characters
Authors: Bustamante Danilo E. , Won Boo Yeon , Miller Kathy Ann , Cho Tae Oh
Published: January 2017

Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot‐shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts.
Empirical Learner Language and the Levels of the Common European Framework of Reference
Authors: Wisniewski Katrin
Published: January 2017

The Common European Framework of Reference (CEFR) is the most widespread reference tool for linking language tests, curricula, and national educational standards to levels of foreign language proficiency in Europe. In spite of this, little is known about how the CEFR levels (A1–C2) relate to empirical learner language(s). This article sums up recent trends to meet the need of empirical CEFR level research, where learner corpus‐based analyses play an increasing role. A first focus of the article is on studies that aim at illustrating CEFR levels by analyzing rated learner texts (“criterial features”). Furthermore, research that tries to disentangle the empirical validity of the CEFR scales by operationalizing its descriptors is presented. Before concluding with an outline of the most urgent research needs, potentials, and boundaries of interdisciplinary work between the fields of language testing and assessment, second language acquisition, and learner corpus research are discussed.
Skin cleansing and emolliating for older people: A quasi‐experimental pilot study
Authors: Brooks Jill , Cowdell Fiona , Ersser Steven J , Gardiner Eric D
Published: January 2017

Aims

The aims of this study were to (i) assess the effect of low‐cost hygiene and emollient regimens on the skin barrier function (SBF) of people aged >65 year with xerosis (dry skin) on their lower legs; (ii) to assess the utility of portable measures of skin barrier function in terms of stratum corneum hydration (SCH) and transepidermal water loss (TEWL) in community settings; and iii) to provide evidence for a randomised controlled trial on the treatment of adults in a resource‐poor country with dry skin on their lower legs which causes and exacerbates the skin disease podoconiosis (non‐filarial elephantiasis).

Background

Age increases the risk of impaired skin barrier function which can precipitate skin breakdown. Older skin is frequently characterised by troublesome xerosis and pruritus (itching). Hygiene and emollient practices are central to maintaining skin integrity but are currently under‐researched.

Method

A quasi‐experimental pilot study of five combinations of cleansing and emollient interventions was applied to the xerotic lower legs of ten participants with no skin disease for five consecutive days. Stratum corneum hydration and transepidermal water loss were measured at baseline and day six. Products were chosen because of effectiveness, low cost and availability in a poor‐resource country.

Results

The greatest difference in transepidermal water loss pre‐intervention–postintervention was indicated by the regimen of soapy water, 2% glycerine soak and Vaseline™ (mean 1.14, SD 1.27). This regimen also indicated the greatest difference in stratum corneum hydration (mean 7.92, SD 3.93). The improvement in stratum corneum hydration was significantly greater than for the control (p = .011), soap (p = .050) or water soak (p = .011).

Conclusion

A regimen of washing skin with soapy water, soaking in 2% glycerine for 30 min and applying Vaseline™ has a beneficial effect on the skin barrier function in older people. The study supports previous findings on the positive effects of glycerine on skin barrier function.

Implications for practice and research

Skin barrier function in older people can be improved using a regimen of washing, soaking in 2% glycerine and applying Vaseline™.
The early response of subtropical tussock grasslands to restoration treatments
Authors: Ladouceur Emma , Mayfield Margaret M.
Published: January 2017

Once widespread, Australia's bluegrass tussock grasslands (dominated by Dichanthium sp.) of the Queensland Central Highlands are now severely endangered. Despite being biodiversity rich and highly valued as low input, nutrient‐dense grazing systems, bluegrass tussock grasslands have suffered extensive clearing and degradation over the last 150 years. Natural recovery of these grasslands is possible but rates of recovery are slow. As such, there is an urgent need to assess practical management strategies to accelerate recovery of these grasslands, with a particular focus on early‐successional stages, when aggressive exotic species are most prevalent. To date, no studies have tested whether commonly used grassland restoration strategies can enhance early‐successional stages and accelerate regeneration in this system. Here, we examine the early short‐term impacts (first two seasons) of two common grassland restoration approaches, with two variations each: direct seeding (single species and low seed diversity) and vegetation clearing (prescribed burning and glyphosate application) across two common starting points: a formerly cropped old field and a historically overgrazed natural grassland. No treatment increased native diversity (Shannon's or richness) in plots but the composition of burned plots in the old field did become more similar to healthy reference sites after two seasons. Burning combined with direct seeding also increased the abundance of the dominant grass, Dichanthium sericeum, toward healthy reference levels within the first two seasons post seeding. This study provides a practical assessment of the short‐term impacts and capacity of common grassland restoration treatments to enhance the recovery of Australia's tussock grassland systems.
Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant
Authors: Bhat Vivek , Vira Hemant , Khattry Navin , Toshniwal Manoj
Published: January 2017

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.
ABNORMAL POLLEN VACUOLATION1 (APV1) is required for male fertility by contributing to anther cuticle and pollen exine formation in maize
Authors: Somaratne Yamuna , Tian Youhui , Zhang Hua , Wang Mingming , Huo Yanqing , Cao Fengge , Zhao Li , Chen Huabang
Published: January 2017

Anther cuticle and pollen exine are the major protective barriers against various stresses. The proper functioning of genes expressed in the tapetum is vital for the development of pollen exine and anther cuticle. In this study, we report a tapetum‐specific gene, Abnormal Pollen Vacuolation1 (APV1), in maize that affects anther cuticle and pollen exine formation. The apv1 mutant was completely male sterile. Its microspores were swollen, less vacuolated, with a flat and empty anther locule. In the mutant, the anther epidermal surface was smooth, shiny, and plate‐shaped compared with the three‐dimensional crowded ridges and randomly formed wax crystals on the epidermal surface of the wild‐type. The wild‐type mature pollen had elaborate exine patterning, whereas the apv1 pollen surface was smooth. Only a few unevenly distributed Ubisch bodies were formed on the apv1 mutant, leading to a more apparent inner surface. A significant reduction in the cutin monomers was observed in the mutant. APV1 encodes a member of the P450 subfamily, CYP703A2‐Zm, which contains 530 amino acids. APV1 appeared to be widely expressed in the tapetum at the vacuolation stage, and its protein signal co‐localized with the endoplasmic reticulum (ER) signal. RNA‐Seq data revealed that most of the genes in the fatty acid metabolism pathway were differentially expressed in the apv1 mutant. Altogether, we suggest that APV1 functions in the fatty acid hydroxylation pathway which is involved in forming sporopollenin precursors and cutin monomers that are essential for the development of pollen exine and anther cuticle in maize.
Analytic Procedures: A Holdback-vetting Forecasting Model
Authors: Lusk Edward J.
Published: January 2017

Introduction: Forecasting is now a best practices requirement for PCAOB audits. This is clear from AS 5 where Analytic Procedures are now a part of the Planning and Substantive Phases of the certification audits. In this regard, we are encouraged by the “On the Go Stores” AP case offered by the AICPA, and have extended their case illustration of AP treatments.Study Précis: In our presentation, we initially consider the OLS Regression model utilized in the AICPA case and offer a vetting protocol to rationalize the use of this forecasting model in the AP phases. Then we move to a disposition analysis stage where the forecast information is posed in relief to the actual client value so as to ascertain if Extended Procedure investigations would be warranted.Results: We offer three Confidence Intervals drawn from the OLS modeling system that are formed from the Fixed Effect, Random Effects, and finally the Excel Platform for the 95% CI parameter set.Impact: The protocol set is programmed in an open-access VBA Decision Support System which is available free as a download with no restriction on its use.
The Role of a Temperament Intervention in Kindergarten Children’s Standardized Academic Achievement
Authors: Collins Ashleigh , O’Connor Erin , McClowry Sandee
Published: January 2017

Previous research finds that children experience a range of school readiness challenges (e.g., Chartier, Walker, & Naimark, 2010; Zill, 1999). Such challenges vary by children’s gender, temperament, and participation in school-based interventions (e.g., Mullola et al., 2011; Bramlett, Scott, Rowell, 2000). However, the examination of child temperament, gender, and children’s participation in school-based, temperament programming has been minimal. This study explores the role of child temperament profiles and child gender on children’s standardized academic outcomes following participation in a school-based, temperament intervention. Study participants included 324 kindergarten students attending urban, low-income schools. A multivariate regression analysis explored associations among child temperament profile, gender, and academic performance.  Cautious and male kindergarten intervention participants attained higher standardized mathematics and literacy scores than their non-intervention participating counterparts.
Elements of an Undergraduate Introductory Materials Engineering Course: Successful Implementation for Students Learning
Authors: Hossain A. , Durfee J.
Published: January 2017

The major emphasis of a Materials Engineering course is to provide a broad level of information on different materials used in industries for various engineering applications. In our institution, working on quarter systems, this course becomes very aggressive and challenging in the amount of information that needs to be presented to the students within a 10weeks-time frame. This course involves different laboratory practices, besides regular class lectures, to obtain knowledge on various material properties to reinforce classroom theories. In addition, to increase exposure to different types of materials and material uses, students in the class are required to research an open topic, which is related to this class. Students have to prepare a brief written report and share what they have learned with the class giving an oral presentation. While a course in Engineering Materials is a common offering in many universities, the authors of this paper present the pedagogical approaches undertaken to successfully implement the course objectives to the undergraduate Engineering and Engineering Technology students. The topics and techniques applied to teach Engineering Materials to enhance student learning outcomes are addressed in this paper.
Design and Implementation of a General Control System Platform
Authors: Peerless Kyle T. , Panosian Jasmine M. , Hassanpour Pezhman A.
Published: January 2017

In this study, the design and implementation of a general control system platform for educational purposes was performed. This project has been designed to facilitate the understanding of control systems in mechanical engineering by creating a foundational system to position-control the rotation of a DC motor, and then employing it as a teaching tool in the undergraduate Control Systems course at Loyola Marymount University (LMU). The objective of this effort was to lay the groundwork for a more “hands-on” control systems education at LMU by designing the general mechanical platform and a pilot on-off controller to illustrate its functionality and feasibility in the classroom. With the foundational stages complete, students in future classes will be able to design and build different controllers for this same device in order to investigate and apply their newly-acquired knowledge of control systems.
Organization and Management of an Industry Sponsored Capstone Senior Design Course
Authors: Moreno Vito , Barber Thomas J.
Published: January 2017

Senior level capstone design courses are run in many different ways in the academic community. A growing number of institutions strive to promote immersion into the real world of engineering through industrially sponsored projects. While this approach offers many immediate benefits to near-graduating seniors, it introduces many unique problems to the academic community. Developing and sustaining an industrially-sponsored capstone design program requires an understanding of the synergies and differences between academia and industry. Key issues discussed in this paper are program management, company sponsorship, diversity of projects, level of oversight required to make a successful project and legal implications of sponsoring a meaningful project.
A Component-Centric Approach to Structural Analysis of Mechanisms
Authors: Stack Christopher , Kumpaty Subha , Mahinfalah Mohammad
Published: January 2017

Structural analyses of mechanisms with components that move relative to each other provide a unique problem to the analyst building and running structural models. In these situations, the analyst usually has to either simplify the problem to a point where the results are unusable or maintain multiple models, which will take more effort to maintain and more resources to run the models. If a mechanism is simplified down to just analyzing one component at a time without regard for the other components in the system, the results will not be accurate because the loading effects of the other components will not be accounted for. In cases where all the components are included in the model the loading effects from the other components will be accounted for, however, a separate model will be required for each position. This paper presents a method of breaking down the complex mechanism into a component level model for each part of the assembly, while still accounting for all loading effects of the other components; in the Pivot Method the component under analysis stays stationary and the loading moves around the component to represent the different positions that it can take.

In order to accomplish this task, a simplified model is used to generate loads at each of the joints. Once the pivot loads are known, a spreadsheet can be used to transform the loads to a coordinate system in which the individual component is being modeled. With the pivot loads known and all the loads transformed into the proper coordinate system the structural analysis of the component under investigation can continue.

The intention of this paper is to introduce the Pivot Method and to demonstrate that it provides a good trade off between both the complexity of methods that model the assembly as a system, and those that focus on the component under question alone. To accomplish this, the analysis results of the Pivot Method models will be compared to results obtained from other methods, with the intention of showing that the Pivot Method will provide the same results while requiring less effort to model and less resources to run.
Challenges in atomic layer deposition of carbon-containing silicon-based dielectrics
Authors: Ovanesyan Rafaiel A. , Hausmann Dennis M. , Agarwal Sumit
Published: January 2017

The authors have designed experiments to test three different approaches for the incorporation of carbon atoms into amorphous SiNx or SiO2 films grown using atomic layer deposition (ALD). In each approach, the surface reactions of the precursors were monitored in situ using attenuated total reflection Fourier transform infrared spectroscopy. In the first approach, for depositing carbon-containing SiNx films using ALD, carbon was introduced into the process through a silicon precursor, SiCl2(CH3)2, followed by NH3 plasma exposure. While our infrared data show that SiCl2(CH3)2 reacts with an –NHx (x = 1, 2) terminated surface created after NH3 plasma exposure, –CH3 groups are eliminated in the precursor adsorption step leading to no significant carbon in the films. In the second approach, the authors hypothesized a three-step ALD process, which would involve Si-, C-, and N-containing precursors, and tested the reactivity of two carbon-containing precursors, CH3I and Al(CH3)3, with H- and Cl-terminated silicon surfaces, respectively. The authors show that both precursors readily react with the silicon surfaces, but neither one provides the appropriate surface termination. CH3I reacts with surface –SiHx (x = 1, 2, 3) to create surface –SiIx (x = 1, 2, 3) species with CH3 as the leaving groups. While Al(CH3)3 reacts with the Cl-terminated Si surface to form a surface –SiCH3 group, residual aluminum remains on the surface as –Al(CH3)x (x = 1, 2) groups that are not completely removed as volatile Al(CH3)xCl3−x (x = 1, 2). Finally, in the third approach for ALD of carbon-containing SiO2 films, the authors used Si2Cl6 with CO and CO/O2 plasmas. A pure CO plasma led to amorphous carbon growth, and a CO plasma diluted with of O2 led to no detectable carbon incorporation in the SiO2 film.
Hard x-ray photoemission study of oxidation states of Ti underlayer in Fe/Ti film system
Authors: Takashima Akito , Ikenaga Eiji , Muro Takayuki , Kawabata Akio , Murakami Tomo , Nihei Mizuhisa , Yokoyama Naoki
Published: January 2017

The Fe/Ti catalyst system that was recently found to be effective for the growth of dense carbon nanotube (CNT) forests was studied using hard x-ray photoemission spectroscopy (HAXPES). It was previously found that the Ti support layer was partially oxidized at room temperature (RT) and absorbed oxygen from the Fe overlayer at higher temperatures, which gave rise to the dense CNT forest growth. The aim of the present study was to elucidate the reason for the initial oxidation of the Ti layer at RT, which remained unclear from the results of the previous study. The control of the initial Ti oxidation is important because it could affect the reduction and activation of the Fe layer at higher temperatures. Depth-dependent HAXPES measurements using different x-ray incidence angles revealed that the degree of oxidation of the 1-nm-thick Ti layer in a sample that had been aged at RT for approximately three months varied depending on the depth. This suggests that oxidation of the Ti layer proceeded after the Fe/Ti film fabrication. Then, the effects of aging on the Ti oxidation states were examined. The Ti 2p3/2 spectrum measured for another sample that had been aged for approximately nine months showed a higher degree of oxidation of the Ti layer than that measured for the sample aged for three months. These results indicate that the Ti layers absorbed oxygen despite the existence of a 2-nm-thick Fe overlayer.
NASA missions aim at asteroid oddballs
Authors: Voosen Paul
Published: January 2017

Lucy and Psyche to explore solar system origins.
Observations hint at a new recipe for giant black holes
Authors: Sokol Joshua
Published: January 2017

Direct collapse from primordial gas clouds could solve a cosmic timing problem.
Editing the editor: Genome editing gets a makeover with CRISPR 2.0
Authors: Smith Caitlin
Published: January 2017

Applications of the genome editing system CRISPR are appearing at a furious pace, and gathering momentum toward therapeutic use in human cells. Indeed, Chinese scientists recently began a human clinical trial using CRISPR-edited cells to fight lung cancer, and U.S. clinical trials are slated to begin in 2017. But leading up to this exciting milestone, researchers performed some editing on the CRISPR system itself. Here's a look at some recent CRISPR upgrades that are helping to move it closer toward use in clinics.

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Using Data from Macaques To Predict Gamma Interferon Responses after Mycobacterium bovis BCG Vaccination in Humans: a Proof-of-Concept Study of Immunostimulation/Immunodynamic Modeling Methods
Authors: Rhodes Sophie J. , Sarfas Charlotte , Knight Gwenan M. , White Andrew , Pathan Ansar A. , McShane Helen , Evans Thomas G. , Fletcher Helen , Sharpe Sally , White Richard G.
Published: January 2017

Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-γ)-secreting CD4
+
T cells over time after recent
Mycobacterium bovis
BCG vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG vaccination status, time since BCG vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-γ T cell response after BCG vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (
P
< 0.05) associated with the BCG-induced immune response. For humans who were BCG naïve at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of immunostimulation/immunodynamic modeling to accelerate TB vaccine development.
Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection
Authors: Woodworth Michael H. , Neish Emma M. , Miller Nancy S. , Dhere Tanvi , Burd Eileen M. , Carpentieri Cynthia , Sitchenko Kaitlin L. , Kraft Colleen S.
Published: January 2017

Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent
Clostridium difficile
infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.
Point-Counterpoint: What Is the Optimal Approach for Detection of Clostridium difficile Infection?
Authors: Fang Ferric C. , Polage Christopher R. , Wilcox Mark H.
Published: January 2017

INTRODUCTION

In 2010, we published an initial Point-Counterpoint on the laboratory diagnosis of
Clostridium difficile
infection (CDI). At that time, nucleic acid amplification tests (NAATs) were just becoming commercially available, and the idea of algorithmic approaches to CDI was being explored. Now, there are numerous NAATs in the marketplace, and based on recent proficiency test surveys, they have become the predominant method used for CDI diagnosis in the United States. At the same time, there is a body of literature that suggests that NAATs lack clinical specificity and thus inflate CDI rates. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing; hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint using a frequently asked question approach, Ferric Fang of the University of Washington, who has been a consistent advocate for a NAAT-only approach for CDI diagnosis, will discuss the value of a NAAT-only approach, while Christopher Polage of the University of California Davis and Mark Wilcox of Leeds University, Leeds, United Kingdom, each of whom has recently written important articles on the value of toxin detection in the diagnosis, will discuss the impact of toxin detection in CDI diagnosis.
Phyloepidemiological Analysis Reveals that Viral Divergence Led to the Paucity of Simian Immunodeficiency Virus SIVmus/gsn/mon Infections in Wild Populations
Authors: Schmidt Fabian , Liegeois Florian , Greenwood Edward J. D. , LeBreton Matthew , Lester James , Deleplancque Luc , Peeters Martine , Aghokeng Avelin , Tamoufe Ubald , Diffo Joseph L. D. , Takuo Jean M. , Wolfe Nathan D. , Leroy Eric , Rouet François , Heeney Jonathan L.
Published: January 2017

Human immunodeficiency virus type 1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red-capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalences and an uneven geographic distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn, respectively, also have low rates of SIV infections in their populations. Compared to that for other monkeys, including red-capped mangabeys and closely related guenon species, such an epidemiology is unusual. By intensifying sampling of geographically distinct populations of mustached and greater spot-nosed guenons in Gabon and including large sample sets of mona guenons from Cameroon, we add strong support to the hypothesis that the paucity of SIV infections in wild populations is a general feature of this monophyletic group of viruses. Furthermore, comparative phylogenetic analysis reveals that this phenotype is a feature of this group of viruses infecting phylogenetically disparate hosts, suggesting that this epidemiological phenotype results from infection with these HIV-1-related viruses rather than from a common host factor. Thus, these HIV-1-related viruses, i.e., SIVcpz and the guenon viruses which share an ancestor with part of the SIVcpz genome, have an epidemiology distinct from that found for SIVs in other African primate species.

IMPORTANCE
Stable virus-host relationships are established over multiple generations. The prevalence of viral infections in any given host is determined by various factors. Stable virus-host relationships of viruses that are able to cause persistent infections and exist with high incidences of infection are generally characterized by a lack of morbidity prior to host reproduction. Such is the case for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections of humans. SIV infections of most African primate species also satisfy these criteria, with these infections found at a high prevalence and with rare cases of clinical disease. In contrast, SIVcpz, the ancestor of HIV-1, has a different epidemiology, and it has been reported that infected animals suffer from an AIDS-like disease in the wild. Here we conclusively demonstrate that viruses which are closely related to SIVcpz and infect a subset of guenon monkeys show an epidemiology resembling that of SIVcpz.
Virion Structure of Black Queen Cell Virus, a Common Honeybee Pathogen
Authors: Spurny Radovan , Přidal Antonín , Pálková Lenka , Kiem Hoa Khanh Tran , de Miranda Joachim R. , Plevka Pavel
Published: January 2017

Viral diseases are a major threat to honeybee (
Apis mellifera
) populations worldwide and therefore an important factor in reliable crop pollination and food security. Black queen cell virus (BQCV) is the etiological agent of a fatal disease of honeybee queen larvae and pupae. The virus belongs to the genus
Triatovirus
from the family
Dicistroviridae
, which is part of the order
Picornavirales
. Here we present a crystal structure of BQCV determined to a resolution of 3.4 Å. The virion is formed by 60 copies of each of the major capsid proteins VP1, VP2, and VP3; however, there is no density corresponding to a 75-residue-long minor capsid protein VP4 encoded by the BQCV genome. We show that the VP4 subunits are present in the crystallized virions that are infectious. This aspect of the BQCV virion is similar to that of the previously characterized triatoma virus and supports the recent establishment of the separate genus
Triatovirus
within the family
Dicistroviridae
. The C terminus of VP1 and CD loops of capsid proteins VP1 and VP3 of BQCV form 34-Å-tall finger-like protrusions at the virion surface. The protrusions are larger than those of related dicistroviruses.

IMPORTANCE
The western honeybee is the most important pollinator of all, and it is required to sustain the agricultural production and biodiversity of wild flowering plants. However, honeybee populations worldwide are suffering from virus infections that cause colony losses. One of the most common, and least known, honeybee pathogens is black queen cell virus (BQCV), which at high titers causes queen larvae and pupae to turn black and die. Here we present the three-dimensional virion structure of BQCV, determined by X-ray crystallography. The structure of BQCV reveals large protrusions on the virion surface. Capsid protein VP1 of BQCV does not contain a hydrophobic pocket. Therefore, the BQCV virion structure provides evidence that capsid-binding antiviral compounds that can prevent the replication of vertebrate picornaviruses may be ineffective against honeybee virus infections.
Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain
Authors: van den Pol Anthony N. , Mao Guochao , Chattopadhyay Anasuya , Rose John K. , Davis John N.
Published: January 2017

Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene. We also test a virus-like vesicle (VLV) in which the VSV glycoprotein gene is expressed from a replicon encoding the nonstructural proteins of Semliki Forest virus. VSVΔG-CHIKV, VSVΔG-H5N1, and VLV were all safe in the adult mouse brain, as were VSVΔG viruses expressing either the Nipah F or G glycoprotein. In contrast, a complementing pair of VSVΔG viruses expressing Nipah G and F glycoproteins were lethal within the brain within a surprisingly short time frame of 2 days. Intranasal inoculation in postnatal day 14 mice with VSVΔG-CHIKV or VLV evoked no adverse response, whereas VSVΔG-H5N1 by this route was lethal in most mice. A key immune mechanism underlying the safety of VSVΔG-CHIKV, VSVΔG-H5N1, and VLV in the adult brain was the type I interferon response; all three viruses were lethal in the brains of adult mice lacking the interferon receptor, suggesting that the viruses can infect and replicate and spread in brain cells if not blocked by interferon-stimulated genes within the brain.

IMPORTANCE
Vesicular stomatitis virus (VSV) shows considerable promise both as a vaccine vector and as an oncolytic virus. The greatest limitation of VSV is that it is highly neurotropic and can be lethal within the brain. The neurotropism can be mostly attributed to the VSV G glycoprotein. Here, we test 4 chimeric viruses of VSV with glycoprotein genes from Nipah, chikungunya, and influenza viruses and nonstructural genes from Semliki Forest virus. Two of the four, VSVΔG-CHIKV and VLV, show substantially attenuated neurotropism and were safe in the healthy adult mouse brain. VSVΔG-H5N1 was safe in the adult brain but lethal in the younger brain. VSVΔG Nipah F+G was even more neurotropic than wild-type VSV, evoking a rapid lethal response in the adult brain. These results suggest that while chimeric VSVs show promise, each must be tested with both intranasal and intracranial administration to ensure the absence of lethal neurotropism.
Efficient Vpu-Mediated Tetherin Antagonism by an HIV-1 Group O Strain
Authors: Mack Katharina , Starz Kathrin , Sauter Daniel , Langer Simon , Bibollet-Ruche Frederic , Learn Gerald H. , Stürzel Christina M. , Leoz Marie , Plantier Jean-Christophe , Geyer Matthias , Hahn Beatrice H. , Kirchhoff Frank
Published: January 2017

Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as a tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion. In this study, we identified an unusual HIV-1 group O strain (RBF206) that evolved Vpu as an effective antagonist of human tetherin. While both RBF206 Vpu and Nef exert anti-tetherin activity in transient-transfection assays, mainly Vpu promotes RBF206 release in infected CD4
+
T cells. Although mutations distinct from the adaptive changes observed in group M Vpus (M-Vpus) were critical for the acquisition of its anti-tetherin activity, RBF206 O-Vpu potently suppresses NF-κB activation and reduces CD4 cell surface expression. Interestingly, RBF206 Vpu counteracts tetherin in a largely species-independent manner, degrading both the long and short isoforms of human tetherin. Downmodulation of CD4, but not counteraction of tetherin, by RBF206 Vpu was dependent on the cellular ubiquitin ligase machinery. Our data present the first example of an HIV-1 group O Vpu that efficiently antagonizes human tetherin and suggest that counteraction by O-Nefs may be suboptimal.

IMPORTANCE
Previous studies showed that HIV-1 groups M and O evolved two alternative strategies to counteract the human ortholog of the restriction factor tetherin. While HIV-1 group M switched from Nef to Vpu due to a deletion in the cytoplasmic domain of human tetherin, HIV-1 group O, which lacks Vpu-mediated anti-tetherin activity, acquired a Nef protein that is able to target a region adjacent to the deletion. Here we report an unusual exception, identifying a strain of HIV-1 group O (RBF206) whose Vpu protein evolved an effective antagonism of human tetherin. Interestingly, the adaptive changes in RBF206 Vpu are distinct from those found in M-Vpus and mediate efficient counteraction of both the long and short isoforms of this restriction factor. Our results further illustrate the enormous flexibility of HIV-1 in counteracting human defense mechanisms.
Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis
Authors: Berger Angela K. , Hiller Bradley E. , Thete Deepti , Snyder Anthony J. , Perez Encarnacion , Upton Jason W. , Danthi Pranav
Published: January 2017

Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the
de novo
synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus.

IMPORTANCE
An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis.
Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor
Authors: Mori Seiichiro , Takeuchi Takamasa , Ishii Yoshiyuki , Yugawa Takashi , Kiyono Tohru , Nishina Hiroshi , Kukimoto Iwao
Published: January 2017

The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers, including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites. Normal immortalized human keratinocytes expressing E6 (NIKS-E6) displayed increased levels of TEAD1/4 protein compared to parental NIKS. A series of E6 mutants revealed that E6-mediated degradation of p53 was important for increasing TEAD4 levels. Knockdown of TEADs in NIKS-E6 significantly reduced A3B mRNA levels, whereas ectopic expression of TEAD4 in NIKS increased A3B mRNA levels. Finally, chromatin immunoprecipitation assays demonstrated increased levels of TEAD4 binding to the A3B promoter in NIKS-E6 compared to NIKS. Collectively, these results indicate that E6 induces upregulation of A3B through increased levels of TEADs, highlighting the importance of the TEAD-A3B axis in carcinogenesis.

IMPORTANCE
The expression of APOBEC3B (A3B), a cellular DNA cytidine deaminase, is upregulated in various human cancers and leaves characteristic, signature mutations in cancer genomes, suggesting that it plays a prominent role in carcinogenesis. Viral oncoproteins encoded by human papillomavirus (HPV) and polyomavirus have been reported to induce A3B expression, implying the involvement of A3B upregulation in virus-associated carcinogenesis. However, the molecular mechanisms causing A3B upregulation remain unclear. Here, we demonstrate that exogenous expression of the cellular transcription factor TEAD activates the A3B promoter. Further, the HPV oncoprotein E6 increases the levels of endogenous TEAD1/4 protein, thereby leading to A3B upregulation. Since increased levels of TEAD4 are frequently observed in many cancers, an understanding of the direct link between TEAD and A3B upregulation is of broad oncological interest.
Herpes Simplex Virus 1 Abrogates the cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway via Its Virion Host Shutoff Protein, UL41
Authors: Su Chenhe , Zheng Chunfu
Published: January 2017

Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although the cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especially for DNA viruses, few viral components have been identified to specifically target this signaling pathway. Herpes simplex virus 1 (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. In the present study, we found that HSV-1 tegument protein UL41 was involved in counteracting the cGAS/STING-mediated DNA-sensing pathway. Our results showed that wild-type (WT) HSV-1 infection could inhibit immunostimulatory DNA-induced activation of the IFN signaling pathway compared with the UL41-null mutant virus (R2621), and ectopic expression of UL41 decreased cGAS/STING-mediated IFN-β promoter activation and IFN-β production. Further study indicated that UL41 reduced the accumulation of cGAS to abrogate host recognition of viral DNA. In addition, stable knockdown of cGAS facilitated the replication of R2621 but not WT HSV-1. For the first time, HSV-1 UL41 was demonstrated to evade the cGAS/STING-mediated DNA-sensing pathway by degrading cGAS via its RNase activity.

IMPORTANCE
HSV-1 is well known for its ability to evade host antiviral responses and establish a lifelong latent infection while triggering reactivation and lytic infection under stress. Currently, whether HSV-1 evades the cytosolic DNA sensing and signaling is still poorly understood. In the present study, we found that tegument protein UL41 targeted the cGAS/STING-mediated cellular DNA-sensing pathway by selectively degrading cGAS mRNA. Knockdown of endogenous cGAS could facilitate the replication of R2621 but not WT HSV-1. Furthermore, UL41 was shown for the first time to act directly on cGAS. Findings in this study could provide new insights into the host-virus interaction and help develop new approaches against HSV-1.