bluuebunny/crossref_metadata_2025 huggingface dataset:
ONE FALSE VIRTUE OF RULE CONSEQUENTIALISM, AND ONE NEW VICE
Authors: Mulgan Tim
Published: August 2017

A common objection to Act Consequentialism (AC) is that it makes unreasonable demands on moral agents. Rule Consequentialism (RC) is often presented as a less demanding alternative. It is argued that this alleged virtue of RC is false, as RC will not be any less demanding in practice than AC. It is then demonstrated that RC has an additional (hitherto unnoticed) vice, as it relies upon the undefended simplifying assumption that the best possible consequences would arise in a society in which everyone followed the same rules. Once this “Homogeneity Assumption” is rejected, RC is unable to provide a workable alternative to AC.
Molecular dynamics study of correlations between IR peak position and bond parameters of silica and silicate glasses: Effects of temperature and stress
Authors: Luo Jiawei , Zhou Yuxing , Milner Scott T. , Pantano Carlo G. , Kim Seong H.
Published: August 2017

In the IR spectra of the silica and silicate glasses, the shifts of the maximum intensity position of the νSi–O–Si,as band upon heating or applying mechanical stress could be attributed to changes in the distribution of bond parameters such as bond length and bond angle. Upon heating, isotropic expansion occurs and the density changes; upon applying mechanical stress, anisotropic strain is induced and a significant change in the Si–O–Si bond angle is observed. From molecular dynamics simulations of a silica glass, we show that the peak position shift correlates better with the asymmetric change in the Si–O bond length distribution, rather than the Si–O–Si bridge angle, the O–Si–O tetrahedral angle, or the density change. This new finding provides an insight into how and why the νSi–O–Si,as IR peak of soda lime silica (SLS) glass shifts upon chemical strengthening via ion exchange and thermal tempering.
Periodontal manifestations of Ehlers–Danlos syndromes: A systematic review
Authors: Kapferer‐Seebacher Ines , Lundberg Pernilla , Malfait Franziska , Zschocke Johannes
Published: August 2017

Aim

Ehlers–Danlos syndromes (EDS) are a group of inherited connective tissue disorders, characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Periodontal EDS (pEDS) is a specific EDS subtype caused by heterozygous mutations in complement 1 subunit genes C1R and C1S, with early severe periodontitis as predominant clinical feature. We aimed to systematically assess the spectrum of periodontal abnormalities in all EDS subtypes.

Materials and Methods

An electronic and manual search was conducted in three databases (Medline, LIVIVO, CENTRAL). Publications of all study designs written in English/German without date restriction evaluating periodontal features in EDS were included.

Results

Thirty articles on pEDS and thirteen articles on other EDS subtypes were analysed. In pEDS, early severe periodontitis (98.4%) and gingival recession (87.1%) are the predominant features. Reports on periodontal manifestations in other EDS subtypes are rare. Described were severe gingival enlargement in dermatosparaxis EDS, and localized periodontal breakdown related to teeth with shortened roots in classical EDS (n = 3, respectively).

Conclusion

Early severe periodontitis is the hallmark of pEDS; there is no evidence that it is part of the clinical phenotype of other EDS subtypes. Stringent analyses of periodontal manifestations in most EDS subtypes are missing. Prospero registration number CRD42017056889.
Efficacy and safety of once‐weekly oral trelagliptin switched from once‐daily dipeptidyl peptidase‐4 inhibitor in patients with type 2 diabetes mellitus: An open‐label, phase 3 exploratory study
Authors: Inagaki Nobuya , Sano Hiroki , Seki Yoshifumi , Kuroda Shingo , Kaku Kohei
Published: August 2017

Introduction

Trelagliptin, a novel once‐weekly oral dipeptidyl peptidase‐4 (DPP‐4) inhibitor, has shown favorable efficacy and safety in type 2 diabetes mellitus patients. Trelagliptin was launched in Japan, and is expected to be initially used for switchover from a daily DPP‐4 inhibitor in the clinical setting. Thus, the present study was carried out to explore the efficacy and safety of trelagliptin after a daily DPP‐4 inhibitor was switched to it.

Materials and Methods

This was an open‐label, phase 3 exploratory study to evaluate the efficacy and safety of trelagliptin in Japanese type 2 diabetes mellitus patients who had stable glycemic control on once‐daily sitagliptin therapy. Eligible patients received trelagliptin 100 mg orally before breakfast once a week for 12 weeks. The primary end‐point was blood glucose by the meal tolerance test, and additional end‐points were glycemic control (efficacy) and safety.

Results

Altogether, 14 patients received the study drug. The blood glucose did not markedly change from baseline at major assessment points in the meal tolerance test, and a decrease in blood glucose was observed at several other assessment points. Adverse events were reported in 42.9% (6/14) of patients, but all adverse events were mild or moderate in severity, and most were not related to the study drug. No cases of death, serious adverse events or hypoglycemia were reported.

Discussion

It is considered possible to switch a once‐daily DPP‐4 inhibitor to trelagliptin in type 2 diabetes mellitus patients with stable glycemic control in combination with diet and exercise therapy without any major influences on glycemic control or safety.
Detection of Herpesvirus anguillae (AngHV‐1) in European eel Anguilla anguilla (L.) originating from northern Poland—assessment of suitability of selected diagnostic methods
Authors: Nguyen Tuan Thuc , Jin Yeonhwa , Kiełpińska Jolanta , Bergmann Sven M. , Lenk Matthias , Panicz Remigiusz
Published: August 2017

The Community Action Plan requests EU member states to implement measures that ensure the recovery of the severely depleted European eel stocks. One of the main threats is posed by Anguillid herpesvirus 1 (AngHV‐1) leading to increased mortality in both wild and farmed eels. Following recommendations of the OIE to minimize the risk of obtaining false‐negative results, the main aim of the study was to optimize diagnostic methods for AngHV‐1 detection using conventional PCR, nested PCR and in situ hybridization assay. While 53.3% of the individual organ samples were tested positive for AngHV‐1 by PCR, the additional virus analysis via nested PCR revealed that the actual prevalence was 93.3%. In the cell cultivation passages, a cytopathic effect was hardly found in the first two rounds. In the third passage onto cell cultures, a lytic CPE was detected. The identification and confirmation of the viruses obtained from cell cultures as well as directly from the organ tissues were proceeded by PCR, nested PCR and sequencing of the PCR products. While no positive signal was detectable in the first round by PCR using samples from the third cell culture passages, the nested PCR provided weak but visible positive signals.
First description of a mortality event in adult Pacific oysters in Italy associated with infection by a Tenacibaculum soleae strain
Authors: Burioli E A V , Varello K , Trancart S , Bozzetta E , Gorla A , Prearo M , Houssin M
Published: August 2017

Summer mortality episodes in adult Pacific oysters have been described since the 1950s in various farming areas. Starting in 2012, a recrudescence of mortalities in commercial‐sized oysters was first observed in France and then in Italy, with seasonality extension and translation later in the year. Moribund individuals collected during an event in Italy in December 2014 showed yellowish lesions of the mantle and adductor muscle. Histological examination revealed filamentous bacteria associated with necrotic areas. Quantitative PCRs targeting OsHV‐1 and Vibrio aestuarianus detected only high loads of the pathogenic bacteria in tissues of symptomatic individuals. A lower diversity of the hemolymph microbiota was also evidenced in moribund individuals, with a predominance of Vibrio and Arcobacter species. A strain of Flavobacteriaceae was isolated from all the symptomatic individuals. Sequence analysis of the 16S rRNA gene identified the strain as Tenacibaculum soleae. When strain pathogenicity was tested by injection in adult individuals, it induced mortality rates of up to 45%, even in the absence of V. aestuarianus. As mortality occurred only 11 days post‐infection, further investigation is needed to determine its effective virulence in natural conditions. This is the first description of a Tenacibaculum strain associated with bivalve mortalities.
A comparative study of practitioner perceptions of selection methods in the United Kingdom
Authors: Jackson Duncan J. R. , Dewberry Chris , Gallagher Jaroslava , Close Liam
Published: August 2017

In this study, 476 participants, divided into occupational psychology (OP)‐, Chartered Institute of Personnel and Development (CIPD)‐, human resource management (HRM)‐qualified, and layperson subgroups, provided their perceptions of the validity, fairness, and frequency of use of employee selection methods. Results of a mixed‐effects analysis of covariance revealed that respondent qualification background predicted the degree to which participant validity perceptions were aligned with research‐based estimates of validity, F [3, 29.39] = 20.06, p < .001, η2 = .67. Corrected pairwise comparisons suggested that perceptions of participants with CIPD and HRM backgrounds were not significantly more aligned with research estimates of validity than were the perceptions of laypeople. OP participant validity perceptions were significantly more aligned with research estimates than all other subgroups, (p < .03). Evidence was also found for some between‐group consistency regarding frequency‐of‐use perceptions, but less between‐group consistency was found vis‐à‐vis perceptions of fairness. Implications for decision‐making in employee selection are discussed.

Practitioner points

Knowledge about employee selection measures might not be effectively shared between those with CIPD‐ and HRM‐related qualifications versus those with OP‐related qualifications.

Laypeople and respondents with CIPD‐ and HRM‐related qualifications were found to deviate similarly from up‐to‐date research findings about the validity of selection measures.

Respondents with OP‐related qualifications were more closely aligned with up‐to‐date findings about the validity of selection measures than were other comparison groups.
Categorization and Willingness to Pay for New Products: The Role of Category Cues as Value Anchors
Authors: Kuijken Bram , Gemser Gerda , Wijnberg Nachoem M.
Published: August 2017

This study focuses on textual category cues and their influence on consumers' willingness to pay for new products. It examines whether an anchoring effect occurs when consumers are provided with textual category cues that refer consumers toward a particular product category. This article argues that consumers' willingness to pay for a product under consideration will tend toward the average price of products in the category in which it is positioned. This average price acts as a reference point that influences consumers' willingness to pay. We hypothesize that the more innovative the product is, the less certain the consumer is about its properties. Therefore, the proposed anchoring mechanism will influence consumers' willingness to pay strongly when the product is radically innovative, while the willingness to pay for an incrementally innovative product will not be affected by the proposed anchoring mechanism. Our hypotheses are tested by means of four experiments using online auctions in which consumers actually pay when they win an auction. The findings provide support for the role of category cues as “semantic anchors.” More specifically, giving the cues of categories in which the products had higher average monetary value compared to cues of categories in which the average monetary value was lower, resulted in an increased consumers' willingness to pay for radically new products. As expected, this effect was not found in the case of incrementally new products. The article concludes with theoretical and managerial implications.
Hospital‐level balloon tamponade use is associated with increased mortality for all patients presenting with acute variceal haemorrhage
Authors: Tapper Elliot B. , Ezaz Ghideon , Patwardhan Vilas , Mellinger Jessica , Bonder Alan , Curry Michael , Saini Sameer D.
Published: August 2017

Background & Aims

Balloon tamponade (BT) can bridge patients to salvage therapy for uncontrollable acute variceal haemorrhage (AVH). However, data are limited regarding the reasons for, rate of and outcomes associated with Balloon tamponade use.

Methods

First, we performed an single‐centre cohort study of all patients (N = 139) with oesophageal acute variceal haemorrhage from 01/2009 to 10/2015. Associations between Balloon tamponade use and adherence to four quality metrics (endoscopy within 12 hours, band‐ligation, pre‐endoscopy antibiotics and octreotide) were evaluated. Second, we analysed the National Inpatient Sample (2005‐2011) to determine the association between in‐hospital mortality for patients and their hospital's Balloon tamponade—utilization to acute variceal haemorrhage volume ratio.

Results

In the national cohort, 5.5% of 140 521 acute variceal haemorrhage admissions required Balloon tamponade utilization. Adjusting for patient‐ and hospital‐level confounders, the rate of Balloon tamponade use per acute variceal haemorrhage managed at any given hospital was associated with increased mortality for all‐comers with acute variceal haemorrhage. Compared to the lowest tertile, acute variceal haemorrhage admissions in the highest Balloon tamponade utilizers were associated with increased mortality of (OR1.17 95%CI (1.01‐1.37).

In the single‐centre cohort, 14 (10.1%) patients required Balloon tamponade. Balloon tamponade utilization was significantly associated with alcohol abuse (50.4% vs 21.4%, P = .04), hepatocellular carcinoma (35.7% vs 8.8%, P = .01), higher median model for end‐stage liver disease (MELD) score (26.3vs15.5, P = .002) and active bleeding during endoscopy (64.3% vs 27.5%, P = .01). Failure to provide all quality metrics was associated with a higher model for end‐stage liver disease‐adjusted risk of Balloon tamponade use: OR 16.7 95% CI(4.17‐100.0, P < .0001).

Conclusion

Balloon tamponade use is associated with severity of bleeding but may also implicate deficits in processes of care. Even for patients who did not need Balloon tamponade, presentation to hospitals with high Balloon tamponade utilization increases their odds of dying from acute variceal haemorrhage.
“Crisis Gets Served Before Anything Else”: Structural constraints on integrating lgbt consciousness‐raising into antiviolence work
Authors: RIOS AISHA
Published: August 2017

This article explores structural constraints on knowledge production and practice among volunteer members of a community‐based coalition in a southern U.S. state that addresses intimate partner violence among those whom identify as lesbian, gay, bisexual, and transgender (LGBT). Male violence against women is a serious social problem and sufficient support systems are lacking. The availability of competent support systems for LGBT‐identified persons affected by intimate partner violence is even grimmer. In response to this epidemic, advocacy organizations have responded through policy, advocacy, service provision, education, and training. This article focuses on one community‐based coalition to explore the ways hegemonic discourses interplay with organizational structure, fear, and a crisis mode orientation to shape the ways people advocate for social change and justice causes. This ethnographic research reveals the ways sociopolitical structures constrain members' willingness to explore alternatives outside of the hegemonic frameworks guiding understandings of and responses to intimate partner violence.
Cerebral amyloid angiopathy initially occurs in the meningeal vessels
Authors: Takeda Shigeki , Yamazaki Kazunori , Miyakawa Teruo , Onda Kiyoshi
Published: August 2017

To clarify the frequency of CAA in the brain parenchyma and subarachnoid space (SAS), we counted sections of blood vessels showing positive staining for Aβ in the SAS, cerebral cortex (CC) and cerebral white matter (WM) using paraffin‐embedded sections of the frontal, temporal and occipital lobes. The specimens had been taken for routine neuropathological examination from the brains of 105 Japanese patients (aged 40–95 years) selected from among 200 consecutive patients autopsied between 1989 and 2015 at our hospital. We examined the anatomical ratios of blood‐vessel sections in the SAS relative to the CC in three selected CAA cases, and those of Aβ‐positive blood‐vessel sections in CAA cases. CAA was found in 53 of the 105 cases (50.5%), and the youngest patient affected was a 51‐year‐old man. The incidence of CAA increased with age. The anatomical ratio of blood vessel sections in the SAS relative to the CC was 1/3.70–1/4.37 (mean: 1/3.94). The ordinary CAA group, in which CAA was seen in both the SAS and CC, included 41 cases (77.4%). In 37 of these cases, the SAS/CC ratio of Aβ‐positive blood vessels was 1/0.05–1/0.66 (mean: 1/0.26), and in the other four cases the ratio was 1/1–1/1.5. In the ordinary CAA group, the SAS/CC ratio of Aβ‐positive blood vessels was smaller than the anatomical ratio. The meningeal CAA group, in which CAA was found only in the SAS, included 12 cases (22.6%). These patients ranged in age from their fifties to their nineties. There was no case in which CAA was limited only to the CC. We concluded that CAA initially develops in the meningeal blood vessels, and not in the cortical blood vessels. CAA in the WM was seen in 10 cases, not only in nine cases that were severe, but also in a mild case.
Overexpression of AtPAD4 in transgenic Brachypodium distachyon enhances resistance to Puccinia brachypodii
Authors: Wang B. , Wang N. , Song N. , Wang W. , Wang J. , Wang X. , Kang Z.
Published: August 2017

Brachypodium distachyon (L.) has recently emerged as a model for temperate grasses for investigating the molecular basis of plant–pathogen interactions. Phytoalexin deficient 4 (PAD4) plays a regulatory role in mediating expression of genes involved in plant defence.

In this research, we generated transgenic B. distachyon plants constitutively overexpressing AtPAD4. Two transgenic B. distachyon lines were verified using PCR and GUS phenotype.

Constitutive expression of AtPAD4 in B. distachyon enhanced resistance to Puccinia brachypodii. P. brachypodii generated less urediniospores on transgenic than on wild‐type plants. AtPAD4 overexpression enhanced salicylic acid (SA) levels in B. distachyon‐infected tissues. qRT‐PCR showed that expression of pathogenesis‐related 1 (PR1) and other defence‐related genes were up‐regulated in transformed B. distachyon following infection with P. brachypodii.

Our results indicate that AtPAD4 overexpression in B. distachyon plants led to SA accumulation and induced PR gene expression that reduced the rate of colonisation by P. brachypodii.
The role of S‐acylation in protein trafficking
Authors: Daniotti Jose L. , Pedro Maria P. , Valdez Taubas Javier
Published: August 2017

Protein S‐acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This modification, which is widespread in eukaryotes, is thought to affect over 12% of the human proteome. S‐acylation allows the reversible association of peripheral proteins with membranes or, in the case of integral membrane proteins, modulates their behavior within the plane of the membrane. This review focuses on the consequences of protein S‐acylation on intracellular trafficking and membrane association. We summarize relevant information that illustrates how lipid modification of proteins plays an important role in dictating precise intracellular movements within cells by regulating membrane‐cytosol exchange, through membrane microdomain segregation, or by modifying the flux of the proteins by means of vesicular or diffusional transport systems. Finally, we highlight some of the key open questions and major challenges in the field.
Metabolic tracing analysis reveals substrate‐specific metabolic deficits in platelet storage lesion
Authors: Sims Carrie , Salliant Noelle , Worth Andrew J. , Parry Robert , Mesaros Clementina , Blair Ian A. , Snyder Nathaniel W.
Published: August 2017

BACKGROUND

Storage of platelets (PLTs) results in a progressive defect termed PLT storage lesion (PSL). The PSL is characterized by poor PLT quality on a variety of assays. Metabolic defects are thought to underlie the PSL; thus this study was designed to quantitatively probe specific metabolic pathways over PLT storage.

STUDY DESIGN AND METHODS

Relative incorporation of stable isotope‐labeled substrates was quantified by isotopologue analysis of key acyl‐coenzyme A (CoA) thioester products for fresh, viable (after collection, Days 2‐5), and expired PLTs (after Day 5). We examined the incorporation of acetate, glucose, and palmitate into acetyl‐ and succinyl‐CoA via liquid chromatography–tandem mass spectrometry.

RESULTS

Storage‐related defects in the incorporation of acetyl‐CoA derived from acetate and palmitate were observed. Carbon derived from palmitate and acetate in succinyl‐CoA was reduced over storage time. Glucose incorporation into succinyl‐CoA increased in viable PLTs and then decreased in expired PLTs. Carbon derived from octanoate and pyruvate remained partially able to incorporate into acetyl‐ and succinyl‐CoA in expired PLTs, with high variability in pyruvate incorporation.

CONCLUSION

Isotopologue analysis is useful in probing substrate specific defects in the PSL.
Risk Measurement of Futures Portfolio: An Empirical Study Based on PGARCH - EVT - Copula Model
Authors: Su Liang , Ma Lan-Ya
Published: August 2017

Financial risk management takes an important part of continuing financial globalization. From the point of financial risk management, financial risk should be controlled at the right level. Considering the characteristics of financial time series, we construct the PGARCH-EVT-Copula model that includes different aspects of statistical features in measuring the risk. With this model, we measure Value at Risk and Expected Shortfall of the futures portfolio and compare them in the risk measurement and testify the reliability with the help of Monte-Carlo simulation method. Finally, we draw a conclusion that at 95% confidence level, Expected Shortfall can better estimate the risk of assets price extreme changing. This paper provides a risk management method for stabilizing the financial market.
Errors in Case Markers Made by Syrian Students Who Learn Turkish in Temporary Education Center
Authors: Kan Mustafa Onur , Utlu Gizem
Published: August 2017

The purpose of this study is to determine the errors in case markers in the texts formed by Syrian students, who learn Turkish as a foreign language. The study group of this research, which is designed as a case study, comprises of a total of 60 Syrian students in A1 and A2 level, studying in the temporary education center of Al-Nassaj, which is affiliated with the district of Antakya, Hatay. The determination of the levels of the students was based on the description of the linguistic competences proposed by The Common European Framework of Reference for Languages (CEFR). A placement test was administered to the students in line with the description proposed by the CEFR, and a total of 30 students in A1 and 30 students in A2 were included to the study. A personal information form as well as writing forms, which had been developed by the researchers, were employed in the data collection. The analysis of the data obtained from the writing forms was performed through descriptive analysis method. An evaluation meeting was held with a faculty member specialized in the field of Turkish education in order to ensure the reliability of the data, and a consensus has been reached on the data.The study revealed that in terms of the total number of words used by the students, the students in A1 made 8 errors in case markers for each 100 words whereas those in A2 made 9.3 errors in case markers for each 100 words. It is remarkable that the students in A1 made the most errors in the genitive case markers whereas those in A2 made the most errors in locative case markers. There was no error in the ablative case markers in the texts produced by the students in A1. The study further found that the number of such errors made by the students in A2 was very low.
Unexpected validity of Schottky's conjecture for two-stage field emitters: A response via Schwarz–Christoffel transformation
Authors: Marcelino Edgar , A. de Assis Thiago , C. de Castilho Caio M.
Published: August 2017

The electric field in the vicinity of the top of an emitter with a profile consisting of a triangular protrusion on an infinite line is analytically obtained when this system is under an external uniform electric field. The same problem is also studied when the profile features a two-stage system, consisting of a triangular protrusion centered on the top of a rectangular one on a line. These problems are approached by using a Schwarz–Christoffel conformal mapping, and the validity of Schottky's conjecture (SC) is discussed. The authors provide an analytical proof of SC when the dimensions of the upper-stage structure are much smaller than those of the lower-stage structure, for large enough aspect ratios and considering that the field enhancement factor (FEF) of the rectangular structure is evaluated on the center of the top of the structure, while the FEF of the triangular stage is evaluated near the upper corner of the protrusion. The numerical solution of our exact equations shows that SC may remain valid even when both stages feature dimensions of the same order of magnitude, reinforcing the validity of SC for multistage field emitters.
Segmented Forefoot Plate in Basketball Footwear: Does it Influence Performance and Foot Joint Kinematics and Kinetics?
Authors: Lam Wing-Kai , Lee Winson Chiu-Chun , Lee Wei Min , Ma Christina Zong-Hao , Kong Pui Wah
Published: August 2017

This study examined the effects of shoes’ segmented forefoot stiffness on athletic performance and ankle and metatarsophalangeal joint kinematics and kinetics in basketball movements. Seventeen university basketball players performed running vertical jumps and 5-m sprints at maximum effort with 3 basketball shoes of various forefoot plate conditions (medial plate, medial + lateral plates, and no-plate control). One-way repeated measures ANOVAs were used to examine the differences in athletic performance, joint kinematics, and joint kinetics among the 3 footwear conditions (α = .05). Results indicated that participants wearing medial + lateral plates shoes demonstrated 2.9% higher jump height than those wearing control shoes (P = .02), but there was no significant differences between medial plate and control shoes (P > .05). Medial plate shoes produced greater maximum plantar flexion velocity than the medial + lateral plates shoes (P < .05) during sprinting. There were no significant differences in sprint time. These findings implied that inserting plates spanning both the medial and lateral aspects of the forefoot could enhance jumping, but not sprinting performances. The use of a medial plate alone, although induced greater plantar flexion velocity at the metatarsophalangeal joint during sprinting, was not effective in improving jump heights or sprint times.
Polymer-modified halide perovskite films for efficient and stable planar heterojunction solar cells
Authors: Zuo Lijian , Guo Hexia , deQuilettes Dane W. , Jariwala Sarthak , De Marco Nicholas , Dong Shiqi , DeBlock Ryan , Ginger David S. , Dunn Bruce , Wang Mingkui , Yang Yang
Published: August 2017

The UCLA team has successfully passivated perovskite film by controlling the film growth with functional polymers as additive.
When immiscible becomes miscible—Methane in water at high pressures
Authors: Pruteanu Ciprian G. , Ackland Graeme J. , Poon Wilson C. K. , Loveday John S.
Published: August 2017

At low pressure, methane dissolves poorly in water, but between 1 and 2 GPa, the solubility increases to almost 50 mol %.
Dynamic conservation for migratory species
Authors: Reynolds Mark D. , Sullivan Brian L. , Hallstein Eric , Matsumoto Sandra , Kelling Steve , Merrifield Matthew , Fink Daniel , Johnston Alison , Hochachka Wesley M. , Bruns Nicholas E. , Reiter Matthew E. , Veloz Sam , Hickey Catherine , Elliott Nathan , Martin Leslie , Fitzpatrick John W. , Spraycar Paul , Golet Gregory H. , McColl Christopher , Low Candace , Morrison Scott A.
Published: August 2017

Citizen science, big data, and a habitat marketplace enable dynamic habitat for migratory birds in California’s Central Valley.
Extensive arsenic contamination in high-pH unconfined aquifers in the Indus Valley
Authors: Podgorski Joel E. , Eqani Syed Ali Musstjab Akber Shah , Khanam Tasawar , Ullah Rizwan , Shen Heqing , Berg Michael
Published: August 2017

Fifty million to 60 million people potentially exposed to high levels of groundwater arsenic, which is coincident with areas of irrigation.
Visualizing redox orbitals and their potentials in advanced lithium-ion battery materials using high-resolution x-ray Compton scattering
Authors: Hafiz Hasnain , Suzuki Kosuke , Barbiellini Bernardo , Orikasa Yuki , Callewaert Vincent , Kaprzyk Staszek , Itou Masayoshi , Yamamoto Kentaro , Yamada Ryota , Uchimoto Yoshiharu , Sakurai Yoshiharu , Sakurai Hiroshi , Bansil Arun
Published: August 2017

A spectroscopic descriptor of the link between lattice distortion and voltage in Li battery materials.
Mother-Newborn Pairs in Malawi Have Similar Antibody Repertoires to Diverse Malaria Antigens
Authors: Boudová Sarah , Walldorf Jenny A. , Bailey Jason A. , Divala Titus , Mungwira Randy , Mawindo Patricia , Pablo Jozelyn , Jasinskas Algis , Nakajima Rie , Ouattara Amed , Adams Matthew , Felgner Philip L. , Plowe Christopher V. , Travassos Mark A. , Laufer Miriam K.
Published: August 2017

Maternal antibodies may play a role in protecting newborns against malaria disease.
Plasmodium falciparum
parasite surface antigens are diverse, and protection from infection requires allele-specific immunity. Although malaria-specific antibodies have been shown to cross the placenta, the extent to which antibodies that respond to the full repertoire of diverse antigens are transferred from the mother to the infant has not been explored. Understanding the breadth of maternal antibody responses and to what extent these antibodies are transferred to the child can inform vaccine design and evaluation. We probed plasma from cord blood and serum from mothers at delivery using a customized protein microarray that included variants of malaria vaccine target antigens to assess the intensity and breadth of seroreactivity to three malaria vaccine candidate antigens in mother-newborn pairs in Malawi. Among the 33 paired specimens that were assessed, mothers and newborns had similar intensity and repertoire of seroreactivity. Maternal antibody levels against vaccine candidate antigens were the strongest predictors of infant antibody levels. Placental malaria did not significantly impair transplacental antibody transfer. However, mothers with placental malaria had significantly higher antibody levels against these blood-stage antigens than mothers without placental malaria. The repertoire and levels of infant antibodies against a wide range of malaria vaccine candidate antigen variants closely mirror maternal levels in breadth and magnitude regardless of evidence of placental malaria. Vaccinating mothers with an effective malaria vaccine during pregnancy may induce high and potentially protective antibody repertoires in newborns.
Chlamydia trachomatis: the Persistent Pathogen
Authors: Witkin Steven S. , Minis Evelyn , Athanasiou Aikaterini , Leizer Julie , Linhares Iara M.
Published: August 2017

Chlamydia trachomatisis an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy.C. trachomatishas evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form,C. trachomatisceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood thatC. trachomatiswill avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.
Assessing Clinical Microbiology Practice Guidelines: American Society for Microbiology
Ad Hoc
Committee on Evidence-Based Laboratory Medicine Practice Guidelines Assessment
Authors: Nachamkin Irving , Kirn Thomas J. , Westblade Lars F. , Humphries Romney
Published: August 2017

As part of the American Society for Microbiology (ASM) Evidence-Based Laboratory Medicine Practice Guidelines Committee of the Professional Practice Committee, an
ad hoc
committee was formed in 2014 to assess guidelines published by the committee using an assessment tool, Appraisal of Guidelines for Research Evaluation II (AGREE II). The AGREE II assessment helps reviewers determine whether published guidelines are robust, transparent, and clear in presenting practice recommendations in a standardized manner. Identifying strengths and weaknesses of practice guidelines by
ad hoc
assessments helps with improving future guidelines through the participation of key stakeholders. This minireview describes the development of the
ad hoc
committee and results from their review of several ASM best practices guidelines and a non-ASM practice guideline from the Emergency Nurses Association.
Murine Olfactory Bulb Interneurons Survive Infection with a Neurotropic Coronavirus
Authors: Wheeler D. Lori , Athmer Jeremiah , Meyerholz David K. , Perlman Stanley
Published: August 2017

Viral infection of the central nervous system (CNS) is complicated by the mostly irreplaceable nature of neurons, as the loss of neurons has the potential to result in permanent damage to brain function. However, whether neurons or other cells in the CNS sometimes survive infection and the effects of infection on neuronal function is largely unknown. To address this question, we used the rJHM strain (rJ) of mouse hepatitis virus (MHV), a neurotropic coronavirus that causes acute encephalitis in susceptible strains of mice. To determine whether neurons or other CNS cells survive acute infection with this virulent virus, we developed a recombinant JHMV that expresses Cre recombinase (rJ-Cre) and infected mice that universally expressed a silent (floxed) version of tdTomato. Infection of these mice with rJ-Cre resulted in expression of tdTomato in host cells. The results showed that some cells were able to survive the infection, as demonstrated by continued tdTomato expression after virus antigen could no longer be detected. Most notably, interneurons in the olfactory bulb, which are known to be inhibitory, represented a large fraction of the surviving cells. In conclusion, our results indicated that some neurons are resistant to virus-mediated cell death and provide a framework for studying the effects of prior coronavirus infection on neuron function.

IMPORTANCE
We developed a novel recombinant virus that allows the study of cells that survive an infection by a central nervous system-specific strain of murine coronavirus. Using this virus, we identified neurons and, to a lesser extent, nonneuronal cells in the brain that were infected during the acute phase of the infection and survived for approximately 2 weeks until the mice succumbed to the infection. We focused on neurons and glial cells within the olfactory bulb because the virus enters the brain at this site. Our results show that interneurons of the olfactory bulb were the primary cell type able to survive infection. Further, these results indicate that this system will be useful for functional and gene expression studies of cells in the brain that survive acute infection.
Attenuated Human Parainfluenza Virus Type 1 Expressing the Respiratory Syncytial Virus (RSV) Fusion (F) Glycoprotein from an Added Gene: Effects of Prefusion Stabilization and Packaging of RSV F
Authors: Liu Xiang , Liang Bo , Ngwuta Joan , Liu Xueqiao , Surman Sonja , Lingemann Matthias , Kwong Peter D. , Graham Barney S. , Collins Peter L. , Munir Shirin
Published: August 2017

Human respiratory syncytial virus (RSV) is the most prevalent worldwide cause of severe respiratory tract infection in infants and young children. Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness, especially croup. Both viruses lack vaccines. Here, we describe the preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that expresses RSV F protein modified for increased stability in the prefusion (pre-F) conformation by previously described disulfide bond (DS) and hydrophobic cavity-filling (Cav1) mutations. RSV F was expressed from the first or second gene position as the full-length protein or as a chimeric protein with its transmembrane and cytoplasmic tail (TMCT) domains substituted with those of HPIV1 F in an effort to direct packaging in the vector particles. All constructs were recovered by reverse genetics. The TMCT versions of RSV F were packaged in the rHPIV1 particles much more efficiently than their full-length counterparts. In hamsters, the presence of the RSV F gene, and in particular the TMCT versions, was attenuating and resulted in reduced immunogenicity. However, the vector expressing full-length RSV F from the pre-N position was immunogenic for RSV and HPIV1. It conferred complement-independent high-quality RSV-neutralizing antibodies at titers similar to those of wild-type RSV and provided protection against RSV challenge. The vectors exhibited stable RSV F expression
in vitro
and
in vivo
. In conclusion, an attenuated rHPIV1 vector expressing a pre-F-stabilized form of RSV F demonstrated promising immunogenicity and should be further developed as an intranasal pediatric vaccine.

IMPORTANCE
RSV and HPIV1 are major viral causes of acute pediatric respiratory illness for which no vaccines or suitable antiviral drugs are available. The RSV F glycoprotein is the major RSV neutralization antigen. We used a rHPIV1 vector, bearing a stabilized attenuating mutation, to express the RSV F glycoprotein bearing amino acid substitutions that increase its stability in the pre-F form, the most immunogenic form that elicits highly functional virus-neutralizing antibodies. RSV F was expressed from the pre-N or N-P gene position of the rHPIV1 vector as a full-length protein or as a chimeric form with its TMCT domain derived from HPIV1 F. TMCT modification greatly increased packaging of RSV F into the vector particles but also increased vector attenuation
in vivo
, resulting in reduced immunogenicity. In contrast, full-length RSV F expressed from the pre-N position was immunogenic, eliciting complement-independent RSV-neutralizing antibodies and providing protection against RSV challenge.
Inherited Chromosomally Integrated Human Herpesvirus 6 Genomes Are Ancient, Intact, and Potentially Able To Reactivate from Telomeres
Authors: Zhang Enjie , Bell Adam J. , Wilkie Gavin S. , Suárez Nicolás M. , Batini Chiara , Veal Colin D. , Armendáriz-Castillo Isaac , Neumann Rita , Cotton Victoria E. , Huang Yan , Porteous David J. , Jarrett Ruth F. , Davison Andrew J. , Royle Nicola J.
Published: August 2017

The genomes of human herpesvirus 6A (HHV-6A) and HHV-6B have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere, and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern nonintegrated HHV-6 strains for which complete sequences are currently available. In addition, ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ± 10,600 years ago. Despite the antiquity of some, and possibly most, germ line HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation.

IMPORTANCE
Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date, but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here, we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes, and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immunocompromised patients, in particular in organ transplantation and in stem cell therapy.
Interferon Regulatory Factor 1 Protects against Chikungunya Virus-Induced Immunopathology by Restricting Infection in Muscle Cells
Authors: Nair Sharmila , Poddar Subhajit , Shimak Raeann M. , Diamond Michael S.
Published: August 2017

The innate immune system protects cells against viral pathogens in part through the autocrine and paracrine actions of alpha/beta interferon (IFN-α/β) (type I), IFN-γ (type II), and IFN-λ (type III). The transcription factor interferon regulatory factor 1 (IRF-1) has a demonstrated role in shaping innate and adaptive antiviral immunity by inducing the expression of IFN-stimulated genes (ISGs) and mediating signals downstream of IFN-γ. Although ectopic expression experiments have suggested an inhibitory function of IRF-1 against infection of alphaviruses in cell culture, its rolein vivoremains unknown. Here, we infectedIrf1−/−mice with two distantly related arthritogenic alphaviruses, chikungunya virus (CHIKV) and Ross River virus (RRV), and assessed the early antiviral functions of IRF-1 prior to induction of adaptive B and T cell responses. IRF-1 expression limited CHIKV-induced foot swelling in joint-associated tissues and prevented dissemination of CHIKV and RRV at early time points. Virological and histological analyses revealed greater infection of muscle tissues inIrf1−/−mice than in wild-type mice. The antiviral actions of IRF-1 appeared to be independent of the induction of type I IFN or the effects of type II and III IFNs but were associated with altered local proinflammatory cytokine and chemokine responses and differential infiltration of myeloid cell subsets. Collectively, ourin vivoexperiments suggest that IRF-1 restricts CHIKV and RRV infection in stromal cells, especially muscle cells, and that this controls local inflammation and joint-associated swelling.

IMPORTANCEInterferon regulatory factor 1 (IRF-1) is a transcription factor that regulates the expression of a broad range of antiviral host defense genes. In this study, usingIrf1−/−mice, we investigated the role of IRF-1 in modulating pathogenesis of two related arthritogenic alphaviruses, chikungunya virus and Ross River virus. Our studies show that IRF-1 controlled alphavirus replication and swelling in joint-associated tissues within days of infection. Detailed histopathological and virological analyses revealed that IRF-1 preferentially restricted CHIKV infection in cells of nonhematopoietic lineage, including muscle cells. The antiviral actions of IRF-1 resulted in decreased local inflammatory responses in joint-associated tissues, which prevented immunopathology.
Epstein-Barr Virus LMP1-Mediated Oncogenicity
Authors: Wang Liang Wei , Jiang Sizun , Gewurz Benjamin E.
Published: August 2017

Epstein-Barr virus latent membrane protein 1 (LMP1) is expressed in multiple human malignancies, including nasopharyngeal carcinoma and Hodgkin and immunosuppression-associated lymphomas. LMP1 mimics CD40 signaling to activate multiple growth and survival pathways, in particular, NF-κB. LMP1 has critical roles in Epstein-Barr virus (EBV)-driven B-cell transformation, and its expression causes fatal lymphoproliferative disease in immunosuppressed mice. Here, we review recent developments in studies of LMP1 signaling, LMP1-induced host dependency factors, mouse models of LMP1 lymphomagenesis, and anti-LMP1 immunotherapy approaches.
A Serendipitous Mutation Reveals the Severe Virulence Defect of a Klebsiella pneumoniae
fepB
Mutant
Authors: Palacios Michelle , Broberg Christopher A. , Walker Kimberly A. , Miller Virginia L.
Published: August 2017

In addition to having a reputation as the causative agent of several types of hospital-acquired infections,
Klebsiella pneumoniae
has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among
Klebsiella
strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target.