bluuebunny/crossref_metadata_2025 huggingface dataset:
The human cytomegalovirus G-protein coupled receptor US28 promotes latency by attenuating c-fos
Authors: Krishna Benjamin A. , Humby Monica S. , Miller William E. , O’Connor Christine M.
Published: October 2018

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that undergoes latency in cells of the hematopoietic compartment, though the mechanisms underlying establishment and maintenance of latency remain elusive. We previously reported that the HCMV-encoded G-protein coupled receptor (GPCR) homolog,US28is required for successful latent infection. We now show that US28 protein (pUS28) providedin transcomplements the US28Δ lytic phenotype in myeloid cells, suggesting that sustained US28 expression is necessary for long-term latency. Furthermore, expression of pUS28 at the time of infection represses transcription from the major immediate early promoter (MIEP) within 24 hours. However, this repression is only maintained in the presence of continual pUS28 expression providedin trans. Our data also reveal that pUS28-mediated signaling attenuates both expression and phosphorylation of cellular fos (c-fos), an AP-1 transcription factor subunit, to repress MIEP-driven transcription. AP-1 binds to the MIEP and promotes lytic replication, and in line with this, we find that US28Δ infection results in an increase in AP-1 binding to the MIEP, compared to wild type latent infection. Pharmacological inhibition of c-fos represses the MIEP during US28Δ infection to similar levels we observe during wild type latent infection. Together, our data reveal that US28 is required for both establishment and long-term maintenance of HCMV latency, which is modulated, at least in part, by repressing functional AP-1 binding to the MIEP.

Significance Statement

Human cytomegalovirus (HCMV) is a wise-spread pathogen that remains with an individual for life in a quiescent/latent state, posing little threat to an otherwise healthy person. However, when an individual’s immune system is severely compromised, HCMV can reactivate to its active/lytic state, resulting in viral spread and disease that is often fatal. The biological mechanisms underlying HCMV latency and reactivation remain poorly understood. Herein we show that the viral-encoded G-protein coupled receptor (GPCR)US28aids in the establishment and the maintenance of viral latency. Furthermore, we find that US28 modulates host cell proteins to suppress viral processes associated with active/lytic replication, thereby promoting latent infection. This work provides mechanism by which HCMV modulates the host cell environment to its advantage.
Domain-specific and nonspecific outcomes of work-family interface
Authors: Bhalla Abha , Kang Lakhwinder Singh
Published: October 2018

Purpose

The purpose of this paper is to examine the pattern of work-family interface outcomes by empirically testing work-family conflict and facilitation bidirectional dimensions simultaneously in relation to domains-specific (job and family) and domain nonspecific (life) satisfactions. In addition, the indirect effects of work-family interface dimensions on life satisfaction (LS), mediated through both domain-specific satisfactions are also examined to understand which domain satisfaction elicits major impact on LS.

Design/methodology/approach

Structural equation modeling analysis was conducted on questionnaire data obtained from 212 fulltime journalists working in top ten dailies of Punjab, India. Parallel multiple mediated regression was used to estimate specific indirect effects caused by each of the two parallel mediators (job satisfaction (JS) and family satisfaction (FS)).

Findings

Results illustrate that both dimensions of work-family conflict strongly decreased satisfaction of an originating domain than satisfaction of the receiving domain while both dimensions of work-family facilitation increased satisfaction of both the domains on equal basis. Results further reveal that the effect of work-family conflict and facilitation dimensions on LS is indirect rather than direct. On comparison of specific indirect effects results demonstrate that only originating domain satisfaction act as a mediator to work-family conflict and LS relationship, while both JS and FS act as mediators to work-family facilitation and LS relationship.

Practical implications

Media organizations can offer interventions like family friendly policies, overtime pay, more autonomy, work rewards and skill variety, so that employees’ workplace resource reservoir can be strongly built up to meet future work and family demands. In this way, positive intrusion from work-to-family takes place, which leads to more JS and FS and in turn increased overall LS.

Originality/value

The study removes inconsistency regarding pattern of work-family conflict and facilitation outcomes by testing a comprehensive model that integrates originating domain, receiving-domain and domain-nonspecific outcomes.
On measuring the quality of hospitals
Authors: Cheng Choon , Scott Anthony , Sundararajan Vijaya , Yong Jongsay
Published: October 2018

Purpose

Researchers, policymakers and hospital managers often encounter numerous quality measures when assessing hospital quality. The purpose of this paper is to address the challenge of summarising, interpreting and comparing multiple quality measures across different quality dimensions by proposing a simple method of constructing a composite quality index. The method is applied to hospital administrative data to demonstrate its use in analysing hospital performance.

Design/methodology/approach

Logistic and fixed effects regression analyses are applied to secondary admitted patient data from all hospitals in the state of Victoria, Australia for the period 2000/2001–2011/2012.

Findings

The derived composite quality index was used to rank hospital performance and to assess changes in state-wide average hospital quality over time. Further regression analyses found private hospitals, day hospitals and non-acute hospitals were associated with higher composite quality, while small hospitals were associated with lower quality.

Practical implications

The method will enable policymakers and hospital managers to better monitor the performance of hospitals. It allows quality to be related to other attributes of hospitals such as size and volume, and enables policymakers and managers to focus on hospitals with relevant characteristics such that quantity and quality changes can be better understood, monitored and acted upon.

Originality/value

A simple method of constructing a composite quality is an indispensable practical tool in tracking the quality of hospitals when numerous measures are used to capture different aspects of quality. The derived composite quality can be used to summarise hospital performance and to identify factors associated with quality via regression analyses.
An empirical study on the factors influencing mobile library usage in IoT era
Authors: Wang Xiwei , Li Jiaxing , Yang Mengqing , Chen Yong , Xu Xiaobo
Published: October 2018

Purpose

The purpose of this paper is to construct an information ecology factor-TAM model to explore how information, people, and information environment impact mobile library users’ behavioral intention.

Design/methodology/approach

An empirical study based on an information ecology factor-TAM model.

Findings

The results of model test indicate that information, people, and information environment affect users’ behavioral intention to use mobile library in the information ecology environment. This paper provides a new theoretical perspective to understand users’ behavior of mobile library. It also provides practical guidelines to promote the usage of mobile library.

Originality/value

Internet of Things makes digital library one important channel for people to obtain information. Mobile internet makes it possible to access a variety of information anytime and anywhere. With the rapid grow of the number of mobile internet users, the usage of mobile library does not grow correspondingly. This paper explores the reasons.
Measuring ease of doing business in India’s sub-national economies: a novel index
Authors: Tan Khee Giap , Gopalan Sasidaran , Nguyen Will
Published: October 2018

Purpose

The purpose of this paper is to contribute to the literature by introducing a novel index that measures ease of doing business (EDB) at the sub-national level. The authors provide a comprehensive assessment of bothde jureandde factobusiness conditions in 21 sub-national economies of India, with the help of a holistic framework that encompasses indicators capturing Attractiveness to Investors, Business Friendliness and Competitive Policies (ABC), the three broad environments that constitute the EDB–ABC index.

Design/methodology/approach

The authors’ index EDB–ABC index is constructed using 81 indicators. The index values reported are standardized scores and the framework is applied to 21 Indian sub-national economies. The bottom-up approach takes into account the various operational issues that firms face at the ground level, with the emphasis being onde factoissues. A unique feature of the index is its emphasis on collecting extensive survey data at the sub-national level, given that several constraints that businesses face lie under the purview of the sub-national governments. It also combines publicly available macroeconomic data through formal statistical publications.

Findings

The findings suggest a positive association between the proposed EDB–ABC index and competitiveness of as well as investments into Indian sub-national economies. In terms of explanatory power, the authors find that indicators capturing attractiveness to investors and business friendliness which are representative ofde factoimplementation issues at the sub-national matter more thande jurecompetitive policies. It is also striking that the results are in stark contrast to the existing doing business studies highlighting the importance of the comprehensiveness of the index.

Originality/value

Easing the impediments to doing business is a pre-requisite to enhance both domestic as well as foreign investments. Existing indicators on doing business provide an incomplete picture about the prevailing business conditions as the basis for such rankings arede jureregulations and notde facto. The authors depart from this tradition by dealing with bothde jureandde factobusiness conditions using a combination of primary and secondary data at the sub-national level in India.
Urbanization‐driven changes in web building and body size in an orb web spider
Authors: Dahirel Maxime , De Cock Maarten , Vantieghem Pieter , Bonte Dries
Published: October 2018

In animals, behavioural responses may play an important role in determining population persistence in the face of environmental changes. Body size is a key trait central to many life‐history traits and behaviours. Correlations with body size may constrain behavioural variation in response to environmental changes, especially when size itself is influenced by environmental conditions.

Urbanization is an important human‐induced rapid environmental change that imposes multiple selection pressures on both body size and (size‐constrained) behaviour. How these combine to shape behavioural responses of urban‐dwelling species is unclear.

Using web building, an easily quantifiable behaviour linked to body size and the garden spider Araneus diadematus as a model, we evaluated direct behavioural responses to urbanization and body size constraints across a network of 63 selected populations differing in urbanization intensity. We additionally studied urbanization at two spatial scales to account for some environmental pressures varying across scales and to obtain first qualitative insights about the role of plasticity and genetic selection.

Spiders were smaller in highly urbanized sites (local scale only), in line with expectations based on reduced prey biomass availability and the Urban Heat Island effect. Web surface and mesh width decreased with urbanization at the local scale, while web surface also increased with urbanization at the landscape scale. The latter two responses are expected to compensate, at least in part, for reduced prey biomass availability in cities. The use of multivariate mixed modelling reveals that although web traits and body size are correlated within populations, behavioural responses to urbanization do not appear to be constrained by size: there is no evidence of size–web correlations among populations or among landscapes, and web traits appear independent from each other.

Our results demonstrate that responses in size‐dependent behaviours may be decoupled from size changes, thereby allowing fitness maximization in novel environments. The spatial scale at which traits respond suggests contributions of both genetic adaptation (for web investment) and plasticity (for mesh width). Although fecundity decreased with local‐scale urbanization, A. diadematus abundances were similar across urbanization gradients; behavioural responses thus appear overall successful at the population level.
The association between complement factor H rs1061170 polymorphism and age‐related macular degeneration: a comprehensive meta‐analysis stratified by stage of disease and ethnicity
Authors: Maugeri Andrea , Barchitta Martina , Agodi Antonella
Published: October 2018

Purpose

The strength of association between complement factor H (CFH) rs1061170 polymorphism and age‐related macular degeneration (AMD) differs between AMD subtypes and ethnicities. The main aim was to provide a systematic review and an updated meta‐analysis stratified by stage of disease and ethnicity.

Methods

A literature search in the PubMed‐Medline, EMBASE and Web of Science databases was conducted to identify epidemiological studies, published before September 2017, that included at least twp comparison groups (a control group with no signs of AMD and a case group of AMD patients). Genotype distribution, phenotype of the cases, ethnicity, mean age and gender ratio were collected. Odds ratios (ORs) and 95%CIs were estimated under the allelic, homozygous and heterozygous models. Sensitivity and subgroup analyses, by AMD subtype and ethnicity, were performed.

Results

The meta‐analysis included data of 27 418 AMD patients and 32 843 controls from 76 studies. In Caucasians, the rs1061170 showed a significant association with early AMD (OR: 1.44; 95%CI 1.27–1.63), dry AMD (OR: 2.90; 95%CI 1.89–4.47) and wet AMD (OR: 2.46; 95%CI 2.15–2.83), under an allelic model. In Asians, the rs1061170 showed a significant association with advanced AMD (OR: 2.09; 95%CI 1.67–2.60), especially wet AMD (OR: 2.24; 95%CI 1.81–2.77).

Conclusion

Our work provides a more comprehensive meta‐analysis of studies investigating the effect of the CFH rs1061170 polymorphism on AMD risk. These findings not only improve the assessment of disease risk associated with the polymorphism, but also constitute a scientific background to be translated into clinical practice for AMD prevention.
Evaluation of tear meniscus by optical coherence tomography after different sodium hyaluronate eyedrops instillation
Authors: Carracedo Gonzalo , Pastrana Cristina , Serramito Maria , Rodriguez‐Pomar Candela
Published: October 2018

Purpose

To evaluate changes in tear meniscus dynamics using optical coherence tomography (OCT) after the instillation of different concentrations of sodium hyaluronate (SH) ophthalmic solutions.

Methods

An experimental, double‐masked, randomized study was performed. Twenty‐three healthy subjects (16 women and seven men; mean age 23.57 ± 2.56 years) participated in this study. About 35 μl of 0.1%, 0.2%, 0.3% SH ophthalmic solutions and saline solution was instilled in a randomly assigned eye. Tear meniscus measurements (height, depth and turbidity) were taken with OCT at 30 seconds and 1, 3, 5, 10 and 20 min after instillation. Subsequently, the Schirmer test and tear break‐up time (TBUT) were evaluated.

Results

Tear meniscus depth and tear meniscus height showed a significant increase with all solutions compared to basal values: up to 3 min for 0.1% SH, up to 5 min for 0.2% and up to 10 min for 0.3% SH ophthalmic solution. Tear meniscus turbidity was also increased at 30 seconds for 0.1%, 0.2% and 0.3% SH artificial tears (p < 0.05). This increase remained significant for up to 1 min for 0.2% and 0.3% SH solutions (p < 0.05). After 5 min of saline and 0.1% SH instillation, the turbidity was lower than basal values (p < 0.05). There was a significant increase in the TBUT for all solutions after instillation (p < 0.05). No differences between the Schirmer pre‐ and postinstillation were found (p > 0.05). Finally, the comfort was significantly improved for all ophthalmic solutions (p < 0.05).

Conclusion

Sodium hyaluronate (SH) ophthalmic solutions increase residence time in healthy subjects and are positively correlated with its concentration and therefore the viscosity.
Psychological autopsy review on mental health crises and suicide among youth in Pakistan
Authors: Abdullah Mudassar , Khalily Muhammad Tahir , Ahmad Irshad , Hallahan Brian
Published: October 2018

Introduction

Ascertaining putative sociodemographic and clinical causes for death by probable suicide can potentially help implement region‐specific strategies to reduce suicide rates. In this study, we wanted to investigate methods utilized and the psychosocial and mental health characteristics of youths (aged 12‐26 y) who died by probable suicide.

Method

We examined data from mental health clinical files and forensic reports and performed qualitative psychological autopsy interview from more than multiple sources for each youth who died by probable suicide between 1 May and 31 December 2015 in the Khyber Pakhtunkhwa Province of Pakistan.

Results

The two most common methods of probable suicide were by firearm use and self‐poisoning utilizing pesticides that were significantly associated with male and female gender, respectively. The most common mental health difficulties were major depressive disorder and harmful use of psychoactive substances. Other clinical features particularly evident included thoughts of self‐harm, irritability and aggression, low self‐esteem, treatment nonadherence, family dispute, and financial distress.

Conclusion

Efforts to reduce the ease of access to firearms and pesticides may potentially have a beneficial effect in reducing the suicide rate in this region of Pakistan.
First‐time‐in‐human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification
Authors: Perelló J. , Joubert P.H. , Ferrer M.D. , Canals A.Z. , Sinha S. , Salcedo C.
Published: October 2018

Aims

SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients.

Methods

This is a first‐time‐in‐human, double‐blind, randomized, placebo‐controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation.

Results

Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg–1 and the dose ascended to 12.5 mg kg–1. The dose selected for HD patients was 9 mg kg–1. Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment‐emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg–1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3–84.8) compared to placebo (8.7 ± 21.0%, P < 0.001, 95% CI, –32.4 to 49.7).

Conclusion

The results from this study showed acceptable safety and tolerability, and lack of significant dialysability of IV SNF472. It is a potential novel treatment for cardiovascular calcification in end‐stage renal disease and calciphylaxis warranting further human studies.
Using the Value of Information to improve conservation decision making
Authors: Bolam Friederike C. , Grainger Matthew J. , Mengersen Kerrie L. , Stewart Gavin B. , Sutherland William J. , Runge Michael C. , McGowan Philip J. K.
Published: October 2018

Conservation decisions are challenging, not only because they often involve difficult conflicts among outcomes that people value, but because our understanding of the natural world and our effects on it is fraught with uncertainty. Value of Information (VoI) methods provide an approach for understanding and managing uncertainty from the standpoint of the decision maker. These methods are commonly used in other fields (e.g. economics, public health) and are increasingly used in biodiversity conservation. This decision‐analytical approach can identify the best management alternative to select where the effectiveness of interventions is uncertain, and can help to decide when to act and when to delay action until after further research. We review the use of VoI in the environmental domain, reflect on the need for greater uptake of VoI, particularly for strategic conservation planning, and suggest promising areas for new research. We also suggest common reporting standards as a means of increasing the leverage of this powerful tool.

The environmental science, ecology and biodiversity categories of theWeb of Knowledgewere searched using the terms ‘Value of Information,’ ‘Expected Value of Perfect Information,’ and the abbreviation ‘EVPI.’Google Scholarwas searched with the same terms, and additionally the terms decision and biology, biodiversity conservation, fish, or ecology. We identified 1225 papers from these searches. Included studies were limited to those that showed an application of VoI in biodiversity conservation rather than simply describing the method. All examples of use of VOI were summarised regarding the application of VoI, the management objectives, the uncertainties, the models used, how the objectives were measured, and the type of VoI.

While the use of VoI appears to be on the increase in biodiversity conservation, the reporting of results is highly variable, which can make it difficult to understand the decision context and which uncertainties were considered. Moreover, it was unclear if, and how, the papers informed management and policy interventions, which is why we suggest a range of reporting standards that would aid the use of VoI.

The use of VoI in conservation settings is at an early stage. There are opportunities for broader applications, not only for species‐focussed management problems, but also for setting local or global research priorities for biodiversity conservation, making funding decisions, or designing or improving protected area networks and management. The long‐term benefits of applying VoI methods to biodiversity conservation include a more structured and decision‐focused allocation of resources to research.
Effect of selenium supplementation on changes in HbA1c: Results from a multiple‐dose, randomized controlled trial
Authors: Stranges Saverio , Rayman Margaret P. , Winther Kristian H. , Guallar Eliseo , Cold Søren , Pastor‐Barriuso Roberto
Published: October 2018

Aim

To investigate the effect of selenium supplementation at different dose levels on changes in HbA1c after 6 months and 2 years in a population of low selenium status.

Materials and Methods

The Denmark PRECISE study was a single‐centre, randomized, double‐blinded, placebo‐controlled, multi‐arm, parallel clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years were randomly assigned to treatment with 100, 200 or 300 μg selenium/day as selenium‐enriched yeast or placebo‐yeast. HbA1c measurements were available for 489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat.

Results

The mean (SD) age, plasma‐selenium concentration, and blood HbA1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6‐month intervention period, mean HbA1c (95% CI) decreased by 1.5 (−2.8 to −0.2) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (−2.0 to 0.6) mmol/mol for the 200 and 300 μg/d groups compared with placebo (P= 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA1c had decreased significantly in all treatment groups, with no difference between active treatment and placebo.

Conclusions

Selenium supplementation in an elderly European population of low selenium status did not significantly affect HbA1c levels after 2 years. Our findings corroborate a possible U‐shaped response of selenium supplementation on glucose metabolism.
Shiller's CAPE: Market Efficiency and Risk
Authors: Dimitrov Valentin , Jain Prem C.
Published: October 2018

Robert Shiller shows that Cyclically Adjusted Price to Earnings Ratio (CAPE) is strongly associated with future long‐term stock returns. This is often interpreted as evidence of market inefficiency. We present two findings contrary to such an interpretation. First, if markets are efficient, stock returns should be higher than the risk‐free rate. We find that even when CAPE is in its ninth decile, future 10‐year stock returns, on average, are higher than future returns on 10‐year U.S. Treasurys. Thus, the results are largely consistent with market efficiency. Second, consistent with a risk–return tradeoff, we find that CAPE is negatively associated with future stock market volatility.
Endoplasmic reticulum stress‐induced accumulation of VAMP721/722 requires CALRETICULIN 1 and CALRETICULIN 2 in Arabidopsis
Authors: Kim Soohong , Choi Yunjin , Kwon Chian , Yun Hye Sup
Published: October 2018

Excessive demand for translation and protein folding in the endoplasmic reticulum (ER) can cause ER stress in plants. Here, we show that CALRETICULIN 1 (CRT1) and CRT2 are critical components in the accumulation of VESICLE‐ASSOCIATED MEMBRANE PROTEIN 721 (VAMP721) and VAMP722 during ER stress responses. We show that CRT2 interacts with VAMP722 and that CRT1/2 post‐translationally maintain elevated VAMP721/722 levels under ER stress. The greater growth inhibition in VAMP721/722‐deficient plants, induced by tunicamycin, suggests that plants under ER stress maintain physiological homeostasis, at least in part, by regulating VAMP721/722 levels, as VAMP721/722 are known to participate in various biological processes.
Exploring bone volume and skeletal weight in the Middle Pleistocene humans from the Sima de los Huesos site (Sierra de Atapuerca, Spain)
Authors: Carretero José‐Miguel , Rodríguez Laura , García‐González Rebeca , Quam Rolf‐Michael , Arsuaga Juan‐Luis
Published: October 2018

Body mass estimation in fossil human species is a crucial topic in paleoanthropology as it yields information about ecologically relevant characteristics. Nevertheless, variables crucial to body mass estimation such as bone volume and skeletal weight have never before been calculated in a fossil human species. The exceptional state of preservation of several fossil human long bones from the Sima de los Huesos (SH) Middle Pleistocene site, in the Sierra de Atapuerca, makes it possible to calculate for the first time the absolute bone volume in five complete long bones (two femora and three humeri) of a fossil human species, an approach not possible in fragmentary or poorly preserved fossils. We have relied on computed tomography scans and 3D reconstructions to calculate bone volume. A sample of 62 complete bones of robust recent humans was also used for comparative purposes. The male SH femora (weight‐bearing bones) and humeri (non‐weight‐bearing bones) have, relative to their size, greater bone volume (volume of bone tissue over total bone volume) than the equivalent bones in our recent human sample. As mass is volume × density, and bone tissue density (as a material) is similar across mammals, we calculate bone mass, and our results show that the SH hominins had on average heavier long bones than extant humans of the same size. From the femoral weight at hand, we have estimated the total skeletal weight in two SH individuals, which is about 36% heavier than in the recent humans of the equivalent body size. Using different methods and skeletal variables, including skeletal weight, to estimate body mass in these two SH humans, we highlight the considerable differences in body mass estimates we obtained, and that the largest body mass estimate is the one based on the skeletal weight. Our results suggest that we cannot assume the same relative proportion of bone volume and bone and skeletal weight characterized the entire genus Homo. Given that skeletal weight has a significant influence on body mass, current body mass estimates of fossil Homo specimens could be systematically underestimated. Thus, the significantly larger bone volume and heavier bones, probably throughout the entire skeleton, of SH humans could have had consequences for many biological parameters in this Pleistocene population and considerable importance for studies focusing on adaptive and ecologically relevant characteristics. Although more recent human samples should be analyzed, in our view, the high skeletal robusticity of the SH sample, including larger bone volume and skeletal weight, is part of their adaptive body type selected for throughout the Pleistocene to support different mechanical and activity regimes and formed under tight genetic control, including control over bone formative and regulatory processes.
The mir‐200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves
Authors: Maleki S. , Cottrill K. A. , Poujade F.‐A. , Bhattachariya A. , Bergman O. , Gådin J. R. , Simon N. , Lundströmer K. , Franco‐Cereceda A. , Björck H. M. , Chan S. Y. , Eriksson P.
Published: October 2018

Background

An individual with a bicuspid aortic valve (BAV) runs a substantially higher risk of developing aneurysm in the ascending aorta compared to the normal population with tricuspid aortic valves (TAV). Aneurysm formation in patients with BAV and TAV is known to be distinct at the molecular level but the underlying mechanisms are undefined. Here, we investigated the still incompletely described role of microRNAs (miRNAs), important post‐transcriptional regulators of gene expression, in such aortic disease of patients with BAV as compared with TAV.

Methods and Results

Using a system biology approach, based on data obtained from proteomic analysis of non‐dilated aortas from BAV and TAV patients, we constructed a gene‐interaction network of regulatory microRNAs associated with the observed differential protein signature. The miR‐200 family was the highest ranked miRNA, hence potentially having the strongest effect on the signalling network associated with BAV. Further, qRT‐PCR and ChIP analyses showed lower expression of miR‐200c, higher expression of miR‐200 target genes, ZEB1/ZEB2 transcription factors, and higher chromatin occupancy of the miR‐200c promoter by ZEB1/ZEB2 in BAV patients, indicating a miR‐200c/ZEBs negative feedback loop and induction of endothelial/epithelial mesenchymal transition (EndMT/EMT).

Conclusion

We propose that a miR‐200‐dependent process of EndMT/EMT is a plausible biological mechanism rendering the BAV ascending aorta more prone to aneurysm development. Although initially supported by a miR‐200c/ZEB feedback loop, this process is most probably advanced by cooperation of other miRNAs.
Carcass yields, muscle amino acid and fatty acid profiles, and antioxidant indices of broilers supplemented with synbiotic and/or organic acids
Authors: Salah Ayman S. , Ahmed‐Farid Omar A. , El‐Tarabany Mahmoud S.
Published: October 2018

The objective of the current research was to explore the possible impacts of dietary supplementation with synbiotic and/or organic acids (OA) on the performance traits, carcass yields and muscle amino acid and fatty acid (FA) profiles of broilers. Randomly, a total of 160 day‐old chicks (Ross 308) were assigned into four equal groups (40 birds each), with each group subdivided into eight replicates (five birds/pen). The control group (CON) fed the basal diet with no supplements, while diets of the treated groups were supplemented with OA (Sodium butyrate 40%; 1 g/kg), synbiotic (comprised Bacillus subtilis, Saccharomyces cerivisiae, Streptococcus faecium, Mannan‐Oligosaccharides and β‐Glucan; 1 g/kg) and equal mix of OA and synbiotic (2 g/kg). Broilers fed the diets supplemented with synbiotic or synbiotic plus OA produced a significantly higher feed utilization efficiency (p = 0.021) and carcass yields (p = 0.038) than the CON and OA‐supplemented groups. The group fed the diet supplemented with the synbiotic showed lowered serum cholesterol (p = 0.049), triglycerides (p = 0.001) and very low density lipoprotein (p = 0.032) when compared with the CON group. Regarding the polyunsaturated FA (PUFA) of breast muscles, synbiotic‐supplemented birds had significantly lower n‐6:n‐3 ratio (p = 0.047), however, a greater hypocholesterolaemic to hypercholesterolaemic FA (H/H) ratio was reported when compared with the CON group (p = 0.002). Among the essential amino acids, the contents of leucine and methionine in the breast (p = 0.032 and 0.007 respectively) and thigh (p = 0.023 and 0.003 respectively) muscles were greater in the synbiotic‐supplemented birds compared with the CON group. In conclusion, the synbiotic‐supplemented diet improved the PUFA:SFA, n‐6:n‐3 and H/H ratios by altering the FA composition of broiler muscles, which are important with regards to human health.
Passive infrared thermography measurement of transverse cracking evolution in cross‐ply laminates
Authors: Berthe J. , Ragonet M.
Published: October 2018

Over the last decades, various experimental methodologies have been used to study the matrix crack density evolution in cross‐ply laminates. The main drawback of these techniques is their difficult use at intermediate and high strain rates. In this study, a new experimental protocol to evaluate matrix crack density evolution at intermediate strain rates is proposed and applied to [0/903]s carbon/epoxy laminate. It is based on the use of passive infrared thermography to monitor the matrix cracking appearance. This methodology is used to first demonstrate that the crack appearance in the 90° ply remains instantaneous from side to side with the increase of the strain rate. Finally, the rate insensitivity of the crack density as a function of the applied stress for the studied material in the studied range of strain rates (8.3 × 10−4 up to 6.69 × 10−2 s−1) is demonstrated.
Risk factors of pre‐hypertension and hypertension among non‐pregnant women of reproductive age in northeastern Tanzania: a community based cross‐sectional study
Authors: Msemo Omari A. , Schmiegelow Christentze , Nielsen Birgitte B. , Kousholt Hannah , Grunnet Louise G. , Christensen Dirk L. , Lusingu John P. A. , Møller Sofie L. , Kavishe Reginald A. , Minja Daniel T. R. , Bygbjerg Ib C.
Published: October 2018

Objectives

To determine risk factors of pre‐hypertension and hypertension in a cohort of 1247 rural Tanzanian women before conception.

Methods

Demographic and socioeconomic data, anthropometric measurements, past medical and obstetric history and other risk factors for pre‐hypertension and hypertension were collected using a structured questionnaire. Multiple logistic regression analysis was used to evaluate the associations between anthropometric indices and other risk factors of pre‐hypertension and hypertension. The predictive power of different anthropometric indicators for identification of pre‐hypertension and hypertension patients was determined by Receiver Operating Characteristic curves (ROC).

Results

The median (range) age was 28.0 (18–40) years. The age‐standardised prevalences of pre‐hypertension and hypertension were 37.2 (95% CI 34.0–40.6) and 8.5% (95%CI 6.7–10.8), respectively. Of hypertensive patients (n = 98), only 20 (20.4%) were aware of their condition. In multivariate analysis, increasing age, obesity and haemoglobin levels were significantly associated with pre‐hypertension and hypertension.

Conclusion

Despite a low prevalence of hypertension, over one third of the women had pre‐hypertension. This poses a great challenge ahead as pre‐hypertensive women may progress into hypertension as they grow older without appropriate interventions. Obesity was the single most important modifiable risk factor for pre‐hypertension and hypertension.
Perceptions and experiences of nurses and midwives in continuing professional development: a systematic review protocol
Authors: Teekens Peter , Wiechula Rick , Cusack Lynette
Published: October 2018

Review question/objective:

The objective of this systematic review is to explore the perceptions and experiences of nurses and midwives in undertaking continuing professional development.
Dietary management in people with an ileostomy: a scoping review protocol
Authors: Mitchell Alexandra , Perry Rachel , England Clare , Searle Aidan , Atkinson Charlotte
Published: October 2018

Review question/objective:

The objective of this scoping review is to identify and map the evidence for oral dietary management of ileostomies.

The primary review question is: what oral dietary strategies for managing ileostomies in humans have been reported?

The secondary review questions are: i) what types of evidence have considered oral dietary strategies for managing ileostomies; ii) what aspects of ileostomy management (for example, stoma output or flatulence) are the oral dietary strategies considered to affect; and iii) what sources do people with an ileostomy receive dietary advice from?
Hydrophobic surface modification of polymethyl methacrylate by two-dimensional plasma jet array at atmospheric pressure
Authors: Liu Feng , Cai Meiling , Zhang Bo , Fang Zhi , Jiang Chunqi , Ostrikov Kostya (Ken)
Published: October 2018

Recently developed atmospheric pressure plasma jet (APPJ) is considered as a novel and efficient technique for uneven surfaces processing and APPJ array effectively expands the treatment area of a single APPJ. In this paper, a two-dimensional (2D) APPJ array in Ar/tetramethylsilane (TMS) is used to improve the surface hydrophobicity of polymethyl methacrylate (PMMA) by depositing polymerized silicalike clusters on the jet-PMMA interface. The electrical and optical characteristics of the 2D Ar/TMS APPJ array are measured to optimize experimental conditions. The wettability of jet-PMMA interface is assessed by measuring water contact angle, which increases from 65° to a maximum value of 115° after 240 s plasma treatment at 0.04% TMS content. Scanning electron microscopy is used to investigate the micro- and nanoscale surface morphology of PMMA after plasma treatment, and it is found that there are clusters of particles with diameters of hundreds of nanometers attached on the PMMA surface. The changes of the chemical composition and chemical bonding on the PMMA surface are further analyzed using Fourier transform infrared and x-ray photoelectron spectroscopies. It is found that the silicon-containing groups, such as Si-CH3, Si-H, and Si-O-Si, replace oxygen-containing hydrophilic polar groups (C—O and C=O), reduce the surface polarity, decrease the surface tension, and increase the surface hydrophobicity. For the intensive peak of Si-O-Si in FTIR spectra, the improvement of hydrophobicity of the PMMA surface is caused by the hydrophobic polymerized Si-O-Si thin film. The results demonstrate that the APPJ array as a novel atmospheric pressure plasma device provides an efficient way to modify large uneven material surfaces.
Opening the window to the Southern Ocean: The role of jet dynamics
Authors: Klocker Andreas
Published: October 2018

Jet dynamics play a crucial role in Southern Ocean ventilation.
Fruit scent as an evolved signal to primate seed dispersal
Authors: Nevo Omer , Razafimandimby Diary , Jeffrey Juan Antonio James , Schulz Stefan , Ayasse Manfred
Published: October 2018

Fruit scent has evolved as a communication channel between plants and primates that disperse their seeds.
AAAS EPI Center launch brings evidence to policy-makers
Authors: Ham Becky
Published: October 2018

Communication will be key in sharing reliable scientific information, says center director
Ancient lowland Maya complexity as revealed by airborne laser scanning of northern Guatemala
Authors: Canuto Marcello A. , Estrada-Belli Francisco , Garrison Thomas G. , Houston Stephen D. , Acuña Mary Jane , Kováč Milan , Marken Damien , Nondédéo Philippe , Auld-Thomas Luke , Castanet Cyril , Chatelain David , Chiriboga Carlos R. , Drápela Tomáš , Lieskovský Tibor , Tokovinine Alexandre , Velasquez Antolín , Fernández-Díaz Juan C. , Shrestha Ramesh
Published: October 2018

Classic Maya civilization in detail

Lidar (a type of airborne laser scanning) provides a powerful technique for three-dimensional mapping of topographic features. It is proving to be a valuable tool in archaeology, particularly where the remains of structures may be hidden beneath forest canopies. Canutoet al.present lidar data covering more than 2000 square kilometers of lowland Guatemala, which encompasses ancient settlements of the Classic Maya civilization (see the Perspective by Ford and Horn). The data yielded population estimates, measures of agricultural intensification, and evidence of investment in landscape-transforming infrastructure. The findings indicate that this Lowland Maya society was a regionally interconnected network of densely populated and defended cities, which were sustained by an array of agricultural practices that optimized land productivity and the interactions between rural and urban communities.

Science, this issue p.eaau0137; see also p.1313
Stories of the sanguine
Nine Pints: A Journey Through the Money, Medicine, and Mysteries of Blood
Rose George
Metropolitan Books, 2018. 368 pp.
Authors: Lederer Susan E.
Published: October 2018

A meandering history of blood tackles transfusions, taboos, and trauma
Regulating 3D-printed medical products
Authors: Ricles Laura M. , Coburn James C. , Di Prima Matthew , Oh Steven S.
Published: October 2018

There are a number of key considerations in the U.S. regulatory landscape regarding approval of 3D-printed medical devices and biologics.
One hepatocyte, two malignant fates
Authors: Lujambio Amaia
Published: October 2018

Hepatic microenvironment dictates lineage commitment of hepatocytes, which can form two completely distinct tumor types.
Engineered Small-Molecule Control of Influenza A Virus Replication
Authors: Fay Elizabeth J. , Aron Stephanie L. , Stone Ian A. , Waring Barbara M. , Plemper Richard K. , Langlois Ryan A.
Published: October 2018

Influenza A virus (IAV) causes significant morbidity and mortality annually worldwide, despite the availability of new formulations of the vaccine each season. There is a critical need to develop more-efficacious vaccines. However, testing novel vaccines in the human population in controlled studies is difficult due to the limited availability and efficacy of intervention strategies should the vaccine fail. There are also significant safety concerns for work with highly pathogenic IAV strains in the laboratory. Therefore, novel strategies are needed to improve the safety of vaccine studies and of research on highly pathogenic IAV. In this study, we developed an IAV strain engineered to contain a small-molecule-mediated safety switch. This tag, when attached to an essential viral protein, allows for the regulation of IAV replication
in vitro
and
in vivo
. This strategy provides a platform for the regulation of virus replication without targeting viral proteins directly.
Draft Genome Sequence of Pseudomonas sp. Strain MWU12-2534b, Isolated from a Wild Cranberry Bog in Truro, Massachusetts
Authors: Ebadzadsahrai Ghazal , Thomson Jonathon , Soby Scott
Published: October 2018

An unknown
Pseudomonas
sp. most closely related to
Pseudomonas ficuserectae
and
Pseudomonas protegens
was isolated from the rhizospheres of wild cranberry plants in the Cape Cod National Seashore, in the United States.
Complete Genome Sequence of Sinorhizobium Phage ΦM6, the First Terrestrial Phage of a Marine Phage Group
Authors: Brewer Tess E. , Washburn Brian K. , Lynn Jason S. , Jones Kathryn M.
Published: October 2018

Sinorhizobium
phage ΦM6 infects the nitrogen-fixing rhizobial bacterium
Sinorhizobium meliloti
. ΦM6 most closely resembles marine phages, such as
Puniceispirillum
phage HMO-2011, rather than previously sequenced rhizobial phages.
Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen
Rhizopus delemar
Authors: Sephton-Clark Poppy C. S. , Muñoz Jose F. , Ballou Elizabeth R. , Cuomo Christina A. , Voelz Kerstin
Published: October 2018

Germination is key to the growth of many organisms, including fungal spores. Mucormycete spores exist abundantly within the environment and germinate to form hyphae. These spores are capable of infecting immunocompromised individuals, causing the disease mucormycosis. Germination from spore to hyphae within patients leads to angioinvasion, tissue necrosis, and often fatal infections. This study advances our understanding of how spore germination occurs in the mucormycetes, identifying processes we may be able to inhibit to help prevent or treat mucormycosis.
Pushing the envelope through the Global Financing Facility: potential impact of mobilising additional support to scale-up life-saving interventions for women, children and adolescents in 50 high-burden countries
Authors: Chou Victoria B , Bubb-Humfryes Oliver , Sanders Rachel , Walker Neff , Stover John , Cochrane Tom , Stegmuller Angela , Magalona Sophia , Von Drehle Christian , Walker Damian G , Bonilla-Chacin Maria Eugenia , Boer Kimberly Rachel
Published: October 2018

Introduction

The Global Financing Facility (GFF) was launched to accelerate progress towards the Sustainable Development Goals (SDGs) through scaled and sustainable financing for Reproductive, Maternal, Newborn, Child and Adolescent Health and Nutrition (RMNCAH-N) outcomes. Our objective was to estimate the potential impact of increased resources available to improve RMNCAH-N outcomes, from expanding and scaling up GFF support in 50 high-burden countries.

Methods

The potential impact of GFF was estimated for the period 2017–2030. First, two scenarios were constructed to reflect conservative and ambitious assumptions around resources that could be mobilised by the GFF model, based on GFF Trust Fund resources of US$2.6  billion. Next, GFF impact was estimated by scaling up coverage of prioritised RMNCAH-N interventions under these resource scenarios. Resource availability was projected using an Excel-based model and health impacts and costs were estimated using the Lives Saved Tool (V.5.69 b9).

Results

We estimate that the GFF partnership could collectively mobilise US$50–75  billion of additional funds for expanding delivery of life-saving health and nutrition interventions to reach coverage of at least 70% for most interventions by 2030. This could avert 34.7  million deaths—including preventable deaths of mothers, newborns, children and stillbirths—compared with flatlined coverage, or 12.4  million deaths compared with continuation of historic trends. Under-five and neonatal mortality rates are estimated to decrease by 35% and 34%, respectively, and stillbirths by 33%.

Conclusion

The GFF partnership through country- contextualised prioritisation and innovative financing could go a long way in increasing spending on RMNCAH-N and closing the existing resource gap. Although not all countries will reach the SDGs by relying on gains from the GFF platform alone, the GFF provides countries with an opportunity to significantly improve RMNCAH-N outcomes through achievable, well-directed changes in resource allocation.