bluuebunny/crossref_metadata_2025 huggingface dataset:
Members of the abscisic acid co-receptor PP2C protein family mediate salicylic acid-abscisic acid crosstalk
Authors: Manohar Murli , Wang Dekai , Manosalva Patricia M. , Choi Hyong Woo , Kombrink Erich , Klessig Daniel F.
Published: April 2017

The interplay between abscisic acid (ABA) and salicylic acid (SA) influences plant responses to various (a)biotic stresses; however, the underlying mechanism(s) for this crosstalk is largely unknown. Here we report that type 2C protein phosphatases (PP2Cs), some of which are negative regulators of ABA signaling, bind SA. SA binding suppressed the ABA-enhanced interaction between these PP2Cs and various ABA receptors belonging to the PYR/PYL/RCAR protein family. Additionally, SA suppressed ABA-enhanced degradation of PP2Cs and ABA-induced stabilization of SnRK2s. Supporting SA’s role as a negative regulator of ABA signaling, exogenous SA suppressed ABA-induced gene expression, whereas SA-deficientsid2-1mutants displayed heightened PP2C degradation and hypersensitivity to ABA-induced suppression of seed germination. Together, these results suggest a new molecular mechanism through which SA antagonizes ABA signaling. A better understanding of the crosstalk between these hormones is important for improving the sustainability of agriculture in the face of climate change.
Revealing the cell-material interface with nanometer resolution by FIB-SEM
Authors: Santoro Francesca , Zhao Wenting , Joubert Lydia-Marie , Duan Liting , Schnitker Jan , van de Burgt Yoeri , Lou Hsin-Ya , Liu Bofei , Salleo Alberto , Cui Lifeng , Cui Yi , Cui Bianxiao
Published: April 2017

The interface between biological cells and non-biological surfaces profoundly influences cellular activities, chronic tissue responses, and ultimately the success of medical implants. Materials in contact with cells can be plastics, metal, ceramics or other synthetic materials, and their surfaces vary widely in chemical compositions, stiffness, topography and levels of roughness. To understand the molecular mechanism of how cells and tissues respond to different materials, it is of critical importance to directly visualize the cell-material interface at the relevant length scale of nanometers. Conventional ultrastructural analysis by transmission electron microscopy (TEM) often requires substrate removal before microtome sectioning, which is not only challenging for most substrates but also can cause structural distortions of the interface. Here, we present a new method forin situexamination of the cell-to-material interface at any desired cellular location, based on focused-ion beam milling and scanning electron microscopy imaging (FIB-SEM). This method involves a thin-layer plastification procedure that preserves adherent cells as well as enhances the contrast of biological specimen. We demonstrate that this unique procedure allows the visualization of cell-to-material interface and intracellular structures with 10nm resolution, compatible with a variety of materials and surface topographies, and capable of volume and multi-directional imaging. We expect that this method will be very useful for studies of cell-to-material interactions and also suitable forin vivostudies such as examining osteoblast adhesion and new bone formation in response to titanium implants.
A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia
Authors: Kuncha Santosh Kumar , Mazeed, Mohd , Singh, Raghvendra , Kattula, Bhavita , Brata Routh, Satya , Sankaranarayanan Rajan
Published: April 2017

D-aminoacyl-tRNA deacylase (DTD), atrans-editing factor found in bacteria and eukaryotes, removes D-amino acids mischarged on tRNAs as well as achiral glycine mischarged on tRNAAla. An invariant cross-subunit Gly-cisPro motif forms the mechanistic basis of strict L-amino acid rejection from the catalytic site. Here, we present the identification of a DTD variant, named ATD (Animalia-specifictRNAdeacylase), that harbors a Gly-transPro motif. Thecis-to-transswitch causes a “gain of function” through L-chiral selectivity in ATD resulting in the clearing of L-alanine mischarged on tRNAThr(G4•U69) by eukaryotic AlaRS. The biochemical proofreading activity of ATD is conserved across diverse classes of phylum Chordata. Animalia genomes enriched in tRNAThr(G4•U69) genes are in strict association with the presence of ATD, underlining the mandatory requirement of a dedicated factor to proofread tRNA misaminoacylation. The study highlights the emergence of ATD during genome expansion as a key event associated with the evolution of Animalia.
Multiple sources of slow activity fluctuations in a bacterial chemosensory network
Authors: Colin R. , Rosazza C. , Vaknin A. , Sourjik V.
Published: April 2017

Cellular networks are intrinsically subject to stochastic fluctuations, but analysis of the resulting noise remained largely limited to gene expression. The pathway controlling chemotaxis ofEscherichia coliprovides one example where posttranslational signaling noise has been deduced from cellular behavior. This noise was proposed to result from stochasticity in chemoreceptor methylation, and it is believed to enhance environment exploration by bacteria. Here we combined single-cell FRET measurements with analysis based on the fluctuation-dissipation theorem (FDT) to characterize origins of activity fluctuations within the chemotaxis pathway. We observed surprisingly large methylation-independent thermal fluctuations of receptor activity, which contribute to noise comparably to the energy-consuming methylation dynamics. Interactions between clustered receptors involved in amplification of chemotactic signals are also necessary to produce the observed large activity fluctuations. Our work thus shows that the high response sensitivity of this cellular pathway also increases its susceptibility to noise, from thermal and out-of-equilibrium processes.
Extensions of BLUP models for genomic prediction in heterogeneous populations: Application in a diverse switchgrass sample
Authors: Ramstein Guillaume P. , Casler Michael D.
Published: April 2017

Genomic prediction is a useful tool to accelerate genetic gain in selection using DNA marker information. However, this technology usually relies on models that are not designed to accommodate population heterogeneity, which results from differences in marker effects across genetic backgrounds. Previous studies have proposed to cope with population heterogeneity using diverse approaches: (i) either ignoring it, therefore relying on the robustness of standard approaches; (ii) reducing it, by selecting homogenous subsets of individuals in the sample; or (iii) modelling it by using interactive models. In this study we assessed all three possible approaches, applying existing and novel procedures for each of them. All procedures developed are based on deterministic optimizations, can account for heteroscedasticity, and are applicable in contexts of admixed populations. In a case study on a diverse switchgrass sample, we compared the procedures to a control where predictions rely on homogeneous subsamples. Ignoring heterogeneity was often not detrimental, and sometimes beneficial, to prediction accuracy, compared to the control. Reducing heterogeneity did not result in further increases in accuracy. However, in scenarios of limited subsample sizes, a novel procedure, which accounted for redundancy within subsamples, outperformed the existing procedure, which only considered relationships to selection candidates. Modelling heterogeneity resulted in substantial increases in accuracy, in the cases where accounting for population heterogeneity yielded a highly significant improvement in fit. Our study exemplifies advantages and limits of the various approaches that are promising in various contexts of population heterogeneity, e.g. prediction based on historical datasets or dynamic breeding.
Sleep-dependent modulation of metabolic rate inDrosophila
Authors: Stahl Bethany A. , Slocumb Melissa E. , Chaitin Hersh , DiAngelo Justin R. , Keene Alex C.
Published: April 2017

Dysregulation of sleep is associated with metabolic diseases, and metabolic rate is acutely regulated by sleep-wake behavior. In humans and rodent models, sleep loss is associated with obesity, reduced metabolic rate, and negative energy balance, yet little is known about the neural mechanisms governing interactions between sleep and metabolism. We have developed a system to simultaneously measure sleep and metabolic rate in individualDrosophila, allowing for interrogation of neural systems governing interactions between sleep and metabolic rate. Like mammals, metabolic rate in flies is reduced during sleep and increased during sleep deprivation suggesting sleep-dependent regulation of metabolic rate is conserved across phyla. The reduction of metabolic rate during sleep is not simply a consequence of inactivity because metabolic rate is reduced ∼30 minutes following the onset of sleep, raising the possibility that CO2production provides a metric to distinguish different sleep states in the fruit fly. To examine the relationship between sleep and metabolism, we determined basal and sleep-dependent changes in metabolic rate is reduced in starved flies, suggesting that starvation inhibits normal sleep-associated effects on metabolic rate. Further,translinmutant flies that fail to suppress sleep during starvation demonstrate a lower basal metabolic rate, but this rate was further reduced in response to starvation, revealing that regulation of starvation-induced changes in metabolic rate and sleep duration are genetically distinct. Therefore, this system provides the unique ability to simultaneously measure sleep and oxidative metabolism, providing novel insight into the physiological changes associated with sleep and wakefulness in the fruit fly.

Significance statement

Metabolic disorders are associated with sleep disturbances, yet our understanding of the mechanisms underlying interactions between sleep and metabolism remain limited. Here, we describe a novel system to simultaneously record sleep and metabolic rate in singleDrosophila. Our findings reveal that uninterrupted sleep bouts of 30 minutes or greater are associated with a reduction in metabolic rate providing a physiological readout of sleep. Use of this system, combined with existing genetic tools inDrosophila, will facilitate identification of novel sleep genes and neurons, with implications for understanding the relationship between sleep loss and metabolic disease.
Client requirement representations and transformations in construction project design
Authors: Collinge William Henry
Published: April 2017

Purpose

This paper aims to examine how client requirements undergo representational and transformational shifts and changes in the design process and explore the consequence of such changes.

Design/methodology/approach

A series of design resources relating to hospital departmental configurations are examined and analysed using a social semiotic framework. The findings are supplemented by practitioner opinion.

Findings

Construction project requirements are represented and transformed through semiotic resource use; such representations deliver specific meanings, make new meanings and affect project relationships. Requirement representations may be understood as socially motivated meaning-making resources.

Research limitations/implications

The paper focuses on one set of project requirements: hospital departmental configurations from a National Health Service hospital construction project in the UK.

Practical implications

The use of semiotic resources in briefing work fundamentally affects the briefing and design discourse between client and design teams; their significance should be noted and acknowledged as important.

Social implications

The findings of the paper indicate that briefing and design work may be understood as a social semiotic practice.

Originality/value

This original paper builds upon scholarly work in the area of construction project communications. Its fine-grained analysis of briefing communications around representations of specific requirements is novel and valuable.
Towards a functional understanding of species coexistence: ecomorphological variation in relation to whole‐organism performance in two sympatric lizards
Authors: Žagar Anamarija , Carretero Miguel A. , Vrezec Al , Drašler Katarina , Kaliontzopoulou Antigoni
Published: April 2017

We examined intra‐ and interspecific variation in functional morphology and whole‐organism performance in a sympatric lizard species pair,Iberolacerta horvathiandPodarcis muralis, in the area with a high potential for competition.

The biggest variation between species was found in two functional traits, bite force and climbing speed, linked with corresponding morphological traits.

The species with larger and taller heads,P. muralis, exhibited correspondingly stronger bite forces. The other species exhibited smaller and flatter head. Both traits may potentially promote segregation between species in trophic niche (stronger bites relate to harder prey) and in refuge use (flatter heads allow using narrower crevices, hence, influencing escaping from common predators). Stronger bites and larger heads also provide one species with a dominant position in interspecific agonistic interactions.

Females had longer trunks that impacted negatively on climbing speed, which may lower anti‐predator escape abilities of the more trunk‐dimorphic species, but positively influence reproductive effort.

Our results exemplify how the joint examination of morphological and functional traits of ecologically similar and sympatric species can provide a mechanistic background for understanding their coexistence, namely, syntopic populations that are frequent in the study area.

The identified roles of functional morphology in this system of sympatric rock lizards support the contribution of functional diversification for the complexity of community structure via coexistence.

Alay summaryis available for this article.
Resting vs. active: a meta‐analysis of the intra‐ and inter‐specific associations between minimum, sustained, and maximum metabolic rates in vertebrates
Authors: Auer Sonya K. , Killen Shaun S. , Rezende Enrico L.
Published: April 2017

Variation in aerobic capacity has far reaching consequences for the physiology, ecology, and evolution of vertebrates. Whether at rest or active, animals are constrained to operate within the energetic bounds determined by their minimum (minMR) and sustained or maximum metabolic rates (upperMR). MinMR and upperMR can differ considerably among individuals and species but are often presumed to be mechanistically linked to one another. Specifically, minMR is thought to reflect the idling cost of the machinery needed to support upperMR. However, previous analyses based on limited datasets have come to conflicting conclusions regarding the generality and strength of their association.

Here we conduct the first comprehensive assessment of their relationship, based on a large number of published estimates of both the intra‐specific (n = 176) and inter‐specific (n = 41) phenotypic correlations between minMR and upperMR, estimated as either exercise‐induced maximum metabolic rate (VO2max), cold‐induced summit metabolic rate (Msum), or daily energy expenditure (DEE).

Our meta‐analysis shows that there is a general positive association between minMR and upperMR that is shared among vertebrate taxonomic classes. However, there was stronger evidence for intra‐specific correlations between minMR and Msum and between minMR and DEE than there was for a correlation between minMR and VO2max across different taxa. As expected, inter‐specific correlation estimates were consistently higher than intra‐specific estimates across all traits and vertebrate classes.

An interesting exception to this general trend was observed in mammals, which contrast with birds and exhibit no correlation between minMR and Msum. We speculate that this is due to the evolution and recruitment of brown fat as a thermogenic tissue, which illustrates how some species and lineages might circumvent this seemingly general association.

We conclude that, in spite of some variability across taxa and traits, the contention that minMR and upperMR are positively correlated generally holds true both within and across vertebrate species. Ecological and comparative studies should therefore take into consideration the possibility that variation in any one of these traits might partly reflect correlated responses to selection on other metabolic parameters.

A lay summary is available for this article.
Beyond troubled waters: the influence of eutrophication on host–parasite interactions
Authors: Budria Alexandre
Published: April 2017

Recent research in biomedicine and in ecology has linked disease emergence and resurgence with human‐induced environmental change. Water bodies, in particular, have dramatically changed during the past century due to artificial enrichment of nutrients from diverse sources (e.g. agriculture, forestry, waste discharges). A growing number of studies, reviewed in this synthesis, highlights how these alterations are tightly linked to changes in host–parasite interactions and impact wildlife health.

Direct responses of aquatic ecosystems to the disturbance include changes in the community of primary producers and cause indirect responses such as turbidity, oxygen depletion and foodweb alteration; a phenomenon known as anthropogenic eutrophication. Ultimately, eutrophication causes a wide range of effects on host–parasite interactions which should all be considered to predict infection probability and outcome in disturbed areas.

Future research should encompass a more fundamental and holistic view of eutrophication, considering altogether the multitude of environmental changes encountered in eutrophied sites. Stronger collaborations among disease biologists and aquatic ecologists are necessary to better understand and manage wildlife health at impacted water bodies.

A lay summary is available for this article.
The causes of dispersal and the cost of carry‐over effects for an endangered bird in a dynamic wetland landscape
Authors: Robertson Ellen P. , Fletcher Robert J. , Austin James D.
Published: April 2017

The decision to disperse or remain philopatric between breeding seasons has important implications for both ecology and evolution, including the potential for carry‐over effects, where an individual's previous history affects its current performance. Carry‐over effects are increasingly documented although underlying mechanisms remain unclear.

Here we test for potential carry‐over effects and their mechanisms by uniting hypotheses for the causes and consequences of habitat selection and dispersal across space and time. We linked hypotheses regarding different types of factors and information (environmental conditions, personal and public information) predicted to impact reproductive success and dispersal for an endangered, wetland‐dependent bird, the snail kite (Rostrhamus sociabilis plumbeus). To do so, we coupled structural equation modelling with 20 years of mark–recapture and nesting data across the breeding range of this species to isolate potential direct and indirect effects of these factors.

We found that water depth at nest sites explained subsequent emigration rates via an indirect path through the use of personal, not public, information. Importantly, we found that these dispersers tended to initiate nests later the following breeding season. This pattern explained a phenological mismatch of nesting with hydrological conditions, whereby immigrants tended to nest later, late nesters tended to experience lower water depths, higher nest failure occurred at lower water depths and higher nest failure explained subsequent breeding dispersal.

These results identified a novel potential mechanism for carry‐over effects: a phenological mismatch with environmental conditions (water depth) that occurred potentially due to time costs of dispersal. Our results also highlighted a substantial benefit of philopatry – earlier initiation of reproduction – which allows philopatric individuals to better coincide with environmental conditions that are beneficial for successful reproduction.

These results have implications for our mechanistic understanding and prediction of carryover effects, and emphasize that local conservation strategies, such as water management, can explain future demography at distant sites connected through dispersal.
C‐reactive protein and ageing
Authors: Tang Ying , Fung Erik , Xu Anping , Lan Hui‐Yao
Published: April 2017

Increasing evidence shows that C‐reactive protein (CRP) is not only an inflammatory biomarker but also an important risk factor associated with ageing‐related diseases including cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Recent studies have demonstrated thatCRPis pathogenic in a number of diseases including hypertensive cardiovascular and kidney complications, diabetic nephropathy, and acute and chronic kidney diseases. It is well known thatCRPbinds its receptor,CD32/CD64, to induce the process of inflammation by activating theNF‐κB signalling pathway. In addition,CRPmediates tissue fibrosis in a number of cardiovascular and kidney diseases by activatingTGF‐β/Smad signalling viaTGF‐β1‐dependent and independent mechanisms. Furthermore,CRPis able to activatemTORsignalling in the diabetic conditions. Our recent studies also revealed thatCRPimpairs cell regeneration by causing the G1 cell cycle arrest and promotes ageing via a Smad3‐dependent p21/p27 mechanism. In this review, we discuss the roles ofCRPin ageing, with a focus on its function and mechanisms in physiological or “healthy” ageing, in ageing‐related diseases, and in cell signalling.
Compared effects on cerebral oxygenation of ephedrine vs phenylephrine to treat hypotension during carotid endarterectomy
Authors: Aliane Jugurtha , Dualé Christian , Guesmi Nader , Baud Charlotte , Rosset Eugenio , Pereira Bruno , Bouvier Damien , Schoeffler Pierre
Published: April 2017

While both ephedrine and phenylephrine are currently used to treat hypotension occurring during carotid endarterectomy (CEA) under general anaesthesia, phenylephrine may have deleterious effects on the cerebral watershed, due to its exclusively vasoconstrictive action. In this controlled, double‐blind randomised trial, we compared the effects of ephedrine and phenylephrine administered in a standardised algorithm to treat the first hypotensive event occurring since induction of anaesthesia until carotid cross‐clamping. The algorithm consisted of 1‐to‐3 boluses of 6 mg of ephedrine or 50 μg of phenylephrine, after a goal‐directed fluid therapy. In case of failure, the treatment switched to the other study drug. Cerebral tissue oxygen saturation (SctO2) was monitored by near infrared spectroscopy (NIRS), and the primary outcome was the restoring effect of SctO2 (ipsilateral to surgery) to baseline values. Secondary postoperative outcomes were: contralateral SctO2, neurological outcomes, and plasma S100B protein measured at discharge from post‐anaesthesia care unit. Ephedrine treatment provided a higher rate of restoration of ipsilateral SctO2 than phenylephrine (93.2% vs 85.1%, P=.034); this was also noted for contralateral SctO2 (93.5% vs 90.7%, P=.026). The gain in SctO2 on the lowest value during hypotension was also higher under ephedrine than phenylephrine (6.4% vs 4.3% ipsilateral, 5.1% vs 4% contralateral), but not significantly so. Clinical outcomes were unaffected by the treatment, but S100B protein plasma concentration was higher in the phenylephrine group. To conclude, this pilot trial, focusing on intermediate outcomes, suggests that ephedrine should be preferred to phenylephrine to treat hypotension during CEA.
Nectary and gender‐biased nectar production in dichogamous Chamaenerion angustifolium (L.) Scop. (Onagraceae)
Authors: Antoń Sebastian , Denisow Bożena , Komoń‐Janczara Elwira , Targoński Zdzisław
Published: April 2017

In dichogamous plants, nectar characteristics (i.e. nectar amount and its composition) can differ between sexual phases. In the present study, we investigated the structural organization of the floral nectary, nectar production and carbohydrate composition in the protandrous Chamaenerion angustifolium (L.) Scop. (Onagraceae). The receptacular nectary consisted of an epidermis with numerous nectarostomata, several layers of photosynthetic secretory parenchyma, and subsecretory parenchyma. Nectariferous tissue was not directly vascularized and starch grains were rarely observed in the secretory cells, occurring exclusively in the guard cells of modified stomata. The nectar was released via nectarostomata. The floral nectar was hexose rich (32.8/39.1/28.1% glucose/fructose/sucrose) and the total concentration was constant throughout the anthesis (47% on average). However, contrasting patterns in nectar amount and carbohydrate composition between the floral sexual phases were observed. On average, female‐phased flowers produced 1.4‐fold more nectar than male‐phased flowers, and although the nectar was sucrose rich during the male phase, it was hexose rich during the female phase, suggesting sucrose hydrolysis.
Foretelling the future: The fashion designer as shaman
Authors: Vangkilde Kasper Tang
Published: April 2017

Based on ethnographic fieldwork in a fashion company, this article explores how fashion designers face the uncertain but critical challenge of foretelling the future. It is argued that fashion designers seek to become possessed by thezeitgeist, which attests to an animistic mode of being and a shamanic practice by means of which they turn into prophetic agents with a particular vision of the future. This makes them able to act on the future, and demonstrates more generally how magical processes are indeed at work in the world of fashion.
Sketching with knives: Architects & the confidence theory of magic
Authors: Hagen Aina Landsverk
Published: April 2017

‘Isn't gravity wonderful? That's the magic trick in a way'. The Malinowskian ‘confidence theory of magic’ (1935) points to how a person, through the ritual act, becomes empowered to believe he can master nature's obstacles, and thus become equipped to undertake tasks from which he would otherwise shrink. The relation between creativity, magic and professional confidence is investigated through ethnographic fieldwork in the internationally renowned architecture company, Snøhetta, based in Oslo and New York. Crafting magic is performed by architects posing as digital experts of software technology and model making, and ritual experts who voice spells and formulas to guide the creative processes throughout competition phases. Inspired by the works of Malinowski (1922, 1935, 1948), Firth (1939) and Gell (1992), this article explores the phenomenon of magical capitalism as it enters the domain of competition and creative collaboration in organizations.
Use of JAR‐Based Analysis for Improvement of Product Acceptance: A Case Study on Flavored Kefirs
Authors: Gere Attila , Szabó Zsófia , Pásztor‐Huszár Klára , Orbán Csaba , Kókai Zoltán , Sipos László
Published: April 2017

A common question of dairy product developments is the possible success of the new product. Several publications reported successful results using just‐about‐right (JAR) scales; although there is some debate about their advantages/disadvantages. This study highlights the limitations and opportunities of JAR scales and penalty analysis of fruit flavored kefirs. The first question is whether penalty analysis results help to improve the product and thus its overall liking (OAL)? The second question is what happens to those who rated the products “ideal” (JAR) before product development when evaluating the new products? Fruit flavored live‐flora stirred‐type kefir samples were formulated and evaluated by 92 consumers before and after the JAR‐based product development. The OAL of two products significantly increased after product development. A new visualization tool is introduced, which shows what happens to those who rated the attribute as JAR but the attribute has been modified. A general product development scheme is also introduced for JAR‐based kefir product development.
POEM for special patient cohorts: A review
Authors: Mu Dan , Li Yue Yue , Zhang Ming Ming , Zhang Yan , Li Zhen , Li Yan Qing
Published: April 2017

Peroral endoscopic myotomy (POEM) is a natural orifice, translumenal endoscopic surgical procedure that achieves endoscopic myotomy by conducting a submucosal tunnel as an operating space. It is conventionally performed in achalasia. Recently, several centers worldwide have reported the feasibility of this procedure not only in early achalasia but also in other particular patient cohorts. Possible indications for POEM include previously failed Heller myotomy, pneumatic balloon dilatation or POEM, sigmoid achalasia, pediatric patients, spastic esophagus disorders, Zenker’s diverticulum and gastroparesis. However, its application in large numbers of special patient groups awaits knowledge of the long‐term outcome and greater experience with POEM.
Further Evidence on Consequences of Debt Covenant Violations
Authors: Gao Yu , Khan Mozaffar , Tan Liang
Published: April 2017

We present new evidence on debt covenant violation (DCV) consequences that have not previously been examined in the literature. In particular, we show that a DCV triggers significant information asymmetry and uncertainty on the part of shareholders and auditors as reflected in higher bid–ask spreads, return volatility, and audit fees. Further, these consequences occur even when lender‐imposed costs are relatively lower, consistent with the act of default itself triggering shareholder and auditor uncertainty. The results highlight costs to the firm of having bright‐line rules in contracts, and add to an understanding of the consequences of DCVs.
The effect of fresh frozen plasma in critically ill patients
Authors: Vibede E. , Hvas C. L. , Tønnesen E. , Hvas A.‐M.
Published: April 2017

Background

Critically ill patients often receive fresh frozen plasma (FFP) if they have abnormal conventional coagulation tests. The aim of this study was to investigate the effect of FFP transfusion judged by a wide range of coagulation tests.

Methods

We included 30 critically ill patients receiving FFP and 30 critically ill patients who did not receive FFP. For patients receiving FFP, blood samples were obtained before and 1 h after FFP transfusion. Conventional coagulation tests, thromboelastometry (ROTEM®, EXTEM, INTEM and FIBTEM) and thrombin generation were performed. Systematic recording of vital signs was performed for all patients.

Results

The median values of the conventional coagulation tests were abnormal before and after FFP (PT: (normal > 0.6) median 0.3 before vs. 0.3 after; INR: (normal < 1.2) median 2 before vs. 1.7 after; APTT: (normal < 38 s) median 45 s before vs. 42 s after). Eight of nine ROTEM® parameters were within the reference interval judged by median values before FFP transfusion, and all median parameters were within the reference interval after FFP transfusion. Median in three of four thrombin generation parameters was within the reference interval both before and after FFP transfusion.

Conclusion

Patients presented abnormal conventional coagulation tests both before and after FFP transfusion. In contrast, ROTEM® and thrombin generation parameters were mainly within the reference interval both before and after FFP transfusion. FFP transfusions caused only negligible, although statically significant, improvements on coagulation measurements judged by conventional coagulation tests, ROTEM® and thrombin generation.
Haplotype structure and copy number polymorphism of the beta‐defensin 7 genes in diverse chicken breeds
Authors: Lee M. O. , Romanov M. N. , Plemyashov K. V. , Dementieva N. V. , Mitrofanova O. V. , Barkova O. Y. , Womack J. E.
Published: April 2017

Beta‐defensins is a family of avian peptides related to the innate immune system. Copy number variation was recently reported for the avian beta‐defensin 7 gene (AvBD7) between the highly inbred Leghorn and Fayoumi lines. Here, we examined copy number variants in 35 different chicken breeds and found that 31 of them have at least the same representation of the duplicated AvBD7 allele. We also found haplotypes upstream of the AvBD6 regions that are strongly linked to the AvBD7 duplication. We observed a strong linkage disequilibrium spanning of the upstream region of the AvBD6 gene, with two SNPs being flanking markers to detect duplication of the AvBD7.
A randomized controlled phase II clinical trial comparing ONO‐4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis
Authors: Okubo K. , Hashiguchi K. , Takeda T. , Baba K. , Kitagoh H. , Miho H. , Tomomatsu H. , Yamaguchi S. , Odani M. , Yamamotoya H.
Published: April 2017

Background

Prostaglandin D2 (PGD2) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.

Objective

This study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO‐4053, in patients with seasonal allergic rhinitis (SAR).

Methods

This study was a multicenter, randomized, double‐blind, parallel‐group study of patients with SAR. Following a one‐week period of placebo run‐in, patients who met the study criteria were randomized to either the ONO‐4053, leukotriene receptor antagonist pranlukast, or placebo group for a two‐week treatment period. A total of 200 patients were planned to be randomly assigned to receive ONO‐4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.

Results

Both ONO‐4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO‐4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO‐4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO‐4053 has a higher efficacy compared with pranlukast. There was no safety‐related issue in this study.

Conclusions

We demonstrated that the efficacy of ONO‐4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO‐4053 for use as a treatment for SAR (JapicCTI‐142706).
Temporal changes in liver tissue metabolome of lambs fed low‐quality roughage
Authors: Xu Wenbin , Okayama Naoto , Iwasawa Atsushi , Yayota Masato
Published: April 2017

Early experience with low‐quality roughage may induce adaptations in ruminants’ metabolism. This study was conducted to explore the variation in the hepatic metabolomes of lambs fed low‐quality roughage beginning early in life. Five lambs were fed Sudan grass hay (crude protein (CP): 4.6% of the dry matter (DM), neutral detergent fiber, 68.5% of DM) for 6 months during time periods P1, P2 and P3, which consisted of 2 months each. The metabolizable energy (ME) and CP intake satisfied lambs’ maintenance requirements in P1 and P2, but the ME intake was 78.5% of the maintenance ME requirement in P3. Liver metabolomics was carried out in P2 and P3 by the capillary electrophoresis and time‐of‐flight mass spectrometry system. Eight amino acids and six amino acid metabolism‐related metabolites were altered between P2 and P3. Several intermediates of glycolysis/gluconeogenesis decreased, while nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate increased in P3. Taurocholic acid and taurine increased, while glycocholic acid decreased in P3. The results suggested that amino acid utilization and the efficiency of glycolysis/gluconeogenesis might be adjusted to accommodate the low‐quality roughage fed to the lambs during early stages of life. The composition of bile acids might also be optimized to promote the efficiency of lipid absorption.
Enrichment of Genetic Variants in the Glucocorticoid Receptor Signalling Pathway in Autoimmune Hepatitis with Failure of Standard Treatment
Authors: Eriksen Peter Lykke , Kreutzfeldt Martin , Grønbæk Henning , Thorsen Kasper , Vang Søren , Jessen Niels , Vilstrup Hendrik
Published: April 2017

The standard treatment for autoimmune hepatitis (AIH) is predniso(lo)ne for remission induction, tapered and followed by azathioprine, which effectively controls the disease in the majority of patients. However, some patients prove to be unresponsive or non‐tolerant and require alternative immunosuppressive regimens for disease control. We aimed to investigate whether these AIH patients who experience failure of standard treatment have a genomic basis for their problem in the form of pharmacogenetic variants. Fifty‐six consecutive patients with AIH [41 female and 15 male; median age 42 years (12–76)] were retrospectively stratified according to being responders to standard therapy (n = 33) or patients with failure of standard therapy (n = 23). Their blood DNA was exome‐captured and sequenced. Genomic variants were filtered and compared between the groups using Ingenuity Variant Analysis (3.1.20150407). The exome sequencing and data processing revealed glucocorticoid receptor signalling to be the most prominently affected pathway among the patients with failure of standard therapy (highly significant). Standard treatment failure was not associated with thiopurine S‐methyltransferase variants or the HLA‐DRB1*03 genotype. In conclusion, enrichment of variants related to glucocorticoid receptor signalling was a particular genomic trait of the AIH patients in whom standard treatment failed and alternative immunosuppression was required. If confirmed, a future application of this finding may be to identify prospective cases of failure of standard treatment already at diagnosis.
Fair Resource Allocation to Health Research: Priority Topics for Bioethics Scholarship
Authors: Pratt Bridget , Hyder Adnan A.
Published: April 2017

This article draws attention to the limited amount of scholarship on what constitutes fairness and equity in resource allocation to health research by individual funders. It identifies three key decisions of ethical significance about resource allocation that research funders make regularly and calls for prioritizing scholarship on those topics – namely, how health resources should be fairly apportioned amongst public health and health care delivery versus health research, how health research resources should be fairly allocated between health problems experienced domestically versus other health problems typically experienced by disadvantaged populations outside the funder's country, and how domestic and non‐domestic health research funding should be further apportioned to different areas, e.g. types of research and recipients. These three topics should be priorities for bioethics research because their outcomes have a substantial bearing on the achievement of health justice. The proposed agenda aims to move discussion on the ethics of health research funding beyond its current focus on the mismatch between worldwide basic and clinical research investment and the global burden of disease. Individual funders’ decision‐making on whether and to what extent to allocate resources to non‐domestic health research, health systems research, research on the social determinants of health, capacity development, and recipients in certain countries should also be the focus of ethical scrutiny.
Intervention radiology for venous thrombosis: early thrombus removal using invasive methods
Authors: Casanegra Ana I. , McBane Robert D. , Bjarnason Haraldur
Published: April 2017

The post thrombotic syndrome is one of the most dreaded complications of proximal deep vein thrombosis. This syndrome leads to pain and suffering with leg swelling, recalcitrant ulceration and venous claudication which greatly impairs mobility and quality of life. The prevalence can be high in patients with iliofemoral venous involvement particularly in the setting of a proximal venous stenosis, such as occurs in May Thurner syndrome. Anticoagulation alone does not reduce the likelihood of this outcome. Compression therapy may be effective but garment discomfort limits its implementation. Pharmacomechanical thrombectomy, which combines catheter‐directed thrombolysis with mechanical thrombus dissolution, provides an attractive treatment strategy for such patients. The rationale and delivery of pharmacomechanical thrombectomy, including patient selection and adjunctive antithrombotic therapy, will be reviewed in addition to tips and tricks for managing difficult patient scenarios.
Increased incidence of VTE in sickle cell disease patients: risk factors, recurrence and impact on mortality
Authors: Brunson Ann , Lei Amy , Rosenberg Aaron S. , White Richard H. , Keegan Theresa , Wun Ted
Published: April 2017

Previous reports show increased incidence of venous thromboembolism [VTE, deep‐vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients but did not account for frequency of hospitalization. We determined the incidence of VTE in a SCD cohort versus matched controls. For SCD patients, risk factors for incident VTE, recurrence and the impact on mortality were also determined. Among 6237 patients with SCD, 696 patients (11·2%) developed incident‐VTE: 358 (51·6%) had PE (±DVT); 179 (25·7%) had lower‐extremity DVT only and 158 (22·7%) had upper‐extremity DVT. By 40 years of age, the cumulative incidence of VTE was 17·1% for severe SCD patients (hospitalized ≥3 times a year) versus 8·0% for the matched asthma controls. Amongst SCD patients, women (Hazard ratio [HR] = 1·22; 95% confidence interval [CI]: 1·05–1·43) and those with severe disease (HR = 2·86; 95% CI: 2·42–3·37) had an increased risk of VTE. Five‐year recurrence was 36·8% in patients with severe SCD. VTE was associated with increased risk of death (HR = 2·88, 95% CI: 2·35–3·52). In this population‐based study, the incidence of VTE was higher in SCD patients than matched controls and was associated with increased mortality. The high incidence of recurrent VTE in patients with severe SCD suggests that extended anticoagulation may be indicated.
THE IMPACT OF PERSONALITY TRAITS ON WAGE GROWTH AND THE GENDER WAGE GAP
Authors: Schäfer Konrad C. , Schwiebert Jörg
Published: April 2017

This paper considers the impact of personality traits on the change of the gender wage gap. Using data from the German Socioeconomic Panel (SOEP), we first explore how personality traits affect wage growth rates. Then, a decomposition analysis is performed to analyse the dynamic effects of personality traits on the change of the gender wage gap over time. Our empirical results indicate that gender differences in conscientiousness and emotional stability lead to a widening of the wage gap over time. By contrast, gender differences in extraversion lead to a narrowing of the wage gap over time.
μ opioid receptor, social behaviour and autism spectrum disorder: reward matters
Authors: Pellissier Lucie P , Gandía Jorge , Laboute Thibaut , Becker Jérôme A J , Le Merrer Julie
Published: April 2017

The endogenous opioid system is well known to relieve pain and underpin the rewarding properties of most drugs of abuse. Among opioid receptors, the μ receptor mediates most of the analgesic and rewarding properties of opioids. Based on striking similarities between social distress, physical pain and opiate withdrawal, μ receptors have been proposed to play a critical role in modulating social behaviour in humans and animals. This review summarizes experimental data demonstrating such role and proposes a novel model, the μ opioid receptor balance model, to account for the contribution of μ receptors to the subtle regulation of social behaviour. Interestingly, μ receptor null mice show behavioural deficits similar to those observed in patients with autism spectrum disorder (ASD), including severe impairment in social interactions. Therefore, after a brief summary of recent evidence for blunted (social) reward processes in subjects with ASD, we review here arguments for altered μ receptor function in this pathology.

This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc
IL‐5‐stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8‐dependent migration
Authors: Johansson M. W. , Khanna M. , Bortnov V. , Annis D. S. , Nguyen C. L. , Mosher D. F.
Published: April 2017

Background

IL‐5 causes suspended eosinophils to polarize with filamentous (F)‐actin and granules at one pole and the nucleus in a specialized uropod, the “nucleopod,” which is capped with P‐selectin glycoprotein ligand‐1 (PSGL‐1). IL‐5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators.

Objective

Determine how the polarized morphology evolves to foster migration of IL‐5‐stimulated eosinophils on a surface coated with periostin.

Methods

Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed.

Results

After 10 minutes in the presence of IL‐5, adherent eosinophils were polarized with PSGL‐1 at the nucleopod tip and F‐actin distributed diffusely at the opposite end. After 30‐60 minutes, the nucleopod had dissipated such that PSGL‐1 was localized in a crescent or ring away from the cell periphery, and F‐actin was found in podosome‐like structures. The periostin layer, detected with monoclonal antibody Stiny‐1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome‐like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti‐ADAM8 inhibited migration of IL‐5‐stimulated eosinophils on periostin.

Conclusions and Clinical Relevance

Migrating IL‐5‐activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny‐1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate on periostin‐rich extracellular matrix in the asthmatic airway in an ADAM8‐dependent manner, making ADAM8 a possible therapeutic target.