bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Pedimap — a pedigree visualization tool — to facilitate the decisioning of rice breeding in Sri Lanka
Authors: Rathnayake P.G.R.G. , Sahibdeen S.M. , Udawela U.A.K.S. , Weebadde C.K. , Weerakoon W.M.W. , Sooriyapathirana S.D.S.S.
Published: January 2020

The development of rice cultivars with desirable traits is essential. The decision-making is a crucial step in rice breeding programs. The breeders can make efficient and pragmatic decisions if an organized pedigree visualization platform is available for the material of the rice breeding germplasm. The staple food in Sri Lanka is rice, and there is a great demand for improved varieties with high yield and other promising traits. In the present study, the available data of all the rice varieties released by Rice Research and Development Institute, Sri Lanka, and the related landraces and genotypes were arranged in Pedimap, a pedigree visualization tool. Pedimap can showcase pedigree relationships, phenotypic, and molecular data. The Identity by Descent (IBD) probabilities were calculated using FlexQTL software and included in the Pedimap database. The parentage selection based on the variations of phenotypic traits, selection of marker alleles for molecular breeding, and detection of the founders of genetic effects can be swiftly conducted using Pedimap. However, the power of harnessing the value of Pedimap for making breeding decisions relies on the availability of data for the traits, markers, and genomic sequences. Thus, it is imperative to characterize the breeding germplasms using standard phenomic and genomic characterization procedures before organized into Pedimap. Thereby, the worldwide breeding programs can benefit from each other to produce improved varieties to meet global challenges.
A partial pathogenicity chromosome inFusarium oxysporumis sufficient to cause disease and can be horizontally transferred
Authors: Li Jiming , Fokkens Like , Conneely Lee James , Rep Martijn
Published: January 2020

During host colonization, plant pathogenic fungi secrete proteins, called effectors, to facilitate infection. Collectively, effectors may defeat the plant immune system, but usually not all effectors are equally important for infecting a particular host plant. InFusarium oxysporumf.sp.lycopersici, all known effector genes – also calledSIXgenes – are located on a single accessory chromosome which is required for pathogenicity and can also be horizontally transferred to another strain. To narrow down the minimal region required for virulence, we selected partial pathogenicity chromosome deletion strains by fluorescence-assisted cell sorting of a strain in which the two arms of the pathogenicity chromosome were labelled withGFPandRFP, respectively. By testing the virulence of these deletion mutants, we show that the complete long arm and part of the short arm of the pathogenicity chromosome are not required for virulence. In addition, we demonstrate that smaller versions of the pathogenicity chromosome can also be transferred to a non-pathogenic strain and they are sufficient to turn the non-pathogen into a pathogen. Surprisingly, originally non-pathogenic strains that had received a smaller version of the pathogenicity chromosome were much more aggressive than recipients with a complete pathogenicity chromosome. Whole genome sequencing analysis revealed that partial deletions of the pathogenicity chromosome occurred mainly close to repeats, and that spontaneous duplication of sequences in accessory regions is frequent both in chromosome deletion strains and in horizontal transfer (recipient) strains.

Author Summary

Fungal genomes can often be divided into a core genome, which is essential for growth, and an accessory genome which is dispensable. The accessory genome in fungi can be beneficial under some conditions. For example, in some plant-pathogenic fungi, virulence genes are present in the accessory genome, which enable these fungi to cause disease on certain hosts. InFusarium oxysporumf.sp.lycopersici, which infects tomato, all host-specific virulence genes are located on a single accessory chromosome. This ‘pathogenicity chromosome’ can be horizontally transferred between strains. Here, we found that many suspected virulence genes are in fact not required for virulence because strains without a large part of the pathogenicity chromosome, including these genes, showed no reduced virulence. In addition, we demonstrate that partial pathogenicity chromosomes can be horizontally transferred to a non-pathogen. Surprisingly, originally non-pathogenic strains that had received a partial pathogenicity chromosome were more virulent than strains that had received the complete pathogenicity chromosome.
CRISPR/Cas with ribonucleoprotein complexes and transiently selected telomere vectors allows highly efficient marker-free and multiple genome editing inBotrytis cinerea
Authors: Leisen Thomas , Bietz Fabian , Werner Janina , Wegner Alex , Schaffrath Ulrich , Scheuring David , Willmund Felix , Mosbach Andreas , Scalliet Gabriel , Hahn Matthias
Published: January 2020

CRISPR/Cas has become the state-of-the-art technology for genetic manipulation in diverse organisms, enabling targeted genetic changes to be performed with unprecedented efficiency. Here we report on the first establishment of robust CRISPR/Cas editing in the important necrotrophic plant pathogenBotrytis cinereabased on the introduction of optimized Cas9-sgRNA ribonucleoprotein complexes (RNPs) into protoplasts. Editing yields were further improved by development of a novel strategy that combines RNP delivery with transiently stable telomeres containing vectors, which allowed temporary selection and convenient screening of marker-free editing. We demonstrate that this approach provides vastly superior editing rates compared to existing CRISPR/Cas-based methods in filamentous fungi, including the model plant pathogenMagnaporthe oryzae. The high performance of telomere vector-mediated coediting was demonstrated by random mutagenesis of codon 272 of thesdhBgene, a major determinant of resistance to succinate dehydrogenase inhibitor (SDHI) fungicides by in bulk replacement of the codon 272 with codons encoding all 20 amino acids. All exchanges were found at similar frequencies in the absence of selection but SDHI selection allowed the identification of novel amino acid substitutions which conferred differential resistance levels towards different SDHI fungicides. The increased efficiency and easy handling of RNP-based cotransformation is expected to greatly facilitate molecular research inB. cinereaand other fungi.
ILoReg enables high-resolution cell population identification from single-cell RNA-seq data
Authors: Smolander Johannes , Junttila Sini , Venäläinen Mikko S , Elo Laura L
Published: January 2020

Single-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging. We introduce ILoReg (https://github.com/elolab/iloreg), an R package implementing a new cell population identification method that achieves high differentiation resolution through a probabilistic feature extraction step that is applied before clustering and visualization.
Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis
Authors: Atzeni Francesco , Pasakarnis Laurynas , Mosca Gabriella , Smith Richard S. , Aegerter Christof M. , Brunner Damian
Published: January 2020

Tissue morphogenesis integrates cell type-specific biochemistry and architecture, cellular force generation and mechanisms coordinating forces amongst neighbouring cells and tissues. We use finite element-based modelling to explore the interconnections at these multiple biological scales in embryonic dorsal closure, where pulsed actomyosin contractility in adjacent Amnioserosa (AS) cells powers the closure of an epidermis opening. Based on ourin vivoobservations, the model implements F-actin nucleation periodicity that is independent of MyoII activity. Our model reveals conditions, where depleting MyoII activity nevertheless indirectly affects oscillatory F-actin behaviour, without the need for biochemical feedback. In addition, it questions the previously proposed role of Dpp-mediated regulation of the patterned actomyosin dynamics in the AS tissue, suggesting them to be emergent. Tissue-specific Dpp interference supports the model’s prediction. The model further predicts that the mechanical properties of the surrounding epidermis tissue feed back on the shaping and patterning of the AS tissue. Finally, our model’s parameter space reproduces mutant phenotypes and provides predictions for their underlying cause. Our modelling approach thus reveals several unappreciated mechanistic properties of tissue morphogenesis.
Development of high-throughput screening assays for profiling snake venom Phospholipase A2activity after high-resolution chromatographic fractionation
Authors: Still Kristina B.M. , Slagboom Julien , Kidwai Sarah , Xie Chunfang , Eisses Bastiaan , Vonk Freek J. , Somsen Govert W. , Casewell Nicholas R. , Kool Jeroen
Published: January 2020

Many organisms, ranging from plants to mammals, contain phospholipase A2enzymes (PLA2s), which catalyze the production of lysophospholipids and fatty acid proinflammatory mediators. PLA2s are also common constituents of animal venoms, including bees, scorpions and snakes, and they cause a wide variety of toxic effects including neuro-, myo-, cyto-, and cardio-toxicity, anticoagulation and edema. The aim of this study was to develop a generic method for profiling enzymatically active PLA2s in snake venoms after chromatographic separation. For this, low-volume high-throughput assays for assessment of enzymatic PLA2activity were evaluated and optimized. Subsequently, the assays were incorporated into a nanofractionation platform that combines high-resolution fractionation of crude venoms by liquid chromatography (LC) with bioassaying in 384-well plate format, and parallel mass spectrometric (MS) detection for toxin identification. The miniaturized assays developed are based on absorbance or fluorescence detection (respectively, using cresol red or fluorescein as pH indicators) to monitor the pH drop associated with free fatty acid formation by enzymatically active PLA2s. The methodology was demonstrated for assessment of PLA2activity profiles of venoms from the snake speciesBothrops asper,Echis carinatus,Echis coloratus, Echis ocellatus,Oxyuranus scutellatusandDaboia russelii russelii.
Cell size regulation in budding yeast does not depend on linear accumulation of Whi5
Authors: Barber Felix , Amir Ariel , Murray Andrew W.
Published: January 2020

Cells must couple cell cycle progress to their growth rate to restrict the spread of cell sizes present throughout a population. Linear, rather than exponential, accumulation of Whi5, was proposed to provide this coordination by causing a higher Whi5 concentration in cells born at smaller size. We tested this model using the inducibleGAL1promoter to make the Whi5 concentration independent of cell size. At an expression level that equalizes the mean cell size with that of wild-type cells, the size distributions of cells with galactose-induced Whi5 expression and wild-type cells are indistinguishable. Fluorescence microscopy confirms that the endogenous andGAL1promoters produce different relationships between Whi5 concentration and cell volume without diminishing size control in the G1 phase. We also expressed Cln3 from the GAL1 promoter, finding that the spread in cell sizes for an asynchronous population is unaffected by this perturbation. Our findings contradict the previously proposed model for cell size control in budding yeast and demonstrate the need for a molecular mechanism that explains how cell size controls passage through Start.

Author Contributions

FB performed the experiments, data analysis and simulations. All authors designed the experiments and wrote the manuscript.

Significance Statement

Despite decades of research, the question of how single cells regulate their size remains unclear. Here we demonstrate that a widely supported molecular model for the fundamental origin of size control in budding yeast is inconsistent with a set of experiments testing the model’s key prediction. We therefore conclude that the problem of cell size control in budding yeast remains unsolved. This work highlights the need for rigorous testing of future models of size control in order to make progress on this fundamental question.
Ribosome heterogeneity inDrosophila melanogastergonads through paralog-switching
Authors: Hopes Tayah , Norris Karl , Agapiou Michaela , McCarthy Charley G.P. , Lewis Philip A. , O’Connell Mary J , Fontana Juan , Aspden Julie L
Published: January 2020

Ribosomes have long been thought of as homogeneous macromolecular machines, but recent evidence suggests they are heterogeneous and could be specialised to regulate translation. Here, we have characterised ribosomal protein heterogeneity across 4 tissues ofDrosophila melanogaster. We find that testes and ovaries contain the most heterogeneous ribosome populations, which occurs through a combination of paralog-enrichment and paralog-switching. We have solved structures of ribosomes purified fromin vivotissues by cryo-EM, revealing differences in precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-switching could alter the ribosome surface, enabling different proteins to regulate translation. One testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of ribosome heterogeneity. Overall, this work allows us to propose that mRNA translation might be regulated in the gonads through ribosome heterogeneity, providing a potential means of ribosome specialisation.
Assessing the accuracy of octanol-water partition coefficient predictions in the SAMPL6 Part II logPChallenge
Authors: Işık Mehtap , Bergazin Teresa Danielle , Fox Thomas , Rizzi Andrea , Chodera John D. , Mobley David L.
Published: January 2020

The SAMPL Challenges aim to focus the biomolecular and physical modeling community on issues that limit the accuracy of predictive modeling of protein-ligand binding for rational drug design. In the SAMPL5 logDChallenge, designed to benchmark the accuracy of methods for predicting drug-like small molecule transfer free energies from aqueous to nonpolar phases, participants found it difficult to make accurate predictions due to the complexity of protonation state issues. In the SAMPL6 logPChallenge, we asked participants to make blind predictions of the octanol-water partition coefficients of neutral species of 11 compounds and assessed how well these methods performed absent the complication of protonation state effects. This challenge builds on the SAMPL6 pKaChallenge, which asked participants to predict pKavalues of a superset of the compounds considered in this logPchallenge. Blind prediction sets of 91 prediction methods were collected from 27 research groups, spanning a variety of quantum mechanics (QM) or molecular mechanics (MM)-based physical methods, knowledge-based empirical methods, and mixed approaches. There was a 50% increase in the number of participating groups and a 20% increase in the number of submissions compared to the SAMPL5 logDChallenge. Overall, the accuracy of octanol-water logPpredictions in SAMPL6 Challenge was higher than cyclohexane-water logDpredictions in SAMPL5, likely because modeling only the neutral species was necessary for logPand several categories of method benefited from the vast amounts of experimental octanol-water logPdata. There were many highly accurate methods: 10 diverse methods achieved RMSE less than 0.5 logPunits. These included QM-based methods, empirical methods, and mixed methods with physical modeling supported with empirical corrections. A comparison of physical modeling methods showed that QM-based methods outperformed MM-based methods. The average RMSE of the most accurate five MM-based, QM-based, empirical, and mixed approach methods based on RMSE were 0.92±0.13, 0.48±0.06, 0.47±0.05, and 0.50±0.06, respectively.
A signal of competitive dominance in mid-latitude herbaceous plant communities
Authors: Capitán José A. , Cuenda Sara , Ordóñez Alejandro , Alonso David
Published: January 2020

Understanding the main determinants of species coexistence across space and time is a central question in ecology. However, ecologists still know little about the scales and conditions at which biotic interactions matter and how these interact with the environment to structure species assemblages. Here we use recent theory developments to analyze plant distribution and trait data across Europe and find that plant height clustering is related to both evapotranspiration and gross primary productivity. This clustering is a signal of interspecies competition between plants, which is most evident in mid-latitude ecoregions, where conditions for growth (reflected in actual evapotranspiration rates and gross primary productivities) are optimal. Away from this optimum, climate severity likely overrides the effect of competition, or other interactions become increasingly important. Our approach bridges the gap between species-rich competition theories and large-scale species distribution data analysis.
DrosophiladTBCE recruits tubulin around chromatin to promote mitotic spindle assembly
Authors: Métivier Mathieu , Gallaud Emmanuel , Pascal Aude , Gagné Jean-Philippe , Poirier Guy G. , Chrétien Denis , Gibeaux Romain , Richard-Parpaillon Laurent , Benaud Christelle , Giet Régis
Published: January 2020

Proper assembly of mitotic spindles requires microtubule nucleation at centrosomes but also around chromatin. In this study, we reveal a novel mechanism by which an enrichment of tubulin in the nuclear space following nuclear envelope breakdown promotes nucleation of spindle microtubules. This event mediated by the tubulin-specific chaperone dTBCE, depends on its tubulin binding CAP-Gly motif and is regulated by Ran. Live imaging, proteomic and biochemical analyses suggest that dTBCE is enriched in the nucleus at nuclear envelope breakdown and interacts with nuclear pore proteins and the Ran machinery to create an environment that facilitates subsequent tubulin enrichment. We propose that dTBCE-dependent increase in tubulin concentration in the nuclear space is an important mechanism for microtubule nucleation in organisms where compartmentalization prevents free diffusion of tubulin.
Crystal structure, Hirshfeld surface analysis and computational study of the 1:2 co-crystal formed between N,N′-bis(pyridin-4-ylmethyl)ethanediamide and 4-chlorobenzoic acid
Authors: Tan Sang Loon , Tiekink Edward R. T.
Published: January 2020

The asymmetric unit of the title 1:2 co-crystal, C14H14N4O2·2C7H5ClO2, comprises two half molecules of oxalamide (4
LH2), as each is disposed about a centre of inversion, and two molecules of 4-chlorobenzoic acid (CBA), each in general positions. Each 4
LH2 molecule has a (+)antiperiplanar conformation with the pyridin-4-yl residues lying to either side of the central, planar C2N2O2 chromophore with the dihedral angles between the respective central core and the pyridyl rings being 68.65 (3) and 86.25 (3)°, respectively, representing the major difference between the independent 4
LH2 molecules. The anti conformation of the carbonyl groups enables the formation of intramolecular amide-N—H...O(amide) hydrogen bonds, each completing an S(5) loop. The two independent CBA molecules are similar and exhibit C6/CO2 dihedral angles of 8.06 (10) and 17.24 (8)°, indicating twisted conformations. In the crystal, two independent, three-molecule aggregates are formed via carboxylic acid-O—H...N(pyridyl) hydrogen bonding. These are connected into a supramolecular tape propagating parallel to [100] through amide-N—H...O(amide) hydrogen bonding between the independent aggregates and ten-membered {...HNC2O}2 synthons. The tapes assemble into a three-dimensional architecture through pyridyl- and methylene-C—H...O(carbonyl) and CBA-C—H...O(amide) interactions. As revealed by a more detailed analysis of the molecular packing by calculating the Hirshfeld surfaces and computational chemistry, are the presence of attractive and dispersive Cl...C=O interactions which provide interaction energies approximately one-quarter of those provided by the amide-N—H...O(amide) hydrogen bonding sustaining the supramolecular tape.
Networked psychostimulants: a web-based ethnographic study
Authors: Robitaille Caroline
Published: January 2020

Purpose

The purpose of this paper is to understand contemporary psychostimulant use among members of online discussion fora. Two objectives are addressed: to describe accounts of practices related to psychostimulant use, and to examine how these pharmaceuticals may shape contemporary subjectivities.

Design/methodology/approach

This paper presents a qualitative analysis of three online discussion fora belonging to Reddit. Drawing on actor-network theory, psychostimulants are envisaged as networked actants to understand the underlying logics related to their use. Non-participant observation of r/Adderall was carried out over an 18-month period. A qualitative analysis of postings on the three selected fora was also performed.

Findings

For each discussion forum, a network comprised of human and non-human actors was observed: members of the forum, psychostimulants as objects and subreddits as agentic spaces. This study reveals the emergence of multiple subjectivities associated with psychostimulant use: productivity, wellness and enhancement‐related.

Practical implications

Findings open to a wider debate regarding public health’s and healthcare professionals’ understanding of psychostimulant use outside of the clinical setting and how this may contrast with how psychostimulant use is practiced in context.

Originality/value

This research shows new online socio-cultural spaces formed around psychostimulant use. Calling upon a web-based ethnographic approach, this research presents a new perspective on the contemporary use of psychostimulants.
Impacts of large-scale interior murals on hospital employees: a pharmacy department case study
Authors: McCunn Lindsay , Frey Cara
Published: January 2020

Purpose

Trending in modern interior design frameworks is an integration of real and simulated (i.e. photographs, murals) elements of nature into buildings, and a number of interdisciplinary studies concern the effects of nature on various aspects of human functioning. The purpose of this paper is to measure employees’ self-reported levels of affective organizational commitment (AOC), perceived productivity, well-being, attention restoration and satisfaction at work to explore how each mural is conceptualized and to make recommendations to hospital administrators and facilities managers as they make decisions concerning mural design and placement. One hospital had a biophilic mural and the other had a bold abstract mural.

Design/methodology/approach

The research was carried out using post-occupancy evaluation and mixed-methods survey design.

Findings

Employees in both hospitals disagreed that their organizational commitment (OC), perceived productivity or well-being at work had improved since the new murals had been installed. Responses from both hospitals were also low concerning perceptions of attention restoration. Indeed, no significant differences between hospitals were found. Correlations among scales were found within hospitals that support published studies. More correlations occurred at the hospital where employees viewed the biophilic mural (e.g. between OC and perceived productivity, and between satisfaction with the physical environment and perceived productivity). At both sites, satisfaction with the physical environment correlated with OC.

Originality/value

The authors expected that those working within view of the biophilic mural would report stronger ratings of AOC, perceived productivity, well-being, attention restoration and satisfaction with the workplace than employees with a view of the abstract scene. No differences between groups were found; responses to psychosocial scale items asking about whether attitudes had improved after the retrofit were low or neutral for employees in either hospital. However, more correlations between scales that support existing literature were revealed for those working near the biophilic mural. Thus, the authors recommend architectural programming before a design change to gather insight on occupants’ preferences at work.
PDC-SiAlCN ceramic based wireless passive temperature sensors using integrated resonator/antenna up to 1100°C
Authors: Yu Yuxi , Han Bin , Xia Fansen
Published: January 2020

Purpose

This paper aims to present wireless passive temperature sensors by using high-temperature stable polymer-derived silicoaluminum carbonitride (PDC-SiAlCN) ceramic materials.

Design/methodology/approach

In this paper, a novel PDC-SiAlCN ceramic was synthesized by using polyvinylsilazne and aluminum-tri-sec-butoxide as precursors. Then, PDC-SiAlCN was used as the sensing material to fabricate sensors. The sensors are based on a cavity resonator and an integrated slot antenna. The resonant frequencies of the sensors are determined by the dielectric constants of PDC-SiAlCN ceramic, which monotonically increase versus temperature.

Findings

The effect of sensor dimension on the performance of the sensors was investigated using simulation and experimental methods. The using temperature, reliability and sensing distance of the sensors were studied experimentally. The sensors performed measurement up to 1100°C with excellent reliability and repeatability. The sensing distance varied from 38 to 14 mm when the temperature increasing from 20°C to 1100°C.

Originality/value

PDC-SiAlCN ceramic based wireless passive temperature sensors have the advantage of seamless integration of slot antennas and resonators, which greatly reduces the size of the sensor, reduces the direction of antenna transmission and increases the transmission space. The sensors can be used for many harsh environment applications such as engine monitoring.
Characteristics and clinical significance of augmentation spectra in solar urticaria
Authors: Uetsu Naoko , Nomura Yuki , Matsuyama Yoshie , Okamoto Hiroyuki
Published: January 2020

Solar urticaria has unique spectra, such as inhibition and augmentation. The clinical significance of these spectra, especially augmentation, is not well understood. Reported cases of solar urticaria with augmentation spectra are extremely rare in the published English‐language work. The purposes of this study were to evaluate the clinical features of solar urticaria with augmentation spectra and to elucidate the mechanisms and clinical importance of the spectra. We experienced 11 cases (five females, six males; mean age, 40.1 years; range, 1–74) of solar urticaria with augmentation spectra from April 2007 to July 2019. Augmentation spectra were UV‐B in three cases, UV‐A in two, visible light in four, UV‐A and UV‐B in one, and UV‐A and visible light in one. Augmentation spectra were observed before action spectra in four cases, after in six, and before and after in one. Injection of sera irradiated with action spectra and augmentation spectra in vitro induced stronger immediate reactions than those of only action spectrum‐irradiated sera in four of five cases. The results of injection tests suggested that augmentation spectra enhance the production of urticaria‐forming factor. Clinically, we observed severe urticarial reactions in four cases, including anaphylaxis in three and moderate urticarial reactions in three. These results suggest that augmentation spectra are not as rare as previously thought and that they are associated with the severity of solar urticaria. Therefore, phototesting for both augmentation and action spectra should be performed to provide appropriate guidance for patients with solar urticaria.
‘A more public arena’: Jeff Koons' Reinvention in the Midst of Reaganism
Authors: Perl AnnMarie
Published: January 2020

Critics have argued since 1986 that Jeff Koons lacks criticality and, moreover, cynically capitalizes on art's commodification. This essay provides a focused historical account of Koons' development during the late 1980s, demonstrating how he reinvented his artistic project following these critiques, in part by adopting a farcical utopian social and political agenda, in which all people would become aristocrats. Koons was not a political activist and never imagined that this agenda could come to pass. Rather, his resulting artwork, which was rich in political references, allusions and associations, revealed how people had been persuaded by a version of this fantastic promise at their expense. Koons provocatively personified and pictured the way that politics was then remaking American society. In particular, his Banality series of 1988–89 produced a jarring picture puzzle that positioned viewers between the extremes of identification with, or differentiation from, either the disenfranchised or the elite.
Effect of foreign exchange intervention: The case of Korea
Authors: Lee Seojin , Kim Young Min
Published: January 2020

Using a rolling‐window approach that allows time‐varying coefficients, we estimate the vector autoregressive model with the Markov chain Monte Carlo method to analyse the effectiveness of foreign exchange interventions in Korea. Our results show that a negative shock in international reserves (buying domestic currency or selling foreign currency) results in a significant appreciation of the domestic currency, a reduction in implied volatility and an increase in capital inflows. We also find that Korean exchange rate policies focus on the stabilization of the foreign exchange market rather than the depreciation of the Korean won. These patterns appear more obvious after the 2008 global financial crisis. This suggests that time variation should be taken into account to better understand the effects of foreign exchange interventions.
Application of harmonic radar to analyze dispersal behavior of the Japanese pine sawyer beetle, Monochamus alternatus (Coleoptera: Cerambycidae)
Authors: Zhang Zi‐Yi , Zha Yu‐Ping , Cai San‐Shan , Hong Cheng‐Hao , Liang Peng , Chen Jing‐Yuan
Published: January 2020

Monochamus alternatus (Hope) is a severe wood‐boring pest in coniferous forests and a major vector of pine wilt disease in East Asia. Harmonic radar is a powerful tool for studying the dispersal behavior of insects and it could be applied to control pine wilt disease. In this study, we validated the application of harmonic radar for analyzing the dispersal behavior of M. alternatus beetles in a field environment. We determined the wing capacities of the beetles and the effects of electronic tagging and marking on their movement, flight ability, survivorship, and food consumption in the laboratory to confirm the suitability of this technique. The detection rate and recovery rate for beetles were analyzed separately using radar on caged pine stands and in the field environment. The results showed that the minimum wing capacity of the Japanese pine sawyer was 24.9 mg, which was seven times the weight of the electronic tag (3.5 mg). Marking and tagging the beetles had no significant adverse effects on their movement, flight capacity, food consumption, and survivorship. The detection rate using the radar system and recovery rate based on visual observations of the beetles in caged pines were both 95.6%. However, in the field environment, the detection and recovery rates were only 55.6% and 37.8% after one week, respectively, and 33.3% and 7.8% after two weeks. Harmonic radar is a promising technique for studying the dispersal behavior of the Japanese pine sawyer, but its performance is not satisfactory and major improvements are required for both the radar system and electronic tags.
Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder
Authors: Hartwell Emily E. , Feinn Richard , Morris Paige E. , Gelernter Joel , Krystal John , Arias Albert J. , Hoffman Michaela , Petrakis Ismene , Gueorguieva Ralitza , Schacht Joseph P. , Oslin David , Anton Raymond F. , Kranzler Henry R.
Published: January 2020

Background and Aims

There is wide inter‐individual variability in response to the treatment of alcohol use disorder (AUD) with the opioid receptor antagonist naltrexone. To identify patients who may be most responsive to naltrexone treatment, studies have examined the moderating effect of rs1799971, a single nucleotide polymorphism (SNP) that encodes a non‐synonymous substitution (Asn40Asp) in the mu‐opioid receptor gene, OPRM1. The aims of this study were to: (1) conduct a systematic review of randomized clinical trials (RCTs); (2) assess the bias of the available studies and gauge publication bias; and (3) meta‐analyze the interaction effect of the Asn40Asp SNP on the response to naltrexone treatment.

Methods

We searched for placebo‐controlled RCTs that examined the effect of Asn40Asp on the response to naltrexone treatment of heavy drinking or AUD. We tested the hypothesis that the minor (Asp40) allele was associated with a greater reduction in five alcohol consumption measures (relapse to heavy drinking, abstinence, percentage of heavy drinking days, percentage of days abstinent and drinks per day) in naltrexone‐treated participants by meta‐analyzing the interaction effects using a random effects model.

Results

Seven RCTs met the study criteria. Overall, risk of bias was low and we observed no evidence of publication bias. Of the five alcohol consumption outcomes considered, there was a nominally significant moderating effect of the Asn40Asp SNP only on drinks per day (d = −0.18, P = 0.02). However, the effect was not significant when multiple comparisons were taken into account.

Conclusions

From the evidence to date, it remains unclear whether rs1799971, the OPRM1 Asn40Asp single nucleotide polymorphism, predicts naltrexone treatment response in individuals with alcohol use disorder or heavy drinking.
The safety and pharmacokinetics of metformin in patients with chronic liver disease
Authors: Smith Felicity C. , Stocker Sophie L. , Danta Mark , Carland Jane E. , Kumar Shaun S. , Liu Zhixin , Greenfield Jerry R. , Braithwaite Hannah E. , Cheng Tim S. , Graham Garry G. , Williams Kenneth M. , Day Richard O.
Published: January 2020

Background

The FDA approved ‘label’ for metformin lists hepatic insufficiency as a risk for lactic acidosis. Little evidence supports this warning.

Aims

To investigate the safety and pharmacokinetics of metformin in patients with chronic liver disease (CLD).

Methods

Chronic liver disease patients with and without type 2 diabetes mellitus (T2DM) were studied by a cross‐sectional survey of patients already prescribed metformin (n = 34), and by a prospective study where metformin (500 mg, immediate release, twice daily) for up to 6 weeks was prescribed (n = 24). Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were obtained and compared to previously published values from healthy and T2DM populations without CLD.

Results

All plasma metformin and lactate concentrations remained below the putative safety thresholds (metformin, 5 mg/L; lactate, 5 mmol/L). Lactate concentrations were unrelated to average steady‐state metformin concentrations. In patients with CLD, T2DM was associated with higher plasma lactate concentrations (48% higher than those without T2DM,P < 0.0001). CLD patients with cirrhosis had 23% higher lactate concentrations than those without cirrhosis (P = 0.01). The pharmacokinetics of metformin in CLD patients were similar to patients with T2DM and no liver disease. The ratio of apparent metformin clearance (CLMet/F) to creatinine clearance was marginally lower in CLD patients compared to healthy subjects (median, interquartile range; 12.6, 9.5‐15.9 vs 14.9, 13.4‐16.4;P = 0.03).

Conclusions

The pharmacokinetics of metformin are not altered sufficiently in CLD patients to raise concerns regarding unsafe concentrations of metformin. There were no unsafe plasma lactate concentrations observed in CLD patients receiving metformin (ACTRN12619001292167; ACTRN12619001348145).
Echinococcus granulosus in the Northern Territory, Australia: hydatid disease reported in beef cattle from the region
Authors: Wilson CS , Brookes VJ , Jenkins DJ
Published: January 2020

Hydatid disease in beef cattle has been reported to be widespread throughout Australia, but cattle bred and raised in the Northern Territory were previously believed to be free of the disease. Between 2010 and 2016, 1061 cattle from the Northern Territory were slaughtered at a New South Wales abattoir and inspected for hydatid disease. The proportion of cattle reported infected with hydatid disease was 3.5%. Individual cattle identification numbers indicated that the cattle included in the study had most likely remained within the Northern Territory from birth until immediately prior to slaughter, so were assumed to have become infected within the region. We suspect that the sylvatic cycle of Echinococcus granulosus transmission could be responsible for infection of cattle in this region.
Theory of mind development from adolescence to adulthood: Testing the two‐component model
Authors: Meinhardt‐Injac Bozana , Daum Moritz M. , Meinhardt Günter
Published: January 2020

The ability to infer mental and affective states of others is crucial for social functioning. This ability, denoted as Theory of Mind (ToM), develops rapidly during childhood, yet results on its development across adolescence and into young adulthood are rare. In the present study, we tested the two‐component model, measuring age‐related changes in social‐perceptual and social‐cognitive ToM in a sample of 267 participants between 11 and 25 years of age. Additionally, we measured language, reasoning, and inhibitory control as major covariates. Participants inferred mental states from non‐verbal cues in a social‐perceptual task (Eye Test) and from stories with faux pas in a social‐cognitive task (Faux Pas Test). Results showed substantial improvement across adolescence in both ToM measures and in the covariates. Analysis with linear mixed models (LMM) revealed specific age‐related growth for the social‐perceptual component, while the age‐related increase of the social‐cognitive component fully aligned with the increase of the covariates. These results support the distinction between ToM components and indicate that adolescence is a crucial period for developing social‐perceptual ToM abilities.

Statement of contribution

What is already known on this subject?

To date, much research has been dedicated to Theory of Mind (ToM) development in early and middle childhood. However, only a few studies have examined development of ToM in adolescence.

Studies so far suggest age‐related differences in ToM between adolescents and young adults.

What this study adds

The study offers several methodological advantages including a large sample size with a continuous distribution of age (age 11–25) and the use of a comprehensive test battery to assess ToM and covariates (language, executive functions, reasoning).

The results provide evidence for asymmetries in the development of two ToM components (social‐perceptual and social‐cognitive; the two‐component account) across the studied age range:

the social perceptual component showed specific development, while the age‐related increase of the social‐cognitive component fully aligned with increase of the covariates.

Adolescence is a crucial period for developing social‐perceptual ToM abilities.
Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma
Authors: Witte Hanno M. , Merz Hartmut , Biersack Harald , Bernard Veronica , Riecke Armin , Gebauer Judith , Lehnert Hendrik , von Bubnoff Nikolas , Feller Alfred C. , Gebauer Niklas
Published: January 2020

Patients with EBV‐positive diffuse large B cell lymphoma not otherwise specified (EBV+ DLBCL (NOS)) recurrently present with advanced age and reduced performance status. They are therefore insufficiently represented in clinical trials and treatment is likely to differ. Here we assess clinicopathological characteristics, therapeutic variability and clinical outcome in the largest consecutively diagnosed EBV+ DLBCL (NOS) cohort published to date (n = 80; median age 70 years; range 19–90). Centralized and systematic haematopathological panel review was performed. By immunohistochemistry 60/80 patients were CD30‐positive. Further, we identified nine EBV+ DLBCL (NOS) patients with associated or composite peripheral T cell lymphoma at diagnosis or relapse (preceded by clonal T cell populations within the initial DLBCL biopsy in 4/5 cases). Most patients (80%) were treated with R‐CHOP‐type therapy and 16 patients received none or less intensiveprotocols. Upon univariate analysis both R‐CHOP‐type therapy (OS: P < 0.0001; PFS: P = 0.0617) and negativity for CD30 (OS: P = 0.0002; PFS: P = 0.0002) showed a protective 66 effect, maintained upon multivariate analysis. In a propensity‐score matched analysis with a cohort of non‐EBV+ DLBCL (NOS) patients, balanced for all revised‐international prognostic index factors, we found an EBV‐association to hold no significant impact on progression‐free and overall survival whilst exhibiting a trend favouring EBV‐negativity (OS: P = 0.116; PFS: P = 0.269). Our findings provide insight into the clinical course of EBV+ DLBCL (NOS), highlight the ramifications of CD30‐expression and underline the superior therapeutic efficacy of R‐CHOP immunochemotherapy. Alternative therapies, incorporating tumour biology (e.g. CD30 directed therapies) need to be explored in EBV+ DLBCL (NOS) patients. Moreover our data advert to the close relationship between EBV+ DLBCL (NOS) and peripheral T cell lymphomas.
Semimechanistic Modeling to Guide Venetoclax Coadministration with Ritonavir and Digoxin
Authors: Alhadab Ali A. , Salem Ahmed Hamed , Freise Kevin J.
Published: January 2020

Venetoclax is a cytochrome P450, family 3, subfamily A (CYP3A) substrate and was shown to inhibit P‐gp efflux transporters in vitro. To quantify the impact of CYP3A inhibition by ritonavir on venetoclax disposition and P‐gp inhibition by venetoclax on digoxin pharmacokinetics, two semimechanistic drug‐drug interaction (DDI) models of venetoclax were developed using clinical data from healthy volunteers who received subtherapeutic doses of venetoclax with ritonavir 50–100 mg or digoxin 0.5 mg. These models were then used to assess the magnitude of interaction at therapeutic venetoclax doses and to explore various clinical dosing strategies that maintain venetoclax and digoxin concentrations within their respective therapeutic windows. Simulations demonstrated that venetoclax dose reductions of at least 75% are needed when venetoclax is coadministered with ritonavir and administering digoxin at least 2 hours before venetoclax would minimize DDI. Semimechanistic modeling leveraging clinical data is a plausible approach to predict DDI and propose dose adjustments, and administration time of interacting drugs.
Developing Family Science Professionals: Towards a Reflexive Process through Student's Development of a Philosophy Statement
Authors: Martin‐Cuellar Ashley , Jaquish Andrea
Published: January 2020

Development of a philosophy statement for family science prompts students to reflect and critically examine their why in relation to their work with families. Such reflexivity orients students toward a specific professional career and may also help them identify within that career as they grow professionally by acknowledging beliefs and values that brought them into the work. This article presents (i) a philosophy statement development process for family science students and (ii) feedback from students enrolled in a family studies field experience class about their engagement in the process. Four themes emerged from 20 student reflections. The themes were as follows: being overwhelmed, challenged to think deeper, designated reflection time, and collective class process.
Decreased carbon accumulation feedback driven by climate‐induced drying of two southern boreal bogs over recent centuries
Authors: Zhang Hui , Väliranta Minna , Piilo Sanna , Amesbury Matthew J. , Aquino‐López Marco A. , Roland Thomas P. , Salminen‐Paatero Susanna , Paatero Jussi , Lohila Annalea , Tuittila Eeva‐Stiina
Published: January 2020

Northern boreal peatlands are important ecosystems in modulating global biogeochemical cycles, yet their biological communities and related carbon dynamics are highly sensitive to changes in climate. Despite this, the strength and recent direction of these feedbacks are still unclear. The response of boreal peatlands to climate warming has received relatively little attention compared with other northern peatland types, despite forming a large northern hemisphere‐wide ecosystem. Here, we studied the response of two ombrotrophic boreal peatlands to climate variability over the last c. 200 years for which local meteorological data are available. We used remains from plants and testate amoebae to study historical changes in peatland biological communities. These data were supplemented by peat property (bulk density, carbon and nitrogen content), 14C, 210Pb and 137Cs analyses and were used to infer changes in peatland hydrology and carbon dynamics. In total, six peat cores, three per study site, were studied that represent different microhabitats: low hummock (LH), high lawn and low lawn. The data show a consistent drying trend over recent centuries, represented mainly as a change from wet habitat Sphagnum spp. to dry habitat S. fuscum. Summer temperature and precipitation appeared to be important drivers shaping peatland community and surface moisture conditions. Data from the driest microhabitat studied, LH, revealed a clear and strong negative linear correlation (R2 = .5031; p < .001) between carbon accumulation rate and peat surface moisture conditions: under dry conditions, less carbon was accumulated. This suggests that at the dry end of the moisture gradient, availability of water regulates carbon accumulation. It can be further linked to the decreased abundance of mixotrophic testate amoebae under drier conditions (R2 = .4207; p < .001). Our study implies that if effective precipitation decreases in the future, the carbon uptake capacity of boreal bogs may be threatened.
Tailoring an information skills programme for Trainee Nursing Associates
Authors: Froste Daniel
Published: January 2020

This feature describes the tailored information skills programme which was delivered for the second cohort of Trainee Nursing Associates (TNAs) at Barnsley Hospital NHS Foundation Trust and presents the results of the evaluation which was undertaken. Literature searching and critical appraisal were offered to the first cohort. Feedback was collated, and sessions were refined and tailored to better meet the information needs of the second cohort of TNAs. A comparison of confidence ratings before and after the programme ascertained whether the information skills programme had a positive benefit in confidence levels of attendees. D.I.