bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the PBS1 Decoy System to Confer Resistance to Potyvirus Infection in Arabidopsis and Soybean
Authors: Pottinger Sarah E. , Bak Aurelie , Margets Alexandra , Helm Matthew , Tang Lucas , Casteel Clare , Innes Roger W.
Published: January 2020

TheArabidopsisresistance protein RPS5 is activated by proteolytic cleavage of the protein kinase PBS1 by thePseudomonas syringaeeffector protease AvrPphB. We have previously shown that replacing seven amino acids at the cleavage site of PBS1 with a motif cleaved by the NIa protease of turnip mosaic virus (TuMV) enables RPS5 activation upon TuMV infection. However, this engineered resistance conferred a trailing necrosis phenotype indicative of a cell death response too slow to contain the virus. We theorized this could result from a positional mismatch within the cell between PBS1TuMV, RPS5 and the NIa protease. To test this, we re-localized PBS1TuMVand RPS5 to cellular sites of NIa accumulation. These experiments revealed that relocation of RPS5 away from the plasma membrane compromised RPS5-dependent cell death inN. benthamiana, even though PBS1 was efficiently cleaved. As an alternative approach, we tested whether overexpression of plasma membrane-localized PBS1TuMVwould enhance RPS5 activation by TuMV. Significantly, over-expressing the PBS1TuMVdecoy protein conferred complete resistance to TuMV when delivered by eitherAgrobacteriumor by aphid transmission, showing that RPS5-mediated defense responses are effective against bacterial and viral pathogens. Lastly, we have now extended this PBS1 decoy approach to soybean by modifying a soybean PBS1 ortholog to be cleaved by the NIa protease of soybean mosaic virus (SMV). Transgenic overexpression of this soybean PBS1 decoy conferred immunity to SMV, demonstrating that we can use endogenous PBS1 proteins in crop plants to engineer economically relevant disease resistant traits.
Palmitvaccenic acid (Δ11-cis-hexadecenoic acid) is synthesized by an OLE1-like desaturase in the arbuscular mycorrhiza fungusRhizophagus irregularis
Authors: Brands Mathias , Cahoon Edgar B. , Dörmann Peter
Published: January 2020

Arbuscular mycorrhiza (AM) fungi deliver mineral nutrients to the plant host in exchange for reduced carbon in the form of sugars and lipids. Colonization with AM fungi upregulates a specific host lipid synthesis pathway resulting in the production of fatty acids. The fungusRhizophagus irregularisaccumulates predominantly palmitic acid (16:0) and the unusual palmitvaccenic acid (16:1Δ11cis). Here, we present the isolation and characterization ofRiOLE1-LIKE, the desaturase involved in palmitvaccenic acid synthesis, by heterologous expression in yeast and plants. Results are in line with the scenario thatRiOLE1-LIKEencodes an acyl-CoA desaturase with substrate specificity for C15-C18 acyl groups, in particular C16. Phylogenetic analysis ofRiOLE1-LIKErelated sequences revealed that this gene is conserved in AM fungi from the Glomales and Diversisporales, but is absent from non-symbiotic Mortierellaceae and Mucoromycotina fungi, suggesting that 16:1Δ11cisprovides a specific function during AM colonization.
Two-step mechanism of J-domain action in driving Hsp70 function
Authors: Tomiczek Bartłomiej , Delewski Wojciech , Nierzwicki Lukasz , Stolarska Milena , Grochowina Igor , Schilke Brenda , Dutkiewicz Rafal , Uzarska Marta A. , Ciesielski Szymon J. , Czub Jacek , Craig Elizabeth A. , Marszalek Jaroslaw
Published: January 2020

J-domain proteins (JDPs), obligatory Hsp70 cochaperones, play critical roles in protein homeostasis. They promote key allosteric transitions that stabilize Hsp70 interaction with substrate polypeptides upon hydrolysis of its bound ATP. Although a recent crystal structure revealed the physical mode of interaction between a J-domain and an Hsp70, the structural and dynamic consequences of J-domain action once bound and how Hsp70s discriminate among its multiple JDP partners remain enigmatic. We combined free energy simulations, biochemical assays and evolutionary analyses to address these issues. Our results indicate that the invariant aspartate of the J-domain perturbs a conserved intramolecular Hsp70 network of contacts that crosses domains. This perturbation leads to destabilization of the domain-domain interface - thereby promoting the allosteric transition that triggers ATP hydrolysis. While this mechanistic step is driven by conserved residues, evolutionarily variable residues are key to initial JDP/Hsp70 recognition - via electrostatic interactions between oppositely charged surfaces. We speculate that these variable residues allow an Hsp70 to discriminate amongst JDP partners, as many of them have coevolved. Together, our data points to a two-step mode of J-domain action, a recognition stage followed by a mechanistic stage.

Abstract Figure
Economic stress in non-poor Spanish households during the Great Recession
Authors: Ródenas Carmen , Martí Mónica , León Ángel
Published: January 2020

Purpose

This paper aims to focus on non-poor households that during the Great Recession experienced economic stress (ES). That is, whose economic comfort was reduced taking into account their previous living standards. The paper seeks to determine how the crisis has affected this extensive (and key) social group.

Design/methodology/approach

The analysis has been performed in a dynamic way. The non-poor households ES situation and its changes are studied throughout the period 2008-2016 by taking the four-year intervals provided by the longitudinal Spanish Living Conditions Survey. The authors discuss and select the circumstances to determine whether ES has occurred. To identify which variables determine the probability of suffering ES the authors use a standard logit model.

Findings

The main variable is the tenure status of the dwelling: property with a mortgage or rented multiply the risk of ES by up to 3.5 times. ES falls as the household’s work intensity increases. However, an improvement in the employment situation cannot be associated with a reduction in ES probability. The main socio-demographic variables behave as predicted: woman householder, grow in the number of household members and bad health increase the risk of ES, and the higher the level of education of the householder, the lower the risk.

Originality/value

There are very few studies regarding the people above the poverty line. Exploring and analyzing the factors determining the sensitivity of the largest part of the population to the crisis is very relevant, as the pace of the economic recovery depends largely on them.
The role of corporate governance on CSR disclosure and firm performance in a voluntary environment
Authors: Chijoke-Mgbame Aruoriwo Marian , Mgbame Chijoke Oscar , Akintoye Simisola , Ohalehi Paschal
Published: January 2020

Purpose

This study aims to investigate the impact of corporate social responsibility disclosure (CSRD) on firm performance and the moderating role of corporate governance on the CSRD–firm performance relationship of listed companies in Nigeria.

Design/methodology/approach

The paper uses a panel data set comprising 841 firm-year observations for the period covering 2007-2016. Fixed effect regression analysis was used to examine the relationship between CSRD and firm performance, and the moderating role of corporate governance in the CSRD–firm performance relationship.

Findings

The results of the study show that there are positive performance implications for firms that engage in CSRD. Although this study finds no effect of board size on the CSRD–firm performance relationship, it provides a strong evidence of a positive effect of board independence on the CSR–firm performance relationship.

Practical implications

The study contributes to the understanding of CSRD–firm performance relationship by providing evidence of the moderating role of corporate governance. It is, therefore, recommended that a stronger regulation be put in place for CSR engagement and the disclosure of same in Nigeria as well as robust measures for the enforcement of corporate governance mechanisms because there are economic benefits to be derived.

Originality/value

The findings contribute to the literature by providing up-to-date and original insights on the CSRD–firm performance relationship within a developing country context. It also uses an uncommon method of measuring CSRD, taking into account the institutional biases that may arise from other methods used in studies on developed countries.
Analysis of content topics, user engagement and library factors in public library social media based on text mining
Authors: Joo Soohyung , Lu Kun , Lee Taehun
Published: January 2020

Purpose

The purpose of this paper is to explore topics of Facebook posts created by public libraries using the bi-term topic model, and examine the relationships between types of topics and user engagement. The authors further investigated the effects of three library factors, namely, staff size, budget and urbanization degrees, on Facebook content and user engagement based on multilevel generalized linear modeling.

Design/methodology/approach

This study suggested a novel method, a combination of the bi-term topic modeling and MGLM, to enhance the understanding of social media in the context of public libraries.

Findings

The findings revealed that posts related to community events, awards and photos were likely to receive more likes and shares, whereas posts about summer reading programs received relatively more comments. In addition, the authors found that a larger staff size and the inclusion of multimedia had positive impacts on user engagement.

Originality/value

This study analyzed the content of public library-generated social media based on text mining. Then, the authors examined the effects of contextual library-level factors on social media practice in public libraries. Based on empirical findings, the study suggested a range of practical implications for effective use of social media in public libraries.
Exploration and refinement of migratory routes in long‐lived birds
Authors: Fayet Annette L.
Published: January 2020

In Focus: Campioni L., Dias M. P., Granadeiro J. P., & Catry P. (2019). An ontogenetic perspective on migratory strategy of a long‐lived pelagic seabird: Timings and destinations change progressively during maturation. Journal of Animal Ecology, 89, 29–43. https://doi.org/10.1111/1365-2656.13044

How migration routes develop in long‐lived migratory animals remains poorly understood. Campioni et al. (2019) tracked the migration of immature and breeding Cory's shearwaters and found that the timings and routes gradually changed with age. Young birds followed more exploratory routes at first, but gradually shortened and defined them as they matured, and they returned to the breeding grounds progressively earlier. These findings suggest that long‐lived species start by exploring potentially suitable areas for the non‐breeding season and progressively refine their migration route as they age.
Young children's narrative retell in response to static and animated stories
Authors: Diehm Emily A. , Wood Carla , Puhlman Jane , Callendar Maya
Published: January 2020

Background

The format of narrative prompts used within language assessment has remained relatively constant; however, the use of animated video prompts deserves exploration given the increase in access to technology.

Aims

To investigate the effect of story presentation format (static picture book versus animated video) on preschool children's narrative retells. It was hypothesized that children would produce more advanced narrative language elements in response to an animated video than a book.

Methods & Procedures

A total of 73 children between the ages of 3 and 5 years completed two narrative retells. One of these retells was in response to a 3‐min animated video presented on a computer; the other retell was in response to static pictures presented in a book format. Children's stories were then transcribed and coded for linguistic and narrative elements.

Outcomes & Results

Paired sample t‐tests revealed that children produced significantly longer stories, greater syntactic complexity and lexical variety, and more action verbs when retelling an animated story compared with a book. Furthermore, a post‐hoc analysis revealed that examiners provided significantly fewer prompts when eliciting the retell with animation.

Conclusions & Implications

Typically developing children demonstrated higher quantity and quality of language within a story retell in response to an animated video than after viewing images from the video presented in a static picture book. Although the extent to which these findings may be similar for children with language disorder has yet to be determined, researchers or clinicians should consider the effect of elicitation procedures on children's retells.
New occurrence of the invasive alien leaf‐footed bug Leptoglossus gonagra (Hemiptera: Coreidae) in South Korea
Authors: Lee Heejo , Kim Mi‐jeong , Bae Yang‐Seop , Kim Dong Eon
Published: January 2020

The invasive alien leaf‐footed bug Leptoglossus gonagra (Fabricius 1775), native to the Americas, is herein recorded from South Korea for the first time. Forty nymphs and adults were collected on 22 September 2016 from arable lands of two separate sites. These individuals were identified based on the analysis of morphological characters and cytochrome oxidase c subunit 1 sequences. A neighbor‐joining tree indicated the existence of two clades: Group A from Brazil, and Group B from Asia and Oceania. Mean genetic distance between clades was 8.11%, range 7.60–8.57%. Within clades, mean genetic distance was 0.42% (0.17–0.83%) in Group A and, 0.45% (0.00–0.83%) in Group B. Colonies of 2nd‐final instar nymphs and adults were found, on top of leaves, flowers, fruits, and between the stems of pumpkins (Cucurbita moschata). Nymphs and adults damaged host plants by sucking their leaves, stems, fruits, and buds. After the first discovery in 2016, we were unable to find the bugs again (in 2017–2019). Therefore, the invasion of this species seems to have occurred only temporarily, during the warm season. We suggest that the species may have failed to overwinter as it is normally distributed in regions warmer than Korea. Nevertheless, possible appearances of this species must be continuously monitored as it is a potential pest of various plants cultivated in South Korea.
Applying genomic data in wildlife monitoring: Development guidelines for genotyping degraded samples with reduced single nucleotide polymorphism panels
Authors: von Thaden Alina , Nowak Carsten , Tiesmeyer Annika , Reiners Tobias E. , Alves Paulo C. , Lyons Leslie A. , Mattucci Federica , Randi Ettore , Cragnolini Margherita , Galián José , Hegyeli Zsolt , Kitchener Andrew C. , Lambinet Clotilde , Lucas José M. , Mölich Thomas , Ramos Luana , Schockert Vinciane , Cocchiararo Berardino
Published: January 2020

The genomic era has led to an unprecedented increase in the availability of genome‐wide data for a broad range of taxa. Wildlife management strives to make use of these vast resources to enable refined genetic assessments that enhance biodiversity conservation. However, as new genomic platforms emerge, problems remain in adapting the usually complex approaches for genotyping of noninvasively collected wildlife samples. Here, we provide practical guidelines for the standardized development of reduced single nucleotide polymorphism (SNP) panels applicable for microfluidic genotyping of degraded DNA samples, such as faeces or hairs. We demonstrate how microfluidic SNP panels can be optimized to efficiently monitor European wildcat (Felis silvestris S.) populations. We show how panels can be set up in a modular fashion to accommodate informative markers for relevant population genetics questions, such as individual identification, hybridization assessment and the detection of population structure. We discuss various aspects regarding the implementation of reduced SNP panels and provide a framework that will allow both molecular ecologists and practitioners to help bridge the gap between genomics and applied wildlife conservation.
Parvovirus B19 DNAemia in pregnant women in relation to perinatal death: A nested case‐control study within a large population‐based pregnancy cohort
Authors: Barlinn Regine , Trogstad Lill , Rollag Halvor , Frøen Fredrik , Magnus Per , Dudman Susanne G.
Published: January 2020

Introduction

Parvovirus B19 (B19V) is the infectious cause of exanthema infectiosum. In Europe around 40% of pregnant women are susceptible to infection. Having small children at home is the main risk factor for contracting an infection during pregnancy. The association between B19V‐infection and perinatal death is not yet settled. The aims of the study were to estimate the association between maternal parvovirus B19 infection in pregnancy and perinatal death, and to assess the significance of a positive B19V PCR in pregnancy.

Material and methods

The study population consists of women included in the Norwegian Mother and Child Cohort Study, a prospective population‐based pregnancy cohort of nearly 100 000 women. Blood samples were obtained during weeks 17‐18 in pregnancy (M1), at birth, and in umbilical cord blood. Within participants in the pregnancy cohort, 138 cases of perinatal death and 1350 controls with live‐born children were included in a nested case‐control study. Samples were analyzed with B19V serology and B19V PCR according to a predefined test algorithm. For cases, medical records and laboratory results from hospitals were combined with the results of B19V serology and PCR. The reported causes of perinatal death were categorized using the classification system: Causes Of Death and Associated Conditions (CODAC).

Results

The B19V seroconversion rates were 9.8% for cases and 6.8% for control mothers. The odds ratio for maternal B19V infection in cases compared with controls was 1.28 (95% CI 0.35‐4.70), adjusted for age, parity, body mass index and tobacco use. B19V‐PCR‐positive samples were detected at weeks 17‐18 of gestation in both cases and controls. The proportion of positive samples was similar in cases and controls, 24% and 28.2%, respectively. Mothers with PCR‐positive M1 samples transmitted B19V vertically in 9.1% of cases and in 11.9% of the controls. Of all perinatal deaths, 53% were attributed to placental pathology or unknown causes.

Conclusions

B19V PCR positivity was high and similar in both cases and controls. In our study B19V DNAemia was not seen to be associated with fatal outcome of pregnancy. The clinical significance of B19V DNA detection during pregnancy is uncertain. Caution is needed when diagnosing a B19V infection based only on B19V DNAemia.
Scaling the environmental commons: Broadening our frame of reference for transboundary governance in Southeast Asia
Authors: Hirsch Philip
Published: January 2020

The transboundary environmental commons in Southeast Asia are normally conceived in terms of shared resources and environmental impacts that transcend national borders. The Mekong's ‘fugitive resources’ of water, fish and sediment and the issue of Indonesia's smoke haze drift into Malaysia and Singapore dominate discussion. Assumed national interests shape actors and institutional arrangements for transboundary commons governance. Failure to address the governance challenges is explained in terms of their politico‐cultural failings (e.g. the ‘ASEAN Way’ of non‐interference), the weak regulatory remit of agencies with a specific transboundary governance role (Mekong River Commission), the dominant developmental agenda of subregional cooperative arrangements (Greater Mekong Subregion) or the geopolitical dominance of China (Lancang–Mekong Cooperation). This article builds on these critiques by considering the relationship between the local commons impacted by transboundary projects and the framing of the commons at an inter‐governmental level. It shows that neglect of the local commons and the impacts on them of projects with transboundary effects is partly to be explained by the institutional scaling of the transboundary commons at a country‐to‐country level. It also argues for an expanded notion of transboundary, including investment and governance flows as well as the material environmental footprint of large‐scale investments.
Pharmacodynamic assessment of mycophenolic acid in resting and activated target cell population during the first year after renal transplantation
Authors: Klaasen Rolf Anton , Bergan Stein , Bremer Sara , Hole Kristine , Nordahl Christine Berg , Andersen Anders Mikal , Midtvedt Karsten , Skauby Morten Heier , Vethe Nils Tore
Published: January 2020

Aims

To explore the pharmacodynamics of mycophenolic acid (MPA) through inosine monophosphate dehydrogenase (IMPDH) capacity measurement and purine levels in peripheral blood mononuclear cells (PBMC) longitudinally during the first year after renal transplantation (TX).

Methods

PBMC were isolated from renal recipients 0–4 days prior to and 6–9 days, 5–7 weeks and 1 year after TX (before and 1.5 hours after dose). IMPDH capacity and purine (guanine and adenine) levels were measured in stimulated and nonstimulated PBMC.

Results

Twenty‐nine patients completed the follow‐up period, of whom 24 received MPA. In stimulated PBMC, the IMPDH capacity (pmol 10−6 cells min−1) was median (interquartile range) 127 (95.8–147) before TX and thereafter 44.9 (19.2–93.2) predose and 12.1 (4.64–23.6) 1.5 hours postdose across study days after TX. The corresponding IMPDH capacity in nonstimulated PBMC was 5.71 (3.79–6.93), 3.35 (2.31–5.62) and 2.71 (1.38–4.08), respectively. Predose IMPDH capacity in nonstimulated PBMC increased with time, reaching pre‐TX values at 1 year. In stimulated PBMC, both purines were reduced before (median 39% reduction across days after TX) and after (69% reduction) dose compared to before TX. No alteration in the purine levels was observed in nonstimulated PBMC. Patients needing dose reductions during the first year had lower pre‐dose IMPDH capacity in nonstimulated PBMC (1.87 vs 3.00 pmol 10−6 cells min−1, P = .049) at 6–9 days.

Conclusion

The inhibitory effect of MPA was stronger in stimulated PBMC. Nonstimulated PBMC became less sensitive to MPA during the first year after TX. Early IMPDH capacity appeared to be predictive of dose reductions.
First‐in‐human clinical trial to assess the safety, tolerability and pharmacokinetics of P218, a novel candidate for malaria chemoprotection
Authors: Chughlay M. Farouk , Rossignol Emilie , Donini Cristina , El Gaaloul Myriam , Lorch Ulrike , Coates Simon , Langdon Grant , Hammond Tim , Möhrle Jörg , Chalon Stephan
Published: January 2020

Aims

This first‐in‐human clinical trial of P218, a novel dihydrofolate reductase inhibitor antimalarial candidate, assessed safety, tolerability, pharmacokinetics and food effects in healthy subjects.

Methods

The study consisted of two parts. Part A was a double‐blind, randomized, placebo‐controlled, parallel group, ascending dose study comprising seven fasted cohorts. Eight subjects/cohort were randomized (3:1) to receive either a single oral dose of P218 (10, 30, 100, 250, 500, 750 and 1000 mg) or placebo. Part B was an open‐label, cross‐over, fed/fasted cohort (eight subjects) that received a 250 mg single dose of P218 in two treatment periods.

Results

P218 was generally well tolerated across all doses; 21 treatment‐emergent adverse events occurred in 15/64 subjects. Nine adverse events in five subjects, all of mild intensity, were judged drug related. No clinically relevant abnormalities in ECG, vital signs or laboratory tests changes were observed. P218 was rapidly absorbed, with Cmax achieved between 0.5 and 2 hours post dose. Plasma concentrations declined bi‐exponentially with half‐life values ranging from 3.1 to 6.7 hours (10 and 30 mg), increasing up to 8.9 to 19.6 hours (doses up to 1000 mg). Exposure values increased dose‐proportionally between 100 and 1000 mg for P218 (parent) and three primary metabolites (P218 β‐acyl glucuronide, P218‐OH and P218‐OH β‐acyl glucuronide). Co‐administration of P218 with food reduced Cmax by 35% and delayed absorption by 1 hour, with no significant impact on AUC.

Conclusion

P218 displayed favourable safety, tolerability and pharmacokinetics. In view of its short half‐life, a long‐acting formulation will be needed for malaria chemoprotection.
The ‘tyranny of reproduction’: Could ectogenesis further women’s liberation?
Authors: MacKay Kathryn
Published: January 2020

This paper imagines what the liberatory possibilities of (full) ectogenesis are, insofar as it separates woman from female reproductive function. Even before use with human infants, ectogenesis productively disrupts the biological paradigm underlying current gender categories and divisions of labour. I begin by presenting a theory of women’s oppression drawn from the radical feminisms of the 1960s, which sees oppression as deeply rooted in biology. On this view, oppressive social meanings are overlaid upon biology and body, as artefacts of culture and history. I then argue that ectogenesis should be pursued to replace two modes of assisted gestation that can be seen as outgrowths of oppressive assumptions about women's function, ectogenesis should be pursued to replace two modes of assisted gestation. These are gestational surrogacy and uterine transplant, which arise partly from gendered, pronatalist, and geneticist norms. These practices are supported by assumptions about women’s identity and value. Pursuing technologies such as ectogenesis, which weaken the presumed link between biology and gender, is beneficial to (trans‐inclusionary radical) feminist aims, as part of a broad project of challenging dominant power relations resting on and maintaining gender categories. By allowing the conceptual separation of female reproductive function from ‘woman’, ectogenesis raises questions about how we determine who counts in this gender identity, and also how we value those who claim the identity ‘woman’. I conclude that ectogenesis has the potential to challenge traditional patriarchal family structures, and thence all other male‐dominated structures (of work, education, cultural production), allowing a reimagining of the family and society in more radical ways than we have yet achieved.
Phenotypes of fetal macrosomia and risk of stillbirth among term deliveries over the previous four decades
Authors: Salihu Hamisu M. , Dongarwar Deepa , King Lindsey M. , Yusuf Korede K. , Ibrahimi Sahra , Salinas‐Miranda Abraham A.
Published: January 2020

Objectives

To evaluate the association between macrosomia and stillbirth over the previous four decades and to determine the consistency of the relationship.

Methods

This was a population‐based retrospective cohort study using United States Natality and Fetal Death Data from 1982 to 2017 and restricted to the gestational age range of 37‐41 weeks inclusive. Macrosomia was defined as birthweight ≥4000 g and subdivided into its grades as previously recommended: grade 1 (4000‐4499 g), grade 2 (4500‐4999 g), and grade 3 (≥5000 g). We calculated temporal trends of stillbirth among fetuses with macrosomia over the years using joinpoint regression. We generated odds ratios from adjusted binomial logistic regression models to examine the association between macrosomia and risk of stillbirth stratified by grades using normal‐weight infants (2500‐3999 g) as referent.

Results

Within the fetal macrosomia group, the rate of stillbirth declined from 2.04/1000 in 1982 to 1.05/1000 by the end of the study period (2017), representing a drop of about 48.5%. For the normal‐weight fetuses, stillbirth rate declined from 1.95/1000 to 0.83/1000, equivalent to a decline of 57.4%. Macrosomia was significantly associated with elevated risk for stillbirth: grade 2 (OR = 1.27; 95% CI = 1.22‐1.32) and grade 3 (OR = 5.97; 95% CI = 5.69‐6.22).

Conclusions

Fetal macrosomia is a significant risk factor for fetal demise with the worst intrauterine survival observed among those classified as grade 3. Fetal macrosomia is a heterogeneous rather than a homogeneous entity in terms of risk profiles, and this needs to be considered in future policy guidelines.
ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target
Authors: Kimura Kenji , Matsumoto Shinji , Harada Takeshi , Morii Eiichi , Nagatomo Izumi , Shintani Yasushi , Kikuchi Akira
Published: January 2020

Lung adenocarcinoma is the most common histological type of lung cancer and is classified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). Atypical adenomatous hyperplasia (AAH) lesions are possible precursors to adenocarcinoma. However, the mechanism underlying the stepwise continuum of lung adenocarcinoma is unclear. In this study, the involvement of ADP‐ribosylation factor (ARF)‐like (ARL) 4C (ARL4C), a member of the small GTP‐binding protein family, in the progression of lung adenocarcinoma and the possibility of ARL4C as a molecular target for lung cancer therapy were explored. ARL4C was frequently expressed in AAH and ARL4C expression in immortalized human small airway epithelial cells promoted cell proliferation and suppressed cell death. In addition, ARL4C was expressed with increased frequency in AIS, MIA and IA in a stage‐dependent manner, and the expression was correlated with histologic grade, fluorine‐18 fluorodeoxyglucose uptake and poor prognosis. An anti–sense oligonucleotide (ASO) against ARL4C (ARL4C ASO‐1316) inhibited RAS‐related C3 botulinum toxin substrate activity and nuclear import of Yes‐associated protein and transcriptional coactivator with PDZ‐binding motif, and suppressed in vitro proliferation and migration of lung cancer cells with KRAS or epidermal growth factor receptor (EGFR) mutations. In addition, transbronchial administration of ARL4C ASO‐1316 suppressed orthotopic tumor formation induced by these cancer cells. Thus, ARL4C is involved in the initiation of the premalignant stage and is associated with the stepwise continuum of lung adenocarcinoma. ARL4C ASO‐1316 would be useful for lung adenocarcinoma patients expressing ARL4C regardless of the KRAS or EGFR mutation.
Extracellular vesicles and asthma: A review of the literature
Authors: Sangaphunchai Phoomphut , Todd Ian , Fairclough Lucy C.
Published: January 2020

Asthma is a chronic, recurrent and incurable allergy‐related respiratory disease characterized by inflammation, bronchial hyperresponsiveness and narrowing of the airways. Extracellular vesicles (EVs) are a universal feature of cellular function and can be detected in different bodily fluids. Recent evidence has shown the possibility of using EVs in understanding the pathogenesis of asthma, including their potential as diagnostic and therapeutic tools. Studies have reported that EVs released from key cells involved in asthma can induce priming and activation of other asthma‐associated cells. A literature review was conducted on all current research regarding the role and function of EVs in the pathogenesis of asthma via the PRISMA statement method. An electronic search was performed using EMBASE and PubMed through to November 2018. The EMBASE search returned 76 papers, while the PubMed search returned 211 papers. Following duplicate removal, titles and abstracts were screened for eligibility with a total of 34 studies included in the final qualitative analysis. The review found evidence of association between the presence of EVs and physiological changes characteristic of asthma, suggesting that EVs are involved in the pathogenesis, with the weight of evidence presently favouring deleterious effects of EVs in asthma. Numerous studies highlighted differences in exosomal contents between EVs of healthy and asthmatic individuals, which could be employed as potential diagnostic markers. In some circumstances, EVs were also found to be suppressive to disease, but more often promote inflammation and airway remodelling. In conclusion, EVs hold immense potential in understanding the pathophysiology of asthma, and as diagnostic and therapeutic markers. While more research is needed for definitive conclusions and their application in medical practice, the literature presented in this review should encourage further research and discovery within the field of EVs and asthma.
Effects of tibolone or continuous combined oestradiol and norethisterone acetate on lipids, high‐density lipoprotein subfractions and apolipoproteins in postmenopausal women in a two‐year, randomized, double‐blind, placebo‐controlled trial
Authors: Kotecha Payal Trupti , Godsland Ian F. , Crook David , Stevenson John C.
Published: January 2020

Objective

To compare the effects of (a) tibolone, (b) continuous combined oestrogen plus progestogen and (c) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy postmenopausal women.

Study design

Randomized, single‐centre, placebo‐controlled, double‐blind study.

Patients

One hundred and one postmenopausal women were randomized (1:1:1) into one of three groups taking daily 2.5 mg tibolone, continuous oral oestradiol‐17β 2 mg plus norethisterone acetate 1 mg daily (E2/NETA) or placebo.

Main outcome measures

Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24 months of treatment.

Results

Both tibolone and E2/NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high‐density lipoprotein cholesterol (HDL‐C) was reduced (−27% at 24 months, P < .001), the greatest effect being in the cholesterol‐enriched HDL2 subfraction (−40%, P < .001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (−29% at 24 months, P < .001). However, there was no significant effect of tibolone on low‐density or very low‐density lipoprotein cholesterol (LDL‐C and VLDL‐C, respectively). By contrast, the greatest reduction in cholesterol with E2/NETA was in LDL‐C (−22% at 24 months, P = .008). E2/NETA reduced HDL‐C to a lesser extent than tibolone (−12% at 24 months, P < .001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E2/NETA had no effect on VLDL‐C or on the protein component of LDL, apolipoprotein B.

Conclusion

Tibolone reduces serum HDL. E2/NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome: Diagnosis, treatment and the current status in Japan
Authors: Suichi Tomoki , Misawa Sonoko
Published: January 2020

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare cause of demyelinating polyneuropathy associated with monoclonal proliferation of plasma cells. Because the disorder shows diverse symptoms, its diagnosis is often difficult. Previously reported diagnostic criteria had many items, and their accuracy was not confirmed. Recently, new diagnostic criteria have been proposed, which consist of just seven items and have better diagnostic accuracy. Since around 2000, treatments for myeloma, such as high‐dose chemotherapy with autologous stem cell transplantation, immunomodulatory drugs and proteasome inhibitors, have been applied to polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome. A recent national survey carried out in Japan showed that the prognosis has been prominently improved by these plasma cell‐targeting therapeutic interventions: 10‐year overall survival was 93%. Conversely, 24% of the patients were still treated with corticosteroid alone as an initial treatment, suggesting that recognition of the disorder is not sufficient. Accurate diagnosis and proper treatment in the early phase of the disease are essential to further improve the prognosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome. The present review focuses on diagnosis, treatment and the current status of the disease in Japan.
Transitions to Adulthood of ‘At Risk’ Young Men: New Analysis from Two Norwegian Qualitative Longitudinal Studies
Authors: Solem May‐Britt , Helgeland Ingeborg Marie , Brannen Julia , Phoenix Ann
Published: January 2020

This paper focuses on two cohorts of Norwegian young men whose behaviour in childhood and adolescence caused serious concern to their parents, teachers, social workers and, in some cases, the police, Despite having been identified as ‘at risk’, they made transitions to positive adult masculine identities in two different historical contexts; the 1980s and 2000s. The paper analyses the difference that historical context makes to these young men’s lives, their gendered identity work and their perspectives on their past, present and future. In particular, it identifies the ways in which supportive intergenerational relationships and significant others serve to produce positive turning points and, over time, help the young men to develop resilience and potentially happy and successful futures.
Gardening in Times of Urban Transitions: Emergence of Entrepreneurial Cultivation in Post–Katrina New Orleans
Authors: Kato Yuki
Published: January 2020

Expanding scholarship on urban farming has not systematically examined what spurs the proliferation of cultivation practices, especially when the city is undergoing economic and social transitions. This study examines the development of the urban cultivation (UC) scene in New Orleans over the decade following Hurricane Katrina with a particular focus on entrepreneurial UC projects. By contextualizing in–depth interviews with the growers in the historical events in the city, the study finds that the dominant motives of cultivation projects shifted from social missions to economic interests over time, as the city transitioned from recovery to redevelopment. The study highlights the heterogeneity of UC practices, and questions the current scholarship's tendency to situate urban gardens in opposing theoretical frameworks: tools for neoliberal urbanism or food justice activism. The findings show that the distinction between socially motivated and economically motivated UC cannot be easily drawn. Most of the socially motivated UC projects began adopting market participation over time, while many of the economically motivated UC projects operated as social entrepreneurialism. While growers tended to view themselves as alternative to the dominant political–economic system, they also undoubtedly benefitted from the market–driven redevelopment of the city that expanded UC opportunities.
Enhancing the wash fastness of disperse dyes on wool with oxidants
Authors: McNeil Steven J. , Zaitseva Larissa I.
Published: January 2020

Disperse dyes are not currently applied to wool commercially, in large part because of inadequate wash fastness, but they do have potential, especially for wool‐polyester blends. In this study, for the first time hydrogen peroxide was investigated to increase the wash fastness of disperse dyes on wool. In the absence of oxidants, 10 disperse dyes from seven classes imparted colours with a range of depths (K/S 2‐26) with wash fastness (grey scale ratings for colour change) grades of 3 to 4‐5. Hydrogen peroxide had only small effects on colours and gave only small enhancements to wash fastness, which were limited to anthraquinone, nitrodiphenylamine, disazo and coumarin dyes. The bleach activators Prestogen W and citric acid enhanced the bleaching effect of hydrogen peroxide but did not assist with raising wash fastness. Hydrogen peroxide in post‐dyeing scouring made the dyeings brighter but did not significantly enhance wash fastness. Ammonium persulphate, which was included for benchmarking with earlier studies, yellowed the wool and decomposed some dyes. This study extends the range of dye classes whose wash fastness on wool can be improved by ammonium persulphate to now include diazo, coumarin and methine, and confirms that oxidants/free radical initiators have potential for enabling the disperse dyeing of wool.
Consistency issues in hair spectral reflectance and colour measurements
Authors: Liberini Simone , Avolio Antonio , Yankowski Stevn Thomas , Rizzi Alessandro
Published: January 2020

The colour shade quality control scenario is ubiquitous within the cosmetic hair colouring industry. Visual inspection is nowadays the go‐to standard for the evaluation of dye application outcomes, even although the increased availability of easily operated spectrophotometers has favoured the introduction of colorimeters in the manufacturing process. Human hairs, however, are very efficient scatterers, and this makes their instrumental measurements more difficult and less consistent. To assess the degree to which this intrinsic property compromises the reliability of spectrophotometric measurements, we tested a variety of samples of human hair locks (swatches), both dyed and undyed, and those of nylon fibre hair swatches. First, we analysed results from two measuring modalities made available by instrumentation: Specular Component Included and Specular Component Excluded. Then, to modify macroscopic spatial orientation, we arranged swatches so that hair strands would cross at varying angles. Measurements confirmed the expected dependencies, namely, the clear influence of the scattered component and of sample orientation on instrumental reading outputs. Having settled on a preferred measuring setup, we analysed measurement variance. Here, we briefly discuss the qualitative visual inspection of spectra, before switching to ΔE to show the unreliability, at least as far as lighter coloured dyes are concerned, of the classic target‐sample measurements which are employed to issue pass‐or‐fail verdicts. Despite quantitative measurements being an asset for quality control, we suggest that greater care should be placed in spectrophotometric readings when human hair is involved, as opposed to more traditional fields of application.
Social Policy, Inequalities and the Battle of Rights in Latin America
Authors: Riggirozzi Pia
Published: January 2020

Targeted social policies and other more universal forms of social protection have shaped (the shifts in) the politics of popular support in Latin America. Since the early 2000s this has led to a tendency towards the election of left‐leaning governments, stimulating stronger political pressure for more extensive redistribution. Yet despite a wide range of cash transfers, subsidies and other social policies, the ‘post‐neoliberal’ ideal of welfare did not reshape the political and relational powers of citizens in the ways necessary to redress the structural determinants of poverty and inequality across the region. This article reveals a ‘dark side’ of social policy in Latin America, arguing that targeted and precariously funded welfare regimes are creating tensions between the socio‐economic and ecological spheres that undermine inclusive citizenship and democracy.
Evaluation of a new e‐learning resource for calibrating OSCE examiners on the use of rating scales
Authors: Moreno‐López Rosa , Sinclair Serena
Published: January 2020

Introduction

Rating scales have been described as better at assessing behaviours such as professionalism during Objective Structured Clinical Examinations (OSCEs). However, there is an increased need to train and calibrate staff on their use prior to student assessment.

Material and methods

An online e‐learning package was developed and made available to all examiners at the Institute of Dentistry at the University of Aberdeen. The package included videos of three OSCE stations (medical emergency, rubber dam placement and handling a complaint) which were recorded in two different scenarios; (excellent and unsatisfactory candidate). These videos were recorded to meet a pre‐defined marking score. The examiners were required to mark the six videos using pre‐set marking criteria (checklist and rating scales). The rating scales included professionalism, general clinical ability and/or communication skills. For each video, examiners were given four possible options (unsatisfactory, borderline, satisfactory or excellent), and they were provided with a description for each domain. They were also required to complete a questionnaire to gather their views on the use of this e‐learning environment.

Results

Fifteen examiners completed the task. The total scores given were very similar to the expected scores for the medical emergency and complaint stations; however, this was not the case for the rubber dam station (P‐value .017 and .036). This could be attributed to some aspects of the placement of the rubber dam being unclear as commented on in the examiners questionnaires. There was consistency in the selection of marks on the rating scales (inter‐examiner correlation ranged between 0.916 and 0.979).

Conclusion

Further studies are required on the field of e‐learning training to calibrate examiners for practical assessment; however, this study provides preliminary evidence to support the use of videos as part of an online training package to calibrate OSCE examiners on the use of rating scales.
Dental educators’ attitudes towards the teaching of dental amalgam
Authors: Alexander George , Hopcraft Matthew S. , Tyas Martin J. , Wong Rebecca H. K.
Published: January 2020

Objective

To ascertain dental educators’ attitudes towards the teaching of dental amalgam at dental schools in Australia and identify preferred curricular approaches in a potentially “amalgamless” profession.

Methods

A mixed methods analysis was employed based on an open‐ended response survey followed by a closed‐ended questionnaire. Identification of key issues from the survey helped frame the questionnaire. Participants included those with expertise in operative and restorative dentistry, with direct involvement in curriculum development or delivery, at Australian dental schools.

Results

Participants numbered fifteen and represented seven of the nine dental schools in Australia. Key themes identified and explored included the following: (in)consistency of approach to teaching restorative dentistry; a perceived disconnect between undergraduate study and the “real world”; a need for a focus on teaching of alternatives to dental amalgam (80 per cent (strongly) agreeing); the contradictory nature of the evidence base and literature that is not readily understood; the need for more post‐graduate education relating to adhesive restorative materials (86 per cent (strongly) agreeing); the need for dental amalgam to continue to be available; formal understandings (guidelines) as to the use of dental amalgam; dental schools in Australia being heard on these issues; and the relevance of this issue (100 per cent (strongly) agreeing the issue is topical and important).

Conclusion

There is a broad consensus of dental educators at Australian dental schools as how best to approach the teaching of amalgam if a phase‐down is to occur and the issues any such approach may face.
Two conceptions of voluntary action in the Nicomachean Ethics
Authors: Wolt Daniel
Published: January 2020

It is nearly universally agreed among commentators that according to Aristotle's account of voluntary action in the Nicomachean Ethics (NE), only voluntary actions are blameworthy. I argue for a qualified rejection of this assumption: some actions that Aristotle counts as blameworthy do not meet the criteria for voluntariness set out in NE 3.1. However, in NE 3.5 and elsewhere, one finds a broader conception of voluntary action, and it is true that, for Aristotle, an action must be voluntary on this broader conception in order to be blameworthy. While the narrow conception only counts actions that are under the agent's direct control as voluntary, the broader conception includes also actions that are under the agent's indirect control. The compresence of these two conceptions in the NE is not simply a matter of sloppiness on Aristotle's part. Rather, he has good philosophical reasons for employing both.