bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcal superantigen-like protein 13 activates neutrophils via Formyl Peptide Receptor 2
Authors: Zhao Yuxi , van Kessel Kok P. M. , de Haas Carla J. C. , Rogers Malbert R. C. , van Strijp Jos A. G. , Haas Pieter-Jan A.
Published: April 2018

Staphylococcal Superantigen-Like (SSL) proteins, one of major virulence factor families produced byStaphylococcus aureus, were previously demonstrated to be immune evasion molecules that interfere with a variety of innate immune defenses. However, in contrast to these characterized SSLs, that inhibit immune functions, we show that SSL13 is a strong activator of neutrophils via the formyl-peptide receptor 2 (FPR2). Moreover, our data show that SSL13 acts as a chemoattractant, induces degranulation and oxidative burst in neutrophils. As with many other staphylococcal immune evasion proteins, SSL13 shows a high degree of human specificity. SSL13 is not able to efficiently activate mouse neutrophils, hamperingin vivoexperiments.

In conclusion, SSL13 is a neutrophil chemoattractant and activator that acts via the FPR2. Therefore, SSL13 is a unique SSL member that does not belong to the immune evasion class, but is a pathogen alarming molecule.
The holdase function of Escherichia coli Hsp70 (DnaK) chaperone
Authors: Winardhi Ricksen S. , Tang Qingnan , You Huijuan , Sheetz Michael , Yan Jie
Published: April 2018

In Escherichia coli, the DnaK/DnaJ/GrpE system plays a critical role in mediating protein refolding and buffering against protein aggregation due to environmental stress. The underlying mechanism remains unclear. In this work, we probe the activity of DnaK/DnaJ/GrpE system with single-molecule protein refolding assay using tandem repeats of titin immunoglobulin 27 (I27)8. We provide direct evidence that DnaK in apo– and ADP-bound state is predominantly a holdase, which kinetically stabilizes the polyprotein in its unfolded form. Binding of ATP relieves DnaK’s holding, allowing protein refolding. The presence of co-chaperone DnaJ and GrpE modulates this holding-release switching, possibly by altering DnaK’s nucleotide state. Our findings thus provide important insights to the molecular mechanism of DnaK/DnaJ/GrpE system.
ARKS: chromosome-scale scaffolding of human genome drafts with linked read kmers
Authors: Coombe Lauren , Zhang Jessica , Vandervalk Benjamin P , Chu Justin , Jackman Shaun D , Birol Inanc , Warren René L
Published: April 2018

Background

The long-range sequencing information captured by linked reads, such as those available from 10x Genomics (10xG), helps resolve genome sequence repeats, and yields accurate and contiguous draft genome assemblies. We introduce ARKS, an alignment-free linked read genome scaffolding methodology that uses linked reads to organize genome assemblies further into contiguous drafts. Our approach departs from other read alignment-dependent linked read scaffolders, including our own (ARCS), and uses a kmer-based mapping approach. The kmer mapping strategy has several advantages over read alignment methods, including better usability and faster processing, as it precludes the need for input sequence formatting and draft sequence assembly indexing. The reliance on kmers instead of read alignments for pairing sequences relaxes the workflow requirements, and drastically reduces the run time.

Results

Here, we show how linked reads, when used in conjunction with Hi-C data for scaffolding, improve a draft human genome assembly of PacBio long-read data five-fold (baseline vs. ARKS NG50=4.6 vs. 23.1 Mbp, respectively). We also demonstrate how the method provides further improvements of a megabase-scale Supernova human genome assembly, which itself exclusively uses linked read data for assembly, with an execution speed six to nine times faster than competitive linked read scaffolders. Following ARKS scaffolding of a human genome 10xG Supernova assembly (of cell line NA12878), fewer than 9 scaffolds cover each chromosome, except the largest (chromosome 1, n=13).

Conclusions

ARKS uses a kmer mapping strategy instead of linked read alignments to record and associate the barcode information needed to order and orient draft assembly sequences. The simplified workflow, when compared to that of our initial implementation, ARCS, markedly improves run time performances on experimental human genome datasets. Furthermore, ARKS utilizes barcoding information from linked reads to estimate gap size. It accomplishes this by modeling the relationship between known distances of a region within contigs and calculating associated Jaccard indices. ARKS has the potential to provide correct, chromosome-scale, genome assemblies, promptly. We expect ARKS to have broad utility in helping refine draft genomes.
Multi-target visual search organisation across the lifespan: Cancellation task performance in a large and demographically stratified sample of healthy adults
Authors: Benjamins Jeroen S. , Dalmaijer Edwin S. , Brink Antonia F. Ten , Nijboer Tanja C.W. , Stigchel Stefan Van der
Published: April 2018

Highlights

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Cancellation tasks are useful clinical tools that probe many cognitive modules

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We used cancellation tests on 523 participants of different ages, sex, and education

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We provide cancellation task norm scores for indices computed from a big sample

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Cancellation indices include attention bias, processing speed and search organisation

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About a quarter of the healthy population shows relatively disorganised search

It is important that accurate tests exist to assess cognition in various groups of individuals. One popular test of attention and executive functioning is the cancellation task, in which participants perform multi-target visual search to find and ‘cancel’ targets among distractors. Although cancellation tasks have been used extensively with neurological patients, it is only partly clear whether performance is affected by demographic variables such as age and education, which can vary wildly among patients. Here, we describe performance in a sample of 523 healthy participants who participated in a web-based cancellation task. Specifically, we examined indices of spatial bias, processing speed, perseveration and revisiting behaviour, and search organisation. In this sample, age, sex, and level of education did not affect cancellation performance. A cluster analysis identified four cognitive profiles: Participants who make many omissions (N=18), who make many revisits (N=18), who have relatively poor search organisation (N=125), and who have relatively good search organisation (N=362). We advise neurologists and neuropsychologists to exercise caution when interpreting scores pertaining to search organisation in patients: Given the large proportion of healthy individuals with poor search organisation, disorganised search in patients might be pre-existing rather than disorder-related. Finally, we include norm scores for indices of spatial bias, perseverations and revisits, processing speed, and search organisation for a popular cancellation task.
Effective population sizes and adaptive genetic variation in a captive bird population
Authors: Athrey Giridhar , Faust Nikolas , Charlotte Hieke Anne-Sophie , Brisbin I. Lehr
Published: April 2018

Captive populations are considered a key component of ex situ conservation programs. Research on multiple taxa have shown the differential success of maintaining demographic versus genetic stability and viability in captive populations. In typical captive populations, usually founded by few or related individuals, genetic diversity can be lost and inbreeding can accumulate rapidly, calling into question their ultimate utility for release into the wild. Furthermore, domestication selection for survival in captive conditions is another concern. Therefore, it is crucial to understand the dynamics of population sizes, particularly the effective population size, and genetic diversity at non-neutral, at adaptive loci in captive populations.

In this study, we assessed effective population sizes and genetic variation at both neutral microsatellite markers, as well as SNP variants from the MHC-B locus of a captive Red Junglefowl population. This population is represents a rare instance of a population with a well-documented history in captivity, following a realistic scenario of chain-of-custody, unlike captive lab populations. Our analysis, which included 27 individuals comprising the entirety of one captive population show very low neutral and adaptive genetic variation, as well as low effective sizes, which are surprising in spite of the known demographic history. Finally, our study also shows the divergent impacts of small effective size and inbreeding in captive populations on microsatellite versus adaptive genetic variation in the MHC-B locus. Our study provides insights into the difficulties of maintaining adaptive genetic variation in small captive populations.
BgTEP: an antiprotease involved in innate immune sensing in Biomphalaria glabrata
Authors: Portet Anaïs , Galinier Richard , Pinaud Silvain , Portela Julien , Nowacki Fanny , Gourbal Benjamin , Duval David
Published: April 2018

Insect Thioester-containing protein (iTEP) is the most recently defined group among the TEP superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterised from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians and mollusks albeit with few functional characterisations. In the freshwater snail Biomphalaria glabrata, a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (FREP) and schistosome parasite mucins (SmPoMuc).

To investigate the potential role of BgTEP in the immune response of the snail, we first characterised its genomic organisation and its predicted protein structure. A phylogenetic analysis clustered BgTEP in a well-conserved subgroup of mollusk TEP. We then investigated the BgTEP expression profile in different snail tissues, and followed immune challenges using different kinds of intruders during infection kinetics. Results revealed that BgTEP is particularly expressed in hemocytes, the immune-specialised cells in invertebrates, and is secreted into the hemolymph. Transcriptomic results further evidenced an intruder-dependent differential expression pattern of BgTEP whilst interactome experiments showed that BgTEP is capable of binding to the surface of different microbes and parasite either in its full length form or in processed forms.

Through this work, we report the first characterisation of a snail TEP. Our study also reveals that BgTEP may display an unexpected functional dual-role. In addition to its previously characterised anti-protease activity, we demonstrate that BgTEP can bind to the intruder surface membrane, which supports a likely opsonin role.
Study of melanin localization in the mature maleCalopteryx haemorrhoidalisdamselfly wings
Authors: Truong Vi Khanh , Vongsvivut Jitraporn , Geeganagamage Nipuni Mahanamanam , Tobin Mark J. , Luque Pere , Baulin Vladimir , Werner Marco , Maclaughlin Shane , Crawford Russell J. , Ivanova Elena P.
Published: April 2018

DamselfliesCalopteryx haemorrhoidalisexhibiting black wings are found in the western Mediterranean, Algeria, France, Italy, Spain and Monaco. Wing pigmentation is caused by the presence of melanin, which is involved in physiological processes including defence reactions, wound healing and sclerotization of the insect. Despite the important physiological roles of melanin, the presence and colour variation among males and females of theC. haemorrhoidalisspecies and the localization of the pigment within the wing membrane remain poorly understood. In this study, infrared (IR) microspectroscopy, coupled with the highly collimated synchrotron IR beam, was employed in order to identify the distribution of the pigments in the wings at a high spatial resolution. It was found that the melanin is localized in the procuticle of theC. haemorrhoidalisdamselfly wings, distributed homogeneously within this layer, and not associated with the lipids of the epicuticle.
Shortening lead-time from project initiation to delivery
Authors: Økland Andreas , Johansen Agnar , Olsson Nils O.E.
Published: April 2018

Purpose

Standardizing the development, planning and construction of public building projects can contribute to timely and efficient project delivery. This is especially relevant when there are urgent needs for capacity. The purpose of this paper is to share the experiences from the development of standardized concepts for school extensions and prison building in Norway.

Design/methodology/approach

The research questions posed in this paper are on the interaction between public entities project delivery models and standardizing building types and the construction method. To investigate the research questions, the paper presents the findings from two case studies: school and prison development and construction projects. It is based on a literature review, semi-structured interviews, document studies and quantitative data on time and cost for the planning and construction phases.

Findings

Standardization and use of modularized building systems can contribute to shortened delivery time by reducing the duration of both the planning and construction phase. The most significant time reduction resulted from less time spent on quality assurance of cost estimates prior to the funding of the projects. Project costs increased in the school case, but were reduced in the prison case. An important challenge faced in both cases is a shallow pool of capable suppliers; the actors have approached the challenge with different strategies, yet neither actor has been successful in their attempts.

Originality/value

The paper provides empirical data to add to the collective knowledge on the project management aspects of using standardized project delivery models and standardized (modular) building. However, by emphasizing the interaction between project delivery models and standardization of the planning and execution of the projects, additional insight into the benefits and challenges are highlighted.
In vogue: demand for scholarly publications among academic librarians
Authors: Quagraine Nana Tuhufo , Agyekum Baffour Ohene
Published: April 2018

Purpose

The lack of a country-wide data on the extent to which academic librarians in Ghana publish combined with perceived publishing challenges as indicated by a number of scholars including Opoku (2012) leaves much to be desired. Therefore, the purpose of this paper is to seek the views of professional librarians in Ghana on the subject.

Design/methodology/approach

Using a sample size of 45 out of 50 academic librarians who make up the membership of the Consortium of Academic and Research Libraries, the study employed the descriptive survey research strategy in identifying the prospects and challenges associated with academic publications among librarians in Ghana.

Findings

Opportunities for growth, institutional encouragement, requirements for promotion, and opportunities for research training are some of the factors that motivated academic librarians to publish in scholarly journals notwithstanding the pressures to perform their professional duties. Challenges often encountered included lack of research grants, high rejection rate of publishing agencies, lack of research skills and difficulty in getting access to research journals.

Practical implications

On the basis of the above, the establishment of research fund and an award scheme for persons or units with the highest number of publications among others are recommended.

Originality/value

With the exception of cited works, all other forms of this research output are the handiwork of the researchers and have neither been a reproduction of existing research nor ever published in any other journal.
“A feminine brand? Never!” Brands as gender threats for “resistant” masculinities
Authors: Ulrich Isabelle , Tissier-Desbordes Elisabeth
Published: April 2018

Purpose

The purpose of this paper is to examine the relationships between men and brands and specifically how they configure their masculinities in relation to daily used brands.

Design/methodology/approach

In-depth interviews with projective technique were conducted with 20 men with different masculinities and sexual orientations to explore their practices regarding and relations to various product categories and brands.

Findings

First, this paper shows how men’s relationships to daily used brands vary according to different forms of masculinities, in a continuum apparently disconnected from sexual orientation. Men with “resistant” masculinities are strongly attached to choosing masculine brands; others with more hybrid masculinities are more open to feminine brands and do not care about brand gender. Second, this paper shows the importance of brand gender salience: Men with more traditional masculinities interpret brands through the prism of gender first and over-interpret gendered cues in brand execution. Third, feminine brands are considered as threats for men with traditional masculinities. Fourth, brand extensions to the opposite sex are criticized by men with more traditional masculinities but appreciated by men with hybrid masculinities, independently of sexual orientation.

Originality/value

This paper investigates the relationships between men and brand gender for daily used brands, by introducing a diversity of masculinities. Furthermore, it builds on a qualitative approach to capture individuals’ diverse masculinities. This helps capture the complexity of gender and better understand the relationships between men, masculinities and brands.
Digital Infrastructure as a Determinant of Health Equity: An Australian Case Study of the Implementation of the National Broadband Network
Authors: Schram Ashley , Friel Sharon , Freeman Toby , Fisher Matthew , Baum Fran , Harris Patrick
Published: April 2018

Inequities in access to fast and reliable internet connections, essential for digital access to services and information that are important for health, can exacerbate social inequalities in health. We evaluated the social equity of the rollout of the National Broadband Network (NBN) in Australia based on the type of digital infrastructure delivered to areas of varying socioeconomic status. We found that areas of greater socioeconomic disadvantage were significantly less likely to receive the highest quality infrastructure, controlling for level of remoteness. These social inequities in provision of quality infrastructure will shape and possibly exacerbate inequities in health. In our discussion we consider how political decisions have obstructed equitable implementation of the policy. Lessons from the Australian case study may be valuable for other countries investing in public digital infrastructure who want to ensure equity of provision and can also inform Australian policy in the NBN's remaining rollout.
Transforming accounting curricula to enhance integrative learning
Authors: Dean Bonnie Amelia , Perkiss Stephanie , Simic Misic Milica , Luzia Karina
Published: April 2018

Higher education is fundamental to the accounting profession. However, increased competition, the need to shape responsible global citizens and global influences impacting the profession have highlighted weaknesses in existing accounting curricula with regard to non‐technical skills, professional values and ethics. This paper reports on an approach to improve student learning in a first‐year undergraduate accounting subject through scholarship of teaching and learning and critical participatory action research. The paper highlights the importance of embedding opportunities for integrative learning in accounting curricula to enable students’ developing professional competencies and lifelong learning. It also provides a model for accounting educators to enhance integrative capabilities in their courses through engagement with scholarly research on teaching.
Florivorous myrmecophilous caterpillars exploit an ant–plant mutualism and distract ants from extrafloral nectaries
Authors: Alves‐Silva Estevao , Bächtold Alexandra , Del‐Claro Kleber
Published: April 2018

Females of myrmecophilous butterflies tend to oviposit in plants visited by ant species that engage in stable associations with its larvae. In Banisteriopsis malifolia, caterpillars are attended by the same ants that feed on extrafloral nectaries. A conflict may arise when both the plant and caterpillars compete for ant attention, and ants are assumed to forage on the highest quality resource. By attending caterpillars, ants can be indirectly detrimental to plant fitness because florivorous larvae feed intensively until pupation. In this study, we specifically investigated (i) whether the occurrence of facultative myrmecophilous Synargis calyce (Riodinidae) caterpillars in B. malifolia was based on ant species (Camponotus blandus or Ectatomma tuberculatum) and abundance; (ii) the monopolization of ants by the butterfly larvae and (iii) the florivory rates incurred by the caterpillars on inflorescences. The abundance of S. calyce was six‐fold greater in plants with C. blandus, compared to E. tuberculatum treatments. Caterpillars monopolized up to 50% of C. blandus on the plants, indicating that the resources offered by S. calyce were more attractive to ants than extrafloral nectaries. Florivory by riodinids incurred losses of almost 60% of flower buds. Myrmecophilous riodinids exploited an ant–plant mutualism by attracting aggressive ants that become larvae bodyguards. Thus, this ecological interaction is potentially detrimental to B. malifolia, since the ants, which can provide protection against herbivores, shift to provide defence for one of these herbivores.
Abundance, density and activity ofSalvator merianae(Reptilia: Teiidae) and the effect of poaching on the site occupancy by the lizard in an Atlantic Forest Reserve, Brazil
Authors: Ferreguetti Átilla Colombo , Pereira‐Ribeiro Juliane , Bergallo Helena Godoy , Rocha Carlos Frederico Duarte
Published: April 2018

We aimed to estimate the density, occupancy and detectability ofSalvator merianae(Tegu) in one of the largest Atlantic rainforest remnants in Espírito Santo, Brazil, theVNR. Species patch occupancy was modelled and used to predict the response direction of six covariates based on prior knowledge of the Tegu's ecology.A priori, we expected that the covariates measured should represent key habitat features for the species (i.e. temperature, forest edge, open habitats) or elements possibly avoided by the species, based on the hypothesis that poaching would have a negative effect on patch occupancy. We used line‐transect surveys to estimate density and abundance. Camera‐traps were used to estimate patch occupancy by the Tegu. Estimated density forS. merianaewas 0.21 ± 0.02 Tegus/ha and estimated population size was 4990 ± 521 individuals. Patch occupancy was best described by two covariates: poaching intensity and distance to the forest edge. Detectability was affected by three covariates: poaching intensity, tree density and temperature. Our study presents robust information on abundance and density, habitat use, and activity ofS. merianaein theVNRand is the first study providing data on the effects that poaching has on patch occupancy of this lizard. The data indicated that the occupancy and detectability of this species were influenced by a set of factors, providing information that can be useful in management plans in areas where this species can potentially decline and in areas where it may be introduced.
Extrafloral nectar as a driver of arboreal ant communities at the site‐scale in Brazilian savanna
Authors: Ribeiro Laila Fieto , Solar Ricardo R. C. , Muscardi Dalana C. , Schoereder José H. , Andersen Alan N.
Published: April 2018

Despite years of study, it remains unclear if and to what extent the effects of extra‐floral nectaries (EFNs) on arboreal ants observed on individual trees scale up to larger spatial scales. Here, we address this issue in Brazilian savanna and tested three predictions: (i) Trees with EFN have higher richness of arboreal ant species than trees without; (ii) Arboreal ant species richness increases with the proportion of total EFN‐bearing trees at the site scale, due to a higher occurrence of non‐core ant species; (iii) Ant species composition changes with the proportion of EFN‐bearing trees at the site scale. We sampled arboreal ants in 32 plots with EFN‐bearing trees ranging from 0% to 60% of all trees. We sampled 72 ant species, from which 17 (mostly belonging to Camponotus, Cephalotes and Crematogaster) were identified as core species in at least one of the ant‐EFN networks in the 32 plots. Ant species richness was significantly higher on EFN‐bearing trees. We identified 11 ant species that preferentially occurred on EFN‐bearing trees, all of which were core partners in networks. Species richness at the site scales increased with the proportion of EFN‐bearing trees, regardless of tree density and richness; this pattern was due to a higher occurrence of non‐core ant species. Finally, species composition also varied with the proportion of EFN‐bearing trees. Therefore, we found that the presence of EFNs not only influences arboreal ants on individual trees but also has a substantial effect on the ant‐EFN network on a broader community scale. The increase in non‐core species site scale reveals that this interaction is unlikely to result in substantially enhanced protection services for EFN‐bearing plants.
Allergen‐specific immunotherapy induces regulatory T cells in an atopic dermatitis mouse model
Authors: Shin J. U. , Kim S. H. , Noh J. Y. , Kim J. H. , Kim H. R. , Jeong K. Y. , Park K. H. , Lee J. , Chu H. , Lee J.‐H. , Yong T.‐S. , Park J.‐W. , Lee K. H.
Published: April 2018

Background

Several studies have demonstrated that allergen‐specific immunotherapy (SIT) can be an effective treatment for atopic dermatitis (AD). However, there is no relevant mouse model to investigate the mechanism and validate the novel modality of SIT in AD.

Methods

NC/Nga mice with induced AD‐like skin lesions received a subcutaneous injection of SIT (an extract of the house dust mite Dermatophagoides farinae [DfE]) or placebo for 5 weeks). Clinical and histological improvements of AD‐like skin lesions were examined. The responses of local and systemic regulatory T (Treg) cells, natural killer (NK) cells, B cells, serum immunoglobulin, and T‐cell cytokine response to DfE were evaluated to determine the underlying mechanism of the observed results.

Results

Specific immunotherapy significantly improved AD‐like skin lesions. Histologically, SIT decreased epidermal thickness and reduced inflammatory cell infiltration, especially that of eosinophils. Concomitantly, SIT suppressed Th2 responses and induced local infiltration of Treg cells into the skin. Also, SIT induced the immunoglobulin G4 and attenuated allergen‐specific immunoglobulin E. Furthermore, SIT induced local and systemic IL‐10‐producing Treg cells and regulatory NK cells.

Conclusion

We established a SIT model on AD mice and showed that our model correlates well with previous reports about SIT‐treated patients. Also, we revealed NK cells as another possible resource of IL‐10 in SIT. Based on our results, we suggest our SIT model as a useful tool to investigate mechanism of action of SIT and to validate the efficacy of new SIT modalities for the treatment of AD.
Pacing spikes following QRS complexes: What is the mechanism?
Authors: Ząbek Andrzej , Małecka Barbara , Nowosielska‐Ząbek Ewa , Dębski Maciej , Boczar Krzysztof , Lelakowski Jacek
Published: April 2018

The electrocardiogram (ECG) interpretation in patients with implantable cardioverter defibrillator (ICD) is often a puzzling problem. The difficulty of the device function evaluation further increases in the presence of unfamiliar timing cycles and additional functions. Authors present a special function of a Biotronik ICD devices called the thoracic impedance monitoring, and demonstrate its behavior in a patient with sinus rhythm, ventricular ectopic beats, and ventricular tachycardia episode. This report shows unexceptional occurrence of tricky ECG finding in patient with Biotronik ICD.
Survey of rabies vaccination status of Queensland veterinarians and veterinary students
Authors: Mendez D , Foyle L , Cobbold R , Speare R
Published: April 2018

Background

To determine the rabies vaccination status of Queensland veterinarians and veterinary students and their perception of zoonotic risk from Australian bat lyssavirus (ABLV).

Design

Cross‐sectional questionnaire surveys.

Methods

Questionnaires were sent by post in 2011 to veterinary surgeons registered in Queensland, to final‐year veterinary students at James Cook University via SurveyMonkey® in 2013 and to final‐year veterinary students at James Cook University and University of Queensland via SurveyMonkey® in 2014.

Results

The response rate for registered veterinarians was 33.5% and for veterinary students 33.3% and 30% in 2013 and 2014, respectively. Of the 466 registered veterinary surgeons, 147 (31.5%) had been vaccinated, with 72 (15.5%) currently vaccinated. For veterinary students the rabies vaccination rate was 20.0% (4/20) and 13.0% (6/46) in the 2013 and 2014 surveys, respectively. More than 95% of veterinary students had received the mandatory Q fever vaccine. Both veterinarians and students regarded bats and horses as high‐risk species for zoonoses.

Conclusions

Queensland veterinarians and veterinary students have low levels of protection against ABLV. Although incidents of ABLV spilling over from a bat to a domestic mammal are likely to remain rare, they pose a significant human health and occupational risk given the outcome of infection in humans is high consequence. Principals of veterinary practices and veterinary authorities in Australia should implement a policy of rabies vaccination for clinical staff and veterinary students.
EWSR1‐PATZ1 gene fusion may define a new glioneuronal tumor entity
Authors: Siegfried Aurore , Rousseau Audrey , Maurage Claude‐Alain , Pericart Sarah , Nicaise Yvan , Escudie Fréderic , Grand David , Delrieu Alix , Gomez‐Brouchet Anne , Le Guellec Sophie , Franchet Camille , Boetto Sergio , Vinchon Matthieu , Sol Jean‐Christophe , Roux Franck‐Emmanuel , Rigau Valérie , Bertozzi Anne‐Isabelle , Jones David T. W. , Figarella‐Branger Dominique , Uro‐Coste Emmanuelle
Published: April 2018

We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1‐PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1‐PATZ1 fusion transcript. RT‐PCR followed by Sanger sequencing confirmed the EWSR1‐PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N‐terminal transcriptional activation domain of EWSR1 gene and the C‐terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB‐ZF (broad‐complex, tramtrack and bric‐à‐brac ‐zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1‐PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAFV600E negative ganglioglioma, the second a BRAFV600E negative glioneuronal tumor, not otherwise specified and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAFV600E negative gangliogliomas were screened by FISH using EWSR1 break‐apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well‐defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1‐PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.
Development of coumarin–benzofuran hybrids as versatile multitargeted compounds for the treatment of Alzheimer’s Disease
Authors: Hiremathad Asha , Chand Karam , Keri Rangappa S.
Published: April 2018

Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by progressive deterioration of memory and cognition. The evidenced multifactorial nature of AD has been considered the main reason for the absence of cure so far. Therefore, the development of novel hybrids to treat the disease is very much essential. Focusing on this, a novel series of coumarin–benzofuran hybrids have been designed and screened as anti‐Alzheimer’s disease agents. The strategy is to obtain an effective mimetic of donepezil, which is acetylcholinesterase inhibitor. Herein, the two main scaffolds namely coumarin and benzofuran are known pharmacophore moieties and we have performed their molecular design, pharmacokinetic descriptor studies for drug‐likeliness. Further, in vitro studies such as antioxidant capacity, acetylcholinesterase (AChE) inhibition and amyloid‐β (Aβ) self‐aggregation inhibition have also been performed. Most importantly, these studies revealed that the newly synthesized hybrids can be versatile and promising drug‐like moieties as efficient anti‐AD agents.
Oropharyngeal squamous cell carcinoma induces an innate systemic inflammation, affected by the size of the tumour and the lymph node spread
Authors: Kågedal Å. , Rydberg Millrud C. , Häyry V. , Kumlien Georén S. , Lidegran M. , Munck‐Wikland E. , Cardell L.‐O.
Published: April 2018

Objectives

Inflammation is known to be associated with the progression of cancer. The study was designed to characterise the systemic inflammation in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigate its relation to tumour size, ability to metastasise and HPV status.

Materials and Methods

Blood was obtained from 58 patients with OPSCC and 90 healthy controls and analysed with leucocyte differential count.

Results

The patients with OPSCC displayed an increased number of neutrophils and monocytes, whereas the lymphocytes were suppressed compared to the healthy controls. The neutrophils‐to‐lymphocyte ratio (NLR) and the monocyte‐to‐lymphocyte ratio (MLR) were calculated, and patients with large tumours exhibited high NLR and MLR. Further, patients with regional lymph node spread displayed a low NLR and MLR. Patients with HPV‐positive tumours (n = 48) had a lower NLR than the patients (n = 8) with HPV‐negative tumours.

Conclusion

This study demonstrates that patients with OPSCC have an increased systemic inflammation that is affected by the HPV status, the size of the tumour and lymph node spread.
Dutch validation of the low anterior resection syndrome score
Authors: Hupkens B. J. P. , Breukink S. O. , Olde Reuver of Briel C. , Tanis P. J. , de Noo M. E. , van Duijvendijk P. , van Westreenen H. L. , Dekker J. W. T. , Chen T. Y. T. , Juul T.
Published: April 2018

Aim

The aim of this study was to validate the Dutch translation of the low anterior resection syndrome (LARS) score in a population of Dutch rectal cancer patients.

Method

Patients who underwent surgery for rectal cancer received the LARS score questionnaire, a single quality of life (QoL) category question and the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐C30 questionnaire. A subgroup of patients received the LARS score twice to assess the test–retest reliability.

Results

A total of 165 patients were included in the analysis, identified in six Dutch centres. The response rate was 62.0%. The percentage of patients who reported ‘major LARS’ was 59.4%. There was a high proportion of patients with a perfect or moderate fit between the QoL category question and the LARS score, showing a good convergent validity. The LARS score was able to discriminate between patients with or without neoadjuvant radiotherapy (P = 0.003), between total and partial mesorectal excision (P = 0.008) and between age groups (P = 0.039). There was a statistically significant association between a higher LARS score and an impaired function on the global QoL subscale and the physical, role, emotional and social functioning subscales of the EORTC QLQ‐C30 questionnaire. The test–retest reliability of the LARS score was good, with an interclass correlation coefficient of 0.79.

Conclusion

The good psychometric properties of the Dutch version of the LARS score are comparable overall to the earlier validations in other countries. Therefore, the Dutch translation can be considered to be a valid tool for assessing LARS in Dutch rectal cancer patients.
A configurational analysis of board involvement in intergovernmental organizations
Authors: Federo Ryan , Saz‐Carranza Angel
Published: April 2018

Manuscript Type

Empirical

Research Issue

Research on board involvement has evolved and shifted towards seeking the appropriate role these boards should play in the strategy process. Current theoretical debates and inconclusive empirical findings in the literature point to an unresolved issue regarding the level of board involvement that is conducive to effective strategy formulation. This study aims to identify the levels of board involvement that are associated with highly effective and less effective strategy formulation.

Research Findings

We examine the boards of 16 intergovernmental organizations by conducting an inductive fuzzy‐set qualitative comparative analysis to identify different levels of board involvement that are associated with highly effective and less effective strategy formulation. Our results illustrate that both active and less active board involvement are associated with highly effective strategy formulation, while an intermediate level of board involvement is associated with less effective strategy formulation.

Theoretical Implications

This study contributes to the literature seeking to understand board involvement in the strategy process. We build a multi‐dimensional board involvement framework consisting of board dynamics, the use of director resources, and context. We use the information‐processing perspective to elucidate the relationship between different levels of board involvement and effective strategy formulation.

Practitioner Implications

Our findings suggest that the optimal level of board involvement in strategy formulation depends on an organization's complexity, a factor which determines its information‐processing needs.
Cognitive predictors of children's development in mathematics achievement: A latent growth modeling approach
Authors: Xenidou‐Dervou Iro , Van Luit Johannes E.H. , Kroesbergen Evelyn H. , Friso‐van den Bos Ilona , Jonkman Lisa M. , van der Schoot Menno , van Lieshout Ernest C.D.M.
Published: April 2018

Research has identified various domain‐general and domain‐specific cognitive abilities as predictors of children's individual differences in mathematics achievement. However, research into the predictors of children's individual growth rates, namely between‐person differences in within‐person change in mathematics achievement is scarce. We assessed 334 children's domain‐general and mathematics‐specific early cognitive abilities and their general mathematics achievement longitudinally across four time‐points within the first and second grades of primary school. As expected, a constellation of multiple cognitive abilities contributed to the children's starting level of mathematical success. Specifically, latent growth modeling revealed that WM abilities, IQ, counting skills, nonsymbolic and symbolic approximate arithmetic and comparison skills explained individual differences in the children's initial status on a curriculum‐based general mathematics achievement test. Surprisingly, however, only one out of all the assessed cognitive abilities was a unique predictor of the children's individual growth rates in mathematics achievement: their performance in the symbolic approximate addition task. In this task, children were asked to estimate the sum of two large numbers and decide if this estimated sum was smaller or larger compared to a third number. Our findings demonstrate the importance of multiple domain‐general and mathematics‐specific cognitive skills for identifying children at risk of struggling with mathematics and highlight the significance of early approximate arithmetic skills for the development of one's mathematical success. We argue the need for more research focus on explaining children's individual growth rates in mathematics achievement.
Retinal nerve fibre layer thinning and childhood acquired demyelinating syndromes
Authors: Pang Ki
Published: April 2018

This commentary is on the original article by Eyre et al. on pages 1244–1250 of this issue.
Webbed left atrial septal pouch—A new anatomical variant
Authors: Kabirdas Deepa , Nekkanti Rajasekhar
Published: April 2018

Atrial septal pouch is a recently described anatomical entity. We describe webbed left atrial septal pouch (LSP), a new variant in the spectrum of fusion of septum primum and septum secundum. In the continuum of the natural history of atrial septal closure from patent foramen ovale (PFO) to complete fusion of the septum, we propose the septal anatomy in our patient to be secondary to partially developed adhesions or septa. Potential association of LSP with stroke due to in situ thrombosis and atrial fibrillation has been described. Recognition of septal anatomy is vital to avoid complications related to transseptal puncture.
Resistance and tolerance of Douglas‐fir seedlings to artificial inoculation with the fungus Ophiostoma pseudotsugae
Authors: Cruickshank M. G. , Bleiker K. P. , Sturrock R. N. , Becker E. , Leal I.
Published: April 2018

We tested the resistance and tolerance of 79 Douglas‐fir halfsibling seedling families to artificial inoculation with Ophiostoma pseudotsugae in a shade house experiment. The Douglas‐fir beetle vectors the fungus where it colonizes the phloem and sapwood, often leading to tree mortality. The 79 halfsibling seedling families originated from four seed planning zones in BC that span ecological gradients ranging from moist‐warm to cool‐wet. We tested resistance to the fungus by measuring lesion size and tolerance by measuring seedling height. We found variation in both resistance and tolerance within seed zones and halfsibling hierarchies. Trees from zones and families that were shortest before inoculation appeared to have the most tolerance after inoculation suggesting a cost for carrying tolerance traits. There was a cost in height growth for resistance after inoculation versus wounding alone. There was no trade‐off between family resistance and tolerance defence strategies indicating that both developed independently in the population. Higher resistance and lower tolerance to the fungus were the least commonly occurring trait combination in families. Douglas‐fir trees are moderately shade intolerant at the sapling stage, and as height increment is crucial for light capture, they probably avoid costly strategies such as resistance alone. This defence strategy may change in older stands.
Paranasal sinus cysts in the horse: Complications related to their presence and surgical treatment in 37 cases
Authors: Fenner M. F. , Verwilghen D. , Townsend N. , Simhofer H. , Schwarzer J. , Zani D. D. , Bienert‐Zeit A.
Published: April 2018

Background

Paranasal sinus cysts (PSC) are a common cause of equine secondary sinusitis. The outcome and associated complications have not been frequently reported.

Objectives

To review the associated clinical signs, associated morbidities and outcomes of horses treated forPSC.

Study design

Retrospective multicentre case series.

Methods

Retrospective analysis of case records and telephone follow up survey.

Results

Subjects were 37 horses 1–24 years old that were presented with nasal discharge (n = 31), facial swelling (n = 25) and epiphora (n = 19). Radiography and computed tomography allowed identification of the cyst‐induced changes including concomitant tissue destruction (n = 31), leading among other things to local nerve damage causing headshaking (n = 6) and unilateral blindness (n = 1). Radiographic changes to adjacent dental apices were present in 10 horses. Horses over 10 years old showed more of the named associated problems. Post‐operative complications included surgical site infection (SSI) (n = 11), nasofrontal suture periostitis (n = 6) and sequestration (n = 1) following removal of thePSCvia osteotomy.

The long‐term response to treatment was available for 28 cases with 22 horses (78.6%) fully cured, 4 (14.3%) partially cured and 2 (7.1%) not responding to treatment. In 7 horses (18.9%) there was recurrence of the cyst post‐operatively.

Main limitations

Due to the study being a multicentre retrospective case series with collection of data over an extended period, there may be inconsistency in data recording and absence of reporting of some findings.

Conclusions

Overall, the diagnosis and treatment of sinus cysts is relatively straightforward and carries a good prognosis. In long‐standing cases complications secondary to the expansive growth of cysts will dramatically affect the prognosis for full recovery due to pressure‐induced changes to facial bones, cheek teeth and nerves. These secondary complications mainly occurring in older horses may be due to a combination of a relatively longer period of affection and the inflexibility of older horses’ bones. Cyst recurrence following treatment can occur in up to 19% of cases.
Linear ubiquitin chain‐binding domains
Authors: Fennell Lilian M. , Rahighi Simin , Ikeda Fumiyo
Published: April 2018

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune responses, cell death and autophagy, and several UBDs ‐ specific for linear ubiquitin chains ‐ have been identified. In this review, we describe the main principles of ubiquitin recognition by UBDs, focusing on linear ubiquitin chains and their roles in biology.
Density, Distance, and Division: Rural Poverty in a Developing‐Country Context
Authors: Wang Yongming , Wu Dianting , Wang Meixia , Zhou Li , Ding Jianjun
Published: April 2018

The 3Ds, namely, density, distance, and division, are important for regional economic development and are integrated into a “3D” analytical framework in the 2009 World Development Report. Few empirical studies have examined the relevance of the 3D framework for explaining rural poverty in a developing‐country context. The effects of density on poverty are seldom studied, and distances to different layers of city centers on poverty may vary across different contexts. This paper aims to fill these gaps. Examining the case of Guizhou Province in China and adopting methods of the ordinary least square, instrument variable, and spatial econometrics, we find the evidence of the 3D framework for explaining rural poverty at the county level. Population density has a negative effect on rural poverty, while division, as measured by share of the ethnic minority population, has a positive effect. The effects of distance are mixed. Distance to Guiyang, which is the provincial political‐economic center of Guizhou province, has a negative effect on rural poverty, whereas distance to the local city center has no effect. These results can provide important policy implications for local poverty‐alleviation.