bluuebunny/crossref_metadata_2025 huggingface dataset:
ThX – A next-generation probe for the early detection of amyloid aggregates
Authors: Needham Lisa-Maria , Weber Judith , Varela Juan A. , Fyfe James W. B. , Do Dung T. , Xu Catherine K , Keenlyside Benjamin , Cliffe Rachel , Klenerman David , Dobson Christopher M. , Hunter Christopher A. , Bohndiek Sarah E. , Snaddon Thomas N. , Lee Steven F.
Published: July 2019

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, we demonstrate that ThX can be used to detect a distinct oligomeric species, not observed via traditional ThT imaging.
Cryo-EM analysis of a viral portal protein in situ reveals a switch in the DNA tunnel
Authors: Bayfield Oliver W. , Steven Alasdair C. , Antson Alfred A.
Published: July 2019

The portal protein is a key component of many double-stranded DNA viruses, governing capsid assembly and genome packaging. Twelve subunits of the portal protein form a ring with a central tunnel, through which DNA is translocated into the capsid. It is unknown how the portal protein functions as a gatekeeper, preventing DNA slippage, whilst allowing its passage into the capsid through its central tunnel, and how these processes can be controlled by capsid and motor proteins. A cryo-EM structure of a portal protein, determined in situ for immature capsids of thermostable bacteriophage P23-45, suggests how domain adjustments can be coupled with a switching of properties of the DNA tunnel. Of particular note is an inversion of the conformation of portal loops which define the tunnel’s constriction, accompanied by a switching of surface properties from hydrophobic to hydrophilic. These observations indicate how translocation of DNA into the viral capsid can be modulated by changes in the properties and size of the central tunnel and how the changing pattern of protein–capsid interactions across a symmetry-mismatched interface can facilitate these dynamic processes.
Phage composition of a fermented milk and colostrum product assessed by microbiome array; putative role of open reading frames in reference to cell signaling and neurological development
Authors: Pacini Stefania , Ruggiero Marco
Published: July 2019

Bacteriophages (phages), Earth’s most numerous biological entities, are natural constituents of alimentary matrices; in this study we describe the characterization of phage populations in a product obtained by fermentation of bovine milk and colostrum. Such characterizations were achieved using a microarray consisting of a chip covered in short DNA sequences that are specific to certain target organisms for a total of approximately 12,000 species. The only viruses evidenced by the array belonged to Siphoviridae, the largest phage family that targets bacteria and archea. The array yielded 27 iterations corresponding to a unique target. We discuss the putative role of some open reading frames of these phages in conferring health-supporting properties with particular reference to cells signaling and neurological development. We also describe the in vitro interaction of this fermented product with alpha-N-acetylgalactosaminidase, an enzyme whose activity in serum is elevated in neurodevelopmental disorders.
Sellimonas caecigallum sp. nov., description and genome sequence of a new member of the Sellimonas genus isolated from the cecum of feral chicken
Authors: Wongkuna Supapit , Ghimire Sudeep , Antony Linto , Chankhamhaengdecha Surang , Janvilisri Tavan , Scaria Joy
Published: July 2019

An obligately anaerobic, non-motile, Gram-positive coccobacillus strain SW451 was isolated from pooled cecum contents of feral chickens. Comparative analysis based on 16s rRNA sequence showed that strain SW451 had 95.24% nucleotide sequence similarity to Sellimonas intestinalis BR31T, the closest species with a valid taxonomy. The genome of SW451 is 2.67 Mbp with 45.23 mol% of G+C content. The major cellular fatty acids were C16: 0, C14: 0 and C16: 0 DMA. Based on taxonogenomic, physiological, and biochemical analysis, the strain SW451 represents a new species of the genus Sellimonas, for which the name Sellimonas caecigallum sp. nov. is proposed. The type strain of Sellimonas caecigallum is SW451 (=DSM 109473T)
An automated data processing and analysis pipeline for transmembrane proteins in detergent solutions
Authors: Molodenskiy D. , Mertens H. , Svergun D.
Published: July 2019

The application of small angle X-ray scattering (SAXS) to the structural characterization of transmembrane proteins (MPs) in detergent solutions has become a routine procedure at the most synchrotron BioSAXS beamlines around the world. SAXS provides overall parameters and low resolution shapes of solubilized MPs, but is also meaningfully employed in hybrid modeling procedures that combine scattering data with information provided by high-resolution techniques (eg.macromolecular crystallography, nuclear magnetic resonance and cryo-electron microscopy). Structural modeling of MPs from SAXS data is non-trivial, and the necessary computational procedures require further formalization and facilitation. We propose an automated pipeline integrated with the laboratory-information management system ISPyB, aimed at preliminary SAXS analysis and the first-step reconstruction of MPs in detergent solutions, in order to streamline high-throughput studies, especially at synchrotron beamlines. The pipeline queries an ISPyB database for availablea prioriinformationviadedicated services, estimates model-free SAXS parameters and generates preliminary models utilizing eitherab initio, high-resolution-based, or mixed/hybrid methods. The results of the automated analysis can be inspected online using the standard ISPyB interface and the estimated modeling parameters may be utilized for further in-depth modeling beyond the pipeline. Examples of the pipeline results for the modelling of the tetrameric alpha-helical membrane channel Aquaporin0 and mechanosensitive channel T2, solubilized by n-Dodecyl β-D-maltoside are presented. We demonstrate how the increasing amounta prioriinformation improves the model resolution and enables deeper insights into the molecular structure of protein-detergent complexes.

STATEMENT OF SIGNIFICANCE

Small angle X-ray scattering (SAXS) using synchrotron radiation is a powerful technique for the structural characterization of transmembrane proteins (MPs) in detergent solutions Overall structural characterization and modeling of MPs from SAXS data is non-trivial, and the necessary computational procedures require further formalization and facilitation. We propose an automated pipeline integrated with the laboratory-information management system ISPyB, aimed at preliminary SAXS analysis and modelling of MPs in detergent solutions, in order to streamline high-throughput studies, especially at synchrotron beamlines.
Microglia depletion disrupts normal functional development of adult-born neurons in the olfactory bulb
Authors: Wallace Jenelle , Lord Julia , Dissing-Olesen Lasse , Stevens Beth , Murthy Venkatesh
Published: July 2019

Microglia play key roles in regulating synapse development and refinement in the developing brain, but it is unknown whether they are similarly involved during adult neurogenesis. By transiently ablating microglia from the healthy adult mouse brain, we show that microglia are necessary for the normal functional development of adult-born granule cells (abGCs) in the olfactory bulb. Microglia ablation reduces the odor responses of developing, but not preexisting GCs in vivo in both awake and anesthetized mice. Microglia preferentially target their motile processes to interact with mushroom spines on abGCs, and when microglia are absent, abGCs develop smaller spines and receive weaker excitatory synaptic inputs. These results suggest that microglia promote the development of excitatory synapses onto developing abGCs, which may impact the function of these cells in the olfactory circuit.
TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis
Authors: An Ju-Hyun , Song Woo-Jin , Li Qiang , Ryu Min-Ok , Nam A-Ryung , Bhang Dong-Ha , Jung Yun-Chan , Youn Hwa-Young
Published: July 2019

Mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, n = 6-8/group) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, qRT-PCR, western blot, and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs in the colon.
Effect of index-based livestock insurance on loan uptake
Authors: Gebrekidan Tnsue , Kaiyu Lyu
Published: July 2019

Purpose

The purpose of this paper is to weigh up the effect of index-based livestock insurance (IBLI) on loan take up behavior of the pastoral households in the Borena zone of Southern Ethiopia. Although the insurance was introduced over the last decade and it appears to have promising welfare benefit, there is a lack of pragmatic evidence on its effect in leveraging the household’s future wealth for the hope of better productivity in the present.

Design/methodology/approach

The authors analyze household-level unique panel data collected in three rounds using descriptive statistics and the fixed effect model estimated by least squares dummy variable analysis.

Findings

The authors found that the IBLI appears to have a positive and significant effect on the loan uptake behavior of the herding households.

Social implications

This increased likelihood of loan uptake suggests that the insurance can reduce the cognitive cost of loan default that would occur due to weather shocks and build-up of the household’s confidence to uptake loan. Consequently, this likelihood can promote the creditworthiness of the insured and reduce his/her fear and worry regarding the possibility of loan delinquency.

Originality/value

The paper is, except where otherwise stated, entirely new work.
Competencies urban planning students need to succeed in professional practices
Authors: Megahed Gehad , Elshater Abeer , Afifi Samy
Published: July 2019

Purpose

This paper focuses on the competencies and skills needed in preparing graduates of urban planning schools to meet the real-world challenges of professional practices. The present work explores the gap between skills and knowledge required to excel in the urban planning discipline and professional practices.

Design/methodology/approach

This research utilises a mix of qualitative and quantitative methods. This study depends on collecting data from descriptive and statistical analysis based on two streams. The first comes from a survey launched among students of urban planning. The second is interviews scheduled with academics that are also practitioners.

Findings

The results outline the missing correlation between what Egyptian students learn in schools of urban planning and professional practices. The findings show that academics, students, and graduates share the same experiences about the education system. Academics agreed that graduates need to be more skilful rather than knowledgeable. The discussion shows that the undefined role of the planner in Egypt influenced the mismatching between the current demand and supply of competencies and skills offered by planning schools. The concluded remarks mentioned that communication skills and negotiation skills are the most crucial skills for graduates, in addition to information finding and data-processing skills.

Originality/value

This research has particular advantages in presenting a model of competencies as results of scanning the expectations of Egyptian students and new graduates vs professional practices. The contribution is in answering the question of what skills students of the urban planning programs should learn in order to meet the continued changes in professional practices.
A comparative study of phase margin based digital and analog controlled synchronous buck with optimum LC filter
Authors: Rashmi Ruchi , Jagtap Shweta
Published: July 2019

Purpose

Traditionally, industrial power supplies have been exclusively controlled through analog control to sustain high reliability with low cost. However, with the perpetual decrement in cost of digital controllers, the feasibility of a digitally controlled switch mode power supply has elevated significantly. This paper aims to outline the challenges related to the design of digital proportional-integral (PI) controlled synchronous rectifier (SR) buck converter by comparing controller performance in continuous and discrete time. The trapezoidal approximation-based digital PI control is designed for low voltage and high-frequency SR buck converter operating under continuous conduction mode.

Design/methodology/approach

The analog and digital controller are designed using a SISO tool of MATLAB. Here, zero-order hold transform is used to convert the transfer function from continuous to discrete time. Frequency and time domain analysis of continuous plant, discrete plant and close loop system is performed. The designed digital PI control is simulated in MATLAB Simulink. The simulated results is also verified on hardware designed around digital signal processing control.

Findings

The continuous and discrete control loops are validated with multiple tests in the time and frequency domain. The detailed steady state theoretical analysis and performance of the SR buck converter is presented and verified by simulation. It is found that the delay in digital control loop results in a low phase margin. This phase margin decreases with higher bandwidth. The hardware experiments with the digital control loop are carried out on a 10 W prototype. The chosen parameters for the SR buck converter are found to be optimum for steady and transient state response.

Originality/value

This paper compares the digital and analog control approach of compensator design. It focuses on the implications created at the time of transforming the control design from continuous to discrete time. Further, it also focuses on the selection of parameters such as phase margin, bandwidth and low pass filter.
Parallel finite-element method using domain decomposition and Parareal for transient motor starting analysis
Authors: Takahashi Yasuhito , Fujiwara Koji , Iwashita Takeshi , Nakashima Hiroshi
Published: July 2019

Purpose

This paper aims to propose a parallel-in-space-time finite-element method (FEM) for transient motor starting analyses. Although the domain decomposition method (DDM) is suitable for solving large-scale problems and the parallel-in-time (PinT) integration method such as Parareal and time domain parallel FEM (TDPFEM) is effective for problems with a large number of time steps, their parallel performances get saturated as the number of processes increases. To overcome the difficulty, the hybrid approach in which both the DDM and PinT integration methods are used is investigated in a highly parallel computing environment.

Design/methodology/approach

First, the parallel performances of the DDM, Parareal and TDPFEM were compared because the scalability of these methods in highly parallel computation has not been deeply discussed. Then, the combination of the DDM and Parareal was investigated as a parallel-in-space-time FEM. The effectiveness of the developed method was demonstrated in transient starting analyses of induction motors.

Findings

The combination of Parareal with the DDM can improve the parallel performance in the case where the parallel performance of the DDM, TDPFEM or Parareal is saturated in highly parallel computation. In the case where the number of unknowns is large and the number of available processes is limited, the use of DDM is the most effective from the standpoint of computational cost.

Originality/value

This paper newly develops the parallel-in-space-time FEM and demonstrates its effectiveness in nonlinear magnetoquasistatic field analyses of electric machines. This finding is significantly important because a new direction of parallel computing techniques and great potential for its further development are clarified.
Holding individuals accountable for engaging in harmful health behaviours when managing scarce resources
Authors: Pinho Micaela , Borges Ana Pinto
Published: July 2019

Purpose

The purpose of this paper is to investigate the views of Bulgarian citizens about the relevance of lifestyles in the management of scarce resources through rationing and explore whether they are associated with participants’ characteristics.

Design/methodology/approach

A self-administered questionnaire was used to collect data from a sample of 322 Bulgarian respondents. Respondents faced a hypothetical rationing scenario where they have to decide whether information about five harmful health behaviours (smoking, excess alcohol consumption, illegal drug use, overeating/poor diet and engaging in dangerous driving (speeding and/or under the influence of alcohol and/or drugs)) should be relevant in priority setting decisions. Descriptive statistics and logistic regressions were performed.

Findings

The majority of respondents disagree with the idea that personal responsibility for illness should count in priority decisions. Notwithstanding, there seems to be a wider consensus in giving lower priorities to patients that engage in dangerous driving (excess of speed and/or under the influence of alcohol and/or drugs), illegal drugs use and excessive alcohol intake. Overeating/poor quality nutrition was the risky behaviour less condemned by respondents followed by smoking. Respondents’ sociodemographic, health and beliefs about rationing criteria had different impact in the penalization of the risk behaviours.

Originality/value

This study is the first attempt to awaken attention to the impact that personal responsibility for health may have on intergenerational access to healthcare.
Sexual orientation and wage discrimination: evidence from Australia
Authors: Preston Alison , Birch Elisa , Timming Andrew R.
Published: July 2019

Purpose

The purpose of this paper is to document the wage effects associated with sexual orientation and to examine whether the wage gap has improved following recent institutional changes which favour sexual minorities.

Design/methodology/approach

Ordinary least squares and quantile regressions are estimated using Australian data for 2010–2012 and 2015–2017, with the analysis disaggregated by sector of employment. Blinder–Oaxaca decompositions are used to quantify unexplained wage gaps.

Findings

Relative to heterosexual men, in 2015–2017 gay men in the public and private sectors had wages which were equivalent to heterosexual men at all points in the wage distribution. In the private sector: highly skilled lesbians experienced a wage penalty of 13 per cent; low-skilled bisexual women faced a penalty of 11 per cent, as did bisexual men at the median (8 per cent penalty). In the public sector low-skilled lesbians and low-skilled bisexual women significant experienced wage premiums. Between 2010–2012 and 2015–2017 the pay position of highly skilled gay men has significantly improved with the convergence driven by favourable wage (rather than composition) effects.

Practical implications

The results provide important benchmarks against which the treatment of sexual minorities may be monitored.

Originality/value

The analysis of the sexual minority wage gaps by sector and position on the wage distribution and insight into the effect of institutions on the wages of sexual minorities.
Enrollment patterns and students’ risk of academic difficulty
Authors: DeMonbrun Robert Matthew , Brown Michael , Teasley Stephanie D.
Published: July 2019

Purpose

Experiencing academic difficulty can deter students’ academic momentum, decreasing the speed with which they complete coursework and increasing the odds that they will not persist to a credential. The purpose of this paper is to expand upon an existing framework that investigates students’ academic difficulty in co-enrolled courses by adding additional co-enrollment variables that may influence academic performance in introductory gateway courses.

Design/methodology/approach

This study uses quantile regression to better understand academic difficulty in co-enrolled courses and the impact that students’ co-enrollment patterns may have on their success in focal introductory gateway courses.

Findings

This study revealed significant relationships between student success and co-enrollment patterns, including: the disciplinary alignment of the course with a student’s major, the student’s co-enrollment in other difficult courses and experiencing below average academic performance in a co-enrolled course. Further, impact of these relationships often differed by students’ performance quantile in the focal course.

Practical implications

The results point to factors related to the student and their co-enrolled courses that faculty, academic advisors and curriculum committees can consider as they design general education requirements within and across disciplinary majors.

Originality/value

This approach advances the understanding of how a prescribed curriculum produces interdependent pathways that can promote or deter students’ success through the organization of curricular requirements and student course taking. The paper provides a generalizable methodology that can be used by other universities to investigate curricular pathways that have the potential to reduce student success.
Halal logistics: practices, integration and performance of logistics service providers
Authors: Karia Noorliza
Published: July 2019

Purpose

This paper aims to examine the halal value creation in halal logistics practices and halal logistics integration in delivering halal products and/or services by investigating the effects of halal logistics practices on halal logistics performance and the role of halal logistics integration as a mediator.

Design/methodology/approach

Partial least square is performed on a survey data of 129 Malaysian logistics service providers.

Findings

The novel findings affirm that halal logistics practices comprising of physical segregation of halal products from non-halal in halal warehousing, halal transportation and halal terminal positively affect halal logistics performance. The most novel finding is that halal logistics integration positively affect halal logistics performance and mediate, significantly the relationship between halal warehousing and halal transportation and halal logistics performance.

Practical implications

Managers/logisticians should aware that halal value creation in halal logistics practices have a positive effect on halal logistics performance and they should appreciate halal logistics practices and halal logistics integration to realize a better halal logistics performance towards halal logistics implementation.

Originality/value

The results draw the novel contributions of halal logistics practices and mediating effects of halal logistics integration between halal logistics practices and halal logistics performance that have never been published.
Honey as a functional additive in yoghurt – a review
Authors: Sarkar S. , Chandra S.
Published: July 2019

Purpose

Recent societal interest in healthful foods has led to the development of functional dairy products that basically provide health benefits in addition to their fundamental nutrients. Yoghurt being most popular fermented milk product due to its healthy image can be an excellent carrier for probiotics. Functional properties of yoghurt can be enhanced with the inclusion of functional ingredients such as probiotics and its conjugate application with prebiotics may be advantageous as it favors probiotic growth. Nutritional and medicinal value of honey coupled with presence of oligosaccharides has projected honey as a functional additive in yoghurt.

Design/methodology/approach

Attempt has been made to review the literature on the biochemical activities of yoghurt cultures and probiotics in presence of honey. Both review and research papers related to biochemical activities and functional properties of yoghurt cultures and probiotics in presence of honey and their health benefits published in diverse journals under Pub Med and Science Direct have been considered. Keywords used for data search included functional foods, yoghurt, probiotic, health benefits, honey, etc.

Findings

Functional properties of yoghurt can be further enhanced with the inclusion of probiotic cultures and honey. Honey can be safely used in association with different probiotic cultures during yoghurt manufacture for augmenting functional properties of yoghurt to extend health benefits. Honey may not be equally a suitable matrix for all yoghurt cultures or probiotic cultures.

Research limitations/implications

Reviewed literature indicated that limited research on animal or human feeding trials with honey containing yoghurt has been done. Clinical trials with honey containing yoghurt are emerging prior to its marketing as functional food.

Originality/value

Application of honey as a functional additive during the manufacture of probiotic yoghurt is suggested to extend the functional properties of normal yoghurt.
The impact of collective action and market prices
Authors: Özcan-Tok Elif , Özmen Mustafa Utku , Tok Ertan , Yılmaz Tuba
Published: July 2019

Purpose

The purpose of this paper is to investigate whether the information sharing in an online discussion forum, over an agricultural market characterized by a large number of small-scale farmers, has an impact on the market prices.

Design/methodology/approach

All the comments posted by farmers and traders on four storable items (potato, onion, lemon and apple) in an online discussion forum over 2013–2017 are collected. By using text mining techniques and regression analysis, words characterizing the actions and expectations of farmers and traders on the course of the market price are identified. Then, summary indicators pointing to positive and negative views on prices are calculated. Finally, the relation between these indicators and market prices is analyzed.

Findings

The results point to economically significant impacts, as one standard deviation increase in the share of net positive comments is associated with 20, 22, 13 and 10 percent increase in the consumer prices of potato, onion, lemon and apple, respectively within three months.

Originality/value

Overall, this study provides an evidence for the link between information sharing of farmers on online domain and their collaboration in the physical domain. Thus, the study implies that the information synthesized from online discussion forums may actually contain valuable information for researchers and policy makers regarding the behavior of agents even on traditional domains such as agriculture.
Embedding transferrable skills into the higher degree by research candidature
Authors: Milos Dani
Published: July 2019

Purpose

Higher degree by research (HDR) graduates are often perceived to be overly specialised and are unable to adapt to non-academic settings (Jaeger and Rudra, 2013). Universities are under increasing pressure to embed research and transferrable skills into the candidature in a flexible and meaningful way to equip graduates with the skills to succeed in a range of careers. The paper aims to study how Flinders University has embedded the Research and Employability Skills Training (REST) Program into the HDR.

Design/methodology/approach

REST was established to replace the workshop-based professional development program, with a structured, compulsory, comprehensive program for HDR students, based on the Vitae Researcher Development Framework (RDF). The Program aims to provide students with the research skills they need to complete their studies and the transferrable skills employers seek, through an online, supported program that helps them identify their needs, plan and control their skills development. Such a comprehensive online candidature management system has enabled Flinders to implement the RDF and successfully and comprehensively embed REST into the HDR candidature, assisting students to articulate and demonstrate their skills with documented evidence.

Findings

The Program has been running for one year, and so far, has been successful. Students are increasingly completing the initial online Skills Needs Analysis assessment component, which helps to identify their skills gaps and recommend workshops to meet their needs. Supervisors and students are engaging with the Program through structured discussion and refection of skills at each annual milestone, thanks to the help of the Inspire online candidature management system.

Originality/value

REST is a valuable resource for HDR students, providing them with a range of skills to progress with their research, writing and professional development training that complements, but is separate from, their degree. Providing a structured training program which follows and supports students’ candidature, and is based around the training needs and career trajectories of the student assists the students be more equipped and supported to complete on time and are well prepared for a range of career outcomes.
Fungal melanonychia caused by Candida parapsilosis successfully treated with oral fosravuconazole
Authors: Noguchi Hiromitsu , Matsumoto Tadahiko , Kimura Utako , Hiruma Masataro , Kano Rui , Yaguchi Takashi , Fukushima Satoshi , Ihn Hironobu
Published: July 2019

A 73‐year‐old healthy woman noticed black pigmentation on both thumbnails for 6 years. Upon her visit to our clinic, she had pigmented onychomycosis with onycholysis in the distal area. There was no evidence of paronychia. Direct microscopy using Zoomblue™ and histopathological examination showed aggregated blastoconidia. Fontana‐Masson staining confirmed fungal melanin production. A combination of morphological features and genetic testing identified the isolates as Candida parapsilosis. Fungal melanonychia due to C. parapsilosis is rare, with only six cases reported since 1979. The minimum inhibitory concentration of the isolates was 0.25 μg/mL for itraconazole, less than 0.03 μg/mL for ravuconazole and 2.0 μg/mL for terbinafine. Both oral terbinafine treatment and itraconazole pulse therapy performed for 6 months were unsuccessful. The disease was ultimately cured with a 3‐month treatment of oral fosravuconazole.
Insights into the antibiotic resistance dissemination in a wastewater effluent microbiome: bacteria, viruses and vesicles matter
Authors: Maestre‐Carballa Lucia , Lluesma Gomez Monica , Angla Navarro Andrea , Garcia‐Heredia Inmaculada , Martinez‐Hernandez Francisco , Martinez‐Garcia Manuel
Published: July 2019

Wastewater treatment plants effluents are considered as hotspots for the dispersion of antibiotic resistance genes (ARGs) into natural ecosystems. The bacterial resistome (ARG collection in a metagenome) analyses have provided clues on antibacterial resistance dynamics. However, viruses and vesicles are frequently ignored. Here, we addressed the bacterial, viral and vesicle resistomes from a representative wastewater effluent in natural conditions and amended with polymyxin, which is used as a last resort antibiotic. Metagenomics showed that the natural prokaryotic resistome was vast (9000 ARG hits/Gb metagenome) and diverse, while viral resistome was two orders of magnitude lower (50 ARG hits/Gb metagenome) suggesting that viruses rarely encoded ARGs. After polymyxin amendment, data showed no ARG enrichment – including to polymyxin – in the microbiome. Remarkably, microbiomes responded to polymyxin with a vast release of putative vesicles (threefold increase compared with the control), which might be used as 'traps' to decrease the antibiotic concentration. Intriguingly, although polymyxin resistance genes (PRGs) were rare in the microbiome (0.018% of total ARG found), in the viral and vesicle fractions, PRGs were more abundant (0.5%–0.8% of total ARG found). Our data suggest that vesicles could have a more active role in the context of transmission of antibiotic resistances.
Tobacco‐21 laws and young adult smoking: quasi‐experimental evidence
Authors: Friedman Abigail S. , Buckell John , Sindelar Jody L.
Published: July 2019

Aims

To estimate the impact of tobacco‐21 laws on smoking among young adults who are likely to smoke, and consider potential social multiplier effects.

Design

Quasi‐experimental, observational study using new 2016–17 survey data.

Setting

United States.

Participants/cases

A total of 1869 18–22‐year‐olds who have tried a combustible or electronic cigarette.

Intervention and comparators

Tobacco‐21 laws raise the minimum legal sales age of cigarettes to 21 years. Logistic regressions compared the association between tobacco‐21 laws and smoking among 18–20‐year‐olds with that for 21–22‐year‐olds. The older age group served as a comparison group that was not bound by these restrictions, but could have been affected by correlated factors. Age 16 peer and parental tobacco use were considered as potential moderators.

Measurements

Self‐reported recent smoking (past 30‐day smoking) and current established smoking (recent smoking and life‐time consumption of at least 100 cigarettes).

Findings

Exposure to tobacco‐21 laws yielded a 39% reduction in the odds of both recent smoking [odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.42, 0.89] and current established smoking (OR = 0.61; 95% CI = 0.39, 0.97) among 18–20‐year‐olds who had ever tried cigarettes. This association exceeded the policy's relationship with smoking among 21–22‐year‐olds. For current established smoking, the tobacco‐21 reduction was amplified among those whose closest friends at age 16 used cigarettes (OR = 0.50; 95% CI = 0.29, 0.87), consistent with peer effects moderating the policy's impact on young adult smoking.

Conclusions

Tobacco‐21 laws appear to reduce smoking among 18–20‐year‐olds who have ever tried cigarettes.
Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture, DNA sequencing and microscopy
Authors: Malone Matthew , Fritz Blaine G. , Vickery Karen , Schwarzer Saskia , Sharma Varun , Biggs Nathan , Radzieta Michael , Jeffries Thomas T. , Dickson Hugh G. , Jensen Slade O. , Bjarnsholt Thomas
Published: July 2019

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra‐operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six‐month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be ‘clean/non‐infected’ were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA‐FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal ‘clean’ margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post‐operative approaches, correlating any outcomes back to culture‐sequence findings.
Mechanisms of the Ase1/PRC1/MAP65 family in central spindle assembly
Authors: She Zhen‐Yu , Wei Ya‐Lan , Lin Yang , Li Yue‐Ling , Lu Ming‐Hui
Published: July 2019

During cytokinesis, the organization of the spindle midzone and chromosome segregation is controlled by the central spindle, a microtubule cytoskeleton containing kinesin motors and non‐motor microtubule‐associated proteins. The anaphase spindle elongation 1/protein regulator of cytokinesis 1/microtubule associated protein 65 (Ase1/PRC1/MAP65) family of microtubule‐bundling proteins are key regulators of central spindle assembly, mediating microtubule crosslinking and spindle elongation in the midzone. Ase1/PRC1/MAP65 serves as a complex regulatory platform for the recruitment of other midzone proteins at the spindle midzone. Herein, we summarize recent advances in understanding of the structural domains and molecular kinetics of the Ase1/PRC1/MAP65 family. We summarize the regulatory network involved in post‐translational modifications of Ase1/PRC1 by cyclin‐dependent kinase 1 (Cdk1), cell division cycle 14 (Cdc14) and Polo‐like kinase 1 (Plk1) and also highlight multiple functions of Ase1/PRC1 in central spindle organization, spindle elongation and cytokinesis during cell division.
Syndromic chorioretinal coloboma associated with heterozygous de novo RARA mutation affecting an amino acid critical for retinoic acid interaction
Authors: Jakubiuk‐Tomaszuk Anna , Murcia Pienkowski Victor , Zietkiewicz Szymon , Rydzanicz Małgorzata , Kosińska Joanna , Stawiński Piotr , Szumiński Michał , Płoski Rafał
Published: July 2019

Retinoid acid receptors (RAR) are transcription factors that bind retinoic acid (RA), a metabolite of vitamin A. RARs are composed of three subunits encoded by RARA, RARB and RARG. In humans, RARB defects cause syndromic microphthalmia. So far, no germline pathogenic variants have been identified in RARA or RARG. We describe a girl with a de novo mutation NM_000964 c.826C > T (p.Arg276Trp) in RARA with symptoms overlapping those described in RARB patients (coloboma, muscular hypotonia, dilated pulmonary artery, ectopic kidney). RARA Arg276 residue is functionally important, as it was previously shown that its substitution for Ala or Gln causes a 50‐ or 21‐fold impairment of RA binding, respectively. Moreover, in leukemic cells, the p.Arg611Trp mutation in a chimeric PML/RARA gene (corresponding to the RARA p.Arg276Trp detected in our patient) conferred resistance to therapy by decreasing binding of all‐trans RA. The functional effect of RARA p.Arg276Trp was further confirmed by in silico modeling which showed that binding of RA by the Trp276 variant was similarly defective as in the deleterious model Ala276 mutant. We propose that RARA p.Arg276Trp causes the disease by affecting RA interaction with the RARA receptor.
Treatment efficacy for human papillomavirus‐related anal squamous cell dysplasia in an under‐represented population: human immunodeficiency‐negative, non‐men having sex with men, and non‐transplant population
Authors: Messick C. A.
Published: July 2019

Aim

Human papillomavirus (HPV)‐related anal squamous cell dysplasia has been well‐reported in high‐risk (HR) patients [human immunodeficiency virus (HIV)‐positive, men having sex with men (MSM) or immune‐suppressed transplant recipients]. However, data are extremely limited for all other patients. This study reports treatment outcomes for HPV‐related dysplasia in a population of non‐HR patients.

Method

A retrospective study was performed to review treatment efficacy in non‐HR patients diagnosed with anal dysplasia or superficially invasive squamous cell carcinoma of the anus (SISCCA) with at least 12‐months’ follow‐up; HR patients were excluded. Medical records were reviewed for demographics, pathology, cytopathology, treatment and recurrences.

Results

Forty‐one patients were identified (34 women). The median age at diagnosis was 58 years (range 26–85) and median follow‐up was 26 months (range 12–51). At diagnosis, 36 patients had anal dysplasia and five patients had SISCCA. Treatment outcomes (resolved versus recurrent) differed between treatment modalities (P = 0.014). Topical and fulguration‐only treatment modalities were superior to wide local excision (WLE) (P < 0.006 and P < 0.008, respectively). Fourteen (39%) patients had recurrent dysplasia at a median of 14 months (range 4–62); eight patients developed a second recurrence at a median of 14 months (range 11–26). No SISCCA patient had a recurrence, but two patients progressed to anal cancer after treatment.

Conclusion

The behaviour of anal dysplasia reported in this under‐represented, small group of non‐HR patients reveals that treatment for anal dysplasia is not necessarily a single event and nonexcisional treatments may be favourable to WLE. Though the true denominator of this population is unknown, treatment may not prevent the recurrence of dysplasia or progression to cancer, warranting close follow‐up.
Tissue inhibitor of metalloproteinase 1 and AST‐to‐Platelet Ratio Index as noninvasive biomarkers predict allograft fibrosis after pediatric liver transplantation
Authors: Beime Jan , Krech Till , Hischke Sandra , Grabhorn Enke , Brinkert Florian
Published: July 2019

Background

Assessing liver fibrosis in patients after liver transplantation is still largely dependent on liver biopsy. Especially in children, noninvasive methods are of utmost importance. We evaluated tissue inhibitor of metalloproteinase 1 (TIMP1) and AST‐to‐Platelet Ratio Index (APRI) and their potential as serum biomarkers to predict liver allograft fibrosis (LAF) in a pediatric cohort.

Methods

In this retrospective, observational study, we analyzed 91 protocol liver biopsy specimens from 73 children after pediatric liver transplantation (PLT) and compared histological stage of liver fibrosis using LAF Score (LAFSc) and Ishak Score (IshakSc) to TIMP1‐serum concentration and APRI using ROC analysis.

Results

In our cohort, TIMP1 and APRI reliably predict LAF. Depending on the histological scoring system, cutoff values for TIMP1 were 328 ng/mL (IshakSc ≥ IV) and 351 ng/mL (LAFSc ≥ 5) with AUC of 0.86 and 0.98. The cutoff for APRI was 0.8 with AUC of 0.87 (IshakSc ≥ IV) and 0.94 (LAFSc ≥ 5). Using LAFSc, TIMP1 and APRI showed excellent diagnostic accuracy to detect severe LAF (LAFSc ≥ 5) with PPV of ≥ 90% and NPV of 100%.

Conclusion

TIMP1 and APRI are accurate biomarkers to predict severe LAF in children. The use of TIMP1 and APRI will not replace but complement liver biopsies after PLT to further improve our understanding of each individual patient.
Co‐declining mammal–dung beetle faunas throughout the Atlantic Forest biome of South America
Authors: Bogoni Juliano André , da Silva Pedro Giovâni , Peres Carlos A.
Published: July 2019

The millennial–scale evolutionary relationships between mammals and dung beetles have been eroded due to several drivers of contemporary biodiversity loss. Although some evidence of co‐decline has been shown for mammals and dung beetles at some Neotropical sites, a biome‐scale analysis for the entire Atlantic Forest of South America would strengthen our understanding of how relictual sets of mammal species can affect dung beetle co‐occurrences and co‐declines. We therefore collated hundreds of assemblages of both dung beetles and medium‐ to large‐bodied mammals throughout the world's longest tropical forest latitudinal gradient to examine to what extent mammal assemblages may exert a positive influence on dung beetle species composition and functional assembly, and whether this relationship is scale dependent. We also collated several climatic and other environmental variables to examine the degree to which they shape mammal–dung beetle relationships. The relationships between local mammal and dung beetle faunas were examined using regression models, variation partitioning, dissimilarity indices and ecological networks. We found a clear positive relationship between mammal and dung beetle species richness across this forest biome, indicating an ongoing process of mammal–dung beetle niche‐mediated co‐decline. We found a strong relationship between the species composition of both taxa, in which dung beetle species dissimilarity apparently track changes in mammalian dissimilarity, typically in 80% of all cases. Co‐variables such as phytomass and climatic variables also influenced mammal–dung beetle patterns of co‐decline along the Atlantic Forest. We conclude that dung beetle diversity and community assembly are shaped by the remaining co‐occurring mammal assemblages and their functional traits, and both groups were governed by environmental features. We emphasize that ecosystem‐wide effects of mammal population declines remain poorly understood both quantitatively and qualitatively, and curbing large vertebrate defaunation will ensure the persistence of co‐dependent species.
Validating standardised personality tests under semi‐natural conditions in wild house mice (Mus musculus domesticus)
Authors: Krebs Rebecca , Linnenbrink Miriam , Guenther Anja
Published: July 2019

Personality traits in animals are often measured using standardised behavioural tests for activity, boldness/shyness, sociability, aggression and exploration. These tests are quick and convenient, as well as easy to repeat. As the interest in studying the impact of animal personality on ecological and evolutionary consequences has been growing rapidly, there is increasing focus on cross‐validating measurements taken during these tests with behaviours shown under natural situations. In our experiment, we aimed to study the relationship between standardised measurements for activity, exploration and anxiety‐like behaviour measured in Open Field, Novel Object and Elevated Plus Maze tests with exploration and colonisation in semi‐natural conditions. We carried out a semi‐natural enclosure experiment in parallel with standardised behavioural tests, creating a scenario similar to an invasion or dispersal event. We compared behaviours in standardised tests and in enclosures for animals of two populations of wild house mice (Mus musculus domesticus). Several behavioural variables taken during the standardised tests, such as distance moved and time spent with novel object, were negatively correlated with space‐use in the enclosure while being highly positively correlated among each other. Based on their relationship with space use, we refer to behavioural measurements from standardised tests as activity/exploration. The time spent near the walls in an open field, probably reflecting anxiety, was not correlated to any other variable or the behaviour in the enclosure. In addition, we found differences in activity/exploration behaviour between the two populations in the standardised tests, but not during the colonisation of the novel environment. These results emphasise that researchers have to be careful when trying to extrapolate behaviour shown in standardised laboratory test setups to more natural, ecologically relevant situations. This has to be taken into account in distantly related species but even when studying the wild relative of laboratory rodents, for which these standardised tests have originally been developed.