bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions in milk suggest a physiological role for β-lactoglobulin
Authors: Crowther J.M. , Broadhurst M. , Laue T. , Jameson G.B. , Hodgkinson A.J. , Dobson R.C.J. 
Published: June 2019

Abstractβ-Lactoglobulin is the most abundant protein in the whey fraction of ruminant milks, yet is absent in human milk. It has been studied intensively due to its impact on the processing and allergenic properties of ruminant milk products. However, the physiological function of β-lactoglobulin remains unclear. Sedimentation velocity experiments have identified new interactions between fluorescently-labelled β-lactoglobulin and other components in milk. Co-elution experiments support that these β-lactoglobulin interactions occur naturally in milk and provide evidence that the interacting partners are immunoglobulins, while further sedimentation velocity experiments confirm that an interaction occurs between these molecules. Ruminants (e.g. cows and goats) are born without circulating immunoglobulins, which they must obtain from their mothers’ milk, whilst humans obtain immunoglobulins both through milk and during gestation via the placenta. We propose that β-lactoglobulin serves to protect immunoglobulins within ruminant milk during digestion, ensuring their efficient transfer from mother to offspring.Statement of Significanceβ-Lactoglobulin is an abundant protein in the whey fraction of ruminant milks (e.g. cow and goat milk), yet it is completely absent in human milk. While this protein has been extensively studied, due to its impact on the processing and allergenic properties of milk, its physiological function remains unclear. We fluorescently labelled β-lactoglobulin to monitor its interactions with other milk components within its physiological environment, milk. Under these near physiological conditions β-lactoglobulin is capable of interacting with several classes of immunoglobulins. Immunoglobulins are susceptible to digestion, but are required to confer immunity from the mother to the offspring. We propose that β-lactoglobulin serves to protect immunoglobulins within ruminant milk during digestion, ensuring their efficient transfer from mother to offspring.
Passenger Hotspot Mutations in Cancer
Authors: Hess Julian M. , Bernards Andre , Kim Jaegil , Miller Mendy , Taylor-Weiner Amaro , Haradhvala Nicholas J. , Lawrence Michael S. , Getz Gad 
Published: June 2019

AbstractHotspots, or mutations that recur at the same genomic site across multiple tumors, have been conventionally interpreted as strong universal evidence of somatic positive selection, unequivocally pinpointing genes driving tumorigenesis. Here, we demonstrate that this convention is falsely premised on an inaccurate statistical model of background mutagenesis. Many hotspots are in fact passenger events, recurring at sites that are simply inherently more mutable rather than under positive selection, which current background models do not account for. We thus detail a log-normal-Poisson (LNP) background model that accounts for variation in site-specific mutability in a manner consistent with models of mutagenesis, use this model to show that the tendency to generate passenger hotspots pervades all common mutational processes, and apply it to a ~10, 000 patient cohort from The Cancer Genome Atlas to nominate driver hotspots with far fewer false positives compared to conventional methods. As the biomedical community faces critical decisions in prioritizing putative driver mutations for deep experimental characterization to assess therapeutic potential, we offer our findings as a guide to avoid wasting valuable scientific resources on passenger hotspots.
Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population
Authors: Lee Youngha , Park Soojin , Lee Jin Sook , Kim Soo Yeon , Cho Jaeso , Yoo Yongjin , Lee Sangmoon , Yoo Taekyeong , Lee Moses , Seo Jieun , Lee Jeongeun , Kneissl Jana , Lee Jean , Jeon Hyoungseok , Jeon Eun Young , Hong Sung Eun , Kim Eunha , Kim Hyuna , Kim Woo Joong , Kim Jon Soo , Ko Jung Min , Cho Anna , Lim Byeong Chan , Kim Won Seop , Choi Murim , Chae Jong-Hee 
Published: June 2019

AbstractBackgroundA substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contribution of recessive variants to Mendelian diseases is still lacking.MethodsGenetic diagnosis and variant discovery of 553 undiagnosed Korean patients with complex neurodevelopmental problems (KND for Korean NeuroDevelopmental cohort) were performed using whole exome sequencing of patients and their parents. Pathogenic variants were selected and evaluated based on a comparison to patient symptoms and genetic properties of the variants were analyzed.ResultsDisease-causing variants, including newly discovered variants, were identified in in 57.5% of the probands of the KND cohort. Of the 553 patients, 47.4% harbored variants that were previously reported as being pathogenic, and 35.1% of the previous reported pathogenic variants were inherited in a recessive manner. Genes that cause recessive disorders tend to be less constrained by loss-of-function variants and enriched in metabolic and mitochondrial pathways. This observation was applied to an estimation that approximately 1 in 17 healthy Korean individuals carry at least one of these pathogenic variants that develop severe neurodevelopmental problems in a recessive manner. Furthermore, the feasibility of these genes for carrier screening was evaluated.ConclusionsWe suggest that the odds are high for healthy individuals carrying a potentially pathogenic variant, and its genetic properties. Our results will serve as a foundation for recessive variant screening to reduce occurrences of rare Mendelian disease patients. Additionally, our results highlight the utility and necessity of whole exome sequencing-based diagnostics for improving patient care in a country with a centralized medical system.
Engineered illumination devices for optogenetic control of cellular signaling dynamics
Authors: Repina Nicole A. , McClave Thomas , Bao Xiaoping , Kane Ravi S. , Schaffer David V. 
Published: June 2019

ABSTRACTSpatially and temporally varying patterns of morphogen signals during development drive cell fate specification at the proper location and time. However, currentin vitromethods typically do not allow for precise, dynamic, spatiotemporal control of morphogen signaling and are thus insufficient to readily study how morphogen dynamics impact cell behavior. Here we show that optogenetic Wnt/β-catenin pathway activation can be controlled at user-defined intensities, temporal sequences, and spatial patterns using novel engineered illumination devices for optogenetic photostimulation and light activation at variable amplitudes (LAVA). The optical design of LAVA devices was optimized for uniform illumination of multi-well cell culture plates to enable high-throughput, spatiotemporal optogenetic activation of signaling pathways and protein-protein interactions. Using the LAVA devices, variation in light intensity induced a dose-dependent response in optoWnt activation and downstream Brachyury expression in human embryonic stem cells (hESCs). Furthermore, time-varying and spatially localized patterns of light revealed tissue patterning that models embryonic presentation of Wnt signalsin vitro. The engineered LAVA devices thus provide a low-cost, user-friendly method for high-throughput and spatiotemporal optogenetic control of cell signaling for applications in developmental and cell biology.
Metagenomic Nanopore sequencing of influenza virus direct from clinical respiratory samples
Authors: Lewandowski Kuiama , Xu Yifei , Pullan Steven T. , Lumley Sheila F. , Foster Dona , Sanderson Nicholas , Vaughan Alison , Morgan Marcus , Bright Nicole , Kavanagh James , Vipond Richard , Carroll Miles , Marriott Anthony C. , Gooch Karen E , Andersson Monique , Jeffery Katie , Peto Timothy EA , Crook Derrick W. , Walker A Sarah , Matthews Philippa C. 
Published: June 2019

AbstractInfluenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential of a diagnostic test for influenza which also provides insights on transmission, evolution and drug resistance, and simultaneously detects other viruses. We therefore set out to apply Oxford Nanopore Technology to metagenomic sequencing of respiratory samples. We generated influenza reads down to a limit of detection of 102-103 genome copies/ml in pooled samples, observing a strong relationship between the viral titre and the proportion of influenza reads (p = 4.7×10-5). Applying our methods to clinical throat swabs, we generated influenza reads for 27/27 samples with high-to-mid viral titres (Cycle threshold (Ct) values <30) and 6/13 samples with low viral titres (Ct values 30-40). No false positive reads were generated from 10 influenza-negative samples. Thus Nanopore sequencing operated with 83% sensitivity (95% CI 67-93%) and 100% specificity (95% CI 69-100%) compared to the current diagnostic standard. Coverage of full length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza titres, we were able to reconstruct >99% complete sequence for all eight gene segments. We also detected Human Coronavirus and generated a near complete Human Metapneumovirus genome from clinical samples. While further optimisation is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza and other respiratory viruses.
Three quantitative trait loci explain more than 60% of phenotypic variation for chill coma recovery time inDrosophila ananassae
Authors: Königer Annabella , Arif Saad , Grath Sonja 
Published: June 2019

AbstractEctothermic species such as insects are particularly vulnerable to climatic fluctuations. Nevertheless, many insects that evolved and diversified in the tropics have successfully colonized temperate regions all over the globe. To shed light on the genetic basis of cold tolerance in such species, we conducted a quantitative trait locus (QTL) mapping experiment for chill coma recovery time (CCRT) inDrosophila ananassae, a cosmopolitan species that has expanded its range from tropical to temperate regions.We created a mapping population of recombinant inbred advanced intercross lines (RIAILs) from two founder strains with diverging CCRT phenotypes. The RIAILs were phenotyped for their CCRT and, together with the founder strains, genotyped for polymorphic markers with double-digest restriction site-associated DNA (ddRAD) sequencing. Using a hierarchical mapping approach that combined standard interval mapping and a multiple-QTL model, we mapped three QTL which altogether explained 64% of the phenotypic variance. For two of the identified QTL, we found evidence of epistasis. To narrow down the list of cold tolerance candidate genes, we cross-referenced the QTL intervals with genes that we previously identified as differentially expressed in response to cold inD. ananassae, and with thermotolerance candidate genes ofD. melanogaster. Among the 58 differentially expressed genes that were contained within the QTL,GF15058showed a significant interaction of the CCRT phenotype and gene expression. Further, we identified the orthologs of fourD. melanogasterthermotolerance candidate genes,MtnA,klarsicht,CG5246(D.ana/GF17132) andCG10383(D.ana/GF14829) as candidates for cold tolerance inD. ananassae.
Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
Authors: Roger Friederike , Picazo Cecilia , Reiter Wolfgang , Libiad Marouane , Asami Chikako , Hanzén Sarah , Gao Chunxia , Lagniel Gilles , Welkenhuysen Niek , Labarre Jean , Nyström Thomas , Grøtli Morten , Hartl Markus , Toledano Michel B. , Molin Mikael 
Published: June 2019

AbstractPeroxiredoxins are H2O2scavenging enzymes that also carry H2O2signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H2O2, but by repressing the nutrient signaling Ras-cAMP-PKA pathway at the level of the protein kinase A (PKA) enzyme. Tsa1 stimulates sulfenylation of cysteines in the PKA catalytic subunit by H2O2and a significant proportion of the catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 inhibits the phosphorylation of a conserved Thr241 in the kinase activation loop and enzyme activity, and preventing Thr241 phosphorylation can overcome the H2O2sensitivity of Tsa1-deficient cells. Results support a model of aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits, including a peroxiredoxin-dependent response to H2O2.
Price analysis of extra virgin olive oil
Authors: D’Adamo Idiano , Falcone Pasquale Marcello , Gastaldi Massimo 
Published: June 2019

Purpose
The price of extra virgin olive oil (EVOO) is highly subjected to variability. In this way, the consumer is not able to perceive a price of reference. The purpose of this paper is to investigate this topic, trying to define a range suitable for the selling of EVOO.

Design/methodology/approach
A mathematical model is applied to the three price levels (i.e. production, intermediate and selling). It studies the relationship among main variables: purchase cost of olives, the production cost of olive oil, the yield of olives obtained by the technological process and the profit margin. To define the input data, 25 producers of olives and 25 owners of olive oil mills are involved.

Findings
The production of EVOO depends strictly on the production of olives, which typically is subdivided in a year of “high production” and in a year of “low production.” The price of EVOO is subjected to a great variability; however, it is possible to propose a range that varies from €7.0 per liter to €8.7 per liter.

Research limitations/implications
The level of acidity influences significantly the quality of olive oil, and this model has the limit to not analyze the variation of the price in function of this parameter.

Originality/value
This study is the first to propose a pricing model to evaluate EVOO. The literature section supports this assumption.
A comparative analysis of the attitudes of rural and urban consumers towards cultured meat
Authors: Shaw Elaine , Mac Con Iomaire Máirtín 
Published: June 2019

Purpose
The purpose of this paper is to perform a comparative analysis on the attitudes of rural and urban Irish consumers towards cultured meat.

Design/methodology/approach
A mixed methods exploratory sequential design was used. This involved collecting qualitative data first, through group interviews, and using the results of these to design the questionnaires for the quantitative data collection, which was analysed using SPSS 24.0 ®.

Findings
Urban consumers were more receptive towards cultured meat and more concerned about the environmental impact of current meat production practices. Rural consumers were more concerned about the possible damaging effect cultured meat production could have on agri-business and the livelihood of Irish farmers. The safety of the technology emerged as the biggest concern for both sets of consumers.

Research limitations/implications
The sample size used for the qualitative research resulted in a 95% confidence level and a confidence interval of 5.55. A larger sample number would give a tighter confidence interval and a more accurate representation of consumers’ attitudes.

Practical implications
This research could give guidance to food companies of how to market cultured meat products towards Irish consumers based on their concerns and their perceived benefits of the technology.

Social implications
This research added to previous research performed in Ireland showing that urban consumers are more receptive towards new food technologies than their rural counterparts.

Originality/value
This is the first paper comparing the attitudes of rural and urban Irish consumers towards cultured meat and adds to the literature on this emerging subject area.
How and when environmental regulation induces middle managers’ proactive behavior
Authors: Bao Haixu , Wang Haizhen (Jane) , Sun Chenglin 
Published: June 2019

PurposeThe purpose of this paper is to explore how middle managers respond to the career challenges caused by environmental regulation. In particular, this paper examines whether environmental regulation strength is positively related to middle managers’ openness toward change, and whether middle managers’ openness toward change is positively related to proactive behavior. Furthermore, the moderating role of top managers’ bottom-line mentality in these two relationships is examined.Design/methodology/approachCross-sectional survey research (n=155) was conducted. During a training program, data were collected from 155 middle managers from a listed company that manufactures primary products. With these data the authors examined the main relationship and also explored the moderating effect of top managers’ bottom-line mentality.FindingsAnalysis of the findings indicates that perceived environmental regulation strength influences middle managers’ openness toward change and consequently their proactive behavior. In addition, top managers’ bottom-line mentality moderates both the link between environmental regulation strength and openness toward change and the link between openness toward change and proactive behavior.Originality/valueThe findings of this study reveal how environmental regulation induces middle managers’ proactive behavior, and the influence of top managers’ mentality on how middle managers respond to environmental regulation both cognitively and behaviorally.
A novel chaotic bat algorithm based on catfish effect for engineering optimization problems
Authors: Xiao Wensheng , Liu Qi , Zhang Linchuan , Li Kang , Wu Lei 
Published: June 2019

PurposeBat algorithm (BA) is a global optimization method, but has a worse performance on engineering optimization problems. The purpose of this study is to propose a novel chaotic bat algorithm based on catfish effect (CE-CBA), which can effectively deal with optimization problems in real-world applications.Design/methodology/approachIncorporating chaos strategy and catfish effect, the proposed algorithm can not only enhance the ability for local search but also improve the ability to escape from local optima traps. On the one hand, the performance of CE-CBA has been evaluated by a set of numerical experiment based on classical benchmark functions. On the other hand, five benchmark engineering design problems have been also used to test CE-CBA.FindingsThe statistical results of the numerical experiment show the significant improvement of CE-CBA compared with the standard algorithms and improved bat algorithms. Moreover, the feasibility and effectiveness of CE-CBA in solving engineering optimization problems are demonstrated.Originality/valueThis paper proposed a novel BA with two improvement strategies including chaos strategy and catfish effect for the first time. Meanwhile, the proposed algorithm can be used to solve many real-world engineering optimization problems with several decision variables and constraints.
Energy absorption properties of thin-walled square tube with lateral piecewise variable thickness under axial crashing
Authors: Liu Shutian , Ding Xueshan , Tong Zeqi 
Published: June 2019

Purpose
This paper aims to study the energy absorption properties of the thin-walled square tube with lateral piecewise variable thickness under axial crashing and the influence of the tube parameters on energy absorption.

Design/methodology/approach
In this work, the energy absorption properties of the thin-walled square tube were analyzed by theoretical, numerical and experimental approach. The numerical results are obtained based on the finite element method. The explicit formulation for predicting the mean crushing force of the tube with lateral piecewise variable thickness was derived based on Super Folding Element method. The limitation of the prediction formulation was analyzed by numerical calculation. The numerical calculation was also used to compare the energy absorption between the tube with lateral piecewise variable thickness and other tubes, and to carry out the parametric analysis.

Findings
Results indicate that the thin-walled tube with lateral piecewise variable thickness has higher energy absorption properties than the uniform thickness tubes and the tubes with lateral linear variable thickness. The thickness of the corner is the key factor for the energy absorption of the tubes. The thickness of the non-corner region is the secondary factor. Increasing the corner thickness and decreasing the non-corner thickness can make the energy absorption improved. It is also found that the prediction formulation of the mean crushing force given in this paper can quickly and accurately predict the energy absorption of the square tube.

Originality/value
The outcome of the present research provides a design idea to improve the energy absorption of thin-walled tube by designing cross-section thickness and gives an explicit formulation for predicting the mean crushing force quickly and accurately.
Evaluating critical success factors for implementing smart devices in the construction industry
Authors: Silverio-Fernandez Manuel Alexander , Renukappa Suresh , Suresh Subashini 
Published: June 2019

Purpose
The decentralisation of information and high rate of mobile content access in the construction industry provides an ideal scenario for improvement of processes via the implementation of the paradigm of the Internet of Things (IoT). Smart devices are considered as the objects interconnected in the IoT; therefore, they play a fundamental role in the implementation of digital solutions during the execution of construction projects. The purpose of this paper is to assess the critical factors for a successful implementation of smart devices in the construction industry.

Design/methodology/approach
An empirical study was performed in the Dominican Republic. This country, located at the heart of the Caribbean, presents an economy that strongly relies on the construction industry. Following a systematic approach, a qualitative data collection and analysis was performed based on semi-structured interviews and content analysis to professionals of construction companies in the Dominican Republic, enquiring the concept of smart devices and critical success factors for implementing the devices in the industry.

Findings
The key success factors obtained from the contestants were leadership, technology awareness, company size, usability of proposed solution, cost of implementation and interoperability.

Originality/value
This paper provides information to clients of the construction sector regarding the benefits of embedding smart devices into their business activities. Furthermore, this study provides a better understanding of the key factors to be considered by construction organisations when embedding smart devices into their projects. This study also provides recommendations for distinct stakeholders of the construction sector, such as policy makers, clients and technology consultants. Policy makers should especially consider factors such as technology awareness and leadership to develop the right policies for the integration of the IoT in construction projects. Technology consultants should be aware of the latest case studies of successful implementation of smart devices and IoT systems in the world in order to adapt and implement smart devices and IoT in their projects.