bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian model comparison for rare variant association studies
Authors: Venkataraman Guhan Ram , DeBoever Christopher , Tanigawa Yosuke , Aguirre Matthew , Ioannidis Alexander G. , Mostafavi Hakhamanesh , Spencer Chris C. A. , Poterba Timothy , Bustamante Carlos D. , Daly Mark J. , Pirinen Matti , Rivas Manuel A. 
Published: February 2018

AbstractWhole genome sequencing studies applied to large populations or biobanks with extensive phenotyping raise new analytic challenges. The need to consider many variants at a locus or group of genes simultaneously and the potential to study many correlated phenotypes with shared genetic architecture provide opportunities for discovery and inference that are not addressed by the traditional one variant, one phenotype association study. Here, we introduce a Bayesian model comparison approach that we refer to as MRP (Multiple Rare-variants and Phenotypes) for rare-variant association studies that considers correlation, scale, and direction of genetic effects across a group of genetic variants, phenotypes, and studies. The approach requires only summary statistic data. To demonstrate the efficacy of MRP, we apply our method to exome sequencing data (N = 184,698) across 2,019 traits from the UK Biobank, aggregating signals in genes. MRP demonstrates an ability to recover previously-verified signals such as associations between PCSK9 and LDL cholesterol levels. We additionally find MRP effective in conducting meta-analyses in exome data. Notable non-biomarker findings include associations between MC1R and red hair color and skin color, IL17RA and monocyte count, IQGAP2 and mean platelet volume, and JAK2 and platelet count and crit (mass). Finally, we apply MRP in a multi-phenotype setting; after clustering the 35 biomarker phenotypes based on genetic correlation estimates into four clusters, we find that joint analysis of these phenotypes results in substantial power gains for gene-trait associations, such as in TNFRSF13B in one of the clusters containing diabetes and lipid-related traits. Overall, we show that the MRP model comparison approach is able to improve upon useful features from widely-used meta-analysis approaches for rare variant association analyses and prioritize protective modifiers of disease risk.
Leveraging allele-specific expression to refine fine-mapping for eQTL studies
Authors: Zou Jennifer , Hormozdiari Farhad , Jew Brandon , Ernst Jason , Sul Jae Hoon , Eskin Eleazar 
Published: February 2018

AbstractMany disease risk loci identified in genome-wide association studies are present in non-coding regions of the genome. It is hypothesized that these variants affect complex traits by acting as expression quantitative trait loci (eQTLs) that influence expression of nearby genes. This indicates that many causal variants for complex traits are likely to be causal variants for gene expression. Hence, identifying causal variants for gene expression is important for elucidating the genetic basis of not only gene expression but also complex traits. However, detecting causal variants is challenging due to complex genetic correlation among variants known as linkage disequilibrium (LD) and the presence of multiple causal variants within a locus. Although several fine-mapping approaches have been developed to overcome these challenges, they may produce large sets of putative causal variants when true causal variants are in high LD with many non-causal variants. In eQTL studies, there is an additional source of information that can be used to improve fine-mapping called allele-specific expression (ASE) that measures imbalance in gene expression due to different alleles. In this work, we develop a novel statistical method that leverages both ASE and eQTL information to detect causal variants that regulate gene expression. We illustrate through simulations and application to the Genotype-Tissue Expression (GTEx) dataset that our method identifies the true causal variants with higher specificity than an approach that uses only eQTL information. In the GTEx dataset, our method achieves the median reduction rate of 11% in the number of putative causal variants.ContactJaeHoonSul@mednet.ucla.edu, eeskin@cs.ucla.edu
Attention seeking in a spatially explicit game of mate choice and the evolution of dimorphic ornaments
Authors: Számadó Szabolcs 
Published: February 2018

AbstractThe evolution of conspicuous signals fascinated biologist ever since Darwin. The Handicap Principle was dominant explanation in the last decades; it proposed that exaggerated and conspicuous signals are costly signals of quality. There are other less popular explanations however, one them is that conspicuous signals function to call the attention of potential receivers. These ‘attention seeking displays’ need not reveal the quality of the signaller. There are many empirical examples and recently the idea was modelled in terms of a simple action-response game. However, action-response games model an interaction of a pair of signaller and receiver, thus they omit potential competition between signallers, which could be a crucial force behind the evolution of attention-seeking displays. Here I model this competition in a spatially explicit model of mate choice where males can give a continuous signal to call the attention of potential mates. The results show that attention-seeking displays readily evolve to the allowed maximum when the cost of signalling is low. However, dimorphism evolves when the cost of signalling is high. The population consist of two types of males at this dimorphic state: males that do not give a signals and males that give the highest intensity signal possible. The results show that variation in quality is not a necessary requirement for the evolution of dimorphic traits.
The plasma miR-122 basal levels respond to circulating catecholamines in rats
Authors: Peng Xu , Li Qiao , Lu Song , He Xueling , Yu Sisi , Zhang Zhihui , Xu Guohui , Li Lu , Yang Tinghan , Zhu Jiang , Zhu Wenli , Wu Zhigang , Luo Delun , Zhu Jie , Xu Binghe , Huang Jian , Yin Hailin , Xu Kai 
Published: February 2018

AbstractmiR-122 in circulation is a promising non-invasive biomarker as a replacement or supplement of current serum biomarkers for liver injuries. But the concept was questioned by recent studies, mainly due to its release from hepatocytes in absence of overt cellular injuries. In this study, we reported that the hepatic metabolism of circulating catecholamines resulted in the release of hepatocyte-specific miR-122. Acute stress-induced hepatocellular deformation was histopathologically different from drug-induced liver injury with significant increases of plasma miR-122 levels. The basal levels of human plasma miR-122 could be significantly altered by emotional responses. Interday variances of plasma miR-122 measurements were reduced effectively by stress-relief measures. The metabolism of basal circulating norepinephrine and epinephrine in liver might contribute to the basal levels of plasma miRNAs expressed in hepatocytes.
Conservation of sex-linked markers among conspecific populations of a viviparous skink, Niveoscincus ocellatus, exhibiting genetic and temperature dependent sex determination
Authors: Hill Peta , Burridge Christopher P. , Ezaz Tariq , Wapstra Erik 
Published: February 2018

AbstractSex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whilst in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater divergence of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems (GSD and TSD-like systems) can be facilitated by subtle genetic differences.
Bounded Rationality in C. elegans
Authors: Cohen Dror , Volovich Meshi , Zeevi Yoav , Elbaum Lilach , Louie Kenway , Levy Dino J , Rechavi Oded 
Published: February 2018

AbstractRational choice theory assumes optimality in decision-making. Violations of a basic axiom of economic rationality known as “Independence of Irrelevant Alternatives” (IIA), have been demonstrated in both humans and animals, and could stem from common neuronal constraints. We developed tests for IIA in the nematode Caenorhabditis elegans, an animal with only 302 neurons, using olfactory chemotaxis assays. We found that in most cases C. elegans make rational decisions. However, by probing multiple neuronal architectures using various choice sets, we show that asymmetric sensation of odor options by the AWCON neuron can lead to violations of rationality. We further show that genetic manipulations of the asymmetry between the AWC neurons can make the worm rational or irrational. Last, a normalization-based model of value coding and gain control explains how particular neuronal constraints on information coding give rise to irrationality. Thus, we demonstrate that bounded rationality could arise due to basic neuronal constraints.
Regulation of (p)ppGpp hydrolysis by a conserved archetypal regulatory domain
Authors: Ronneau Séverin , Caballero-Montes Julien , Mayard Aurélie , Garcia-Pino Abel , Hallez Régis 
Published: February 2018

AbstractSensory and regulatory domains allow bacteria to adequately respond to environmental changes. The regulatory ACT domains are mainly found in metabolic-related proteins as well as in long (p)ppGpp synthetase/hydrolase (SD/HD) enzymes. Here, we investigate the functional role of the ACT domain of SpoT, the only (p)ppGpp SD/HD ofCaulobacter crescentus. We show that SpoT requires the ACT domain to hydrolyse ppGpp in an efficient way. In addition, ourin vivoandin vitrodata show that the phosphorylated version of EIIANtr(EIIANtr~P) interacts directly with the ACT to inhibit the hydrolase activity of SpoT. Finally, we highlight the conservation of the ACT-dependent interaction between EIIANtr~P and SpoT/Rel along with the PTSNtr-dependent regulation of (p)ppGpp accumulation upon nitrogen starvation inSinorhizobium meliloti, a plant-associated α-proteobacterium. Thus, this work suggests that α-proteobacteria might have inherited from a common ancestor, a PTSNtrdedicated to modulate (p)ppGpp levels.
A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy
Authors: Nikopoulos Konstantinos , Cisarova Katarina , Quinodoz Mathieu , Koskiniemi-Kuending Hanna , Miyake Noriko , Farinelli Pietro , Ur Rehman Atta , Imran Khan Muhammad , Prunotto Andrea , Akiyama Masato , Kamatani Yoichiro , Terao Chikashi , Miya Fuyuki , Ikeda Yasuhiro , Ueno Shinji , Fuse Nobuo , Murakami Akira , Wada Yuko , Terasaki Hiroko , Sonoda Koh-Hei , Ishibashi Tatsuro , Kubo Michiaki , Cremers Frans P. M. , Kutalik Zoltán , Matsumoto Naomichi , Nishiguchi Koji M. , Nakazawa Toru , Rivolta Carlo 
Published: February 2018

ABSTRACTHereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e. a 3.5-fold enrichment; p-value = 9.2×10−5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation, in trans with the Alu insertion, but might also cause disease in association with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.
ANIMA: Association Network Integration for Multiscale Analysis
Authors: Deffur Armin , Wilkinson Robert J , Mayosi Bongani M , Mulder Nicola 
Published: February 2018

AbstractContextual functional interpretation of -omics data derived from clinical samples is a classical and difficult problem in computational systems biology. The measurement of thousands of datapoints on single samples has become routine but relating ‘big data’ datasets to the complexities of human pathobiology is an area of ongoing research. Complicating this is the fact that many publically available datasets use bulk transcriptomics data from complex tissues like blood. The most prevalent analytic approaches derive molecular ‘signatures’ of disease states or apply modular analysis frameworks to the data. Here we show, using a network-based data integration method using clinical phenotype and microarray data as inputs, that we can reconstruct multiple features (or endophenotypes) of disease states at various scales of organization, from transcript abundance patterns of individual genes through co-expression patterns of groups of genes to patterns of cellular behavior in whole blood samples, both in single experiments as well as in a meta-analysis of multiple datasets.
Strategic foresight for organizational agility at Nedbank Area Collaboration
Authors: Oosthuizen Marius , Scheepers Caren 
Published: February 2018

Subject area
The case study uses a strategic foresight method, scenario-planning, to examine the strategic options for a financial services firm. As such, it covers the fields of strategy, environment of business, innovation, digital disruption and organizational change as they relate to the firm’s ability to adapt to changes in the environment of business in an emerging market context.

Study level/applicability
The case was developed with master's-level students in mind, particularly those seeking a master of business administration, masters in strategic foresight or related management degrees.

Case overview
The case of NEDBANK, a longstanding and successful financial services firm based in South Africa is confronted with major challenges from competitors because of technological change in the industry as well as having to expand their market penetration across Africa. A rising regulatory burden, tough economic conditions and the need to access low income markets, provide a significant organizational development challenge as a decades-old bank, known for a relational approach to banking, has to navigate the new domains of “fintech”, micro-lending and public sector banking.

Expected learning outcomes
Students will gain comprehensive insight into the industry environment in emerging markets, understand the strategic management challenge before financial services firms in this environment and be able to consider the alternative strategic interventions that may be used to ensure corporate sustainability amid these challenges. Simultaneously, the case provides a comprehensive view into the use and application of scenario-planning for strategic management.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 11: Strategy
An innovative work behaviour-enhancing employability model moderated by age
Authors: Stoffers Jol M.M. , Van der Heijden Béatrice I.J.M. 
Published: February 2018

PurposeThis study aims to empirically validate an innovative work behaviour-enhancing model of employability in small- and medium-sized enterprises (SMEs), and to examine possible moderating effects of age.Design/methodology/approachData have been collected from 487 pairs of employees and their immediate supervisors who worked in 151 SMEs. Structural equation modelling (SEM) has been used to investigate the predictive validity of employability on innovative work behaviour using a multi-source approach. The moderating effect of employee age on the relationship between, on the one hand, self-ratings and supervisor ratings of employability, and, on the other hand, innovative work behaviour has been tested using multi-group SEM.FindingsResults suggest that self-rated employability correlates positively with supervisor-rated innovative work behaviour, and that supervisor-rated employability correlates positively with self-rated innovative work behaviour. Age appeared to have a weak influence on the relationship between employability and innovative work behaviour; more specifically, in case of a higher age, the relationship was stronger.Research limitations/implicationsThe cross-sectional design is a limitation of this study. Another limitation relates to the generalizability of the study findings outside the context in which the research has been undertaken. The relational meaning of employee age might be different in other cultures.Practical implicationsSupervisors appear to play an essential role in providing an age-friendly working life for employees. Moreover, as SMEs often do not employ professionals to manage human resources, supervisors themselves have to carry the responsibility to encourage aging employees to develop themselves the enhancing innovative work behaviour.Originality/valueThis study is the first to investigate the predictive validity of employability on innovative work behaviour and the effects of age on this relationship.
Factors influencing price premiums of Australian wine in the UK market
Authors: Shane Elyse , Murad MD Wahid , Freeman Susan 
Published: February 2018

Purpose
The purpose of this paper is to determine and analyse that factors that could potentially influence price premiums of Australian wine in the UK market. The authors integrated the economic-based hedonic pricing theory and marketing export pricing literature. The authors demonstrate a potential solution to limitations in knowledge of market-level data and industry wide competition, currently lacking in export pricing studies.

Design/methodology/approach
Using data extracted from wine-searcher.com and using multiple regression as the main analytical technique, the authors examined the relationships between actual retail prices UK consumers pay for Australian wine and product attributes. The authors compared the moderating influence of distribution channel (retail choice) on these relationships.

Findings
The results provide insights in export pricing literature, and the authors support better theoretical explanations for hedonic pricing studies in export marketing. The authors found two types of wine attributes – “brand” and “region of origin” – that attract price premiums. While relationships between variety and retail price, as well as age and retail price are less clear, the authors provide some support.

Research limitations/implications
One limitation of this hedonic pricing study is the inability to explain why certain relationships between product attributes and price premiums exist. Studies such as these could be improved by utilising both consumer- and firm-level data.

Practical implications
Whilst final prices paid by consumers are beyond the control of producers, understanding the relationships between retail prices, retail choices and product attributes are of strategic importance. Understanding the role consumer preferences play in determining prices they ultimately pay is of great value when determining export/retail pricing strategies.

Social implications
Consumers and firm managers are jointly able to provide comprehensive explanations on why certain attributes attract price premiums. The integration of economic and consumer-based theories provides a holistic understanding of the influence of retail choices and product attributes on retail prices.

Originality/value
The authors drew on the hedonic pricing theory linking product attributes with retail prices, which is vital for understanding market share and brand image. The authors identified which product attributes and which distribution channels (retail choices) are valuable to consumers. Deeper understanding of these issues is important for producers.
Consumers’ willingness to pay for local muscadine wine
Authors: Everett Connie , Jensen Kimberly , Boyer Christopher , Hughes David 
Published: February 2018

PurposeThis paper aims to identify factors influencing the likelihood of consumers trying muscadine wines and among those who have tried them, willingness to pay (WTP) for an in-state produced muscadine wine.Design/methodology/approachThe study uses a 2015 survey of wine consumers residing in Tennessee (TN). The survey presented respondents with a referendum choice experiment between a ‘base’ wine (represented by a North Carolina (NC) muscadine wine) and a TN muscadine wine. The study uses probit regressions to estimate factors influencing the probability of trying muscadine, and those influencing TN muscadine wine choice. Estimates of WTP for TN muscadine wine are derived from the model coefficients.FindingsOlder age, living in non-metro households being a weekly wine consumer, preferring red wines, and having visited a winery in the past year positively influence trying muscadines. Older age, liking muscadines and lower product price positively influence TN muscadine choice. Greater importance of wines being local and premiums paid for local foods have positive influences on trying muscadines and WTP for TN muscadine wine. A premium WTP for a TN muscadine over a NC muscadine exists among TN consumers. Among the most influential reasons why consumers chose the TN muscadine were beliefs that purchasing local wines helps local wine grape growers and local economies.Originality/valueThis study provides the muscadine wine industry with estimates of WTP for locally produced muscadines and demonstrates that attitudes toward local wines and premium paid for local foods positively influence trying muscadine wine and WTP for locally produced muscadine.
Intangible resources influencing the international performance of professional service SMEs in an emerging market
Authors: Radulovich Lori , Javalgi Rajshekhar (Raj) G. , Scherer Robert F. 
Published: February 2018

PurposeThe purpose of this paper is to empirically examine the relationships between the drivers of economic growth in emerging markets to include entrepreneurial orientation (EO), human capital (HC), relational capital (RC), and international performance (IP).Design/methodology/approachData were collected from 199 small- to medium-sized Indian professional service entrepreneurs that employ less than 500 employees and engage in international business. Given the multidimensional nature of IP, structural equation modeling (SEM) was used to test the measurement and substantive models.FindingsSEM and mediation tests confirmed significant relationships among the constructs in the model and indicated that HC can be leveraged for international growth using RC to deliver new professional services across borders. EO, the strongest predictor, along with HC and RC, directly influenced IP. The effect of HC is mediated by an EO and RC.Research limitations/implicationsBy design, only successful professional service firms in India were studied, which limited generalizability.Practical implicationsEntrepreneurs can enhance the likelihood of international expansion success by utilizing highly skilled HC and developing strong network relationships. Entrepreneurial managers should leverage their professional service resources through judicious investments in personnel and relationship-building skills to develop RC.Originality/valueThis study examined entrepreneurial professional HC and RC as related to international entrepreneurship emerging market research. Data collection in India contributes to empirical research on internationalization from emerging markets.