bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOGAN: A framework for LOssless Graph-based ANalysis of high throughput sequence data
Authors: Bolger Anthony , Denton Alisandra , Bolger Marie , Usadel Björn 
Published: August 2017

AbstractRecent massive growth in the production of sequencing data necessitates matching improve-ments in bioinformatics tools to effectively utilize it. Existing tools suffer from limitations in both scalability and applicability which are inherent to their underlying algorithms and data structures. We identify the key requirements for the ideal data structure for sequence analy-ses: it should be informationally lossless, locally updatable, and memory efficient; requirements which are not met by data structures underlying the major assembly strategies Overlap Layout Consensus and De Bruijn Graphs. We therefore propose a new data structure, the LOGAN graph, which is based on a memory efficient Sparse De Bruijn Graph with routing information. Innovations in storing routing information and careful implementation allow sequence datasets forEscherichia coli(4.6Mbp, 117x coverage),Arabidopsis thaliana(135Mbp, 17.5x coverage) andSolanum pennellii(1.2Gbp, 47x coverage) to be loaded into memory on a desktop computer in seconds, minutes, and hours respectively. Memory consumption is competitive with state of the art alternatives, while losslessly representing the reads in an indexed and updatable form. Both Second and Third Generation Sequencing reads are supported. Thus, the LOGAN graph is positioned to be the backbone for major breakthroughs in sequence analysis such as integrated hybrid assembly, assembly of exceptionally large and repetitive genomes, as well as assembly and representation of pan-genomes.
Identification and kinetics characterization of a wax ester hydrolase from a feather-degrading actinomycete
Authors: Barcus Matthew , Mizrachi Dario , Lei Xin Gen 
Published: August 2017

AbstractStreptomyces fradiaevar. k11 is a Gram-positive soil microorganism capable of degrading chicken feathers. Apart from being mostly protein, chicken feathers have a considerable level of lipids, with wax esters being the largest lipid class. The waxes may pose a challenge while rendering the feathers into coproducts, such as feather meal, and so the identification of a wax-ester hydrolase is warranted. A draft genome sequence ofS. fradiaevar. k11 was used to identify 14 gene sequences of potential lipid-degrading enzymes. The genes were expressed inE. coliBL21(DE3) cells on a pET vector and screened for activity. Four of the 14 enzymes had detectable activity, with two of the enzymes, SFK3309 and SFK3087, active against p-nitrophenyl palmitate, a representative water-insoluble substrate. A modified enzymatic assay was designed to measure activity against three model wax substrates: jojoba oil, beeswax, and cetyl-palmitate. SFK3309 was characterized to hydrolyze all three wax substrates. Kinetic experiments for SFK3309 were performed with cetyl-palmitate at 37°C, pH 8.0. TheKmwas determined to be 850 µM and theKcatwas 11.63 s-1. Through the characterization of SFK3309 as a wax-ester hydrolase, biotechnological implications of wax ester hydrolases in the rendering of many industrial wastes can be substantiated for further studies.
CTCF mediated genome architecture regulates the dosage of mitotically stable mono-allelic expression of autosomal genes
Authors: Raanin Chandradoss Keerthivasan , Singh Sandhu Kuljeet 
Published: August 2017

AbstractMammalian genomes exhibit widespread mono-allelic expression of autosomal genes. However, the mechanistic insight that allows specific expression of one allele remains enigmatic. Here, we present evidence that the linear and the three dimensional architectures of the genome ascribe the appropriate framework that guides the mono-allelic expression of genes. We show that: 1) mono-allelically expressed genes are assorted into genomic domains that are insulated from domains of bi-allelically expressed genes through CTCF mediated chromatin loops; 2) evolutionary and cell-type specific gain and loss of mono-allelic expression coincide respectively with the gain and loss of chromatin insulator sites; 3) dosage of mono‐ allelically expressed genes is more sensitive to loss of chromatin insulationn associated with CTCF depletion as compared to bi-allelically expressed genes; 4) distinct susceptibility of mono‐ and bi-allelically expressed genes to CTCF depletion can be attributed to distinct functional roles of CTCF around these genes. Altogether, our observations highlight a general topological framework for the mono-allelic expression of genes, wherein the alleles are insulated from the spatial interference of chromatin and transcriptional states from neighbouring bi-allelic domains via CTCF mediated chromatin loops. The study also suggests that the three-dimensional genome organization might have evolved under the constraint to mitigate the fluctuations in the dosage of mono-allelically expressed genes, which otherwise are dosage sensitive.
Genome-wide association studies of brain structure and function in the UK Biobank
Authors: Elliott Lloyd T. , Sharp Kevin , Alfaro-Almagro Fidel , Shi Sinan , Miller Karla , Douaud Gwenaëlle , Marchini Jonathan , Smith Stephen 
Published: August 2017

SummaryThe genetic basis of brain structure and function is largely unknown. We carried out genome-wide association studies of 3,144 distinct functional and structural brain imaging derived phenotypes in UK Biobank (discovery dataset 8,428 subjects). We show that many of these phenotypes are heritable. We identify 148 clusters of SNP-imaging associations with lead SNPs that replicate at p<0.05, when we would expect 21 to replicate by chance. Notable significant and interpretable associations include: iron transport and storage genes, related to changes in T2* in subcortical regions; extracellular matrix and the epidermal growth factor genes, associated with white matter micro-structure and lesion volume; genes regulating mid-line axon guidance development associated with pontine crossing tract organisation; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide new insight into the genetic architecture of the brain with relevance to complex neurological and psychiatric disorders, as well as brain development and aging. The full set of results is available on the interactive Oxford Brain Imaging Genetics (BIG) web browser.
Association of mitochondria with microtubules inhibits mitochondrial fission by precluding Dnm1 assembly
Authors: Mehta Kritika , Chacko Leeba Ann , Chug Manjyot Kaur , Jhunjhunwala Siddharth , Ananthanarayanan Vaishnavi 
Published: August 2017

AbstractMitochondria are organized as tubular networks in the cell and undergo fission and fusion. While several of the molecular players involved in mediating mitochondrial dynamics have been identified, the precise cellular cues that initiate fission or fusion remain largely unknown. In fission yeast, mitochondria are organized along microtubule bundles. Here, we employed deletions of kinesin-like proteins to perturb microtubule dynamics, and determined that cells with long microtubules exhibited long, but fewer mitochondria, whereas cells with short microtubules exhibited short, but several mitochondria due to reduced mitochondrial fission in the former and elevated fission in the latter. Correspondingly, upon onset of closed mitosis in fission yeast, wherein interphase microtubules assemble to form the spindle within the nucleus, we measured increased mitochondrial fission. We determined that the consequent rise in the mitochondrial copy number was necessary to reduce partitioning errors while stochastically partitioning mitochondria between daughter cells. We discovered that the association of mitochondria with microtubules physically impeded the assembly of the fission protein Dnm1 around mitochondria, resulting in inhibition of mitochondrial fission. Taken together, we demonstrate a novel mechanism for regulation of mitochondrial fission that is dictated by the interaction between mitochondria and the microtubule cytoskeleton.
A major locus controls local adaptation and adaptive life history variation in a perennial plant
Authors: Wang Jing , Ding Jihua , Tan Biyue , Robinson Kathryn M. , Michelson Ingrid H. , Johansson Anna , Nystedt Björn , Scofield Douglas G. , Nilsson Ove , Jansson Stefan , Street Nathaniel R. , Ingvarsson Pär K. 
Published: August 2017

AbstractBackgroundThe initiation of growth cessation and dormancy represent critical life-history tradeoffs between survival and growth, and have important fitness effects in perennial plants. Such adaptive life history traits often show strong local adaptation along environmental gradients but despite their importance, the genetic architecture of these traits remains poorly understood.ResultsWe integrate whole genome re-sequencing with environmental and phenotypic data from common garden experiments to investigate the genomic basis of local adaptation across a latitudinal gradient in European aspen (Populus tremula). We discover a single genomic region containing thePtFT2gene that mediates local adaptation in the timing of bud set and that explains 65% of the observed genetic variation in bud set. This locus is the likely target of a recent selective sweep that originated right before or during colonization of northern Scandinavia following the last glaciation. Field and greenhouse experiments confirm that variation inPtFT2gene expression affect the phenotypic variation in bud set that we observe in wild natural populations.ConclusionsOur results reveal a major effect locus that determine the timing of bud set and that have facilitated rapid adaptation to shorter growing seasons and colder climates in European aspen. The discovery of a single locus explaining a substantial fraction of the variation in a key life history trait is remarkable given that such traits are generally considered to be highly polygenic. These findings provide a dramatic illustration of how loci of large-effect for adaptive traits can arise and be maintained over large geographical scales in natural populations.
Taking a semi-local dynamic snapshot as a possibility for local homing in initially naïve bumblebees
Authors: Lobecke Anne C. , Kern Roland , Egelhaaf Martin 
Published: August 2017

AbstractFor central place foragers, such as bumblebees, it is essential to return reliably to their nest. Instead of just flying away to forage, bumblebees, leaving their inconspicuous nest hole for the first time, need to gather and learn sufficient information about the surroundings to allow them to return to the nest at the end of their trip. Therefore, we assume an intrinsic learning program that manifests itself in the flight structure immediately after leaving the nest for the first time.In this study, we recorded and analysed the first outbound flight of individually marked naïve bumblebees in an indoor environment. We found characteristic loop-like features in the flight pattern that appear to be necessary for the bees to acquire environmental information and might be relevant for finding the nest hole after a foraging trip.Despite common features in their spatio-temporal organisation, the first departure flights from the nest are characterised by a high level of variability in their loop-like flight structure across animals. Changes in turn direction of body orientation, for example, are distributed evenly across the entire area used for the flights without any systematic relation to the nest location. By considering the common flight motifs as well as this variability, we came to the hypothesis, that a kind of dynamic snapshot is taken during the early phase of departure flights in the close vicinity of the nest location. The quality of this snapshot is hypothesised to be ‘ tested’ during the later phases of the departure flights concerning its usefulness for local homing.
A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations
Authors: Fogel J. L. , Lakeland D. L. , Mah I. K. , Mariani F. V. 
Published: August 2017

ABSTRACTFor decades, the mechanism of skeletal patterning along a proximal-distal axis has been an area of intense inquiry. Here we examine the development of the ribs, simple structures that in most terrestrial vertebrates consist of two skeletal elements— a proximal bone and a distal cartilage portion. While the ribs have been shown to arise from the somites, little is known about how the two segments are specified. During our examination of genetically modified mice, we discovered a series of progressively worsening phenotypes that could not be easily explained. Here, we combine genetic analysis of rib development with agent-based simulations to conclude that proximal-distal patterning and outgrowth could occur based on simple rules. In our model, specification occurs during somite stages due to varying Hedgehog protein levels, while later expansion refines the pattern. This framework is broadly applicable for understanding the mechanisms of skeletal patterning along a proximal-distal axis.
Genetic and real-world clinical data, combined with empirical validation, nominate JAK-STAT signalling as a target for Alzheimer’s Disease therapeutic development
Authors: Nevado-Holgado Alejo J. , Ribe Elena , Thei Laura , Furlong Laura , Angel-Mayer Miguel , Quan Jie , Richardson Jill C. , Cavanagh Jonathan ,   NIMA Consortium, Lovestone Simon 
Published: August 2017

AbstractAs Genome Wide Association Studies (GWAS) have grown in size, the number of genetic variants that have been nominated for an increasing number of diseases has correspondingly increased. Despite this increase in the number of associated SNPs per disease, their biological interpretation has in many cases remained elusive. To address this, we have combined GWAS results with an orthogonal source of evidence, namely real-world, routinely collected clinical data from more than 6 million patients in order to drive target nomination. First we show that when examined at a pathway level, analysis of all GWAS studies groups Alzheimer’s disease (AD) in a cluster with disorders of immunity and inflammation. Using clinical data we show that the degree of comorbidity of these diseases with AD correlates with the strength of their genetic association with molecular participants in the JAK-STAT pathway. Using four independent open-science datasets we then find evidence for altered regulation of JAK-STAT pathway genes in AD. Finally, we use both in vitro and in vivo rodent models to demonstrate that Aβ induces gene expression of key drivers of this pathway, providing experimental evidence validating these data-driven observations. These results therefore nominate JAK-STAT anomalies as a prominent aetiopathological event in AD and hence potential target for therapeutic development, and moreover demonstrate a de-novo multi-modal approach to derive information from rapidly increasing genomic datasets.One Sentence SummaryCombining evidence from genome wide association studies, real-world clinical and cohort molecular data together with experimental studies in rodent model systems nominates JAK-STAT signaling as an aetiopathological event in Alzheimer’s disease
From initiatives to employee-driven innovations
Authors: Haapasaari Arja , Engeström Yrjö , Kerosuo Hannele 
Published: August 2017

PurposeThe purpose of this paper is to examine the generation of innovations by employees and the creation of initiative paths, and to discover which factors contribute to the implementation of an initiative.Design/methodology/approachBased on longitudinal qualitative research, the study explores the profiles of initiative paths and the types of innovations and relationships among the generated innovations.FindingsIt was found that, to become an innovation, an initiative followed different paths along which the processing and outcomes varied, as did the time needed for experimentation. The creation of initiative paths required the transformative agency of the actors involved. Power relations had an impact on the generation of initiatives and implementation of innovations.Originality/valueInnovations research has concentrated on the generation of ideas and the implementation of innovations. This study focuses on the process path along which ideas become innovations and on the role of power relations in the innovations process.
Collaborating across the researcher-practitioner divide
Authors: Vo Linh Chi , Kelemen Mihaela 
Published: August 2017

PurposeThe purpose of this paper is to contribute to bridging the gap between researchers and practitioners. It does so by comparing the various models of academic-practitioner collaboration and introducing Dewey’s democratic experimentalism as a promising alternative.Design/methodology/approachThe conceptual implications are drawn from an analysis and discussion of the literatures in the field of organizational knowledge production, co-production and Deweyan studies.FindingsDemocratic experimentalism offers a much needed platform for a collaborative relationship between academics and practitioners that leads to knowledge that is rigorous and relevant to practice.Originality/valueWhile the current models of academic-practitioner collaboration provide mechanisms for knowledge co-production, the Dewey’s democratic experimentalism goes further to emphasize the nature of the relationship between academics and practitioners in such common endeavor to ensure that all of them are equal co-creators of knowledge.
The relationship between subjective well-being and workplace ostracism
Authors: Zhang Suchuan , Shi Qiao 
Published: August 2017

Purpose
The purpose of this paper is to examine the effect of subjective well-being (SWB) on workplace ostracism, by focusing on the moderating role of emotional intelligence (EI). SWB is taken here as a construct of three components: life satisfaction, positive affect (PA), and negative affect (NA).

Design/methodology/approach
The theoretical model was tested using data collected from employees in different firms from different provinces in China. Analyses of multisource and lagged data from 677 employees indicate that as predicted, EI moderates the relationship between SWB (life satisfaction, PA, and NA) and workplace ostracism.

Findings
The findings show that when employees demonstrate high levels of EI, the negative relationships between life satisfaction, PA and workplace ostracism were strengthened, and the positive relationship between NA and workplace ostracism was weakened.

Originality/value
First, the results empirically demonstrate that EI is one moderator of the relationship between SWB and workplace ostracism. Second, the study contributes to the field of workplace ostracism by indicating some critical antecedents. Third, the present study examines the moderating role of EI in the relationship between SWB and workplace ostracism among Chinese employees.
Mediation effect of novelty ecosystems on intrapreneurial behaviour process within an organisational dynamic environment among Kenyan universities
Authors: Kibirango Moses Mpiima , Munene John C. , Balunywa Waswa J. , Obbo Jovent K. 
Published: August 2017

Purpose
The purpose of this paper is to examine, explain, predict and guide the processes, mechanisms and outcomes of intrapreneurial behaviour to provide evidence that novelty ecosystems mediate the relationships between generative influence, positive deviance and intrapreneurial behaviour. It also enlightens the capacity of replicating the intrapreneurial best practices.

Design/methodology/approach
The study uses an integrated approach of entrepreneurship and complexity theories. Its subjects were full-time designated university employees in the Republic of Kenya. A total number of 244 employees were selected using snowball sampling technique from ten public and private universities in the Kenya. A self-administered questionnaire was used to collect data.

Findings
The structural equation modelling path analysis and the bootstrapping results confirmed full mediation of novelty ecosystems in the relationship between generative influence and intrapreneurial behaviour. The findings, further, verified that novelty ecosystems partially mediate the relationship between positive deviance and intrapreneurial behaviour.

Research limitations/implications
Subjective appraisals were used, despite the fact that studied variables are ultimately based on what employees perceive. Future research should generate and include more objective measures.

Practical implications
Intrapreneurial behaviour can only be explained and predicted through novelty ecosystems. University leaders need to fully understand and facilitate novelty ecosystems.

Social implications
A deeper understanding of the power of generative influence, positive deviance and novelty ecosystems will not be fully realized until researchers devote as much energy and attention to facilitation as has been devoted to conflict.

Originality/value
This study extends existing intrapreneurial research into complexity approach.
Strengthening the bond and enhancing team performance
Authors: Lu Luo , Fan Hsueh-Liang 
Published: August 2017

PurposeUsing interpersonal relationship development as a metaphor for team process, the purpose of this paper is to explore critical psychological mechanisms transforming team inputs into successful work outcomes, at the individual level.Design/methodology/approachThe participants in this study were full-time employees in Taiwan. The authors employed a two-phase design to examine the developmental aspect of, and the enhancer for the team process. Paper-based questionnaires were used to collect data. All the research constructs were assessed at the individual level, thus analysis was conducted at the same level.FindingsThe results from 338 Taiwanese employees revealed that perceived psychological similarity (i.e. value and attitudinal congruence, a team input) led to favorable work outcomes (i.e. job satisfaction and team performance) through the linking mechanism of team cohesion. Furthermore, team members’ trait emotional intelligence (EI) amplified the positive relationship between psychological similarity and team cohesion.Practical implicationsFirst, managers should purposefully assemble employees with similar values and interests to work together, giving the team a good start with the like minds. Second, the results indicated that trait EI as a key personal resource enhances the positive relationship between psychological similarity and team cohesion. Workplace learning interventions should be implemented to improve employees’ emotion management skills.Originality/valueAdopting the interpersonal relationship development perspective to study team process, the findings have confirmed the important roles of perceived psychological similarity among members and individual’s EI for team functioning. The authors’ endeavor has demonstrated the value of solid theoretical basis and the benefit of an individual-level analysis in delineating the mediating processes that explain why certain inputs affect team effectiveness and viability.