bluuebunny/crossref_metadata_2025 huggingface dataset:
A gene expression atlas of embryonic neurogenesis inDrosophilareveals complex spatiotemporal regulation of lncRNAs
Authors: McCorkindale Alexandra L. , Wahle Philipp , Werner Sascha , Jungreis Irwin , Menzel Peter , Shukla Chinmay J. , Pereira Abreu Rúben Lopes , Irizarry Rafael , Meyer Irmtraud M. , Kellis Manolis , Zinzen Robert P.
Published: December 2018

Summary statement

We present a spatiotemporal transcriptome during earlyDrosophilaembryonic nervous system development, revealing a complex cell type-specific network of mRNAs and lncRNAs.

Cell type specification during early nervous system development inDrosophila melanogasterrequires precise regulation of gene expression in time and space. Resolving the programs driving neurogenesis has been a major challenge owing to the complexity and rapidity with which distinct cell populations arise. To resolve the cell type-specific gene expression dynamics in early nervous system development, we have sequenced the transcriptomes of purified neurogenic cell types across consecutive time points covering critical events in neurogenesis. The resulting gene expression atlas comprises a detailed resource of global transcriptome dynamics that permits systematic analysis of how cells in the nervous system acquire distinct fates. We resolve known gene expression dynamics and uncover novel expression signatures for hundreds of genes among diverse neurogenic cell types, most of which remain unstudied. We also identified a set of conserved and tissue-specifically regulated long-noncoding RNAs (lncRNAs) that exhibit spatiotemporal expression during neurogenesis with exquisite specificity. LncRNA expression is highly dynamic and demarcates specific subpopulations within neurogenic cell types. Our spatiotemporal transcriptome atlas provides a comprehensive resource to investigate the function of coding genes and noncoding RNAs during critical stages of early neurogenesis.
Circuit dysfunction in SOD1-ALS model first detected in sensory feedback prior to motor neuron degeneration is alleviated by BMP signaling
Authors: Held Aaron , Major Paxton , Sahin Asli , Reenan Robert , Lipscombe Diane , Wharton Kristi
Published: December 2018

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose origin and underlying cellular defects are still not fully understood. While motor neuron degeneration is the signature feature of ALS, it is not yet clear if motor neurons, or other cells of the motor circuit, are the site of disease initiation. To better understand the contribution of multiple cell types in ALS, we made use of a Drosophila Sod1G85R knock-in model, in which all cells harbor the disease allele. End-stage dSod1G85R animals exhibit severe motor deficits with clear degeneration of motor neurons. Interestingly, earlier in dSod1G85R larvae motor function is also compromised, but their motor neurons exhibit only subtle morphological and electrophysiological changes, that are unlikely to cause the observed decrease in locomotion. We analyzed the intact motor circuit and identified a defect in sensory feedback that likely accounts for the altered motor activity of dSod1G85R. Furthermore, we found that the cell-autonomous activation of BMP signaling in proprioceptor sensory neurons that relay the contractile status of muscles back to the central nerve cord, is able to completely rescue early stage motor defects and partially rescue late stage motor function to extend lifespan. Identifying a defect in sensory feedback as a potential initiating event in ALS motor dysfunction, coupled with the ability of modified proprioceptors to alleviate such motor deficits, underscores the critical role that non-motor neurons play in disease progression and highlights their potential as a site to identify early-stage ALS biomarkers and for therapeutic intervention.
VAMP8 contributes to TRIM6-mediated type-I interferon antiviral response during West Nile virus infection
Authors: Atkins Colm , Tol Sarah van , Bharaj Preeti , Rajsbaum Ricardo , Freiberg Alexander N.
Published: December 2018

Members of the tripartite motif (TRIM) family of E3 ubiquitin ligases regulate immune pathways including the antiviral type I interferon (IFN-I) system. Previously, we demonstrated that TRIM6 is involved in IFN-I induction and signaling. In absence of TRIM6 function, optimal IFN-I signaling is reduced, allowing increased replication of interferon-sensitive viruses. Despite numerous mechanisms to restrict vertebrate host’s IFN-I response, West Nile Virus (WNV) replication is sensitive to pre-treatment with IFN-I. However, the regulators and products of the IFN-I pathway important in regulating WNV replications are incompletely defined. Consistent with WNV’s sensitivity to IFN-I, we found that in TRIM6 knockout (TRIM6 KO) A549 cells WNV replication is significantly increased. Additionally, induction of Ifnb mRNA was delayed and the expression of several IFN-stimulated genes (ISGs) was reduced in TRIM6 KO cells. IFNβ pre-treatment was more effective in protecting against subsequent WNV infection in wt cells, indicating that TRIM6 contributes to the establishment of an IFN-induced antiviral response against WNV. Using next generation sequencing, we identified potential factors involved in this TRIM6-mediated antiviral response. One identified gene, VAMP8, is a soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) in the vesicle-associated membrane protein subfamily. Knockdown of VAMP8 resulted in reduced STAT1 phosphorylation and impaired induction of several ISGs following WNV infection or IFNβ treatment. Therefore, VAMP8 is a novel gene involved in the regulation of IFN-I signaling, and its expression is dependent on TRIM6 function. Overall, these results indicate that TRIM6 contributes to the antiviral response against WNV by regulating the IFN-I system.

IMPORTANCE

WNV is a mosquito-borne flavivirus that poses threat to human health across large discontinuous areas throughout the world. Infection with WNV results in febrile illness, which can progress to severe neurological disease. Currently, there are no approved treatment options to control WNV infection. Understanding the cellular immune responses that regulate viral replication is important in diversifying the resources available to control WNV. Here we show that the elimination of TRIM6 in human cells results in an increase in WNV replication and alters the expression and function of other components of the IFN-I pathway through VAMP8. Dissecting the interactions between WNV and host defenses both informs basic molecular virology and promotes the development of host- and viral-targeted antiviral strategies.
Shallow MinION sequencing to assist de novo assembly of the Streptococcus agalactiae genome
Authors: Hernandez-Beeftink Tamara , Rodriguez-Perez Hector , Usera Ana Díaz-de , Gonzalez-Montelongo Rafaela , Lorenzo-Salazar José M. , Lorenzo-Díaz Fabián , Flores Carlos
Published: December 2018

Despite the reduced read length, the so-called Next-Generation Sequencing (NGS) of second-generation has allowed rapid and complete genome characterization of many species. MinION (Oxford Nanopore Technologies), a portable third-generation NGS device, enables sequencing of long DNA fragments at low cost. Here we used a low-coverage MinION sequencing in combination with short-read NGS to improve genome assembly. We tested this possibility by using MinION R9.0 with Rapid 1D kit and MiSeq with >300X paired-end 300 bp reads (Illumina, Inc.) for the genome assembly of a Streptococcus agalactiae clinical isolate (2.2 Mb). With as few as 1,171 MinION reads that covered the genome at 2.4X (the longest read being 186 Kb long), the hybrid assembly combining MinION and Illumina reads increased the N50 by 4.9-fold compared to the assembly using Illumina data alone. Almost 50% of the genome was represented into a single contig (1.02 Mb). Besides, this allowed the full reconstruction of mobile elements, including a plasmid, and improved gene annotation. Taken together, our results support that shallow MinION sequencing combined with high-throughput second-generation NGS constitutes a cost-efficient strategy for the assembly of whole genomes.
Novitski’s Distal shift in Paracentric Inversion Evolution
Authors: Koury Spencer A.
Published: December 2018

InDrosophila pseudoobscurayounger chromosomal inversions tend to be found distal to older inversions. By examining phylogenetic series of overlapping inversions for 134 gene arrangements of 13 chromosomes this pattern was extended to five additionalDrosophilaspecies. This distinct pattern arose repeatedly and independently in all six species and likely reflects an underlying principle of chromosome evolution. In this study it is illustrated how transmission of distal inversions isalwaysfavored in female meiosis when crossing over in homosequential regions of overlapping inversions generates asymmetric dyads. This cytogenetic mechanism for female meiotic drive is described in detail and advanced as an explanation for the distal shift in phylogenetic series of overlapping inversions as well as several better known patterns in the evolution of serially inverted chromosomes.
Small molecule docking of DNA repair proteins associated with cancer survival following PCNA metagene adjustment: A potential novel class of repair inhibitors
Authors: Peterson Leif
Published: December 2018

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.
Geographic variation and bias in polygenic scores of complex diseases and traits in Finland
Authors: Kerminen Sini , Martin Alicia R. , Koskela Jukka , Ruotsalainen Sanni E. , Havulinna Aki S. , Surakka Ida , Palotie Aarno , Perola Markus , Salomaa Veikko , Daly Mark J. , Ripatti Samuli , Pirinen Matti
Published: December 2018

Polygenic scores (PS) are becoming a useful tool to identify individuals with high genetic risk for complex diseases and several projects are currently testing their utility for translational applications. It is also tempting to use PS to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how population genetic properties of the training and target samples affect the geographic distribution of PS. Here, we evaluate geographic differences, and related biases, of PS in Finland with geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PS for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waits-hip ratio (WHR), body-mass index (BMI) and height, but not for Crohn’s disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PS and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulation of geographic differences for CAD, WHR, BMI and height, suggesting bias arising from population genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PS are for small biases even within relatively homogenous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PS is essential for translational applications of PS.
Ykt6 membrane-to-cytosol cycling regulates exosomal Wnt secretion
Authors: Linnemannstöns Karen , Karuna M Pradhipa , Witte Leonie , Kittel Jeanette Clarissa , Danieli Adi , Müller Denise , Nitsch Lena , Honemann-Capito Mona , Grawe Ferdi , Wodarz Andreas , Gross Julia Christina
Published: December 2018

Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. We identified conserved phosphorylation sites within the SNARE domain of Ykt6, which block Ykt6 cycling from the membrane to the cytosol. In Drosophila, Ykt6-RNAi mediated block of Wg secretion is rescued by wildtype but not phosphomimicking Ykt6. The latter accumulates at membranes, while wildtype Ykt6 regulates Wnt trafficking between the plasma membrane and multivesicular bodies. Taken together, we show that a regulatory switch in Ykt6 fine-tunes sorting of Wnts in endosomes.
Comparative genomics reveals contraction in cytosolic glutathione transferase genes in cetaceans: implications for oxidative stress adaptation
Authors: Tian Ran , Seim Inge , Ren Wenhua , Xu Shixia , Yang Guang
Published: December 2018

Cetaceans, a highly specialized group of aquatic mammals, experience oxidative stress induced by reactive oxygen species (ROS) production associated with the apnea/reoxygenation. The glutathione transferases (GST) family possesses multiple functions in detoxification and antioxidant defenses. However, the molecular evolution of GST family in cetaceans is still poorly investigated. Here, we characterized the GST gene family across 21 mammalian genomes including cetaceans and terrestrial relatives. Overall, 7 GST classes were identified, showing GSTs are ubiquitous and conservative to all mammals. Some of GSTs are lineage-specific duplication and loss, in line with a birth-and-death evolutionary model. We detected positive selection sites that possibly influence GST structure and function, suggesting adaptive evolution of GSTs is important for defending mammals from various types of noxious environmental compounds. There is evidence for loss of alpha and mu GST class in cetacean lineages when compared to their terrestrial relatives, consisting with the lower GST activities observed in cetaceans. Notably, we find that retained GSTA1, GSTA4 and GSTM1 in cetaceans, indicating a vital role in against lipid peroxidation and superoxide. Besides, variation in gene number, enzyme activity and selection pressure of GSTs between marine mammals suggests there is a divergent evolution of GSTs in aquatic species that might be associated to diving ability and oxidative status with different habitats. Summarily, our findings demonstrate that the GST family in cetaceans has been subject to evolutionary dynamics as response for their adaptations to oxidative stress, and highlighted the differential selection associated with different life history traits among mammals.
Metabolic Control Analysis of Exponential Growth and Product Formation
Authors: Fell David Andrew
Published: December 2018

Metabolic Control Analysis defines the relationships between the change in activity of an enzyme and the resulting impacts on metabolic fluxes and metabolite concentrations at steady state. In many biotechnological applications of metabolic engineering, however, the goal is to alter the product yield. In this case, although metabolism may be at a pseudo-steady state, the amount of biomass catalysing the metabolism can be growing exponentially. Here, expressions are derived that relate the change in activity of an enzyme and its flux control coefficient to the change in yield from an exponentially growing system. Conversely, the expressions allow estimation of an enzyme's flux control coefficient over the pathway generating the product from measurements of the changes in enzyme activity and yield.
Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations
Authors: Gothe Henrike Johanna , Bouwman Britta Annika Maria , Gusmao Eduardo Gade , Piccinno Rossana , Sayols Sergi , Drechsel Oliver , Petrosino Giuseppe , Minneker Vera , Josipovic Natasa , Mizi Athanasia , Nielsen Christian Friberg , Wagner Eva-Maria , Takeda Shunichi , Sasanuma Hiroyuki , Hudson Damien Francis , Kindler Thomas , Baranello Laura , Papantonis Argyris , Crosetto Nicola , Roukos Vassilis
Published: December 2018

How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer.
The shape of density dependence and the relationship between population growth, intraspecific competition and equilibrium population density
Authors: Fronhofer Emanuel A. , Govaert Lynn , O’Connor Mary I. , Schreiber Sebastian J. , Altermatt Florian
Published: December 2018

The logistic growth model is one of the most frequently used formalizations of density dependence affecting population growth, persistence and evolution. Ecological and evolutionary theory and applications to understand population change over time often include this model. However, the assumptions and limitations of this popular model are often not well appreciated.

Here, we briefly review past use of the logistic growth model and highlight limitations by deriving population growth models from underlying consumer-resource dynamics. We show that the logistic equation likely is not applicable to many biological systems. Rather, density-regulation functions are usually non-linear and may exhibit convex or both concave and convex curvatures depending on the biology of resources and consumers. In simple cases, the dynamics can be fully described by the continuous-time Beverton-Holt model. More complex consumer dynamics show similarities to a Maynard Smith-Slatkin model.

Importantly, we show how population-level parameters, such as intrinsic rates of increase and equilibrium population densities are not independent, as often assumed. Rather, they are functions of the same underlying parameters. The commonly assumed positive relationship between equilibrium population density and competitive ability is typically invalid. As a solution, we propose simple and general relationships between intrinsic rates of increase and equilibrium population densities that capture the essence of different consumer-resource systems.

Relating population level models to underlying mechanisms allows us to discuss applications to evolutionary outcomes and how these models depend on environmental conditions, like temperature via metabolic scaling. Finally, we use time-series from microbial food chains to fit population growth models and validate theoretical predictions.

Our results show that density-regulation functions need to be chosen carefully as their shapes will depend on the study system’s biology. Importantly, we provide a mechanistic understanding of relationships between model parameters, which has implications for theory and for formulating biologically sound and empirically testable predictions.
Replication dynamics of individual loci in single living cells reveal variation of stochasticity
Authors: Duriez Bénédicte , Chilaka Sabarinadh , Bercher Jean-François , Hercul Eslande , Boggetto Nicole , Prioleau Marie-Noëlle
Published: December 2018

Eukaryotic genomes are replicated under the control of a highly sophisticated program during the restricted time period corresponding to S-phase. The most widely used replication timing assays, which are performed on populations of millions of cells, suggest that most of the genome is synchronously replicated on homologous chromosomes. We investigated the stochastic nature of this temporal program, by comparing the precise replication times of allelic loci within single vertebrate cells progressing through S-phase at six loci replicated from very early to very late. We show that replication timing is strictly controlled for the three loci replicated in the first half of S-phase. Out of the three loci replicated in the second part of S-phase, two present a significantly more stochastic pattern. Surprisingly, we find that the locus replicated at the very end of S-phase, presents stochasticity similar to those replicated in early S-phase. We suggest that the richness of loci in efficient origins of replication, which decreases from early-to late-replicating regions, may underlie the variation of timing control during S-phase.
cGAS is predominantly a nuclear protein
Authors: Volkman Hannah E , Cambier Stephanie , Gray Elizabeth E , Stetson Daniel B
Published: December 2018

cGAS is an intracellular innate immune sensor that detects double-stranded DNA. The presence of billions of base pairs of genomic DNA in all nucleated cells raises the question of how cGAS is not constitutively activated. A widely accepted explanation for this is the sequestration of cGAS in the cytosol, which is thought to prevent cGAS from accessing nuclear DNA. Here, we demonstrate that cGAS is predominantly a nuclear protein, regardless of cell cycle phase or cGAS activation status. We show that nuclear cGAS is tethered tightly by a salt-resistant interaction. This tight tethering is independent of the domains required for cGAS activation, and it requires intact nuclear chromatin. We propose that tethering prevents activation of cGAS by genomic DNA, and that it might enable cGAS to distinguish between self DNA and foreign DNA within the nucleus.
Does protein A mirror image exist in solution? Outline of an experimental design aimed to detect it
Authors: Martin Osvaldo A. , Vorobjev Yury , Scheraga Harold A. , Vila Jorge A.
Published: December 2018

There is abundant theoretical evidence indicating that a mirror image of ProteinA may occur during the protein folding process. However, as to whether such mirror image exists in solution is an unsolved issue. Here we provide outline of an experimental design aimed to detect the mirror image of Protein A in solution. The proposal is based on computational simulations indicating that the use of a mutant of protein A, namely 01 OH, could be used to detect the mirror image conformation in solution. Our results indicate that the native conformation of the protein A should have a pKa, for the 01 OH mutant, at r06.2, while the mirror image conformation should have a pKa close to ≈7.3. Naturally, if all the population is in the native state for the 01 OH mutant, the pKa should be ≈6.2, while, if all are in the mirror image state, it would be ≈7.3, and, if it is a mixture, the pKa should be larger than 6.2, presumably in proportion to the mirror population. In addition, evidence is provided indicating the tautomeric distribution of H1O must also change between the native and mirror conformations. Although this may not be completely relevant for the purpose of determining whether the protein A mirror image exists in solution, it could provide valuable information to validate the pKa findings. We hope this proposal will foster experimental work on this problem either by direct application of our proposed experimental design or serving as inspiration and motivation for other experiments.
Cas4 nucleases can effect specific integration of CRISPR spacers
Authors: Zhang Zhufeng , Pan Saifu , Liu Tao , Li Yingjun , Peng Nan
Published: December 2018

CRISPR-Cas systems incorporate short DNA fragments from invasive genetic elements into host CRISPR arrays in order to generate host immunity.Recently, we demonstrated that the Csa3a regulator protein triggers CCN PAM-dependent CRISPR spacer acquisition in the subtype I-A CRISPR-Cas system of Sulfolobus islandicus. However, the mechanisms underlying specific protospacer selection and spacer insertion remained unclear. Here, we demonstrate that two Cas4 family proteins (Cas4 and Csa1) have essential roles (a) in recognizing the 5' PAM and 3' nucleotide motif of protospacers and (b) in determining both the spacer length and its orientation. Furthermore, we identify uncovered amino acid residues of the Cas4 proteins that facilitate these functions. Overexpression of the Cas4 and Csa1 proteins, and also of an archaeal virus-encoded Cas4 protein, resulted in strongly reduced adaptation efficiency and the formers yielded a high incidence of PAM-dependent atypical spacer integration, or of PAM-independent spacer integration. We further demonstrated that, in the plasmid challenging experiments, overexpressed Cas4-mediated defective spacer acquisition, in turn, potentially enabled targeted DNA to escape subtype I-A CRISPR-Cas interference. In summary, these results define the specific involvement of diverse Cas4 proteins in in vivoCRISPR spacer acquisition. Furthermore, we provide support for an anti-CRISPR role for virus-encoded Cas4 proteins that involves compromising CRISPR-Cas interference activity by hindering spacer acquisition.
A tool for computation of changes in Na+, K+, Cl− channels and transporters due to apoptosis by data on cell ion and water content alteration
Authors: Yurinskaya Valentina E. , Vereninov Igor A. , Vereninov Alexey A.
Published: December 2018

The study aims to know how the apoptotic alteration of cell ionic balance follows from the quantitatively characterised time dependent decrease in the sodium pump rate constant and changes in permeability coefficients of Cl−, K+, and Na+ channels. New experimental data on changes in cell K+, Na+, Cl−, water contents, and the Na+/ K+-ATPase-mediated K+ influx during the first 4 h of the staurosporine (STS) induced apoptosis are used as a basis for quantitative characterisation of channels and transporters responsible for apoptotic cell ion balance alteration. New computational tool is developed. It is found that the dynamics of alteration of ion and water balance in the studied U937 cells were associated with the decrease in the Na+/K+-ATPase rate coefficient by 2.2 times for 4 h, and a time-dependent increase in potassium channel permeabilitry, and a decrease in the sodium channel permeability, whereas the early decrease in [Cl−]i and cell volume were associated with an approximately 5-fold increase in the chloride channel permeability. The developed approach and the provided executable file can be used to identify the channels and transporters responsible for alterations of cell ion and water balance not only during apoptosis but in other physiological scenarios.
The draft genome of an octocoral, Dendronephthya gigantea
Authors: Jeon Yeonsu , Park Seung Gu , Lee Nayun , Weber Jessica A. , Kim Hui-Su , Hwang Sung-Jin , Woo Seonock , Kim Hak-min , Bhak Youngjune , Jeon Sungwon , Lee Nayoung , Jo Yejin , Blazyte Asta , Ryu Taewoo , Cho Yun Sung , Kim Hyunho , Lee Jung-Hyun , Yim Hyung-Soon , Bhak Jong , Yum Seungshic
Published: December 2018

Background: Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities composed of octocorallian species, appear more resilient. The genomes of several species of cnidarians have been published, including stony corals, sea anemones, and hydra, but as of yet no octocoral species. To fill this phylogenetic gap within the cnidarian, we sequenced the octocoral, Dendronephthya gigantea, a non-symbiotic soft coral, commonly known as the carnation coral.
Findings: The D. gigantea genome size is approximately 276 Mb. A high-quality genome assembly was constructed using 29.85Gb (108x coverage) of PacBio long reads and 35.54Gb (128x coverage) of Illumina short paired-end reads resulting in the largest N50 value reported among cnidarian of 1.4 Mb. About 12 % of the genome consisted of repetitive elements. We found 28,879 protein-coding genes. This gene set contained about 94% metazoan single-copy orthologs, indicating the gene models were predicted with high quality compared to other cnidarians. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence occurred approximately 544 million years ago. Moreover, there is a clear difference in Hox gene composition: unlike in hexacorals, Antp superclass member Evx gene was absent in D. gigantea.
Conclusions: We present the first genome assembly of a non-symbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including comparisons of stony and soft corals and symbiotic and non-symbiotic corals. In addition, the genome of this species may provide clues about differential genetic coping mechanisms between soft and stony coral regarding the global warming.
Cortico-genetic mapping links individual brain maturity in youths to cognitive and psychiatric traits
Authors: Kaufmann Tobias , van der Meer Dennis , Alnaes Dag , Frei Oleksandr , Smeland Olav B. , Andreassen Ole A. , Westlye Lars T.
Published: December 2018

Neurodevelopmental trajectories are shaped by interactions between coordinated biological processes and individual experiences throughout ontogeny, yet the specific genetic and environmental impact on brain development is enigmatic. Here, we map the genetic architectures of cognitive traits and psychiatric disorders onto the brain, show that such canonical genetic maps are associated with individual normative patterns in youths, and provide evidence that trauma exposure and parental education may alter this relationship.
Antiviral Functions of ARGONAUTE Proteins During Turnip Crinkle Virus Infection Revealed by Image-based Trait Analysis in Arabidopsis
Authors: Zheng Xingguo , Carrington James C. , Fahlgren Noah , Abbasi Arash , Berry Jeffrey C.
Published: December 2018

RNA-based silencing functions as an important antiviral immunity mechanism in plants. Plant viruses evolved to encode viral suppressors of RNA silencing (VSRs) that interfere with the function of key components in the silencing pathway. As effectors in the RNA silencing pathway, ARGONAUTE (AGO) proteins are targeted of by some VSRs, such as that encoded by Turnip crinkle virus (TCV). A VSR-deficient TCV mutant was used to identify AGO proteins with antiviral activities during infection. A quantitative phenotyping protocol using an image-based color trait analysis pipeline on the PlantCV platform, with temporal red, green and blue (RGB) imaging and a computational segmentation algorithm, was used to measure plant disease after TCV inoculation. This process captured and analyzed growth and leaf color of Arabidopsis plants in response to virus infection over time. By combining this quantitative phenotypic data with molecular assays to detect local and systemic virus accumulation, AGO2, AGO3, and AGO7 were shown to play antiviral roles during TCV infection. In leaves, AGO2 and AGO7 functioned as prominent non-additive, anti-TCV effectors, while AGO3 played a minor role. Other AGOs were required to protect inflorescence tissues against TCV. Overall, these results indicate that distinct AGO proteins have specialized, modular roles in antiviral defense across different tissues, and demonstrate the effectiveness of image-based phenotyping to quantify disease progression.
Comparison and assessment of family- and population-based genotype imputation methods in large pedigrees
Authors: Ullah Ehsan , Mall Raghvendra , Abbas Mostafa M. , Kunji Khalid , Nato Alejandro Q. , Bensmail Halima , Wijsman Ellen M. , Saad Mohamad
Published: December 2018

Genotype imputation is widely used in genome-wide association studies to boost variant density, allowing increased power in association testing. Many studies currently include pedigree data due to increasing interest in rare variants coupled with the availability of appropriate analysis tools. The performance of population-based (subjects are unrelated) imputation methods is well established. However, the performance of family- and population-based imputation methods on family data has been subject to much less scrutiny. Here, we extensively compare several family- and population-based imputation methods on family data of large pedigrees with both European and African ancestry. Our comparison includes many widely used family- and population-based tools and another method, Ped_Pop, which combines family- and population-based imputation results. We also compare four subject selection strategies for full sequencing to serve as the reference panel for imputation: GIGI-Pick, ExomePicks, PRIMUS, and random selection. Moreover, we compare two imputation accuracy metrics: the Imputation Quality Score and Pearson's correlation R2 for predicting power of association analysis using imputation results. Our results show that (1) GIGI outperforms Merlin; (2) family-based imputation outperforms population-based imputation for rare variants but not for common ones; (3) combining family- and population-based imputation outperforms all imputation approaches for all minor allele frequencies; (4) GIGI-Pick gives the best selection strategy based on the R2 criterion; and (5) R2 is the best measure of imputation accuracy. Our study is the first to extensively evaluate the imputation performance of many available family- and population-based tools on the same family data and provides guidelines for future studies.
Change management overlooked: physician perspectives on EHR implementation
Authors: Heath Michele , Porter Tracy H.
Published: December 2018

Purpose

The purpose of this paper is to gain understanding into the human factors which might impede the change process. Change is inevitable in contemporary organizations and particularly within the healthcare field with respect to information technology (IT). Regardless of the amount of literature surrounding change management process organizational leaders will often ignore the human factors associated with the introduction of new IT.

Design/methodology/approach

This study sought to examine physician resistance surrounding the Electronic health record (EHR) change process through the lens of each of these three aspects of the Bovey and Hede (2001a) model through semi-structured interviews with physicians. Semi-structured interviews were conducted with physicians from hospitals within the Midwest.

Findings

The findings suggest that physicians have been impacted by the EHR change management system within their hospitals. Though each of the participants experienced different issues; it was clear from the data the change to an EHR system was disruptive to their day-to-day routines and caused various challenges. EHR change management research demonstrates physicians are resisting the change despite recognizing its potential benefits.

Originality/value

This paper contributes to the change management literature by examining how physician resistance can have a negative impact on healthcare organizations during a precipitous technology change. The study also provides a unique understanding of how technology resistance can disrupt an organizational change process.
Service design for marketing in construction
Authors: Smyth Hedley , Duryan Meri , Kusuma Illona
Published: December 2018

Purpose

Project execution is dependent upon management support from the firm. The purpose of this paper is to examine the extent to which main contractors and supply chain members design their service provision in order to enhance the service experience. Marketing and service design (SD), theorized in terms of business development management, are examined to assess their effect upon service experience during project execution.

Design/methodology/approach

An interpretative methodology was used to identify patterns and significant factors perceived through the lens of business development managers in ten main contractors.

Findings

Main contractors provide a systems integration service, yet service provision was found to be limited and was frequently stated as “off the radar.” Clients are realizing sub-optimal value in service experience, and users and other societal stakeholders are realizing sub-optimal value in context during use.

Research limitations/implications

There is a need to address marketing and SD research to offer prescriptive guidance to practitioners, in particular using knowledge management as lever for improvement.

Social implications

Society is in receipt of sub-optimal facilities and therefore both socially falls short of meeting well-being and policy goals, and economically under-performs.

Originality/value

Contributions are made to the marketing and management theory on project markets where selling occurs ahead of provision. Scant support for construction marketing; a lack of the guidance on managing interactions in co-creating value; and the absence of SD among leading main contractors to deliver value had been reported.
The challenges of gamifying CSR communication
Authors: Maltseva Kateryna , Fieseler Christian , Trittin-Ulbrich Hannah
Published: December 2018

Purpose

A growing number of research report positive effects of gamification, that is the introduction of game elements to non-game contexts, on stakeholder intentions and behaviors. Hence, gamification is proposed as an effective tool for organizations to educate their stakeholders about corporate social responsibility (CSR) and sustainability-related topics. The paper aims to discuss these issues.

Design/methodology/approach

In this paper, the authors ask whether gamification can communicate matters of social and environmental concern. Based on three consecutive experimental studies, the authors show that there are boundary conditions to the effectiveness of gamified communication on stakeholder attitude, intention and behavior.

Findings

The authors find positive, negative and insignificant effects of gamification on pro-environmental attitude, intention and behavior. Based on these ambiguous results, the authors conclude with a call for more rigorous forms of designing gamified experiences to foster stakeholder learning and highlight and develop several such future research and engagement opportunities.

Originality/value

The study is the first to apply gamification to the context of corporate and in particular CSR communication. It is furthermore one of the first studies that actually research the effects of gamification empirically, and in controlled experimental conditions.
Employee involvement and job satisfaction: a tale of the millennial generation
Authors: García Gustavo A. , Gonzales-Miranda Diego René , Gallo Oscar , Roman-Calderon Juan Pablo
Published: December 2018

Purpose

The purpose of this paper is to empirically study the effect of employee involvement in the workplace on job satisfaction for millennial workers in Colombia.

Design/methodology/approach

Data were obtained from a sample of 2103 millennial employees working in 11 companies of different sectors located in the five main cities of Colombia. Ordered probit models were estimated to study the effect of employee involvement on job satisfaction, in general, and how different forms of participative decision making in the workplace produce different impacts on individual satisfaction with objective and intrinsic aspects of the job, in particular.

Findings

The empirical results show that, for millennial workers, there is a positive link between employee involvement and job satisfaction. Moreover, there is a higher positive impact on job satisfaction when millennial workers participate in decisions on general aspects of the company than when they participate in specific decisions such as those concerning teamwork or main tasks at work. Another interesting result is that millennial workers attach high importance to intrinsic aspects of their jobs (such as the possibility to use their knowledge in the work), which may improve their satisfaction in a higher participative environment.

Research limitations/implications

The results can present bias due to the use of self-report data from millennial workers. Another potential limitation is the cross-sectional nature of the data, which does not control for unobserved individual effects. The study may be extended to other developing countries to help identify results more precisely for different contexts.

Originality/value

The value lies in exploring the relationship between employee involvement and job satisfaction for millennial workers in the context of a developing country. The paper simultaneously considers different types of employee involvement and estimates their effects on different facets of job satisfaction.
The implications of fiscal decentralization and budget governance on economic capacity and community welfare
Authors: Purbadharmaja Ida Bagus Putu , Maryunani  , Ananda Candra Fajri , Santoso Dwi Budi
Published: December 2018

Purpose

The purpose of this study is to investigate the relationship between government and Balinese society in tax decentralization through budgeting seem to insignificantly improve the welfare of Balinese society.

Design methodology/approach

This research was conducted in Bali Province involving eight regencies and one city. The data used in this study were secondary data, derived from relevant institutions or from websites through internet browsing and other documentations in the form of official reports/publications, such as regional budget, accountability reports, regional regulations and documents on budget and development of the regional economy. The present research used the partial least squares analysis technique.

Findings

Fiscal decentralization does not necessarily lead to better budget management. The success of fiscal decentralization can be found in the quality of the regional budget and the quality of budget management. The allocation of the regional budget for public service improvement and the development of infrastructure will increase the economic capacity of the regions. Improvement in regional economic capacity encourages the improvement of community welfare.

Originality/value

This income inequality points to the issue of fiscal capacity. The development of the financial role of district/city regions in the Province of Bali remains at a level gap with the development level of community welfare. During this period, the financial role of the government as estimated from the ratio of the national budget to the regional budget is higher than that of the society development. The acceleration role of the government is not proportional to the development of Human Development Index outcomes.
Potential of gear-ring turbulator in three-dimensional heat exchanger tube from second law of thermodynamic viewpoint
Authors: Moghaddaszadeh Navid , Rashidi Saman , Abolfazli Esfahani Javad
Published: December 2018

Purpose

This paper aims to use the second law of thermodynamic to evaluate the potential of gear-ring turbulator in a three-dimensional heat exchanger tube. Accordingly, a numerical simulation is performed to obtain the irreversibilities in a three-dimensional heat exchanger tube equipped with some gear-ring turbulators for turbulence regime.

Design/methodology/approach

A numerical simulation is performed to obtain the irreversibilities in a three-dimensional heat exchanger tube equipped with some gear-ring turbulators for turbulence regime. The analysis is carried out based on shear stress transport (SST) k-ω turbulent model. The influences of different parameters containing tooth number, free-space length ratios and Reynolds number on frictional and thermal irreversibilities and Bejan number are discussed.

Findings

The results indicated that the thermal irreversibility reduces by decreasing the tooth number. For example, the thermal entropy generation decreases about 25.81 per cent by decreasing the tooth number in the range of 24 to 0 at Re = 6,000. Moreover, the frictional entropy generation decreases by increasing the tooth number as the gear with more tooth number causes a lower flow disturbance.

Originality/value

The present study arranged a numerical work to study the potential of a gear-ring turbulator in a heat exchanger tube from first and second laws of thermodynamic viewpoint. The turbulent flow is considered for this problem. The literature review showed that the usage of a gear-ring turbulator in a heat exchanger tube is not investigated from the second law of thermodynamic viewpoint by previous studies. As a result, the influences of different parameters containing tooth number, free-space length ratios and Reynolds number on frictional and thermal irreversibilities and Bejan number are discussed.