bluuebunny/crossref_metadata_2025 huggingface dataset:
Trevolver: simulating non-reversible DNA sequence evolution in trinucleotide context on a bifurcating tree
Authors: Nelson Chase W. , Fu Yunxin , Li Wen-Hsiung
Published: June 2019

Recent de novo mutation data allow the estimation of non-reversible mutation rates for trinucleotide sequence contexts. However, existing tools for simulating DNA sequence evolution are limited to time-reversible models or do not consider trinucleotide context-dependent rates. As this ability is critical to testing evolutionary scenarios under neutrality, we created Trevolver. Sequence evolution is simulated on a bifurcating tree using a 64 × 4 trinucleotide mutation model. Runtime is fast and results match theoretical expectation for CpG sites. Simulations with Trevolver will enable neutral hypotheses to be tested at within-species (polymorphism), between-species (divergence), within-host (e.g., viral evolution), and somatic (e.g., cancer) levels of evolutionary change.

Availability and Implementation

Trevolver is implemented in Perl and available on GitHub under GNU General Public License (GPL) version 3 at https://github.com/chasewnelson/trevolver.

Contact

cnelson@amnh.org

Supplementary information

Further details and example data are available on GitHub.
Coping with Pleistocene climatic fluctuations: demographic responses in remote endemic reef fishes
Authors: Delrieu-Trottin Erwan , Hubert Nicolas , Giles Emily C. , Chifflet-Belle Pascaline , Suwalski Arnaud , Neglia Valentina , Rapu-Edmunds Cristian , Mona Stefano , Saenz-Agudelo Pablo
Published: June 2019

Elucidating demographic history during the settlement of ecological communities is crucial for properly inferring the mechanisms that shape patterns of species diversity and their persistence through time. Here, we used genomic data and coalescent-based approaches to elucidate for the first time the demographic dynamics associated with the settlement by endemic reef fish fauna of one of the most remote peripheral islands of the Pacific Ocean, Rapa Nui (Easter Island). We compared the demographic history of nine endemic species in order to explore their demographic responses to Pleistocene climatic fluctuations. We found that Rapa Nui endemic species share a common demographic history as signatures of population expansions were retrieved for almost all of the species studied here, and synchronous demographic expansions initiated during the last glacial period were recovered for more than half of the studied species. These results suggest that eustatic fluctuations associated with Milankovitch cycles have played a central role in species demographic histories and in the final stage of the community assembly of many Rapa Nui reef fishes. Specifically, sea level low stands resulted in the maximum reef habitat extension for Rapa Nui endemic species; we discuss the potential role of seamounts in allowing endemic species to cope with Pleistocene climatic fluctuations, and we highlight the importance of local historical processes over regional ones. Overall, our results shed light on the mechanisms by which endemism arises and is maintained in peripheral reef fish fauna.
Exhaustive identification of conserved upstream open reading frames with potential translational regulatory functions from animal genomes
Authors: Takahashi Hiro , Miyaki Shido , Onouchi Hitoshi , Motomura Taichiro , Idesako Nobuo , Takahashi Anna , Murase Masataka , Fukuyoshi Shuichi , Endo Toshinori , Satou Kenji , Naito Satoshi , Itoh Motoyuki
Published: June 2019

Upstream open reading frames (uORFs) are present in the 5’-untranslated regions of many eukaryotic mRNAs, and some peptides encoded by these regions play important regulatory roles in controlling main ORF (mORF) translation. We previously developed a novel pipeline, ESUCA, to comprehensively identify plant uORFs encoding functional peptides, based on genome-wide identification of uORFs with conserved peptide sequences (CPuORFs). Here, we applied ESUCA to diverse animal genomes, because animal CPuORFs have been identified only by comparing uORF sequences between a limited number of species, and how many previously identified CPuORFs encode regulatory peptides is unclear. By using ESUCA, 1,517 (1,373 novel and 144 known) CPuORFs were extracted from four evolutionarily divergent animal genomes. We examined the effects of 17 human CPuORFs on mORF translation using transient expression assays. Through these analyses, we identified seven novel regulatory CPuORFs that repressed mORF translation in a sequence-dependent manner, including one conserved only among Eutheria. We discovered a much higher number of animal CPuORFs than previously identified. Since most human CPuORFs identified in this study are conserved across a wide range of Eutheria or a wider taxonomic range, many CPuORFs encoding regulatory peptides are expected to be found in the identified CPuORFs.
Generation of comprehensive ecosystems-specific reference databases with species-level resolution by high-throughput full-length 16S rRNA gene sequencing and automated taxonomy assignment (AutoTax)
Authors: Dueholm Morten Simonsen , Andersen Kasper Skytte , McIlroy Simon Jon , Kristensen Jannie Munk , Yashiro Erika , Karst Søren Michael , Albertsen Mads , Nielsen Per Halkjær
Published: June 2019

High-throughput 16S rRNA gene amplicon sequencing is an essential method for studying the diversity and dynamics of microbial communities. However, this method is presently hampered by the lack of high-identity reference sequences for many environmental microbes in the public 16S rRNA gene reference databases, and by the absence of a systematic and comprehensive taxonomy for the uncultured majority. Here we demonstrate how high-throughput synthetic long-read sequencing can be applied to create ecosystem-specific full-length 16S rRNA gene amplicon sequence variant (FL-ASV) reference databases that include high-identity references (>98.7% identity) for nearly all abundant bacteria (>0.01% relative abundance) using Danish wastewater treatment systems and anaerobic digesters as an example. In addition, we introduce a novel sequence identity-based approach for automated taxonomy assignment (AutoTax) that provides a complete seven-rank taxonomy for all reference sequences, using the SILVA taxonomy as a backbone, with stable placeholder names for unclassified taxa. The FL-ASVs are perfectly suited for the evaluation of taxonomic resolution and bias associated with primers commonly used for amplicon sequencing, allowing researchers to choose those that are ideal for their ecosystem. The AutoTax taxonomy greatly improves the classification of short-read 16S rRNA gene amplicon sequence variants (ASVs) at the genus- and species-level, compared to the commonly used universal reference databases. Importantly, the placeholder names provide a way to explore the unclassified environmental taxa at different taxonomic ranks, which in combination within situanalyses can be used to uncover their ecological roles.
Working out Classic Examples of Metabolic Networks Structural Analysis with Wolfram Language
Authors: Liang Kuo Kan
Published: June 2019

Metabolic reaction networks usually include a large number of enzymatic reaction steps. Nowadays, people desire to work on larger and larger metabolic networks, in the research fields of for example systems or synthetic biology. With the growing sizes of the metabolic networks considered, it is more and more tedious and cumbersome for a human to perform routine processing and analysis of the networks. Computer programs that automate metabolic analysis will be beneficial. In this work, the use of Wolfram Language to automate metabolic analysis is demonstrated. Although there are many different analyses to perform in a metabolic network analysis project, the analysis of metabolic network structure may be the most common first step and one of the most troublesome tasks. Therefore, instead of demonstrating a lot of different analyses, the structures of a few important examples from one chapter in the classic textbook by Professor Gregory Stephanopoulos are analyzed with a program written in Wolfram Language and the models are book-kept in JSON format.
Effects of temperature andpCO2on the respiration, biomineralization and photophysiology of the giant clamTridacna maxima
Authors: Brahmi Chloé , Chapron Leila , Le Moullac Gilles , Soyez Claude , Beliaeff Benoît , Lazareth Claire E. , Gaertner-Mazouni Nabila , Vidal-Dupiol Jeremie
Published: June 2019

Such as many other reef organisms, giant clams are today confronted to global change effects and can suffer mass bleaching or mortality events mainly related to abnormally high seawater temperatures. Despite its strong ecological and socio-economical importance, its responses to the two most alarming threats linked to global change (i.e., ocean warming and acidification) still need to be explored. We investigated physiological responses of 4-years-oldTridacna maximaspecimens to realistic levels of temperature and partial pressure of carbon dioxide (pCO2) (+1.5°C and +800μatm of CO2) predicted for 2100 in French Polynesian lagoons during the warmer season. During a 65-days crossed-factor experiment, individuals were exposed to two temperatures (29.2°C; 30.7°C) and twopCO2(430µatm; 1212µatm) conditions. Impact of each parameter and their potential synergetic effect were evaluated on respiration, biomineralization and photophysiology. Kinetics of thermal and acidification stress were evaluated by performing measurements at different times of exposure (29, 41, 53, 65 days). At 30.7°C, the holobiont O2production, symbiont photosynthetic yield, and density were negatively impacted. HighpCO2had a significant negative effect on shell growth rate, symbiont photosynthetic yield and density. Shell microstructural modifications were observed from 41 days in all temperature andpCO2conditions. No significant synergetic effect was found. Today thermal conditions (29.2°C) appeared to be sufficiently stressful to induce a host acclimatization process. All these observations indicate that temperature andpCO2are both forcing variables affectingT. maximaphysiology and jeopardize its survival under environmental conditions predicted for the end of this century.
Classification-based Inference of Dynamical Models of Gene Regulatory Networks
Authors: Fehr David A. , Manu  , Loh Yen Lee
Published: June 2019

Cell-fate decisions during development are controlled by densely interconnected gene regulatory networks (GRNs) consisting of many genes. Inferring and predictively modeling these GRNs is crucial for understanding development and other physiological processes. Gene circuits, coupled differential equations that represent gene product synthesis with a switch-like function, provide a biologically realistic framework for modeling the time evolution of gene expression. However, their use has been limited to smaller networks due to the computational expense of inferring model parameters from gene expression data using global non-linear optimization. Here we show that the switch-like nature of gene regulation can be exploited to break the gene circuit inference problem into two simpler optimization problems that are amenable to computationally efficient supervised learning techniques. We present FIGR (Fast Inference of Gene Regulation), a novel classification-based inference approach to determining gene circuit parameters. We demonstrate FIGR’s effectiveness on synthetic data as well as experimental data from the gap gene system ofDrosophila. FIGR is faster than global non-linear optimization by nearly three orders of magnitude and its computational complexity scales much better with GRN size. On a practical level, FIGR can accurately infer the biologically realistic gap gene network in under a minute on desktop-class hardware instead of requiring hours of parallel computing. We anticipate that FIGR would enable the inference of much larger biologically realistic GRNs than was possible before. FIGR Source code is freely available athttp://github.com/mlekkha/FIGR.
A predicted deleterious allele of the essential meiosis geneMND1, present in ~3% of East Asians, does not disrupt reproduction in mice
Authors: Tran Tina N. , Martinez Julianna , Schimenti John C.
Published: June 2019

Infertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily-detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of “variants of unknown significance” (VUS), typically SNPs (single nucleotide polymorphisms), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating CRISPR-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis geneMnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present allele frequency of ~3% in East Asians, has no discernable effect upon fertility, fecundity, or gametogenesis, although it may cause sex skewing of progeny from homozygous males. In sum, this appears to be a benign allele that can be eliminated or de-prioritized in clinical genomic analyses of infertility patients.
High-throughput multiplexed tandem repeat genotyping using targeted long-read sequencing
Authors: Ganesamoorthy Devika , Yan Mengjia , Murigneux Valentine , Zhou Chenxi , Cao Minh Duc , Duarte Tania PS , Coin Lachlan JM
Published: June 2019

Tandem repeats (TRs) are highly prone to variation in copy numbers due to their repetitive and unstable nature, which makes them a major source of genomic variation between individuals. However, population variation of TRs have not been widely explored due to the limitations of existing tools, which are either low-throughput or restricted to a small subset of TRs. Here, we used SureSelect targeted sequencing approach combined with Nanopore sequencing to overcome these limitations. We achieved an average of 3062-fold target enrichment on a panel of 142 TR loci, generating an average of 97X sequence coverage on 7 samples utilizing 2 MinION flow-cells with 200ng of input DNA per sample. We identified a subset of 110 TR loci with length less than 2kb, and GC content greater than 25% for which we achieved an average genotyping rate of 75% and increasing to 91% for the highest-coverage sample. Alleles estimated from targeted long-read sequencing were concordant with gold standard PCR sizing analysis and moreover highly correlated with alleles estimated from whole genome long-read sequencing. We demonstrate a targeted long-read sequencing approach that enables simultaneous analysis of hundreds of TRs and accuracy is comparable to PCR sizing analysis. Our approach is feasible to scale for more targets and more samples facilitating large-scale analysis of TRs.
Subject, session and task effects on power, connectivity and network centrality: a source-based EEG study
Authors: Pani Sara M. , Ciuffi Marta , Demuru Matteo , Bazzano Giovanni , D’aloja Ernesto , Fraschini Matteo
Published: June 2019

Inter-subjects’ variability in functional brain networks has been extensively investigated in the last few years. In this context, unveiling subject-specific characteristics of EEG features may play an important role for both clinical (e.g., biomarkers) and bio-engineering purposes (e.g., biometric systems and brain computer interfaces). Nevertheless, the effects induced by multi-sessions and task-switching are not completely understood and considered. In this work, we aimed to investigate how the variability due to subject, session and task affects EEG power, connectivity and network features estimated using source-reconstructed EEG time-series. Our results point out a remarkable ability to identify subject-specific EEG traits within a given task together with striking independence from the session. The results also show a relevant effect of task-switching, which is comparable to individual variability. This study suggests that power and connectivity EEG features may be adequate to detect stable (over-time) individual properties within predefined and controlled tasks.
LAVENDER: latent axes discovery from multiple cytometry samples with non-parametric divergence estimation and multidimensional scaling reconstruction
Authors: Nakamura Naotoshi , Okada Daigo , Setoh Kazuya , Kawaguchi Takahisa , Higasa Koichiro , Tabara Yasuharu , Matsuda Fumihiko , Yamada Ryo
Published: June 2019

Computational cytometry methods are now frequently used in flow and mass cytometric data analyses. However, systematic bias-free methodologies to assess inter-sample variability have been lacking, thereby hampering efficient data mining from a large set of samples. Here, we devised a computational method termed LAVENDER (latent axes discovery from multiple cytometry samples with nonparametric divergence estimation and multidimensional scaling reconstruction). It measures the Jensen-Shannon distances between samples using the k-nearest neighbor density estimation and reconstructs samples in a new coordinate space, called the LAVENDER space. The axes of this space can then be compared against other omics measurements to obtain biological information. Application of LAVENDER to multidimensional flow cytometry datasets of 301 Japanese individuals immunized with a seasonal influenza vaccine revealed an axis related to baseline immunological characteristics of each individual. This axis correlated with the proportion of plasma cells and the neutrophil-to-lymphocyte ratio, a clinical marker of the systemic inflammatory response. The same method was also applicable to mass cytometry data with more molecular markers. These results demonstrate that LAVENDER is a useful tool for identifying critical heterogeneity among similar, yet different, single-cell datasets.
Highly Accelerated Vessel-Selective Arterial Spin Labelling Angiography using Sparsity and Smoothness Constraints
Authors: Schauman Sophie , Chiew Mark , Okell Thomas W.
Published: June 2019

Purpose

To demonstrate that vessel-selectivity in arterial spin labeling angiography can be achieved without any scan time penalty or noticeable loss of image quality compared to conventional arterial spin labeling angiography.

Methods

Simulations on a numerical phantom were used to assess whether the increased sparsity of vessel-encoded angiograms compared to non-vessel-encoded angiograms alone can improve reconstruction results in a compressed sensing framework. Further simulations were performed to study whether the difference in relative sparsity between non-selective and vessel-selective dynamic angiograms were sufficient to achieve similar image quality at matched scan times in the presence of noise. Finally, data were acquired from 5 healthy volunteers to validate the technique in vivo. All data, both simulated and in vivo, were sampled in 2D using a golden angle radial trajectory and reconstructed by enforcing both image domain sparsity and temporal smoothness on the angiograms in a parallel imaging and compressed sensing framework.

Results

Relative sparsity was established as a primary factor governing the reconstruction fidelity. Using the proposed reconstruction scheme, differences between vessel-selective and non-selective angiography were negligible compared to the dominant factor of total scan time in both simulations and in vivo experiments at acceleration factors up to R = 34. The reconstruction quality was not heavily dependent on hand-tuning the parameters of the reconstruction.

Conclusion

The increase in relative sparsity of vessel-selective angiograms compared to non-selective angiograms can be leveraged to achieve higher acceleration without loss of image quality, resulting in the acquisition of vessel-selective information at no scan time cost.
Body size but not age influences phototaxis in bumble bee (Bombus terrestris, L.) workers
Authors: Merling Michal , Eisenmann Shmuel , Bloch Guy
Published: June 2019

We studied phototaxis, the directional movement relative to light, in the bumble bee Bombus terrestris. We first developed and validated a MATLAB based system enabling reliable high-resolution tracking of a bee and a measurement of her distance relative to a changing LED light source. Using this system we found in all our experiments that workers show positive phototaxis. The strength of the phototactic response was influenced by body size but not age, and this effect was significant when the light source was weak. In a separate experiment, foragers showed stronger phototactic response compared to nurses only in one of two trials in which they were larger and tested with weak light intensity. The evidence that phototaxis is associated with size-based division of labor in the bumble bee and with age-related division of labor in the honey bee, lends credence to response threshold models implicating the response to light in the organization of division of labor in cavity dwelling social insects.
A microtubule RELION-based pipeline for cryo-EM image processing
Authors: Cook Alexander D. , Manka Szymon W. , Wang Su , Moores Carolyn A. , Atherton Joseph
Published: June 2019

Microtubules are polar filaments built from αβ-tubulin heterodimers that exhibit a range of architectures in vitro and in vivo. Tubulin heterodimers are arranged helically in the microtubule wall but many physiologically relevant architectures exhibit a break in helical symmetry known as the seam. Noisy 2D cryo-electron microscopy projection images of pseudo-helical microtubules therefore depict distinct but highly similar views owing to the high structural similarity of α- and β-tubulin. The determination of the αβ-tubulin register and seam location during image processing is essential for alignment accuracy that enables determination of biologically relevant structures. Here we present a pipeline designed for image processing and high-resolution reconstruction of cryo-electron microscopy microtubule datasets, based in the popular and user-friendly RELION image-processing package, Microtubule RELION-based Pipeline (MiRP). The pipeline uses a combination of supervised classification and prior knowledge about geometric lattice constraints in microtubules to accurately determine microtubule architecture and seam location. The presented method is fast and semi-automated, producing near-atomic resolution reconstructions with test datasets that contain a range of microtubule architectures and binding proteins.

Abbreviations

MiRP, Microtubule RELION-based Pipeline; cryo-EM, cryo-electron microscopy; MT, microtubule; CTF, contrast transfer function; PF, protofilament.
FOXC1 negatively regulates BMP-SMAD activity and Id1 expression during osteoblast differentiation
Authors: Caddy Jordan. C. , Luoma Leiah. M. , Berry Fred. B.
Published: June 2019

Bone morphogenetic proteins regulate a diverse range of biological processes through their activation of SMAD1, 5, or 8 proteins that in turn regulate gene expression. These SMAD transcription factors achieve a layer of functional specificity in different cells types largely through actions with additional transcriptional regulatory molecules. In this report we demonstrate that the Forkhead Box C1 (FOXC1) transcription factor can modulate BMP signalling to impair expression of BMP4-responsive genes and prevent efficient osteoblast differentiation. We demonstrate that repression occurs downstream of BMP signalling and impacts the ability SMAD1 or 5 to activate gene expression. Repression of SMAD activity requires FOXC1 DNA-binding capacity and the transcriptional inhibitory domain of FOXC1. We report that FOXC1 inhibits BMP4 induction of Id1 expression and identify a motif in the regulatory region of mouse Id1 gene that FOXC1 binds. We determine that this inhibition by FOXC1 binding does not affect SMAD1, 5, or 8 binding to its target sequence in the Id1 gene. Finally we determine that elevated expression of FOXC1 can reduces expression osteogenic differentiation genes in mouse embryonic stems directed to the osteoblast lineage through BMP4 treatment. Together, these findings indicate that FOXC1 can negative regulate certain aspects of BMP4 signalling required for osteoblast differentiation. We propose that FOXC1 acts to attenuate the initial BMP-activated pathways that establishes osteoblast differentiation and allow for terminal osteoblast differentiation to conclude.
Plasmodium condensin core subunits (SMC2/SMC4) mediate atypical mitosis and are essential for parasite proliferation and transmission
Authors: Pandey Rajan , Abel Steven , Boucher Matthew , Wall Richard J. , Zeeshan Mohammad , Rea Edward , Freville Aline , Lu Xueqing Maggie , Brady Declan , Daniel Emilie , Stanway Rebecca R. , Wheatley Sally , Batugedara Gayani , Hollin Thomas , Bottrill Andrew R. , Gupta Dinesh , Holder Anthony A. , Le Roch Karine G. , Tewari Rita
Published: June 2019

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and ChIP-seq analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and II complexes form at these stages. Knockdown of smc2 and smc4 gene expression revealed essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle.
yacrd and fpa: upstream tools for long-read genome assembly
Authors: Marijon Pierre , Chikhi Rayan , Varré Jean-Stéphane
Published: June 2019

Motivation

Genome assembly is increasingly performed on long, uncorrected reads. Assembly quality may be degraded due to unfiltered chimeric reads; also, the storage of all read overlaps can take up to terabytes of disk space.

Results

We introduce two tools, yacrd and fpa, preform respectively chimera removal, read scrubbing, and filter out spurious overlaps. We show that yacrd results in higher-quality assemblies and is one hundred times faster than the best available alternative.

Availability

https://github.com/natir/yacrd and https://github.com/natir/fpa

Contact

pierre.marijon@inria.fr

Supplementary information

Supplementary data are available online.
Simultaneous integration of gene expression and nutrient availability for studying metabolism of hepatocellular carcinoma
Authors: Weglarz-Tomczak Ewelina , Mondeel Thierry D.G.A. , Piebes Diewertje G.E. , Westerhoff Hans V.
Published: June 2019

How cancer cells utilize nutrients to support their growth and proliferation in complex nutritional systems is still an open question. However, it is certainly determined by both genetics and an environmental-specific context. The interactions between them lead to profound metabolic specialization, such as consuming glucose and glutamine and producing lactate at prodigious rates. To investigate whether and how glucose and glutamine availability impact metabolic specialization, we integrated computational modeling on the genome-scale metabolic reconstruction with an experimental study on cell lines. We used the most comprehensive human metabolic network model to date, Recon3D, to build cell line-specific models. RNA-Seq data was used to specify the activity of genes in each cell line and the uptake rates were quantitatively constrained according to nutrient availability. To integrated both constraints we applied a novel method, named GENSI (Gene Expression and Nutrients Simultaneous Integration), that translates the relative importance of gene expression and nutrient availability data into the metabolic fluxes based on an observed experimental feature(s). We applied GENSI to study hepatocellular carcinoma addiction to glucose/glutamine. We were able to identify that proliferation, and lactate production is associated with the presence of glucose but does not necessarily increase with its concentration when the latter exceeds the physiological concentration. There was no such association with glutamine. We show that the integration of gene expression and nutrient availability data into genome-wide models improves the prediction of metabolic phenotypes.
Successful forecasting of harmful cyanobacteria blooms with high frequency lake data
Authors: Kehoe M.J. , Ingalls B.P. , Venkiteswaran J.J. , Baulch H.M.
Published: June 2019

Cyanobacterial blooms are causing increasing issues across the globe. Bloom forecasting can facilitate adaptation to blooms. Most bloom forecasting models depend on weekly or fortnightly sampling, but these sparse measurements can miss important dynamics. Here we develop forecasting models from five years of high frequency summer monitoring in a shallow lake (which serves as an important regional water supply). A suite of models were calibrated to predict cyanobacterial fluorescence (a biomass proxy) using measurements of: cyanobacterial fluorescence, water temperature, light, and wind speed. High temporal autocorrelation contributed to relatively strong predictive power over 1, 4 and 7 day intervals. Higher order derivatives of water temperature helped improve forecasting accuracy. While traditional monitoring and modelling have supported forecasting on longer timescales, we show high frequency monitoring combined with telemetry allows forecasting over timescales of 1 day to 1 week, supporting early warning, enhanced monitoring, and adaptation of water treatment processes.
Efficient and Modular CRISPR-Cas9 Vector System for Physcomitrella patens
Authors: Mallett Darren R. , Chang Mingqin , Cheng Xiaohang , Bezanilla Magdalena
Published: June 2019

CRISPR-Cas9 has been shown to be a valuable tool in recent years, allowing researchers to precisely edit the genome using an RNA-guided nuclease to initiate double-strand breaks. Until recently, classical RAD51-mediated homologous recombination has been a powerful tool for gene targeting in the moss Physcomitrella patens. However, CRISPR-Cas9 mediated genome editing in P. patens was shown to be more efficient than traditional homologous recombination (Collonnier et al. 2017). CRISPR-Cas9 provides the opportunity to efficiently edit the genome at multiple loci as well as integrate sequences at precise locations in the genome using a simple transient transformation. To fully take advantage of CRISPR-Cas9 genome editing in P. patens, here we describe the generation and use of a flexible and modular CRISPR-Cas9 vector system. Without the need for gene synthesis, this vector system enables editing of up to 12 loci simultaneously. Using this system, we generated multiple lines that had null alleles at four distant loci. We also found that targeting multiple sites within a single locus can produce larger deletions, but the success of this depends on individual protospacers. To take advantage of homology-directed repair, we developed modular vectors to rapidly generate DNA donor plasmids to efficiently introduce DNA sequences encoding for fluorescent proteins at the 5’ and 3’ ends of gene coding regions. With regards to homology-directed repair experiments, we found that if the protospacer sequence remains on the DNA donor plasmid, then Cas9 cleaves the plasmid target as well as the genomic target. This can reduce the efficiency of introducing sequences into the genome. Furthermore, to ensure the generation of a null allele near the Cas9 cleavage site, we generated a homology plasmid harboring a “stop codon cassette” with down-stream near-effortless genotyping.
High throughput imaging identifies a spatially localized response of primary fetal pulmonary artery endothelial cells to insulin-like growth factor 1 treatment
Authors: Kim Christina , Seedorf Gregory J , Abman Steven H , Shepherd Douglas P
Published: June 2019

A common strategy to measure the efficacy of drug treatment is the in vitro comparison of ensemble readouts with and without treatment, such as proliferation and cell death. A fundamental assumption underlying this approach is there is minimal cell to cell variability in the response to drug. Here, we demonstrate that ensemble and non-spatial single cell readouts applied to primary cells lead to incomplete conclusions due to cell to cell variability. We exposed primary fetal pulmonary artery endothelial cells (PAEC) isolated from healthy newborn healthy and persistent pulmonary hypertension of the newborn (PPHN) sheep to the growth hormone insulin-like growth factor 1 (IGF-1). We found that IGF-1 increased proliferation and branch points in tube formation assays but not angiogenic signaling proteins at the population level for both cell types. We hypothesized that this molecular ambiguity was due to the presence of cellular subpopulations with variable responses to IGF-1. Using high throughput single cell imaging, we discovered a spatially localized response to IGF-1. This suggests localized signaling or heritable cell response to external stimuli may ultimately be responsible for our observations. Discovering and further exploring these rare cells is critical to finding new molecular targets to restore cellular function.
Physical activity, aerobic fitness and brain white matter: their role for executive functions in adolescence
Authors: Ruotsalainen Ilona , Gorbach Tetiana , Perkola Jaana , Renvall Ville , Syväoja Heidi J. , Tammelin Tuija H. , Karvanen Juha , Parviainen Tiina
Published: June 2019

Physical activity and exercise beneficially link to brain properties and cognitive functions in older adults, but it is unclear how these results generalise to other age groups. During adolescence, the brain undergoes significant changes, which are especially pronounced in white matter. Existing studies provide contradictory evidence regarding the influence of physical activity or aerobic-exercise on executive functions in youth. Little is also known about the link between both aerobic fitness and physical activity with white matter during puberty. For this reason, we investigated the connection between both aerobic fitness (20-m shuttle run) and physical activity (moderate-to-vigorous intensity physical activity) with white matter in 59 adolescents (12.7–16.2 years). We further determined whether white matter interacts with the connection of fitness or physical activity with three core executive functions (sustained attention, spatial working memory and response inhibition). Our results showed that only the level of aerobic fitness, but not of physical activity was related to white matter properties. Furthermore, the white matter of specific tracts also moderated the links of aerobic fitness and physical activity with working memory. Our results suggest that aerobic fitness and physical activity have an unequal contribution to the properties of white matter in adolescent brains. We propose that the differences in white matter properties could underlie the variations in the relationship between either physical activity or aerobic fitness with working memory.

Highlights

Aerobic fitness level, but not physical activity, is associated with white matter properties in several white matter tracts in the brain.

The relationship between aerobic fitness and working memory was moderated by fractional anisotropy of the body of corpus callosum and in the right superior corona radiata.

The relationship between physical activity and working memory was moderated by fractional anisotropy of the body and genu of corpus callosum.
Neural, functional, and aesthetic impacts of spatially heterogeneous flicker: A potential role of natural flicker
Authors: Menceloglu Melisa , Grabowecky Marcia , Suzuki Satoru
Published: June 2019

Spatially heterogeneous flicker, characterized by probabilistic and locally independent luminance modulations, abounds in nature. It is generated by flames, water surfaces, rustling leaves, and so on, and it is pleasant to the senses. It affords spatiotemporal multistability that allows sensory activation conforming to the biases of the visual system, thereby generating the perception of spontaneous motion and likely facilitating the calibration of motion detectors. One may thus hypothesize that spatially heterogeneous flicker might potentially provide restoring stimuli to the visual system that engage fluent (requiring minimal top-down control) and self-calibrating processes. Here, we present some converging behavioral and electrophysiological evidence consistent with this idea. Spatially heterogeneous (multistable) flicker (relative to controls matched in temporal statistics) reduced posterior EEG (electroencephalography) beta power implicated in long-range neural interactions that impose top-down influences on sensory processing. Further, the degree of spatiotemporal multistability, the amount of posterior beta-power reduction, and the aesthetic responses to flicker were closely associated. These results are consistent with the idea that the pleasantness of natural flicker may derive from its spatiotemporal multistability that affords fluent and self-calibrating visual processing.
C. elegans heritably adapts to P. vranovensis infection via a mechanism that requires the cysteine synthases cysl-1 and cysl-2
Authors: Burton Nicholas O. , Riccio Cristian , Dallaire Alexandra , Price Jon , Jenkins Benjamin , Koulman Albert , Miska Eric A.
Published: June 2019

Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. Here we report that the soil bacteria Pseudomonas vranovensis is a natural pathogen of the nematode Caenorhabditis elegans and that parental exposure of animals to P. vranovensis promotes offspring resistance to infection. Furthermore, we demonstrate a transgenerational enhancement of progeny survival when three consecutive generations of animals are exposed to P. vranovensis. By investigating the mechanisms by which animals heritably adapt to P. vranovensis infection, we found that parental infection by P. vranovensis results in increased expression of the cysteine synthases CYSL-1 and CYSL-2 and the regulator of hypoxia inducible factor RHY-1 in progeny and that these three genes are required for adaptation to P. vranovensis. To our knowledge, these observations represent the largest heritable increase in offspring survival in response to a pathogen infection reported in any organism to date and establish a new CYSL-1, CYSL-2, and RHY-1 dependent mechanism by which animals adapt to infection.
Metrology characterization of ultraprecise bendable mirrors for the European XFEL: from offsite calibration to installation and commissioning
Authors: Vannoni Maurizio , Freijo Martín Idoia , Schmidtchen Silja , Baumann Thomas M. , Meyer Michael , Music Valerija
Published: June 2019

The European XFEL requires long and ultraflat X-ray mirrors of high precision for the beam offset and distribution system [Altarelli et al. (2006), XFEL Technical Design Report, DESY 2006-097. DESY, Hamburg, Germany]. A general specification of the beam transport mirrors is a length of up to 950 mm and an optical surface with a deviation from a perfectly flat surface of <30 nm peak-to-valley and a figure error of <2 nm peak-to-valley. From a production point of view, such a mirror cannot be easily fabricated so, in each beamline, it is foreseen to have at least one mirror with bending capabilities. In this way, it is possible to correct the residual divergence of the beam in order to focus it in the correct position with high accuracy and repeatability. This is practically implemented using a mechanical bender in which the mirror is mounted and bent through a motorized actuator. One such system was characterized in the metrology lab using a large-aperture Fizeau interferometer and a capacitive sensor. It was then installed in the beamline and calibrated again using the X-ray beam. Here, the procedure is described and the two different methods are compared, stressing the differences and the possible explanations and improvements.
Museums, heritage and the politics of pursuing indigenous rights in Taiwan
Authors: Wang Shu-Li
Published: June 2019

Purpose

The purpose of this paper is to trace the development of indigenous heritage rights in Taiwan. It examines how this pursuit is intertwined with the global indigenous movement, national political interests and rising local cultural awareness.

Design/methodology/approach

This paper focuses on the rise of indigenous rights in Taiwan by looking at political shifts, indigenous museums and changing frameworks through which heritage is understood. The paper uses two case studies: one is the implementation of a heritage protection law in Taiwan; the other is the launch of indigenous museums.

Findings

In Taiwan, heritage is often associated with political ideology, power relations and resource distribution. The development of heritage discourse is inseparable from the international heritage trend as well as the local political situation.

Originality/value

The pursuit of indigenous heritage rights in Taiwan is supported on the one hand by the government so as to define a distinctive Taiwanese culture and on the other to meet the demands of Taiwan’s indigenous movement. Two case studies are provided to examine the pros and cons of current indigenous heritage projects in Taiwan.
Scientometric analysis of BIM-based research in construction engineering and management
Authors: Jin Ruoyu , Zou Yang , Gidado Kassim , Ashton Phillip , Painting Noel
Published: June 2019

Purpose

The purpose of this paper is to summarize the latest research of BIM adoption in construction engineering and management (CEM) and propose research directions for future scholarly work. During the recent decade, building information modeling (BIM) has gained increasing applications and research interest in the construction industry. Although there have been review-based studies that summarized BIM-based research in the overall architecture, engineering and construction (AEC) area, there is limited review that evaluates the current stage of BIM-based research specifically in the CEM sub-area.

Design/methodology/approach

CEM falls into the scope of AEC. It involves construction-related tasks, activities and processes (e.g. scheduling and cost estimates), issues (e.g. constructability), as well as human factors (e.g. collaboration). This study adopted a holistic literature review approach that incorporates bibliometric search and scientometric analysis. A total of 276 articles related to BIM applied in CEM were selected from Scopus as the literature sample for the scientometric analysis.

Findings

Some key CEM research areas (e.g. CEM pedagogy, integrated project delivery, lean and off-site construction) were identified and evaluated. Research trends in these areas were identified, and analyses were carried out with regard to how they could be integrated with BIM. For example, BIM, as a data repository for ACE facilities, has substantial potential to be integrated with a variety of other digital technologies, project delivery methods and innovative construction techniques throughout the whole process of CEM.

Practical implications

As BIM is one of the key technologies and digital platforms to improve the construction productivity and collaboration, it is important for industry practitioners to be updated of the latest movement and progress of the academic research. The industry, academics and governmental authorities should work with joint effort to fill the gap by first recognizing the current needs, limitations and trends of applying BIM in the construction industry. For example, it needs more understanding about how to address technical interoperability issues and how to introduce the integrated design and construction delivery approach for BIM implementation under the UK BIM Level 2/3 framework.

Originality/value

This study contributed to the body of knowledge in BIM by proposing a framework leading to research directions including the differences of BIM effects between design-bid-build and other fast-track project delivery methods; the integration of BIM with off-site construction; and BIM pedagogy in CEM. It also addressed the need to investigate the similarities and differences between academia and industry toward perceiving the movement of BIM in construction field work.
Tourists’ intention to use location-based services (LBS)
Authors: Meng Bo , Choi Kyuhwan
Published: June 2019

Purpose

This study aims to investigate the tourists’ intentions to use LBS within a tourism sector by integrating the elaboration likelihood model (ELM) into the framework of the theory of planned behavior (TPB).

Design/methodology/approach

This study is conducted by an online survey and a snowball sampling method with 353 respondents. The present study used a two-step method suggested by Anderson and Gerbing’s (1988).

Findings

Study results from structural equation modeling (SEM) revealed that the new model has a better predictive ability. Additionally, study results from SEM demonstrated the causal relationships in the proposed model and identified a mediating role of attitude. Further, the moderating effects of involvement across the different relationships in ELM were also verified.

Originality/value

This study is the first to explain individuals’ decision-making process by using the TPB framework with the integration of meaningful constructs rooted in ELM. Therefore, the study results help the tourist application developers to use better marketing and service strategies through effective management of tourists’ central routes, peripheral routes, normatives and non-volitional processes of tourism LBS decision-making.
The effect of management response similarity on online hotel booking
Authors: Zhang Zili , Li Hengyun , Meng Fang , Li Yuanshuo
Published: June 2019

Purpose

This paper aims to examine the influences of the number of hotel management responses and especially the textual similarity in hotel management responses to online reviews on hotel online booking.

Design/methodology/approach

This study used the data from 437 hotels in New York City on Expedia. The data specifically include online reviews, management responses and real-time number of online hotel bookings, which were merged to create one dataset for this study. To calculate the management response similarity, three widely recognized text mining functions of calculating textual similarity were adopted in this model. Fixed-effect panel data model was then used to examine the influence of management response to consumer online reviews on online hotel booking volume.

Findings

The empirical results demonstrate that the number of management responses to consumer online reviews does not significantly affect hotel booking; compared to none or only one management response, or management responses with low similarity, management responses with high similarity can significantly reduce the hotel booking on Expedia.

Practical implications

This study suggests that the similarity of management responses influences customers’ hotel booking, and hotel managers should avoid providing too similar management responses.

Originality/value

First, this study, for the first time, proposes the concept of management response similarity and its measurement methods. Second, this study takes an initial attempt to empirically test the influence of response similarity on hotel booking by using secondary data online.