bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonal occurrence of diamondback moths Plutella xylostella and their parasitoid wasps Cotesia vestalis in greenhouses and their surrounding areas
Authors: Abe Junichiro , Uefune Masayoshi , Yoneya Kinuyo , Shiojiri Kaori , Takabayashi Junji 
Published: July 2018

AbstractWe observed the seasonal occurrence of diamondback moth (DBM) larvae, Plutella xylostella (Lepidoptera: Plutellidae), and their native parasitoid wasps, Cotesia vestalis (Hymenoptera: Braconidae), on mizuna plants, Brassica rapa var. laciniifolia (Brassicales: Brassicaceae), in three commercial greenhouses and on wild cruciferous weeds, Rorippa indica (Brassicales: Brassicaceae), in the surrounding area in the Miyama countryside in Kyoto, Japan. The occurrences of DBM larvae in greenhouses followed their occurrence in the surrounding area: however, some occurrences of DBM in greenhouses took place when the DBM population in the surrounding was rather low. This suggests that the occurrence of DBM in greenhouses cannot always be explained by its seasonal occurrence in the surrounding areas. The occurrence of C. vestalis followed that of DBM larvae in mizuna greenhouses and in the surrounding areas. No C. vestalis were recorded in greenhouses when DBM was not present. Cotesia vestalis females preferred volatiles emitted from DBM-infested mizuna plants to those from uninfested conspecifics under laboratory conditions. Natural HIPVs (herbivory-induced plant volatiles) emitted from DBM-infested mizuna plants in greenhouses probably attracted C. vestalis from the surrounding area to cause their co-occurrence.
Structure of the ciliary axoneme at nanometer resolution reconstructed by TYGRESS
Authors: Song Kangkang , Shang Zhiguo , Fu Xiaofeng , Lou Xiaochu , Grigorieff Nikolaus , Nicastro Daniela 
Published: July 2018

AbstractThe resolution of subtomogram averages calculated from cryo-electron tomograms (cryo-ET) of crowded cellular environments is often limited due to signal loss in, and misalignment of the subtomograms. In contrast, single-particle cryo-electron microcopy (SP-cryo-EM) routinely reaches near-atomic resolution of isolated complexes. We developed a novel hybrid-method called “TomographY-Guided 3DREconstruction ofSubcellularStructures” (TYGRESS) that combines cryo-ET with SP-cryo-EM to achieve close-to-nanometer resolution of complexes inside crowded environments. Using TYGRESS, we determined the native 3D structures of the intact ciliary axoneme with up to 12 Å resolution. These results reveal many structures and details that were not visible by cryo-ET. TYGRESS is generally applicable to cellular complexes that are amenable to subtomogram averaging, bringing us a step closer to (pseudo-)atomic models of cells.One Sentence SummaryA hybrid cryo-electron microscopy method reveals subcellular structures at unprecedented resolution.
The Effect of Phylogenetic Uncertainty and Imputation on EDGE Scores
Authors: Weedop K. Bodie , Mooers Arne Ø. , Tucker Caroline M. , Pearse William D. 
Published: July 2018

AbstractFaced with the challenge of saving as much diversity as possible given financial and time constraints, conservation biologists are increasingly prioritizing species on the basis of their overall contribution to evolutionary diversity. Metrics such as EDGE (Evolutionary Distinct and Globally Endangered) have been used to set such evolutionarily-based conservation priorities for a number of taxa, such as mammals, birds, corals, amphibians, and sharks. Each application of EDGE has required some form of correction to account for species whose position within the tree of life are unknown. Perhaps the most advanced of these corrections is phylogenetic imputation, but to date there has been no systematic assessment of both the sensitivity of EDGE scores to a phylogeny missing species, and the impact of using imputation to correct for species missing from the tree. Here we perform such an assessment, by simulating phylogenies, removing some species to make the phylogeny incomplete, imputating the position of those species, and measuring (1) how robust ED scores are for the species that are not removed and (2) how accurate the ED scores are for those removed and then imputed. We find that the EDGE ranking for species on a tree is remarkably robust to missing species from that tree, but that phylogenetic imputation for missing species, while unbiased, does not accurately reconstruct species’ evolutionary distinctiveness. On the basis of these results, we provide clear guidance for EDGE scoring in the face of phylogenetic uncertainty.
A natural killer cell gene signature predicts melanoma patient survival
Authors: Cursons Joseph , Souza-Fonseca-Guimaraes Fernando , Anderson Ashley , Foroutan Momeneh , Hediyeh-Zadeh Soroor , Behren Andreas , Huntington Nicholas D. , Davis Melissa J 
Published: July 2018

AbstractAnimal models have demonstrated that natural killer (NK) cells can limit the metastatic dissemination of tumors, however their ability to combat established human tumors has been difficult to investigate.A number of computational methods have been developed for the deconvolution of immune cell types within solid tumors. We have taken the NK cell gene signatures from several tools, then curated and expanded this list using recent reports from the literature. Using a gene set scoring method to investigate RNA-seq data from The Cancer Genome Atlas (TCGA) we show that patients with metastatic cutaneous melanoma have an improved survival rate if their tumor shows evidence of greater NK cell infiltration. Furthermore, these survival effects are enhanced in tumors which have a higher expression of NK cell stimuli such as IL-15, suggesting NK cells are part of a coordinated immune response within these patients. Using this signature we then examine transcriptomic data to identify tumor and stromal components which may influence the penetrance of NK cells into solid tumors.These data support a role for NK cells in the regulation of human tumors and highlight potential survival effects associated with increased NK cell activity. Furthermore, our computational analysis identifies a number of potential targets which may help to unleash the anti-tumor potential of NK cells as we enter the age of immunotherapy.
LDpred-funct: incorporating functional priors improves polygenic prediction accuracy in UK Biobank and 23andMe data sets
Authors: Márquez-Luna Carla , Gazal Steven , Loh Po-Ru , Kim Samuel S. , Furlotte Nicholas , Auton Adam ,   23andMe Research Team, Price Alkes L. 
Published: July 2018

AbstractGenetic variants in functional regions of the genome are enriched for complex trait heritability. Here, we introduce a new method for polygenic prediction, LDpred-funct, that leverages trait-specific functional priors to increase prediction accuracy. We fit priors using the recently developed baseline-LD model, which includes coding, conserved, regulatory and LD-related annotations. We analytically estimate posterior mean causal effect sizes and then use cross-validation to regularize these estimates, improving prediction accuracy for sparse architectures. LDpred-funct attained higher prediction accuracy than other polygenic prediction methods in simulations using real genotypes. We applied LDpred-funct to predict 21 highly heritable traits in the UK Biobank. We used association statistics from British-ancestry samples as training data (avgN=373K) and samples of other European ancestries as validation data (avgN=22K), to minimize confounding. LDpred-funct attained a +4.6% relative improvement in average prediction accuracy (avg predictionR2=0.144; highestR2=0.413 for height) compared to SBayesR (the best method that does not incorporate functional information). For height, meta-analyzing training data from UK Biobank and 23andMe cohorts (totalN=1107K; higher heritability in UK Biobank cohort) increased predictionR2to 0.431. Our results show that incorporating functional priors improves polygenic prediction accuracy, consistent with the functional architecture of complex traits.
Costimulation through TLR2 drives polyfunctional CD8+T cell responses
Authors: Salerno Fiamma , Freen-van Heeren Julian J. , Guislain Aurelie , Nicolet Benoit P. , Wolkers Monika C. 
Published: July 2018

AbstractOptimal T cell activation requires antigen recognition through the T cell receptor (TCR), engagement of costimulatory molecules, and cytokines. T cells can also directly recognize danger signals through the expression of toll-like receptors (TLRs). Whether TLR ligands have the capacity to provide costimulatory signals and enhance antigen-driven T cell activation is not well understood. Here, we show that TLR2 and TLR7 ligands potently lower the antigen threshold for cytokine production in T cells. To investigate how TLR triggering supports cytokine production, we adapted the protocol for flow cytometry-based fluorescencein situhybridization (Flow-FISH) to mouse T cells. The simultaneous detection of cytokine mRNA and protein with single-cell resolution revealed that TLR triggering primarily drivesde novomRNA transcription.IfngmRNA stabilization only occurs when the TCR is engaged. TLR2, but not TLR7-mediated costimulation, can enhance mRNA stability at low antigen levels. Importantly, TLR2 costimulation increases the percentage of polyfunctional T cells, a hallmark of potent T cell responses. In conclusion, TLR-mediated costimulation effectively potentiates T cell effector function to suboptimal antigen levels.
A new actin depolymerase: a Myosin 1 motor
Authors: Pernier Julien , Kusters Remy , Bousquet Hugo , Lagny Thibaut , Morchain Antoine , Joanny Jean-François , Bassereau Patricia , Coudrier Evelyne 
Published: July 2018

AbstractThe regulation of actin dynamics is essential for various cellular processes. Former evidence suggests a correlation between the function of non-conventional myosin motors and actin dynamics. We investigate the contribution of myosin1b to actin dynamics using sliding motility assays. We observe that sliding on myosin1b immobilized or bound to a fluid bilayer enhances actin depolymerization at the barbed end, while sliding on myosin II, although 5 times faster, has no effect. This work reveals a non-conventional myosin motor as a new type of depolymerase and points to its singular interactions with the actin barbed end.
Combinatorial Genetic Control of Rpd3S through histone H3K4 and H3K36 Methylation in Budding Yeast
Authors: Lee Kwan Yin , Ranger Mathieu , Meneghini Marc D. 
Published: July 2018

AbstractMuch of euchromatin regulation occurs through reversible methylation of histone H3 lysine-4 and lysine-36 (H3K4me and H3K36me). Using the budding yeast Saccharomyces cerevisiae, we previously found that levels of H3K4me modulated temperature sensitive alleles of the transcriptional elongation complex Spt6-Spn1 through an unknown H3K4me effector pathway. Here we identify the Rpd3S histone deacetylase complex as the H3K4me effector underlying these Spt6-Spn1 genetic interactions. Exploiting these Spt6-Spn1 genetic interactions, we show that H3K4me and H3K36me collaboratively impact Rpd3S function in an opposing manner. H3K36me is deposited by the histone methyltransferase Set2 and is known to promote Rpd3S function at RNA PolII transcribed open reading frames. Using genetic epistasis experiments, we find that mutations perturbing the Set2-H3K36me-Rpd3S pathway suppress the growth defects caused by temperature sensitive alleles of SPT6 and SPN1, illuminating that this pathway antagonizes Spt6-Spn1. Using these sensitive genetic assays, we also identify a role for H3K4me in antagonizing Rpd3S that functions through the Rpd3S subunit Rco1, which is known to bind H3 N-terminal tails in a manner that is prevented by H3K4me. Further genetic experiments reveal that the H3K4 and H3K36 demethylases JHD2 and RPH1 mediate this combinatorial control of Rpd3S. Finally, our studies also show that the Rpd3L complex, which acts at promoter-proximal regions of PolII transcribed genes, counters Rpd3S for genetic modulation of Spt6-Spn1, and that these two Rpd3 complexes balance the activities of each other. Our findings present the first evidence that H3K4me and H3K36me act combinatorially to control Rpd3S.
Extracellular matrix regulates morphogenesis and function of ciliated sensory organs inCaenorhabditis elegans
Authors: De Vore Deanna M. , Knobel Karla M. , Nguyen Ken C.Q. , Hall David H. , Barr Maureen M. 
Published: July 2018

ABSTRACTCilia and extracellular vesicles (EVs) are signaling organelles that play important roles in human health and disease. InC. elegansand mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. Hence, the nematode offers an excellent system in which to address central questions regarding the biology of cilia, EVs, and the polycystins. We discovered an unexpected role of themec-1, mec-5, andmec-9genes encoding extracellular matrix (ECM) components. We determined that these ECM encoding genes regulate polycystin localization and function, ciliary EV release, cilia length, dendritic morphology, and neuron-glia interactions. Abnormal ECM and fibrosis are observed in ciliopathies such as ADPKD, nephronophthisis, and Bardet-Biedl Syndrome. Our studies reveal multifaceted roles for ECM proteins in the ciliated nervous system of the worm and provide a powerful newin vivomodel to study the relationship between ECM, the polycystins, and ciliopathies.
Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer
Authors: Bhatia Vipul , Yadav Anjali , Tiwari Ritika , Nigam Shivansh , Goel Sakshi , Carskadon Shannon , Gupta Nilesh , Goel Apul , Palanisamy Nallasivam , Ateeq Bushra 
Published: July 2018

AbstractPurposeSerine Peptidase Inhibitor, Kazal type-1 (SPINK1) overexpression defines the second most recurrent and aggressive prostate cancer (PCa) subtype. However, the underlying molecular mechanism and pathobiology of SPINK1 in PCa remains largely unknown.Experimental DesignMicroRNA-prediction tools were employed to examine theSPINK1-3’UTR for miRNAs binding. Luciferase reporter assays were performed to confirm theSPINK1-3’UTR binding of shortlisted miR-338-5p/miR-421. Further, miR-338-5p/-421 overexpressing cancer cells (SPINK1-positive) were evaluated for oncogenic properties using cell-based functional assays and mice xenograft model. Global gene expression profiling was performed to unravel the biological pathways altered by miR-338-5p/-421. Immunohistochemistry and RNAin-situhybridization was carried-out on PCa patients’ tissue microarray for SPINK1 andEZH2expression respectively. Chromatin immunoprecipitation assay was performed to examine EZH2 occupancy on the miR-338-5p/-421 regulatory regions. Bisulfite sequencing and methylated DNA-immunoprecipitation was performed on PCa cell lines and patients’ specimens.ResultsWe established a critical role of miRNA-338-5p/-421 in post-transcriptional regulation ofSPINK1. Ectopic expression of miRNA-338-5p/-421 in SPINK1-positive PCa cells abrogate oncogenic properties including cell-cycle progression, stemness and drug resistance, and show reduced tumor burden and distant metastases in mice model. Importantly, we show SPINK1-positive PCa patients exhibit increased EZH2 expression, suggesting its role in miRNA-338-5p/-421 epigenetic silencing. Furthermore, presence of CpG dinucleotide DNA methylation marks on the regulatory regions of miR-338-5p/-421 in SPINK1-positive PCa cells and patients’ specimens confirms epigenetic silencing.ConclusionOur findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive PCa, while restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis.TRANSLATIONAL IMPACTWe establish a regulatory model involving the functional interplay between SPINK1, miRNA-338-5p/miRNA-421 and EZH2, thereby, revealing hitherto unknown mechanism of SPINK1 up-regulation in SPINK1-positive subtype. Our findings provide a strong rationale for the development of potential therapeutic strategies for SPINK1-positive malignancies. We demonstrate that restoring miRNA-338-5p/miRNA-421 expression using epigenetic drugs including DNMTs inhibitors in combination with HDACs or HKMTs inhibitors or miRNA synthetic mimics in SPINK1-positive prostate cancer abrogate SPINK1-mediated oncogenicity. The major findings of this study will not only advance the prostate cancer field, but will also be valuable for treatment and disease management of other SPINK1-positive malignancies.
Cellular acidosis triggers MondoA transcriptional activity by driving mitochondrial ATP production
Authors: Wilde Blake R. , Ye Zhizhou , Ayer Donald E. 
Published: July 2018

ABSTRACTMondoA and its transcriptional target thioredoxin-interacting protein (TXNIP) constitute a regulatory loop that senses glycolytic flux and controls glucose availability. Cellular stress also triggers MondoA activity and TXNIP expression. To understand how MondoA integrates glucose and stress signals, we studied its activation by acidosis. We found that acidosis drives mitochondrial ATP (mtATP) synthesis. The subsequent export of mtATP from mitochondria via adenine-nucleotide transporter and voltage-dependent anion channel, and the enzymatic activity of mitochondria-bound hexokinase results in the production of glucose-6-phosphate (G6P), a known activator of MondoA transcriptional activity. MondoA localizes to the outer-mitochondrial membrane (OMM), and in response to G6P, shuttles to the nucleus and activates transcription. Our data suggests that MondoA is a required feature of a glucose- and mtATP-dependent, OMM-localized signaling center. We propose MondoA functions as a coincidence detector and its ability to sense glucose and cellular stress is coupled to the concerted production of G6P.
Developmental Regulation of an Organelle Tether Coordinates Mitochondrial Remodeling in Meiosis
Authors: Sawyer Eric M. , Joshi Pallavi R. , Berchowitz Luke E. , Ünal Elçin 
Published: July 2018

ABSTRACTCellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation as well as organelle architecture are known, but the interface between them remains unexplored. We found that mitochondria abruptly detach from the cell cortex shortly before segregating into gametes. Mitochondrial detachment is enabled by the programmed destruction of themitochondria-endoplasmic reticulum-cortexanchor (MECA), an organelle tether that forms contact sites between mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We found that MECA undergoes Ime2-dependent phosphorylation. Furthermore, Ime2 promotes MECA degradation in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.
The 11 commandments of publishing
Authors: De Lange Paul , Daff Lyn , Jackling Beverley 
Published: July 2018

Purpose
Publishing in scholarly journals is a practical necessity for academics. Put simply, this reality can be described as “publish or perish”. To be treated as a serious contender for tenure and promotion, scholarly research and activities directed towards publication are necessary aspects of faculty life. The purpose of this paper is to provide insights into “dealing” with the editorial review process of publishing from the perspective of a relatively new author.

Design/methodology/approach
Using the lens of Q and R theory, a case study approach combined with critical reflection provides a documented tour to enable other authors to enhance their understanding of the publication process through including references to associated reviews and correspondence with a journal editor. The review extracts from the editor and authors’ responses are discussed within the context of a theoretical schema and timeline.

Findings
Drawing from the theoretical schema, the paper identifies 11 lessons learned along the way to publishing, and these are summarised as the 11 commandments of publishing.

Research limitations/implications
Utilisation of the Q and R theory can assist researchers as they reflect on how to maximise their publication outcomes.

Practical implications
The 11 commandments provide a practical approach for those wanting to improve their understanding and likelihood of publishing success.

Originality/value
The originality of this paper is that it considers the publication process from a novice author who subsequently draws on the knowledge of more experienced co-authors. The findings are based on a theoretical schema that is transferable and able to be adopted by others to guide publication outcomes.
Determinants of women representation on corporate boards: evidence from Australia
Authors: Ahmed Ammad , Higgs Helen , Ng Chew , Delaney Deborah Anne 
Published: July 2018

PurposeThis paper aims to investigate the determinants of women representation on Australian corporate boards under the ASX’s “if not, why not” corporate governance framework. It further aims to improve the study of Geiger and Marlin (2012) by using a theoretically sound two-limit Tobit model to examine the determinants.Design/methodology/approachThis study uses the two-limit Tobit model to examine the determinants of women representation on ASX 500 boards. This approach is used due to the censored nature of the dependent variable.FindingsThis study finds that the two-limit Tobit model is an appropriate methodology to accommodate the censored dependent variable. It further finds that firm size, women as chair of boards, corporate governance index, Global Reporting Initiative signatory, debt ratio, average board age, BIG4 auditors, chief executive officer tenure and shareholder concentration are major determinants of women on boards.Research limitations/implicationsThe use of only ASX 500 companies and the sample years (2011-2014) may limit the generalisation of the findings.Originality/valueThis is the first extensive longitudinal Australian study to examine the drivers of women representation on corporate boards. It is also the first of its kind to use the two-limit Tobit model to consider these determinants.