bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scheme for 3-dimensional morphological reconstruction and force inference in the earlyC. elegansembryo
Authors: Xu Muzhi , Wu Yicong , Shroff Hari , Wu Min , Mani Madhav 
Published: August 2017

AbstractIn this study, we present novel schemes for the reconstruction of cellular morphology and the inference of forces in the earlyC. elegansembryo. We have developed and bench-marked a morphological reconstruction scheme that transforms live-imaging of cellular membranes into a point cloud of smoothed surface patches, which facilitates accurate estimation of membrane curvatures and the angles between membranes.Assuming an isotropic and homogeneous distribution of tensions along a membrane, we infer a pattern of forces that are 7% deviated from force balance at edges, and 10% deviated from the Young-Laplace relation at membrane faces. We have also demonstrated the stability of our scheme by sensitivity analysis of the coefficient matrices involved and the reproducibility of our image-analysis and force inference pipeline.
Preservation of three-dimensional spatial structure in the gut microbiome
Authors: Hasegawa Yuko , Mark Welch Jessica L. , Rossetti Blair J. , Borisy Gary G. 
Published: August 2017

AbstractPreservation of three-dimensional structure in the gut is necessary in order to analyze the spatial organization of the gut microbiota and gut luminal contents. In this study, we evaluated preparation methods for mouse gut with the goal of preserving micron-scale spatial structure while performing fluorescence imaging assays. Our evaluation of embedding methods showed that commonly used media such as Tissue-Tek Optimal Cutting Temperature (OCT) compound, paraffin, and polyester waxes resulted in redistribution of luminal contents. By contrast, a hydrophilic methacrylate resin, Technovit H8100, preserved three-dimensional organization. Our mouse intestinal preparation protocol optimized using the Technovit H8100 embedding method was compatible with microbial fluorescencein situhybridization (FISH) and other labeling techniques, including immunostaining and staining with both wheat germ agglutinin (WGA) and 4’,6-diamidino-2-phenylindole (DAPI). Mucus labeling patterns of the samples fixed with paraformaldehyde (PFA) and Carnoy’s fixative were comparable. The protocol optimized in this study enabled simultaneous visualization of micron-scale spatial patterns formed by microbial cells in the mouse intestines along with biogeographical landmarks such as host-derived mucus and food particles.
Bacmeta: simulation for genomic evolution in bacterial metapopulations
Authors: Sipola Aleksi , Marttinen Pekka , Corander Jukka 
Published: August 2017

AbstractThe advent of genomic data from densely sampled bacterial populations has created a need for flexible simulators by which models and hypotheses can be efficiently investigated in the light of empirical observations. Bacmeta provides fast stochastic simulation of neutral evolution within a large collection of interconnected bacterial populations with completely adjustable connectivity network. Stochastic events of mutations, recombinations, insertions/deletions, migrations and microepidemics can be simulated in discrete non-overlapping generations with a Wright-Fisher model that operates on explicit sequence data of any desired genome length. Each model component, including locus, bacterial strain, population, and ultimately the whole metapopulation, is efficiently simulated using C++ objects, and detailed metadata from each level of the simulation can be acquired. The software can be executed in a cluster environment using simple textual input files, enabling, e.g., large-scale simulations and likelihood-free inference. Bacmeta is implemented with C++ for Linux, Mac and Windows. It is available athttps://bitbucket.org/aleksisipola/bacmetaunder the BSD 3-clause license.Contactaleksi.sipola@helsinki.fi,jukka.corander@medisin.uio.noSupplementary informationSupplementary data are available online at bioRxiv.
Cooperative mechanosensitivity and allostery of focal adhesion clusters
Authors: Foo D. C. W. , Terentjev E. M. 
Published: August 2017

AbstractWe analyse an Ising-like Hamiltonian describing the free energy of cell adhesion on a substrate as a lattice of 3-state mechanosensing sites involving focal adhesion kinase (FAK). We use Monte Carlo stochastic algorithm to find equilibrium configurations of these mechanosensors in two representative geometries: on a 1D ring representing the rim of a cell on flat surface, and a 2D bounded surface representing the whole area of cell contact with flat surface. The level of FAK activation depend on the pulling force applied to the individual FAKintegrin via actin-myosin contractile networks, and the details of the coupling between individual sensors in a cluster. Strong coupling is shown to make the FAK sensors experience a sharp on-off behaviour in their activation, while at low coupling the activation/autoinhibition transition occurs over a broad range of pulling force. We find that the activation/autoinhibition transition of FAK in the 2D system with strong coupling occurs with a hysteresis, the width of which depends on the rate of change of force. The effect of introducing a mediating protein (such as Src) in limited quantity to control FAK activation is explored, and visualizations of clustering in both topologies are presented. In particular the results on the bounded 2D surface indicate that clustering of active FAK occurs preferentially at the boundary, in agreement with experimental observations of focal adhesions in cells.
Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection
Authors: Noh Heeju , Shoemaker Jason E. , Gunawan Rudiyanto 
Published: August 2017

ABSTRACTGenome-wide transcriptional profiling provides a global view of cellular state and how this state changes under different treatments (e.g. drugs) or conditions (e.g. healthy and diseased). Here, we present ProTINA (Protein Target Inference by Network Analysis), a network perturbation analysis method for inferring protein targets of compounds from gene transcriptional profiles. ProTINA uses a dynamic model of the cell-type specific protein-gene transcriptional regulation to infer network perturbations from steady state and time-series differential gene expression profiles. A candidate protein target is scored based on the gene network’s dysregulation, including enhancement and attenuation of transcriptional regulatory activity of the protein on its downstream genes, caused by drug treatments. For benchmark datasets from three drug treatment studies, ProTINA was able to provide highly accurate protein target predictions and to reveal the mechanism of action of compounds with high sensitivity and specificity. Further, an application of ProTINA to gene expression profiles of influenza A viral infection led to new insights of the early events in the infection.
Improving on a modal-based estimation method: model averaging for consistent and efficient estimation in Mendelian randomization when a plurality of candidate instruments are valid
Authors: Burgess Stephen , Zuber Verena , Gkatzionis Apostolos , Rees Jessica MB , Foley Christopher N 
Published: August 2017

AbstractBackgroundA robust method for Mendelian randomization does not require all genetic variants to be valid instruments to give consistent estimates of a causal parameter. Several such methods have been developed, including a mode-based estimation method giving consistent estimates if a plurality of genetic variants are valid instruments; that is, there is no larger subset of invalid instruments estimating the same causal parameter than the subset of valid instruments.MethodsWe here develop a model averaging method that gives consistent estimates under the same ‘plurality of valid instruments’ assumption. The method considers a mixture distribution of estimates derived from each subset of genetic variants. The estimates are weighted such that subsets with more genetic variants receive more weight, unless variants in the subset have heterogeneous causal estimates, in which case that subset is severely downweighted. The mode of this mixture distribution is the causal estimate. This heterogeneity-penalized model averaging method has several technical advantages over the previously proposed mode-based estimation method.ResultsThe heterogeneity-penalized model averaging method outperformed the mode-based estimation in terms of effciency and outperformed other robust methods in terms of Type 1 error rate in an extensive simulation analysis. The proposed method suggests two distinct mechanisms by which inflammation affects coronary heart disease risk, with subsets of variants suggesting both positive and negative causal effects.ConclusionsThe heterogeneity-penalized model averaging method is an additional robust method for Mendelian randomization with excellent theoretical and practical properties, and can reveal features in the data such as the presence of multiple causal mechanisms. (249 words)Key messagesWe propose a heterogeneity-penalized model averaging method that gives consistent causal estimates if a weighted plurality of the genetic variants are valid instruments.The method calculates causal estimates based on all subsets of genetic variants, and upweights subsets containing several genetic variants with similar causal estimates.The method is asymptotically effcient and does not rely on bootstrapping to obtain a confidence interval, nor is the confidence interval constrained to be symmetric.In particular, the confidence interval can include multiple disjoint intervals, suggesting the presence of multiple causal mechanisms by which the risk factor influences the outcome.The method can incorporate biological knowledge to upweight the contribution of genetic variants with stronger plausibility of being valid instruments.
Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells
Authors: Pavlaki Ioanna , Docquier France , Chernukhin Igor , Kita Georgia , Gretton Svetlana , Clarkson Christopher T. , Teif Vladimir B. , Klenova Elena 
Published: August 2017

AbstractCTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. CTCF can undergo a number of post-translational modifications which change its properties and functions. One such modifications linked to cancer is poly(ADP-ribosyl)ation (PARylation). The highly PARylated CTCF form has an apparent molecular mass of 180 kDa (referred to as CTCF180), which can be distinguished from hypo- and non-PARylated CTCF with the apparent molecular mass of 130 kDa (referred to as CTCF130). The existing data accumulated so far have been mainly related to CTCF130. However, the properties of CTCF180 are not well understood despite its abundance in a number of primary tissues. In this study we performed ChIP-seq and RNA-seq analyses in human breast cells 226LDM, which display predominantly CTCF130 when proliferating, but CTCF180 upon cell cycle arrest. We observed that in the arrested cells the majority of sites lost CTCF, whereas fewer sites gained CTCF or remain bound (i.e. common sites). The classical CTCF binding motif was found in the lost and common, but not in the gained sites. The changes in CTCF occupancies in the lost and common sites were associated with increased chromatin densities and altered expression from the neighboring genes. Based on these results we propose a model integrating the CTCF130/180 transition with CTCF-DNA binding and gene expression changes. This study also issues an important cautionary note concerning the design and interpretation of any experiments using cells and tissues where CTCF180 may be present.
Common variants ofNRXN1, LRP1BandRORAare associated with increased ventricular volumes in psychosis - GWAS findings from the B-SNIP deep phenotyping study
Authors: Alliey-Rodriguez Ney , Grey Tamar A , Shafee Rebecca , Padmanabhan Jaya , Tandon Neeraj , Klinger Madeline , Spring Jonathan , Coppes Lucas , Reis Katherine , Keshavan Matcheri S , Gage Diane , McCarroll Steven , Bishop Jeffrey R , Hill Scot , Reilly James L , Lencer Rebekka , Clementz Brett , Buckley Peter , Meda Shashwath , Narayanan Balaji , Glahn David C , Pearlson Godfrey , Ivleva Elena I , Tamminga Carol , Sweeney John A , Curtis David , Keedy Sarah , Badner Judith A , Liu Chunyu , Gershon Elliot S 
Published: August 2017

ABSTRACTSchizophrenia, Schizoaffective, and Bipolar Disorders share common illness traits, intermediate phenotypes and a partially overlapping polygenic basis. We performed GWAS on deep phenotyping data, including structural MRI and DTI, clinical, and behavioral scales from 1,115 cases and controls. Significant associations were observed with two cerebrospinal fluid volumes: the temporal horn of left lateral ventricle was associated withNRXN1, and the volume of the cavum septum pellucidum was associated withLRP1BandRORA. Both volumes were associated with illness. Suggestive associations were observed with local gyrification indices, fractional anisotropy and age at onset. The deep phenotyping approach allowed unexpected genetic sharing to be found between phenotypes, including temporal horn of left lateral ventricle and age at onset.
Proofreading-deficient coronaviruses adapt over long-term passage for increased fidelity and fitness without reversion of exoribonuclease-inactivating mutations
Authors: Graepel Kevin W. , Lu Xiaotao , Case James Brett , Sexton Nicole R. , Smith Everett Clinton , Denison Mark R. 
Published: August 2017

ABSTRACTThe coronavirus (CoV) RNA genome is the largest among single-stranded positive sense RNA viruses. CoVs encode a proofreading 3′→5′exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in SARS-CoV and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold decreased fidelity, and increased susceptibility to nucleoside analogs. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with WT-MHV. Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication, reduced susceptibility to nucleoside analogs, and increased competitive fitness. However, passage did not select for complete or partial reversion at the ExoN-inactivating mutations. We identified novel amino acid changes within the RNA-dependent RNA polymerase (nsp12-RdRp) and nsp14 of MHV-ExoN(-) P250 that partially account for the observed changes in replication, susceptibility to nucleoside analogs, and competitive fitness observed in the passaged virus population, indicating that additional determinants can compensate for the activities of nsp14-ExoN. Our results suggest that while selection favors restoration of replication fidelity in ExoN(-) CoVs, there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and identify additional candidate proteins that may regulate CoV replication fidelity.IMPORTANCEUnique among RNA viruses, CoVs encode a proofreading exoribonuclease (ExoN) in nsp14 that mediates high-fidelity RNA genome replication. Proofreading-deficient CoVs with disrupted ExoN activity [ExoN(-)] are either non-viable or have significant defects in replication, RNA synthesis, fidelity, fitness, and virulence. In this study, we show that ExoN(-) murine hepatitis virus can adapt over long-term passage for increased replication and fitness without reverting the ExoN-inactivating mutations. Passage-adapted ExoN(-) mutants also demonstrate increasing resistance to nucleoside analogs that is only partially explained by secondary mutations in nsp12 and nsp14. These data suggest that enhanced resistance to nucleoside analogs is mediated by the interplay of multiple replicase proteins and support the proposed link between CoV fidelity and fitness.
Livestock activity increases exotic plant richness, but wildlife increases native richness, with stronger effects under low productivity
Authors: Eldridge David J. , Delgado‐Baquerizo Manuel , Travers Samantha K. , Val James , Oliver Ian , Dorrough Josh W. , Soliveres Santiago 
Published: August 2017

Abstract

Grazing by domestic livestock is one of the most widespread land uses world‐wide, particularly in rangelands, where it co‐occurs with grazing by wild herbivores. Grazing effects on plant diversity are likely to depend on intensity of grazing, herbivore type, co‐evolution with plants and prevailing environmental conditions.

We collected data on climate, plant productivity, soil properties, grazing intensity and herbivore type, and we measured their effects on plant species richness from 451 sites across 0.4 M km2 of semi‐arid rangelands in eastern Australia. We used structural equation modelling to examine the direct and indirect effects of increasing grazing intensity by different herbivores (cattle, sheep, kangaroos, rabbits) on native and exotic plant species richness across all sites, and in subsets focusing on three woodland communities spanning a gradient in productivity.

Direct effects of grazing by all herbivores were strongest under low productivity but waned with increasing productivity. Increases in the intensity of recent and historic livestock grazing corresponded with greater exotic plant richness under low productivity and less native plant richness under both low and moderate productivity. Rabbit effects were greatest under moderate productivity. Overall, the effects of kangaroos were benign. Grazing indirectly affected native and exotic plant richness by increasing soil phosphorus and reducing soil health (i.e. nutrient cycling).

Synthesis and applications. Our study shows that livestock grazing increases exotic species richness but reduces native richness, while kangaroo grazing increases native richness in environments with low productivity. The results provide clear messages for land managers and policy makers: (1) the coexistence of livestock grazing and plant diversity is only possible within more productive environments and (2) grazing under low or moderate productivity will impact upon native and exotic plant richness.
Structural Changes to the Public Sector and Cultural Incompatibility: The Consequences of Inadequate Cultural Integration
Authors: Buick Fiona , Carey Gemma , Pescud Melanie 
Published: August 2017

AbstractStructural changes are commonly undertaken to achieve gains, such as enhanced efficiency and performance. In this paper, we explore the cultural issues associated with a structural change in the Australian Public Service. We argue that cultural differences across merged functions were disruptive and challenging to overcome. We posit, however, that these challenges were exacerbated by the lack of systemic effort to integrate cultures, thus impeding synergy realization. Our findings are consistent with the private sector literature that warns mergers and acquisitions undertaken with too much haste and without adequate planning can lead to cultural issues when not managed appropriately.
Tax policy and tax protest in 20 rich democracies, 1980–2010
Authors: William Martin Isaac , Gabay Nadav 
Published: August 2017

AbstractWhy are some policies protested more than others? New data on protest against eight categories of taxation in twenty rich democracies from 1980 to 2010 reveal that economically and socially concentrated taxes are protested most, whereas taxes that confer entitlement to benefits are protested least. Other features of policy design often thought to affect the salience or visibility of costs are unimportant for explaining the frequency of protest. These findings overturn a folk theory that political sociology has inherited from classical political economy; clarify the conditions under which policy threats provoke protest; and shed light on how welfare states persist.
The Worth of Fair Value Accounting: Dissonance between Users and Standard Setters
Authors: Georgiou Omiros 
Published: August 2017

AbstractInvestors and analysts are designated as the primary users of financial reports by standard setters, yet we know very little about their use of accounting information and about their relationship with standard setters. This paper explores how investors and analysts evaluate the usefulness of fair values to their work. Standard setters typically presume that investors and analysts view accounting as a practice of valuation and, therefore, favor the greater use of fair value measurement. However, using interview evidence, it is shown here that investors and analysts expect accounting to provide them with insights into the performance of a business, and are quite cautious about the limits of using fair values in financial reports. Overall, the paper contributes to a better understanding of the relationship between accounting and its users. It adds specifically to research which has analyzed the disconnect between users and standard setters in terms of standard setters ignoring user needs (Young ), and in terms of users being indifferent about, or uncritical of, outcomes of standard‐setting processes (Durocher, Fortin, and Cote ; Durocher and Gendron ). The paper suggests a re‐theorization of the disconnect between the two groups that involves thinking away from tension, or blame. Drawing on the work of David Stark (), the situation observed is conceptualized as one of “dissonance,” where the different ways of evaluating fair values coexist without being involved in a fierce contest. That is, even though the principles of valuation and performance differ, this difference does not lead to open disagreement and political lobbying from investors and analysts. Consequences of this dissonance to our understandings of the (absence of) worth of fair values in capital markets are discussed.
Acacia saligna's soil legacy effects persist up to 10 years after clearing: Implications for ecological restoration
Authors: Nsikani Mlungele M. , Novoa Ana , van Wilgen Brian W. , Keet Jan‐Hendrik , Gaertner Mirijam 
Published: August 2017

AbstractTo reduce the negative impacts of invasive plants, management interventions such as control or eradication are usually necessary. It is often assumed that the impacts of invasive plants will diminish immediately after such interventions. However, in some cases the invader can have legacy effects in the soil that might persist for long periods, preventing the natural restoration of the areas managed. Therefore, to achieve the re‐establishment of a functional native ecosystem it is important to understand for how long such legacies can persist in the soil. This paper explores this issue, using Acacia saligna in South Africa as case study. We collected soil samples in invaded, non‐invaded and previously invaded sites (representing 2, 6 and 10 years after clearing) and analysed the levels of pH, carbon, nitrogen, available phosphorus, ammonium, nitrate and electrical conductivity. We also analysed enzyme activities (β‐1,4‐glucosidase, urease and acid phosphatase). Acacia saligna invasion alters overall soil characteristics but specifically raises pH by 0.6–1.8. Moreover, soil characteristics (e.g. pH) are not restored to natural conditions after control (soil legacy effects persist up to 10 years after clearing). Furthermore, A. saligna control elevates soil levels and these can remain higher than in invaded (1.55–6.67 mg kg−1) and non‐invaded (2.16–4.35 mg kg−1) sites up to 10 years after clearing. Elevated often facilitates secondary invasion and/or weedy native species dominance which may hinder the restoration of functional native ecosystems. Therefore, strategies to manage areas previously invaded by A. saligna should take into account the removal of litter from the target invader, secondary invaders and weedy native species.