bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermodynamic Integration in 3n Dimensions without Biases or Alchemy for Protein Interactions
Authors: Chen Liao Y 
Published: June 2017

ABSTRACTThermodynamic integration (TI), a powerful formalism for computing the Gibbs free energy, has been implemented for many biophysical processes characterized by one-dimensional order parameters with alchemical schemes that require delicate human efforts to choose/design biasing potentials for sampling the desired biophysical events and to remove their artifactitious consequences afterwards. Theoretically, an alchemical scheme is exact but practically, it causes error amplification. Small relative errors in the interaction parameters can be amplified many times in their propagation into the computed free energy [due to subtraction of similar numbers such as (105 ± 5) − (100 ± 5) = 5 ± 7], which would render the results significantly less accurate than the input interaction parameters. In this paper, we present an unsophisticated implementation of TI in 3n dimensions (3nD) (n=1,2,3…) without alchemy or biasing potentials. In TI3nD, the errors in the interaction parameters will not be amplified and human efforts are not required to design biasing potentials that generate unphysical consequences. Using TI3nD, we computed the standard free energies of three protein complexes: trometamol in Salmonella effector SpvD (n=1), biotin in avidin (n=2), and Colicin E9 endonuclease with cognate immunity protein Im9 (n=3) and the hydration energies of ten biologically relevant compounds (n=1 for water, acetamide, urea, glycerol, trometamol, ammonium and n=2 for erythritol, 1,3-propanediol, xylitol, biotin). The computed results all agree with available experimental data. Each of the 13 computations is accomplishable within two (for a hydration problem) to ten (for the protein-recognition problem) days on an inexpensive workstation (two Xeon E5-2665 2.4GHz CPUs and one nVidia P5000 GPU).
RNA-mediated Genomic Arrangements in Mammalian Cells
Authors: Gupta Sachin Kumar , Luo Liming , Yen Laising 
Published: June 2017

SummaryOne of the hallmarks of cancer is the formation of oncogenic fusion genes as a result of chromosomal translocations. Fusion genes are presumed to occur prior to fusion RNA expression. However, studies have reported the presence of fusion RNAs in individuals who were negative for chromosomal translocations. These observations give rise to “the cart before the horse” hypothesis, in which fusion RNA precedes the fusion gene and guides the genomic rearrangements that ultimately result in gene fusions. Yet RNA-mediated genomic rearrangement in mammalian cells has never been demonstrated. Here we provide evidence that expression of a chimeric RNA drives formation of a specified gene fusion via genomic rearrangement in mammalian cells. The process is (1) specified by the sequence of chimeric RNA involved, (2) facilitated by physiological hormone levels, (3) permissible regardless of intra-chromosomal (TMPRSS2-ERG) or inter-chromosomal (TMPRSS2-ETV1) fusion, and (4) can occur in normal cells prior to malignant transformation. We demonstrate that, contrary to “the cart before the horse” model, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion, and that this disparity can be explained by transcriptional conflict. Furthermore, we identified an endogenous RNAAZI1that acts as the ‘initiator’ RNA to induceTMPRSS2-ERGfusion. RNA-driven gene fusion demonstrated in this report provides important insight in early disease mechanism, and could have fundamental implications in the biology of mammalian genome stability, as well as gene editing technology via mechanisms native to mammalian cells.
ProbAnnoWeb and ProbAnnoPy: probabilistic annotation and gap-filling of metabolic reconstructions
Authors: King Brendan , Farrah Terry , Richards Matthew , Mundy Michael , Simeonidis Evangelos , Price Nathan D. 
Published: June 2017

AbstractSummaryGap-filling is a necessary step to produce quality genome-scale metabolic reconstructions capable of flux-balance simulation. Most available gap-filling tools use an organism-agnostic approach, where reactions are selected from a database to fill gaps without consideration of the target organism. Conversely, our likelihood based gap-filling with probabilistic annotations selects candidate reactions based on a likelihood score derived specifically from the target organism’s genome. Here, we present two new implementations of probabilistic annotation and likelihood based gap-filling: a web service called ProbAnnoWeb, and a standalone python package called ProbAnnoPy.Availability and ImplementationOur tools are available as a web service with no installation needed (ProbAnnoWeb), available athttp://probannoweb.systemsbiology.net, and as a local python package implementation (ProbAnnoPy), available for download athttp://github.com/PriceLab/probannopy.Contacthttp://Evangelos.Simeonidis@systemsbiology.org;http://Nathan.Price@systemsbiology.org
Weighted integration of short term memory and sensory signals in the oculomotor system
Authors: Deravet Nicolas , Blohm Gunnar , Orban de Xivry Jean-Jacques , Lefèvre Philippe 
Published: June 2017

AbstractOculomotor behaviors integrate sensory and prior information to overcome sensory-motor delays and noise. After much debate about this process, reliability-based integration has recently been proposed and several models of smooth pursuit now include recurrent Bayesian integration or Kalman filtering. However, there is a lack of behavioral evidence supporting these theoretical predictions.Here, we independently manipulated the reliability of visual and prior information in a smooth pursuit task. Our results show that both smooth pursuit eye velocity and catch-up saccade amplitude were modulated by visual and prior information reliability.We interpret these findings as the continuous reliability-based integration of a short-term memory of target motion with visual information, which support modelling work. Furthermore, we suggest that saccadic and pursuit systems share this short-term memory. We propose that this short-term memory of target motion is quickly built and continuously updated, and constitutes a general building-block present in all sensorimotor systems.
Comparative transcriptomics provides insight into the evolution of cold response in Pooideae
Authors: Grønvold Lars , Schubert Marian , Sandve Simen R. , Fjellheim Siri , Hvidsten Torgeir R. 
Published: June 2017

AbstractBackgroundUnderstanding how complex traits evolve through adaptive changes in gene regulation remains a major challenge in evolutionary biology. Over the last ~50 million years, Earth has experienced climate cooling and ancestrally tropical plants have adapted to expanding temperate environments. The grass subfamily Pooideae dominates the grass flora of the temperate regions, but conserved cold-response genes that might have played a role in the cold adaptation to temperate climate remain unidentified.ResultsTo establish if molecular responses to cold are conserved throughout the Pooideae phylogeny, we assembled the transcriptomes of five species spanning early to later diverging lineages, and compared short-and long-term cold response in orthologous genes based on gene expression data. We confirmed that most genes previously identified as cold responsive in barley also responded to cold in our barley experiment. Interestingly, comparing cold response across the lineages using 8633 high confidence ortholog groups revealed that nearly half of all cold responsive genes were species specific and more closely related species did not share higher numbers of cold responsive genes than more distantly related species. Also, the previously identified cold-responsive barley genes displayed low conservation of cold response across species. Nonetheless, more genes than expected by chance shared cold response, both based on previously studied genes and based on the high confidence ortholog groups. Noticeable, all five species shared short-term cold response in nine general stress genes as well as the ability to down-regulate the photosynthetic machinery during cold temperatures.ConclusionsWe observed widespread lineage specific cold response in genes with conserved sequence across the Pooideae phylogeny. This is consistent with phylogenetic dating and historic temperature data which suggest that selection pressure resulting from dramatic global cooling must have acted on already diverged lineages. To what degree lineage specific evolution acted primarily through gain or loss of cold response remains unclear, however, phylogeny-wide conservation of certain genes and processes indicated that the last common ancestor may have possessed some cold response.
Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
Authors: Mol Milsee , Kosey Dipali , Bopanna Ramanamurthy , Singh Shailza 
Published: June 2017

AbstractStochastic variations in the transcription factor target gene network influences the dynamics of protein levels. The mathematical model built, here, is useful to study the cytokine response and the resulting dynamical patterns in leishmaniasis. The fluctuations produced affect the expression rate of its target in the regulatory synthetic circuit designed by means of a negative feedback loop insertion. Thus, the faster the response time, smaller is the fluctuation of the system observed and it can be justified that the TFTG network embedded can be understood with the recurring dynamics of the designed synthetic circuit.List of AbbreviationsTFtranscription factorPPARαperoxisome proliferator-activated receptor-FAsfatty acidsDCsdendritic cellsTFTG networkTranscription Factor Target Gene NetworkIFNginterferon gVLvisceral leishmaniasisCLcutaneous leishmaniasisG-MCFgranulocyte macrophage colony-stimulating factorILinterleukinPKCProtein Kinase CPBCPeriodic boundary conditionNPTNormal Pressure temperatureNVTNormal Volume TemperatureMDMolecular DynamicsRMSDroot mean square deviationRMSFroot mean square fluctuationLBLuria BerttiniIInfectionCTChimeric PKCCTIChimeric PKC + InfectionCTMChimeric PKC + MiltefosineCTIMChimeric PKC + Infection + MiltefosineCCCloseness centralityIPTGIsopropyl β-D-1-thiogalactopyranoside
Expanding discovery from cancer genomes by integrating protein network analyses with in vivo tumorigenesis assays
Authors: Horn Heiko , Lawrence Michael S. , Chouinard Candace R. , Shrestha Yashaswi , Hu Jessica Xin , Worstell Elizabeth , Shea Emily , Ilic Nina , Kim Eejung , Kamburov Atanas , Kashani Alireza , Hahn William C. , Campbell Joshua D. , Boehm Jesse S. , Getz Gad , Lage Kasper 
Published: June 2017

AbstractApproaches that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes, but are challenging to validate at scale and their predictive value remains unclear. We developed a robust statistic (NetSig) that integrates protein interaction networks and data from 4,742 tumor exomes and used it to accurately classify known driver genes in 60% of tested tumor types and to predict 62 new candidates. We designed a quantitative experimental framework to compare thein vivotumorigenic potential of NetSig candidates, known oncogenes and random genes in mice showing that NetSig candidates induce tumors at rates comparable to known oncogenes and 10-fold higher than random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2andTFDP2) are significantly amplified. Overall, we illustrate a scalable integrated computational and experimental workflow to expand discovery from cancer genomes.
Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates
Authors: McCall Patrick M. , Srivastava Samanvaya , Perry Sarah L. , Kovar David R. , Gardel Margaret L. , Tirrell Matthew V. 
Published: June 2017

ABSTRACTBiomolecules exist and function in cellular micro-environments that control their spatial organization, local concentration and biochemical reactivity. Due to the complexity of native cytoplasm, the development of artificial bioreactors and cellular mimics to compartmentalize, concentrate and control the local physicochemical properties is of great interest. Here, we employ self-assembling polypeptide coacervates to explore the partitioning of the ubiquitous cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin spontaneously partitions into coacervate droplets and is enriched by up to ≈30-fold. Actin polymerizes into micrometer-long filaments and, in contrast to the globular protein BSA, these filaments localize predominately to the droplet periphery. We observe up to a 50-fold enhancement in the actin filament assembly rate inside coacervate droplets, consistent with the enrichment of actin within the coacervate phase. Together these results suggest that coacervates can serve as a versatile platform in which to localize and enrich biomolecules to study their reactivity in physiological environments.SIGNIFICANCE STATEMENTLiving cells harbor many protein-rich membrane-less organelles, the biological functions of which are defined by compartment composition and properties. Significant differences between the physico-chemical properties of these crowded compartments and the dilute solutions in which biochemical reactions are traditionally studied pose a major challenge for understanding regulation of organelle composition and component activity. Here, we report the spontaneous partitioning and accelerated polymerization of the cytoskeletal protein actin inside model polypeptide coacervates as a proof-of-concept demonstration of coacervates as bioreactors for studying biomolecular reactions in cell-like environments. Our work introduces exciting avenues for the use of synthetic polymers to control the physical and biological properties of bioreactors in vitro, enabling studies of biochemical reactions in cell-like micro-environments.
A Positive Feedback Loop Ensures Propagation of ROS Production and JNK Signaling ThroughoutDrosophilaTissue Regeneration
Authors: Khan Sumbul Jawed , Nayab Fatima Abidi Syeda , Skinner Andrea , Tian Yuan , Smith-Bolton Rachel K. 
Published: June 2017

AbstractRegenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed wholegenome mRNAseq of actively regenerating tissue from damagedDrosophilawing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescent labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the genemoladietz(mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulatesmolexpression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by wholegenome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.Author summaryRegenerating tissue must initiate the signaling that drives regenerative growth, and then sustain that signaling long enough for regeneration to complete.Drosophilaimaginal discs, the epithelial structures in the larva that will form the adult animal during metamorphosis, have been an important model system for tissue repair and regeneration for over 60 years. Here we show that damage-induced JNK signaling leads to the upregulation of a gene calledmoladietz, which encodes a co-factor for an enzyme, NADPH dual oxidase (DUOX), that generates reactive oxygen species (ROS), a key tissue-damage signal. High expression ofmoladietzinduces continuous production of ROS in the regenerating tissue. The sustained production of ROS then continues to activate JNK signaling throughout the course of regeneration, ensuring maximal tissue regrowth.
Students’ perceived impact of learning and satisfaction with blogs
Authors: Ifinedo Princely 
Published: June 2017

Purpose
Students’ use of blogging tools in learning environments is increasing across the world. The purpose of this paper is to contribute to the literature by examining the effects of relevant factors that engender satisfaction and positive impacts of the technology for learning.

Design/methodology/approach
A cross-sectional survey was used to collect data from 108 undergraduate students taking a management information systems course. The partial least squares technique of structural equation modelling was used to test the reliability and validity of the data, and the study’s hypothesised relationships or paths.

Findings
This study revealed that perceived enjoyment, compatibility, usefulness, ease of use, and confirmation have positive influence on students’ satisfaction with blog use. Perceived enjoyment had the greatest influence on students’ satisfaction with blog use for learning. Perceived impact on learning was positively influenced by perceived ease of use, enjoyment, and satisfaction.

Originality/value
A limited amount of empirical research has focussed on students’ perceptions of satisfaction and perceived impact on learning through blog use in higher educational contexts. This study adds to the growing literature in this area of study.
Interpreting variation to advance predictive restoration science
Authors: Brudvig Lars A. , Barak Rebecca S. , Bauer Jonathan T. , Caughlin T. Trevor , Laughlin Daniel C. , Larios Loralee , Matthews Jeffrey W. , Stuble Katharine L. , Turley Nash E. , Zirbel Chad R. 
Published: June 2017

Summary

Ecological restoration is a global priority that holds great potential for benefiting natural ecosystems, but restoration outcomes are notoriously unpredictable. Resolving this unpredictability represents a major, but critical challenge to the science of restoration ecology.

In an effort to move restoration ecology toward a more predictive science, we consider the key issue of variability. Typically, restoration outcomes vary relative to goals (i.e. reference or desired future conditions) and with respect to the outcomes of other restoration efforts. The field of restoration ecology has largely considered only this first type of variation, often focusing on an oversimplified success vs. failure dichotomy. The causes of variation, particularly among restoration efforts, remain poorly understood for most systems.

Variation associated with restoration outcomes is a consequence of how, where and when restoration is conducted; variation is also influenced by how the outcome of restoration is measured. We propose that variation should decrease with the number of factors constraining restoration and increase with the specificity of the goal. When factors (e.g. harsh environmental conditions, limited species reintroductions) preclude most species, little variation will exist among restorations, particularly when goals are associated with metrics such as physical structure, where species may be broadly interchangeable. Conversely, when few constraints to species membership exist, substantial variation may result and this will be most pronounced when restoration is assessed by metrics such as taxonomic composition.

Synthesis and applications. The variability we observe during restoration results from both restoration context (how, where and when restoration is conducted) and how we evaluate restoration outcomes. To advance the predictive capacity of restoration, we outline a research agenda that considers metrics of restoration outcomes, the drivers of variation among existing restoration efforts, experiments to quantify and understand variation in restoration outcomes, and the development of models to organise, interpret and forecast restoration outcomes.
Effects of uranium concentration on microbial community structure and functional potential
Authors: Sutcliffe Brodie , Chariton Anthony A. , Harford Andrew J. , Hose Grant C. , Greenfield Paul , Elbourne Liam D. H. , Oytam Yalchin , Stephenson Sarah , Midgley David J. , Paulsen Ian T. 
Published: June 2017

SummaryLocated in the Northern Territory of Australia, Ranger uranium mine is directly adjacent to the UNESCO World Heritage listed Kakadu National Park, with rehabilitation targets needed to ensure the site can be incorporated into the park following the mine's closure in 2026. This study aimed to understand the impact of uranium concentration on microbial communities, in order to identify and describe potential breakpoints in microbial ecosystem services. This is the first study to report in situ deployment of uranium‐spiked sediments along a concentration gradient (0–4000 mg U kg−1), with the study design maximising the advantages of both field surveys and laboratory manipulative studies. Changes to microbial communities were characterised through the use of amplicon and shotgun metagenomic next‐generation sequencing. Significant changes to taxonomic and functional community assembly occurred at a concentration of 1500 mg U kg−1 sediment and above. At uranium concentrations of ≥ 1500 mg U kg−1, genes associated with methanogenic consortia and processes increased in relative abundance, while numerous significant changes were also seen in the relative abundances of genes involved in nitrogen cycling. Such alterations in carbon and nitrogen cycling pathways suggest that taxonomic and functional changes to microbial communities may result in changes in ecosystem processes and resilience.
Partial characterisation of a bacteriocin produced by Leuconostoc mesenteroides A11 and evaluation of bacteriocin production using whey as culture medium
Authors: Okuda Nelly K , Tulini Fabricio L , Winkëlstroter Lizziane K , De Martinis Elaine Cristina P 
Published: June 2017

This study aimed to partially purify and characterise the bacteriocin produced by Leuconostoc mesenteroides A11 and to evaluate the bacteriocin production in whey at different concentrations and temperatures (30 and 25 °C). The partially purified bacteriocin was obtained by chromatography and analysed by electrophoresis. Thus, the molecular weight of the bacteriocin was estimated by electrophoresis, ranging from 3.5 to 8.5 kDa. Leu conostoc mesenteroides A11 produced bacteriocins in all concentrations of whey and temperatures evaluated, indicating that it would be feasible to employ low whey concentrations and room temperature for the production of bacteriocins, thereby reducing processing costs.