bluuebunny/crossref_metadata_2025_split huggingface dataset:
eQTL network analysis reveals that regulatory genes are evolutionarily older and bearing more types of PTM sites in Coprinopsis cinerea
Authors: Chang Jinhui , Au Tommy CH , Cheng CK , Kwan HS 
Published: September 2018

AbstractUnderstanding the DNA variation in regulation of carbohydrate-active enzymes (CAZymes) is fundamental to the use of wood-decaying basidiomycetes in lignocellulose conversion into renewable energy. Our goal is to identify the regulators of lignocellulolytic enzymes in Coprinopsis cinerea, of which the genome harbors high number of Auxiliary Activities enzymes.The DNA sequence of C. cinerea family including 46 single spore isolates (SSIs) from crosses of two homozygous strains are used to develop a panel of SNP markers. Then the RNA sequence were used to characterize the gene expression profiles. The RNA were extracted from cultures grown on softwood-enriched sawdust to induce lignocellulolytic enzymes and CCR de-repression genes. To assess the genetic contribution to enzyme expression variations among the 46 SSIs, associations between SNPs and gene expressions were examined genome-widely. 5148 local eQTLs and 7738 distant eQTLs were obtained. By analyzing these eQTLs, the potential regulatory factors of the CAZymes expression and the de-repression of Carbon Catabolism Repression (CCR) were identified,.The eQTL network is characterized in terms of hotspots, evolutionary age and post-translational modifications (PTMs). In the eQTL network of C. cinerea, the non-regulatory genes are younger than the regulatory genes. The proteins regulated by combinational multiple types of PTMs are more likely to function as super regulatory hotspots in protein-protein interactions. The evolutionary age analysis and the PTMome analysis could serve as alternative methods to identify master regulators from genomic data.This work demonstrates a comprehensive bioinformatics approach to identify regulatory factors with next-generation sequencing data. The results provide candidate genes for bioengineering to increase the enzyme production, which will practically benefit the bioethanol production from lignocellulose.SignificanceThis eQTL analysis is designed to study the fungal CAZymes and carbon catabolism repression, especially during the mycelium stage.In Coprinopsis cinerea, only the regions near two ends of the chromosomes have high recombination rate, and suitable for family based eQTL analysis.A sugar transporter is a hotspot controlling many CCR genes.CAZymes are not regulated by a master regulator, but by individual regulators. This indicates that CAZymes are under specific regulatory pathways, so can response to specific conditions.In the eQTL network, the rGenes are evolutionarily older, with more types of PTM sites than eGenes.In the eQTL network, the proteins with more types of PTM sites are more likely associated with Information Storage and Processing, and act as super-hub in the network.
Cex1 is a new component of the COPI Golgi-to-vacuole intracellular trafficking machinery
Authors: Enkler Ludovic , de Craene Johann Owen , Rinaldi Bruno , Hammann Philippe , Nureki Osamu , Senger Bruno , Friant Sylvie , Becker Hubert D. 
Published: September 2018

AbstractDuring translational elongation, aminoacylated tRNA are supplied to the ribosome by RNA-interacting proteins. Cex1, a HEAT-containing protein, has been shown to participate to this tRNA channeling by interacting with aminoacylated tRNA during their export from the nucleus. Here, we show that Cex1 is a component of COPI (coatomer complex I) coated vesicles involved in the Golgi-to-vacuole trafficking pathway in Saccharomyces cerevisiae. Cex1 interacts with key components of the COPI coat Sec27, Sec28 and Sec33 proteins. Moreover, fluorescent microscopy indicates that Cex1 is not localized at the nuclear periphery as expected for an effector of nuclear tRNA channeling, but is observed on endosomal trans-Golgi network (TGN) positive structures. This localization relies on the vacuolar protein sorting receptor Vps10. Our data not only resolve the functional ambiguity regarding Cex1 homologues across species, but also point to the possibility to develop yeast-based models to study neurodegenerative disorders linked to the Human Cex1 homologue SCYL1.
Thyroid hormone modulation during zebrafish development recapitulates evolved diversity in danionin jaw protrusion mechanics
Authors: Galindo Demi , Sweet Elly , DeLeon Zoey , Wagner Mitchel , DeLeon Adrian , Carter Casey , McMenamin Sarah , Cooper W. James 
Published: September 2018

AbstractOne of three vertebrates belongs to a fish lineage for which protrusile jaws are a synapomorphy. Identifying the developmental determinants of protrusion ability will improve our understanding of an important area of evolutionary diversification. The high water viscosities experienced by tiny fish larvae inhibit the viability of protrusile jaws. In the zebrafish protrusion does not arise until after metamorphosis. Fish metamorphosis typically includes significant changes in trophic morphology, accompanies a shift in feeding niche and coincides with increased thyroid hormone production. We tested whether thyroid hormone affects the development of zebrafish feeding mechanics. We found that it affected all developmental stages examined, but that these effects were most pronounced after metamorphosis. Thyroid hormone levels affected the development of jaw morphology, feeding mechanics, shape variation and cranial ossification. Adult zebrafish utilize protrusile jaws, but an absence of thyroid hormone eliminated postmetamorphic remodeling of the premaxilla and the premaxillary structure that permits protrusion never formed. The premaxillae of late juvenile and adult zebrafish are similar to those found in the adults of otherDaniospecies. Premaxillae from early juvenile zebrafish and hypothyroid adult zebrafish resemble those from adults in the generaDanionella,DevarioandMicrodevariothat show little to no jaw protrusion.
Candida albicansbiofilms are generally devoid of persister cells
Authors: Denega Iryna , d’Enfert Christophe , Bachellier-Bassi Sophie 
Published: September 2018

AbstractCandida albicansis known for its ability to form biofilms – communities of microorganisms embedded in an extracellular matrix developing on different surfaces. Biofilms are highly tolerant to antifungal therapy. This phenomenon has been partially explained by the appearance of so-called persister cells, phenotypic variants of wild-type cells, capable of surviving very high concentrations of antimicrobial agents. Persister cells inC. albicanswere found exceptionally in biofilms while none were detected in planktonic cultures of this fungus. Yet, this topic remains controversial as others could not observe persister cells in biofilms formed by theC. albicansSC5314 laboratory strain. Due to ambiguous data in the literature, this work aimed to reevaluate the presence of persister cells inC. albicansbiofilms. We demonstrated that isolation ofC. albicans“persister cells” as described previously was likely to be the result of survival of biofilm cells that were not reached by the antifungal. We tested biofilms of SC5314 and its derivatives, as well as 95 clinical isolates, using an improved protocol, demonstrating that persister cells are not a characteristic trait ofC. albicansbiofilms. Although some clinical isolates are able to yield survivors upon the antifungal treatment of biofilms, this phenomenon is rather stochastic and inconsistent.
Quantifying Heterogeneity in the Genetic Architecture of Complex Traits Between Ethnically Diverse Groups using Random Effect Interaction Models
Authors: Veturi Yogasudha , de los Campos Gustavo , Yi Nengjun , Huang Wen , Vazquez Ana I. , Kühnel Brigitte 
Published: September 2018

AbstractIn humans, most genome-wide association studies have been conducted using data from Caucasians and many of the reported findings have not replicated in other populations. This lack of replication may be due to statistical issues (small sample size, confounding) or perhaps more fundamentally to differences in the genetic architecture of traits between ethnically diverse subpopulations. What aspects of the genetic architecture of traits vary between subpopulations and how can this be quantified? We consider studying effect heterogeneity using random-effect Bayesian interaction models. The proposed methodology can be applied using shrinkage and variable selection methods and produces useful information about effect heterogeneity in the form of whole-genome summaries (e.g., SNP-heritability and the average correlation of effects) as well as SNP-specific attributes. Using simulations, we show that the proposed methodology yields (nearly) unbiased estimates of genomic heritability and of the average correlation of effects between groups when the sample size is not too small relative to the number of SNPs used. Subsequently, we used the proposed methodology for the analyses of four complex human traits (standing height, high-density lipoprotein, low-density lipoprotein, and serum urate levels) in European-Americans (EAs) and African-Americans (AAs). The estimated correlations of effects between the two subpopulations was well below unity for all the traits, ranging from 0.73 to 0.50. The extent of effect heterogeneity varied between traits and SNP-sets. Height showed less differences in SNP effects between AAs and EAs whereas HDL, a trait highly influenced by life-style, exhibited greater extent of effect heterogeneity. For all the traits we observed substantial variability in effect heterogeneity across SNPs, suggesting it varies between regions of the genome.
Distinct spread of DNA and RNA viruses among mammals amid prominent role of domestic species
Authors: Wells Konstans , Morand Serge , Wardeh Maya , Baylis Matthew 
Published: September 2018

AbstractEmerging infectious diseases arising from pathogen spillover from mammals to humans comprise a substantial health threat. Tracing virus origin and predicting the most likely host species for future spillover events are major objectives in One Health disciplines. However, the species that share pathogens most widely with other mammals, and the role of different wildlife groups in sharing viruses with humans remain poorly identified. To address this challenge, we applied network analysis and Bayesian hierarchical models to a global database of mammal-virus associations. We show that domesticated mammals and some primates hold the most central positions in networks of known mammal-virus associations. We revealed strong evidence that DNA viruses were phylogenetically more host specific than RNA viruses, while the frequencies of sharing viruses among hosts and the proportion of zoonotic viruses in hosts were larger for RNA than DNA viruses. Among entire host-virus networks, Carnivora and Chiroptera hold central positions for mainly sharing RNA viruses with other host species, while network centrality of Primates scored relatively high for sharing DNA viruses. Ungulates hold central positions for sharing both RNA and DNA viruses. Acknowledging the role of domestic species in addition to host and virus traits in patterns of virus sharing is necessary to improve our understanding of virus spread and spillover in times of global change.
Agent-Based Modeling Demonstrates How Local Chemotactic Behavior Can Shape Biofilm Architecture
Authors: Sweeney Emily G. , Nishida Andrew , Weston Alexandra , Bañuelos Maria S. , Potter Kristin , Conery John , Guillemin Karen 
Published: September 2018

AbstractMature bacterial biofilms have elaborate three-dimensional architectures that endow these structures with their durability and resistance to environmental perturbations. We used agent-based modeling to explore whether local cellular interactions were sufficient to give rise to global structural features of biofilms. Specifically, we asked whether chemorepulsion from a self-produced quorum-sensing molecule, autoinducer-2 (AI-2), was sufficient to recapitulate biofilm growth and cellular organization observed for biofilms of the human pathogen Helicobacter pylori. To carry out this modeling, we modified an existing platform, Individual-based Dynamics of Microbial Communities Simulator (iDynoMiCS), to incorporate three-dimensional chemotaxis, planktonic cells that could join or leave the biofilm structure, and cellular production of AI-2. We simulated biofilm growth of previously characterized H. pylori strains with varying AI-2 production and sensing capacities. Using biologically plausible parameters, we were able to recapitulate both the variation in biofilm mass and cellular distributions observed with these strains. Specifically, the strains that were competent to chemotax away from AI-2 produced smaller and more heterogeneously spaced biofilms, whereas the AI-2 chemotaxis defective strains produced larger and more homogeneously spaced biofilms. The model also provided new insights into the cellular demographics contributing to the biofilm patterning of each strain. Our analysis supports the idea that cellular interactions at small spatial and temporal scales are sufficient to give rise to larger scale emergent properties of biofilms.ImportanceMost bacteria exist in aggregated, three-dimensional structures called biofilms. Biofilms are resistant to antimicrobials and can pose societal problems, for example when they grow in plumbing systems or on medical implants. Understanding the processes that promote the growth and disassembly of biofilms could lead to better strategies to manage these structures. We had previously shown that Helicobacter pylori bacteria are repulsed by high concentrations of a self-produced molecule, autoinducer-2 (AI-2) and that H. pylori mutants deficient in AI-2 sensing form larger and more homogeneously spaced biofilms. Here we used computer simulations of biofilm formation to show that local H. pylori behavior of repulsion from high AI-2 could explain the overall architecture of H. pylori biofilms. Our findings demonstrate that it is possible to change global biofilm organization by manipulating local cell behaviors, which suggests that simple strategies targeting cells at local scales could be useful for controlling biofilms in industrial and medical settings.
Single fiber proteomics of respiratory chain defects in mitochondrial disorders
Authors: Murgia Marta , Tan Jing , Geyer Philipp E. , Doll Sophia , Mann Matthias , Klopstock Thomas 
Published: September 2018

AbstractMitochondrial DNA mutations progressively compromise the respiratory chain of skeletal muscle, resulting in a mosaic of metabolically healthy and defective fibers. The single fiber investigation of this important diagnostic feature has been beyond the capability of large-scale technologies so far. We used laser capture microdissection (LCM) to excise thin sections of individual muscle fibers from frozen biopsies of patients suffering from chronic progressive external ophthalmoplegia. We then applied a highly sensitive mass spectrometry (MS)-based proteomics workflow to analyze healthy and defective muscle fibers within the same biopsy. We quantified more than 4000 proteins in each patient, covering 75% of all respiratory chain subunits, and compared their expression in metabolically healthy and defective muscle fibers. Our findings show that mitochondrial disease causes extensive proteomic rearrangements, affecting the OPA1-dependent cristae remodeling pathway and mitochondrial translation. We provide fiber type-specific information showing that increased expression of fatty acid oxidation enzymes occurs in defective slow but not fast muscle fibers. Our findings shed light on compensatory mechanisms in muscle fibers that struggle with energy shortage and metabolic stress.
Cationic charge and polyspecificity of an integrin domain regulates infectivity of malaria parasites
Authors: Klug Dennis , Goellner Sarah , Sattler Julia , Strauss Leanne , Kehrer Jessica , Beyer Konrad , Reinig Miriam , Singer Mirko , Lu Chafen , Springer Timothy A. , Frischknecht Friedrich 
Published: September 2018

AbstractCell-cell and cell-substrate adhesion is critical for many functions in life. In eukaryotes, I-domains mediate functions as divergent as tissue traversal by malaria-causingPlasmodiumparasites as well as cell adhesion and migration by human leucocytes. The I-domain containing protein TRAP is important forPlasmodiumsporozoite motility and invasion. Here we show that the I-domain of TRAP is required to mediate adhesional properties which can be partially preserved when the native I-domain is replaced by I-domains from human integrins or from an apicomplexan parasite that does not infect insects. By putting in vivo data and structural features in perspective we conclude that polyspecificity and positive charge around the ligand binding site of the I-domain are important for TRAP function. Our data suggest a highly preserved functionality of I-domains across eukaryotic evolution that is used by apicomplexan parasites to invade a broad range of tissues in a variety of hosts.
Policy lessons from spatiotemporal enrollment patterns of Payment for Ecosystem Service Programs in Argentina
Authors: Núñez-Regueiro Mauricio M. , Branch Lyn C. , Hiller Josh , Núñez Godoy Cristina , Siddiqui Sharmin , Volante José , Soto José R. 
Published: September 2018

AbstractOver the last 50 years, payment for ecosystem services schemes (PES) have been lauded as a market-based solution to curtail deforestation and restore degraded ecosystems. However, PES programs often fail to conserve sites under strong long-term deforestation pressures and allocate financial resources without having a sizeable impact on long-term land use change. Underperformance, in part, is likely due to adverse selection as landowners with land at the lowest threat from conversion or loss may be most likely to enroll or enrollment may be for short time-periods. Improving program performance to overcome adverse selection requires understanding attributes of landowners and their land across large scales to identify spatial and temporal enrollment patterns that drive adverse selection. In this paper, we examine these patterns in Argentina’s PES program in the endangered Chaco forest ecoregion, which was established in 2007 under the National Forest Law. Our study area covers 252,319 km2. Among our most important findings is that large parcels of enrolled land and land owned by absentee landowners show greater evidence of spatiotemporal adverse selection than smaller plots of land and land owned by local actors. Furthermore, lands managed for conservation and restoration are more likely to be associated with adverse selection than lands that provide financial returns such as harvest of non-timber forest products, silviculture, and silvopasture. However, prior to recommending that PES programs focus on land uses with higher potential earnings, a greater understanding is needed of the degree to which these land uses meet ecological and biodiversity goals of PES programs. Because of this, we posit that a PES incorporating a market-based compensation strategy that varies with commodity prices, along with approaches that provide incentives for conservation and restoration land uses and enrollment of local landowners, could promote long-term conservation of endangered lands.
Hierarchical structure and memory retrieval mechanisms in agreement attraction
Authors: Franck Julie , Wagers Matthew 
Published: September 2018

AbstractSpeakers occasionally cause the verb to agree with an element that is not the subject, a so-called ‘attractor’; likewise, comprehenders occasionally fail to notice agreement errors when the attractor agrees with the verb. Cross-linguistic studies converge in showing that attraction is modulated by the hierarchical position of the attractor in the sentence structure. We report two experiments exploring the link between structural position and memory representations in attraction. The method used is innovative in two respects: we used jabberwocky materials to control for semantic influences and focus on structural agreement processing, and we used a Speed-Accuracy Trade-off (SAT) design combined with a memory probe recognition task, as classically used in list memorization tasks. SAT allowed us to investigate the full time-course of processing and it enabled the joint measurement of retrieval speed and retrieval accuracy. Experiment 1 first established that attraction arises in jabberwocky sentences, to a similar extent and following the same structure-dependency as in natural sentences. Experiment 2 showed a close alignment between the attraction profiles found in Experiment 1 and memory parameters. Results support a content-addressable architecture of memory representations for sentences in which nouns’ accessibility depends on their syntactic position, while subjects are kept in the focus of attention.
The Oligomerization Landscape of Histones
Authors: Zhao Haiqing , Winogradoff David , Dalal Yamini , Papoian Garegin A. 
Published: September 2018

ABSTRACTIn eukaryotes, DNA is packaged within nucleosomes. The DNA of each nucleosome is typically centered around an octameric histone protein core: one central tetramer plus two separate dimers. Studying the assembly mechanisms of histones is essential for understanding the dynamics of entire nucleosomes and higher-order DNA packaging. Here we investigate canonical histone assembly and that of the centromere-specific histone variant CENP-A using molecular dynamics simulations. We quantitatively characterize their thermodynamical and dynamical features, showing that two H3/H4 dimers form a structurally floppy, weakly-bound complex, the latter exhibiting large instability around the central interface manifested via a swiveling motion of two halves. This finding is consistent with the recently observed DNA handedness flipping of the tetrasome. In contrast, the variant CENP-A encodes distinctive stability to its tetramer with a rigid but twisted interface compared to the crystal structure, implying diverse structural possibilities of the histone variant. Interestingly, the observed tetramer dynamics alter significantly and appear to reach a new balance when H2A/H2B dimers are present. Furthermore, we found that the preferred structure for the (CENP-A/H4)2 tetramer is incongruent with the octameric structure, explaining many of the unusual dynamical behaviors of the CENP-A nucleosome. In all, these data reveal key mechanistic insights and structural details for the assembly of canonical and variant histone tetramers and octamers, providing theoretical quantifications and physical interpretations for longstanding and recent experimental observations. Based on these findings, we propose different chaperone-assisted binding and nucleosome assembly mechanisms for the canonical and CENP-A histone oligomers.
BRICseq bridges brain-wide interregional connectivity to neural activity and gene expression in single animals
Authors: Huang Longwen , Kebschull Justus M , Furth Daniel , Musall Simon , Kaufman Matthew T , Churchland Anne K , Zador Anthony M 
Published: September 2018

SummaryComprehensive analysis of neuronal networks requires brain-wide measurement of connectivity, activity, and gene expression. Although high-throughput methods are available for mapping brain-wide activity and transcriptomes, comparable methods for mapping region-to-region connectivity remain slow and expensive because they require averaging across hundreds of brains. Here we describe BRICseq, which leverages DNA barcoding and sequencing to map connectivity from single individuals in a few weeks and at low cost. Applying BRICseq to the mouse neocortex, we find that region-to-region connectivity provides a simple bridge relating transcriptome to activity: The spatial expression patterns of a few genes predict region-to-region connectivity, and connectivity predicts activity correlations. We also exploited BRICseq to map the mutant BTBR mouse brain, which lacks a corpus callosum, and recapitulated its known connectopathies. BRICseq allows individual laboratories to compare how age, sex, environment, genetics and species affect neuronal wiring, and to integrate these with functional activity and gene expression.