bluuebunny/crossref_metadata_2025_split huggingface dataset:
A low-mass triple system with a wide L/T transition brown dwarf component: NLTT 51469AB/SDSS 2131−0119
Authors: Gauza B , Béjar V J S , Pérez-Garrido A , Lodieu N , Rebolo R , Zapatero Osorio M R , Pantoja B , Velasco S , Jenkins J S 
Published: May 2019

Abstract
We demonstrate that the previously identified L/T transition brown dwarf SDSS J213154.43−011939.3 (SDSS 2131−0119) is a widely separated (82${^{\prime\prime}_{.}}$3, ∼3830 au) common proper motion companion to the low-mass star NLTT 51469, which we reveal to be a close binary itself, separated by 0${^{\prime\prime}_{.}}$64 ± 0${^{\prime\prime}_{.}}$01 (∼30 au). We find the proper motion of SDSS 2131−0119 of μαcos δ = −100 ± 20 mas yr−1 and μδ = −230 ± 20 mas yr−1 consistent with the proper motion of the primary provided by Gaia DR2: μαcos δ = −95.49 ± 0.96 mas yr−1 and μδ = −239.38 ± 0.96 mas yr−1. Based on optical and near-infrared spectroscopy, we classify the primary NLTT 51469A as an M3 ± 1 dwarf, estimate photometrically the spectral type of its close companion NLTT 51469B at ∼M6, and confirm the spectral type of the brown dwarf to be L9 ± 1. Using radial velocity, proper motion, and parallax, we derived the UVW Galactic space velocities of NLTT 51469A, showing that the system does not belong to any known young stellar moving group. The high V, W velocities, lack of a 670.8 nm Li i absorption line, and absence of H α emission, detected X-rays, or UV excess, indicate that the system is likely a member of the thin disc population and is older than 1 Gyr. For the parallactic distance of 46.6 ± 1.6 pc from Gaia DR2, we determined luminosities of $-1.50^{+0.02}_{-0.04}$ and −4.4 ± 0.1 dex of the M3 and L9, respectively. Considering the spectrophotometric estimation, which yields a slightly lower distance of $34^{+10}_{-13}$ pc, the obtained luminosities are $-1.78^{+0.02}_{-0.04}$ and $-4.7^{+0.3}_{-0.5}$ dex. We also estimated their effective temperatures and masses, and obtained 3410$^{+140}_{-210}$ K and 0.42 ± 0.02 M⊙ for the primary, and 1400–1650 K and 0.05–0.07 M⊙ for the wide companion. For the ∼M6 component, we estimated Teff = 2850 ± 200 K and m = 0.10$^{+0.06}_{-0.01}$ M⊙.
Assembly bias evidence in close galaxy pairs
Authors: Ferreras I , Hopkins A M , Lagos C , Sansom A E , Scott N , Croom S , Brough S 
Published: May 2019

ABSTRACT
The growth channel of massive galaxies involving mergers can be studied via close pairs as putative merger progenitors, where the stellar populations of the satellite galaxies will be eventually incorporated into the massive primaries. We extend our recent analysis of the GAMA-based sample of close pairs presented in Ferreras et al. to the general spectroscopic data set of SDSS galaxies (DR14), for which the high S/N of the data enables a detailed analysis of the differences between satellite galaxies with respect to the mass of the primary galaxy. A sample of approximately 2000 satellites of massive galaxies is carefully selected within a relatively narrow redshift range (0.07&lt;z&lt;0.14). Two main parameters are considered as major drivers of the star formation history of these galaxies, namely: the stellar velocity dispersion of the satellite (σ), as a proxy of ‘local’ drivers, and the ratio between the stellar mass of the satellite and the primary, μ = MSAT/MPRI, meant to serve as an indicator of environment. Consistently with the independent, GAMA-based work, we find that satellites around the most massive primaries appear older, at fixed velocity dispersion, than satellites of lower mass primaries. This trend is more marked in lower mass satellites (σ ∼ 100 km s−1), with SSP-equivalent age differences up to ∼0.5 Gyr, and can be interpreted as a one-halo assembly bias, so that satellites corresponding to smaller values of μ represent older structures, akin to fossil groups.
Many Options, Few Solutions: Over 60 My Snakes Converged on a Few Optimal Venom Formulations
Authors: Barua Agneesh , Mikheyev Alexander S 
Published: May 2019

AbstractGene expression changes contribute to complex trait variations in both individuals and populations. However, the evolution of gene expression underlying complex traits over macroevolutionary timescales remains poorly understood. Snake venoms are proteinaceous cocktails where the expression of each toxin can be quantified and mapped to a distinct genomic locus and traced for millions of years. Using a phylogenetic generalized linear mixed model, we analyzed expression data of toxin genes from 52 snake species spanning the 3 venomous snake families and estimated phylogenetic covariance, which acts as a measure of evolutionary constraint. We find that evolution of toxin combinations is not constrained. However, although all combinations are in principle possible, the actual dimensionality of phylomorphic space is low, with envenomation strategies focused around only four major toxin families: metalloproteases, three-finger toxins, serine proteases, and phospholipases A2. Although most extant snakes prioritize either a single or a combination of major toxin families, they are repeatedly recruited and lost. We find that over macroevolutionary timescales, the venom phenotypes were not shaped by phylogenetic constraints, which include important microevolutionary constraints such as epistasis and pleiotropy, but more likely by ecological filtering that permits a small number of optimal solutions. As a result, phenotypic optima were repeatedly attained by distantly related species. These results indicate that venoms evolve by selection on biochemistry of prey envenomation, which permit diversity through parallelism, and impose strong limits, since only a few of the theoretically possible strategies seem to work well and are observed in extant snakes.
IAMBEE: a web-service for the identification of adaptive pathways from parallel evolved clonal populations
Authors: Perez-Romero Camilo Andres , Weytjens Bram , Decap Dries , Swings Toon , Michiels Jan , De Maeyer Dries , Marchal Kathleen 
Published: May 2019

Abstract
IAMBEE is a web server designed for the Identification of Adaptive Mutations in Bacterial Evolution Experiments (IAMBEE). Input data consist of genotype information obtained from independently evolved clonal populations or strains that show the same adapted behavior (phenotype). To distinguish adaptive from passenger mutations, IAMBEE searches for neighborhoods in an organism-specific interaction network that are recurrently mutated in the adapted populations. This search for recurrently mutated network neighborhoods, as proxies for pathways is driven by additional information on the functional impact of the observed genetic changes and their dynamics during adaptive evolution. In addition, the search explicitly accounts for the differences in mutation rate between the independently evolved populations. Using this approach, IAMBEE allows exploiting parallel evolution to identify adaptive pathways. The web-server is freely available at http://bioinformatics.intec.ugent.be/iambee/ with no login requirement.
IEDB-AR: immune epitope database—analysis resource in 2019
Authors: Dhanda Sandeep Kumar , Mahajan Swapnil , Paul Sinu , Yan Zhen , Kim Haeuk , Jespersen Martin Closter , Jurtz Vanessa , Andreatta Massimo , Greenbaum Jason A , Marcatili Paolo , Sette Alessandro , Nielsen Morten , Peters Bjoern 
Published: May 2019

AbstractThe Immune Epitope Database Analysis Resource (IEDB-AR, http://tools.iedb.org/) is a companion website to the IEDB that provides computational tools focused on the prediction and analysis of B and T cell epitopes. All of the tools are freely available through the public website and many are also available through a REST API and/or a downloadable command-line tool. A virtual machine image of the entire site is also freely available for non-commercial use and contains most of the tools on the public site. Here, we describe the tools and functionalities that are available in the IEDB-AR, focusing on the 10 new tools that have been added since the last report in the 2012 NAR webserver edition. In addition, many of the tools that were already hosted on the site in 2012 have received updates to newest versions, including NetMHC, NetMHCpan, BepiPred and DiscoTope. Overall, this IEDB-AR update provides a substantial set of updated and novel features for epitope prediction and analysis.
Histone H4 H75E mutation attenuates global genomic and Rad26-independent transcription-coupled nucleotide excision repair
Authors: Selvam Kathiresan , Rahman Sheikh Arafatur , Li Shisheng 
Published: May 2019

AbstractNucleotide excision repair (NER) consists of global genomic NER (GG-NER) and transcription coupled NER (TC-NER) subpathways. In eukaryotic cells, genomic DNA is wrapped around histone octamers (an H3–H4 tetramer and two H2A–H2B dimers) to form nucleosomes, which are well known to profoundly inhibit the access of NER proteins. Through unbiased screening of histone H4 residues in the nucleosomal LRS (loss of ribosomal DNA-silencing) domain, we identified 24 mutations that enhance or decrease UV sensitivity of Saccharomyces cerevisiae cells. The histone H4 H75E mutation, which is largely embedded in the nucleosome and interacts with histone H2B, significantly attenuates GG-NER and Rad26-independent TC-NER but does not affect TC-NER in the presence of Rad26. All the other histone H4 mutations, except for T73F and T73Y that mildly attenuate GG-NER, do not substantially affect GG-NER or TC-NER. The attenuation of GG-NER and Rad26-independent TC-NER by the H4H75E mutation is not due to decreased chromatin accessibility, impaired methylation of histone H3 K79 that is at the center of the LRS domain, or lowered expression of NER proteins. Instead, the attenuation is at least in part due to impaired recruitment of Rad4, the key lesion recognition and verification protein, to chromatin following induction of DNA lesions.
A post-transcriptional respiratome regulon in trypanosomes
Authors: Trenaman Anna , Glover Lucy , Hutchinson Sebastian , Horn David 
Published: May 2019

Abstract
Post-transcriptional regulons coordinate the expression of groups of genes in eukaryotic cells, yet relatively few have been characterized. Parasitic trypanosomatids are particularly good models for studies on such mechanisms because they exhibit almost exclusive polycistronic, and unregulated, transcription. Here, we identify the Trypanosoma brucei ZC3H39/40 RNA-binding proteins as regulators of the respiratome; the mitochondrial electron transport chain (complexes I–IV) and the FoF1-ATP synthase (complex V). A high-throughput RNAi screen initially implicated both ZC3H proteins in variant surface glycoprotein (VSG) gene silencing. This link was confirmed and both proteins were shown to form a cytoplasmic ZC3H39/40 complex. Transcriptome and mRNA-interactome analyses indicated that the impact on VSG silencing was indirect, while the ZC3H39/40 complex specifically bound and stabilized transcripts encoding respiratome-complexes. Quantitative proteomic analyses revealed specific positive control of >20 components from complexes I, II and V. Our findings establish a link between the mitochondrial respiratome and VSG gene silencing in bloodstream form T. brucei. They also reveal a major respiratome regulon controlled by the conserved trypanosomatid ZC3H39/40 RNA-binding proteins.
NMD-Based Gene Regulation—A Strategy for Fitness Enhancement in Plants?
Authors: Ohtani Misato , Wachter Andreas 
Published: May 2019

Abstract
Post-transcriptional RNA quality control is a vital issue for all eukaryotes to secure accurate gene expression, both on a qualitative and quantitative level. Among the different mechanisms, nonsense-mediated mRNA decay (NMD) is an essential surveillance system that triggers degradation of both aberrant and physiological transcripts. By targeting a substantial fraction of all transcripts for degradation, including many alternative splicing variants, NMD has a major impact on shaping transcriptomes. Recent progress on the transcriptome-wide profiling and physiological analyses of NMD-deficient plant mutants revealed crucial roles for NMD in gene regulation and environmental responses. In this review, we will briefly summarize our current knowledge of the recognition and degradation of NMD targets, followed by an account of NMD’s regulation and physiological functions. We will specifically discuss plant-specific aspects of RNA quality control and its functional contribution to the fitness and environmental responses of plants.
Salt-Responsive Genes are Differentially Regulated at the Chromatin Levels Between Seedlings and Roots in Rice
Authors: Zheng Dongyang , Wang Lei , Chen Lifen , Pan Xiucai , Lin Kande , Fang Yuan , Wang Xiu-e , Zhang Wenli 
Published: May 2019

Abstract
The elucidation of epigenetic responses of salt-responsive genes facilitates understanding of the underlying mechanisms that confer salt tolerance in rice. However, it is still largely unknown how epigenetic mechanisms are associated with the expression of salt-responsive genes in rice and other crops. In this study, we reported tissue-specific gene expression and tissue-specific changes in chromatin modifications or signatures between seedlings and roots in response to salt treatment. Our study indicated that among six of individual mark examined (H3K4me3, H3K27me3, H4K12ac, H3K9ac, H3K27ac and H3K36me3), a positive association between salt-related changes in histone marks and the expression of differentially expressed genes (DEGs) was observed only for H3K9ac and H4K12ac in seedlings and H3K36me3 in roots. In contrast, chromatin states (CSs) with combinations of six histone modification marks played crucial roles in the differential expression of salt-responsive genes between seedlings and roots. Most importantly, CS7 containing the bivalent marks H3K4me3 and H3K27me3, with a mutual exclusion of functions with each other, displayed distinct functions in the expression of DEGs in both tissues. Specifically, H3K27me3 in CS7 mainly suppressed the expression of DEGs in roots, while H3K4me3 affected the expression of down- and up-regulated genes, possibly by antagonizing the repressive role of H3K27me3 in seedlings. Our findings indicate distinct impacts of the CSs on the differential expression of salt-responsive genes between seedlings and roots in rice, which provides an important background for understanding chromatin-based epigenetic mechanisms that might confer salt tolerance in plants.
Fc-gamma receptors and S100A8/A9 cause bone erosion during rheumatoid arthritis. Do they act as partners in crime?
Authors: Di Ceglie Irene , Kruisbergen Nik N L , van den Bosch Martijn H J , van Lent Peter L E M 
Published: May 2019

AbstractBone erosion is one of the central hallmarks of RA and is caused by excessive differentiation and activation of osteoclasts. Presence of autoantibodies in seropositive arthritis is associated with radiographic disease progression. ICs, formed by autoantibodies and their antigens, activate Fcγ-receptor signalling in immune cells, and as such stimulate inflammation-mediated bone erosion. Interestingly, ICs can also directly activate osteoclasts by binding to FcγRs on their surface. Next to autoantibodies, high levels of alarmins, among which is S100A8/A9, are typical for RA and they can further activate the immune system but also directly promote osteoclast function. Therefore, IC-activated FcγRs and S100A8/A9 might act as partners in crime to stimulate inflammation and osteoclasts differentiation and function, thereby stimulating bone erosion. This review discusses the separate roles of ICs, FcγRs and alarmins in bone erosion and sheds new light on the possible interplay between them, which could fuel bone erosion.
Treatment failure in inflammatory arthritis: time to think about syndemics?
Authors: Nikiphorou Elena , Lempp Heidi , Kohrt Brandon A. 
Published: May 2019

AbstractSocial determinants of health play a crucial role in health and disease. In current times, it has become increasingly known that biological and non-biological factors are potentially linked and help to drive disease. For example, links between various comorbidities, both physical and mental illnesses, are known to be driven by social, environmental and economic determinants. This contributes to worse disease outcomes. This article discusses the concept of syndemics, which although well-described in some conditions, represents a novel concept in the context of rheumatic and musculoskeletal diseases. Written in the form of a viewpoint, the article focuses on a novel theoretical framework for studying inflammatory arthritis, based on a syndemic approach that takes into account the social context, biocultural disease interaction, and socio-economic characteristics of the setting. Syndemics involving inflammatory arthritis may be most likely in a social context involving limited access to health care, lack of physical activity and obesogenic diets, high rates of alcohol consumption, and high exposure to stressful life events.
Statistical Comparison of Trait-Dependent Biogeographical Models Indicates That Podocarpaceae Dispersal Is Influenced by Both Seed Cone Traits and Geographical Distance
Authors: Klaus Kristina V , Matzke Nicholas J 
Published: May 2019

Abstract
The ability of lineages to disperse long distances over evolutionary timescales may be influenced by the gain or loss of traits adapted to enhance local, ecological dispersal. For example, some species in the southern conifer family Podocarpaceae have fleshy cones that encourage bird dispersal, but it is unknown how this trait has influenced the clade’s historical biogeography, or its importance compared with other predictors of dispersal such as the geographic distance between regions. We answer these questions quantitatively by using a dated phylogeny of 197 species of southern conifers (Podocarpaceae and their sister family Araucariaceae) to statistically compare standard, trait-independent biogeography models with new BioGeoBEARS models where an evolving trait can influence dispersal probability, and trait history, biogeographical history, and model parameters are jointly inferred. We validate the method with simulation-inference experiments. Comparing all models, those that include trait-dependent dispersal accrue 87.5% of the corrected Akaike Information Criterion (AICc) model weight. Averaged across all models, lineages with nonfleshy cones had a dispersal probability multiplier of 0.49 compared with lineages with fleshy cones. Distance is included as a predictor of dispersal in all credible models (100% model weight). However, models with changing geography earned only 22.0% of the model weight, and models submerging New Caledonia/New Zealand earned only 0.01%. The importance of traits and distance suggests that long-distance dispersal over macroevolutionary timespans should not be thought of as a highly unpredictable chance event. Instead, long-distance dispersal can be modeled, allowing statistical model comparison to quantify support for different hypotheses.
A Phenome-wide Mendelian Randomisation study on genetically determined serum urate levels in UK Biobank cohort
Authors: Li Xue , Meng Xiangrui , He Yazhou , Spiliopoulou Athina , Timofeeva Maria , Wei Wei-Qi , Gifford Aliya , Yang Tian , Varley Tim , Tzoulaki Ioanna , Joshi Peter , Denny Joshua C. , Mckeigue Paul , Campbell Harry , Theodoratou Evropi 
Published: May 2019

ABSTRACTIntroductionThe role of serum urate level has been extensively investigated in observational studies. However, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.ObjectivesTo explore any causal or pleiotropic association between serum urate level and a broad spectrum of disease outcomes.MethodsPhenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic models (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 UK Biobank participants. Mendelian Randomisation (MR) analyses were performed to replicate significant findings using various GWAS consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for serum urate.ResultsPheWAS analysis, examining the association with 1,431 disease outcomes, identified a multitude of disease outcomes including gout, hypertension, hypercholesterolemia, and heart diseases (e.g., coronary atherosclerosis, myocardial infarction, and ischaemic heart disease) that were associated (p<3.35e-04) with genetically determined serum urate levels. TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases and blood lipid levels, but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with cardiovascular diseases.ConclusionsHigh serum urate levels are associated with different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a more distal mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.
B-SIDER: Computational Algorithm for the Design of Complementary β-sheet Sequences
Authors: Yu Tae-Geun , Kim Hak-Sung , Choi Yoonjoo 
Published: May 2019

AbstractThe β-sheet is an element of protein secondary structure, and intra-/inter-molecular β-sheet interactions play pivotal roles in biological regulatory processes including scaffolding, transporting, and oligomerization. In nature, a β-sheet formation is tightly regulated because dysregulated β-stacking often leads to severe diseases such as Alzheimer’s, Parkinson’s, systemic amyloidosis, or diabetes. Thus, the identification of intrinsic β-sheet forming propensities can provide valuable insight into protein designs for the development of novel therapeutics. However, structure-based design methods may not be generally applicable to such amyloidogenic peptides mainly owing to high structural plasticity and complexity. Therefore, an alternative design strategy based on complementary sequence information is of significant importance. Herein, we developed a database search method called B-SIDER for the design of complementary β-strands. This method makes use of the structural database information and generates query-specific score matrices. The discriminatory power of the B-SIDER score function was tested on representative amyloidogenic peptide substructures against a sequence-based score matrix (PASTA2.0) and two popularab initioprotein design score functions (Rosetta and FoldX). B-SIDER is able to distinguish wild-type amyloidogenic β-strands as favored interactions in a more consistent manner than other methods. B-SIDER was prospectively applied to the design of complementary β-strands for a splitGFP scaffold. Three variants were identified to have stronger interactions than the original sequence selected through a directed evolution, emitting higher fluorescence intensities. Our results indicate that B-SIDER can be applicable to the design of other β-strands, assisting in the development of therapeutics against disease-related amyloidogenic peptides.