bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Bayesian Networks for Genomic Prediction of Developmental Traits in Biomass Sorghum
Authors: dos Santos Jhonathan P. R. , Fernandes Samuel B. , Lozano Roberto , Brown Patrick J. , Buckler Edward S. , Garcia Antonio A. F. , Gore Michael A. 
Published: June 2019

ABSTRACTThe ability to connect genetic information between traits over time allow Bayesian networks to offer a powerful probabilistic framework to construct genomic prediction models. In this study, we phenotyped a diversity panel of 869 biomass sorghum (Sorghum bicolor(L.) Moench] lines, which had been genotyped with 100,435 SNP markers, for plant height (PH) with biweekly measurements from 30 to 120 days after planting (DAP) and for end-of-season dry biomass yield (DBY) in four environments. We evaluated five genomic prediction models: Bayesian network (BN), Pleiotropic Bayesian network (PBN), Dynamic Bayesian network (DBN), multi-trait GBLUP (MTr-GBLUP), and multi-time GBLUP (MTi-GBLUP) models. In 5-fold cross-validation, prediction accuracies ranged from 0.48 (PBN) to 0.51 (MTr-GBLUP) for DBY and from 0.47 (DBN, DAP120) to 0.74 (MTi-GBLUP, DAP60) for PH. Forward-chaining cross-validation further improved prediction accuracies of the DBN, MTi-GBLUP and MTr-GBLUP models for PH (training slice: 30-45 DAP) by 36.4-52.4% relative to the BN and PBN models. Coincidence indices (target: biomass, secondary: PH) and a coincidence index based on lines (PH time series) showed that the ranking of lines by PH changed minimally after 45 DAP. These results suggest a two-level indirect selection method for PH at harvest (first-level target trait) and DBY (second-level target trait) could be conducted earlier in the season based on ranking of lines by PH at 45 DAP (secondary trait). With the advance of high-throughput phenotyping technologies, our proposed two-level indirect selection framework could be valuable for enhancing genetic gain per unit of time when selecting on developmental traits.
Accurate inference of the full base-pairing structure of RNA by deep mutational scanning and covariation-induced deviation of activity
Authors: Zhang Zhe , Xiong Peng , Zhang Tongchuan , Wang Junfeng , Zhan Jian , Zhou Yaoqi 
Published: June 2019

ABSTRACTDespite the transcription of noncoding RNAs in 75% of the human genome and their roles in many diseases include cancer, we know very little about them due to lack of structural clues. The centerpiece of the structural clues is the full RNA base-pairing structure of secondary and tertiary contacts that can be precisely obtained only from costly and inefficient 3D structure determination. Here, we performed deep mutational scanning of self-cleaving CPEB3 ribozyme by error-prone PCR and showed that a library of <5×104 single-to-triple mutants is sufficient to infer all 26 including nonhelical and noncanonical base pairs at the precision of a single false positive. The accurate inference, further confirmed by a twister ribozyme, is resulted from covariation analysis by utilizing both functional and nonfunctional variants for unsupervised learning, followed by restrained optimization. The result highlights the usefulness of deep mutational scanning for high-accuracy structural inference.
DeepTetrad: high-throughput analysis of meiotic tetrads by deep learning in plants
Authors: Lim Eun-Cheon , Kim Jaeil , Park Jihye , Kim Eun-Jung , Kim Juhyun , Cho Hyun Seob , Byun Dohwan , Henderson Ian R , Copenhaver Gregory P , Hwang Ildoo , Choi Kyuha 
Published: June 2019

AbstractMeiotic crossovers facilitate chromosome segregation and create new combinations of alleles in gametes. Crossover frequency varies along chromosomes and crossover interference limits the coincidence of closely spaced crossovers. Crossovers can be measured by observing the inheritance of linked transgenes expressing different colors of fluorescent protein in Arabidopsis pollen tetrads. Here we establish DeepTetrad, a deep learning-based image recognition package for pollen tetrad analysis that enables high-throughput measurements of crossover frequency and interference in individual plants. DeepTetrad will accelerate genetic dissection of mechanisms that control meiotic recombination.
Genetic diversity of Collaborative Cross mice controls viral replication, clinical severity and brain pathology induced by Zika virus infection, independently of Oas1b
Authors: Manet Caroline , Simon-Lorière Etienne , Jouvion Grégory , Hardy David , Prot Matthieu , Flamand Marie , Panthier Jean-Jacques , Sakuntabhai Anavaj , Montagutelli Xavier 
Published: June 2019

ABSTRACTThe explosive spread of Zika virus (ZIKV) has been associated with major variations in severe disease and congenital afflictions among infected populations, suggesting an influence of host genes. We investigated how genome-wide variants could impact susceptibility to ZIKV infection in mice. We first describe that the susceptibility of Ifnar1 knockout mice is largely influenced by their genetic background. We then show that the broad genetic diversity of Collaborative Cross mice, which receptor to type I interferon (IFNAR) was blocked by anti-IFNAR antibody, expressed phenotypes ranging from complete resistance to severe symptoms and death with large variations in the peak and rate of decrease of plasma viral load, in brain viral load, in brain histopathology and in viral replication rate in infected cells. Differences of susceptibility between CC strains were correlated between Zika, Dengue and West Nile viruses. We identified highly susceptible and resistant mouse strains as new models to investigate the mechanisms of human ZIKV disease and other flavivirus infections. Genetic analyses revealed that phenotypic variations are driven by multiple genes with small effects, reflecting the complexity of ZIKV disease susceptibility in human population. Notably, our results rule out a role of the Oas1b gene in the susceptibility to ZIKV. Altogether, this study emphasizes the role of host genes in the pathogeny of ZIKV infection and lays the foundation for further genetic and mechanistic studies.IMPORTANCEIn recent outbreaks, ZIKV has infected millions of people and induced rare but potentially severe complications, including Guillain-Barré syndrome and encephalitis in adults. While several viral sequence variants were proposed to enhance the pathogenicity of ZIKV, the influence of host genetic variants in the clinical heterogeneity remains mostly unexplored. We have addressed this question using a mouse panel which models the genetic diversity of human population and a ZIKV strain from a recent clinical isolate. Through a combination of in vitro and in vivo approaches, we demonstrate that multiple host genetic variants determine viral replication in infected cells, and clinical severity, kinetics of blood viral load and brain pathology in mice. We describe new mouse models expressing high susceptibility or resistance to ZIKV and to other flaviviruses. These models will facilitate the identification and mechanistic characterization of host genes that influence ZIKV pathogenesis.
Adaptive evolution targets a piRNA precursor transcription network
Authors: Parhad Swapnil S. , Yu Tianxiong , Zhang Gen , Rice Nicholas P. , Weng Zhiping , Theurkauf William E. 
Published: June 2019

SUMMARYInDrosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but thecuffgene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show thatDrosophila simulans cuffis a dominant negative allele when expressed inDrosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP in stable nuclear complexes. Cuff promotes Rhino and Deadlock localization, driving non-canonical transcription. CtBP, by contrast, suppresses canonical cluster and transposon transcription, which interferes with downstream non-canonical transcription and piRNA production. Cuff, TRF2 and CtBP thus form a network that balances canonical and non-canonical piRNA precursor transcription.
The Goldilocks effect of lake size on within-population diversity in stickleback
Authors: Bolnick Daniel I. , Ballare Kimberly 
Published: June 2019

AbstractMany generalist species consist of disparate specialized individuals, a phenomenon known as ‘individual specialization’. This within-population niche variation can stabilize population dynamics, reduce extinction risk, and alter community composition. But, we still only vaguely understand the ecological contexts that promote niche variation and its stabilizing effects. Adaptive dynamics models predict that intraspecific variation should be greater in environments with two or more equally-profitable resources, but reduced in environments dominated by one resource. Here, we confirm this prediction using a comparison of threespine stickleback in 33 lakes in on Vancouver Island, Canada. Stickleback consume a combination of benthic and limnetic invertebrates, focusing on the former in small lakes, the latter in large lakes. Intermediate-sized lakes support generalist populations, which arise via greater among-individual diet variation, not by greater individual diet breadth. These intermediate lakes exhibit correspondingly greater morphological diversity, while genomic diversity increases linearly with lake size. These results support the theoretical expectation that habitats with an intermediate ratio of resources are “just right” for promoting ecologically relevant intraspecific diversification.
A chromosome folding intermediate at the condensin-to-cohesin transition during telophase
Authors: Abramo Kristin , Valton Anne-Laure , Venev Sergey V. , Ozadam Hakan , Fox A. Nicole , Dekker Job 
Published: June 2019

SummaryChromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient folding intermediate devoid of most loops forms. By late telophase, cohesin-mediated CTCF-CTCF loops and positions of TADs start to emerge rapidly. Compartment boundaries are also established in telophase, but long-range compartmentalization is a slow process and proceeds for several hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin and cohesin driven chromosome folding.
The draft nuclear genome assembly ofEucalyptus pauciflora: new approaches to comparingde novoassemblies
Authors: Wang Weiwen , Das Ashutosh , Kainer David , Schalamun Miriam , Morales-Suarez Alejandro , Schwessinger Benjamin , Lanfear Robert 
Published: June 2019

AbstractBackgroundSelecting the best genome assembly from a collection of draft assemblies for the same species remains a difficult task. Here, we combine new and existing approaches to help to address this, using the non-model plantEucalyptus pauciflora(snow gum) as a test case.Eucalyptus pauciflorais a long-lived tree with high economic and ecological importance. Currently, little genomic information forEucalyptus pauciflorais available.FindingsWe generated high coverage of long-(Nanopore, 174x) and short-(Illumina, 228x) read data from a singleEucalyptus paucifloraindividual and compared assemblies from four assemblers with a variety of settings: Canu, Flye, Marvel, and MaSuRCA. A key component of our approach is to keep a randomly selected collection of ~10% of both long- and short-reads separate from the assemblies to use as a validation set with which to assess the assemblies. Using this validation set along with a range of existing tools, we compared the assemblies in eight ways: contig N50, BUSCO scores, LAI scores, assembly ploidy, base-level error rate, computing genome assembly likelihoods, structural variation and genome sequence similarity. Our result showed that MaSuRCA generated the best assembly, which is 594.87 Mb in size, with a contig N50 of 3.23 Mb, and an estimated error rate of ~0.006 errors per base.ConclusionsWe report a draft genome ofEucalyptus pauciflora, which will be a valuable resource for further genomic studies of eucalypts. These approaches for assessing and comparing genomes should help in assessing and choosing among many potential genome assemblies for a single species.
Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
Authors: Akamatsu Matthew , Vasan Ritvik , Serwas Daniel , Ferrin Michael , Rangamani Padmini , Drubin David G. 
Published: June 2019

SUMMARYForce generation due to actin assembly is a fundamental aspect of membrane sculpting for many essential processes. In this work, we use a multiscale computational model constrained by experimental measurements to show that a minimal branched actin network is sufficient to internalize endocytic pits against physiological membrane tension. A parameter sweep identified the number of Arp2/3 complexes as particularly important for robust internalization, which prompted the development of a molecule-counting method in live mammalian cells. Using this method, we found that ~200 Arp2/3 complexes assemble at sites of clathrin-mediated endocytosis in human cells. Our simulations also revealed that actin networks self-organize in a radial branched array with barbed filament ends oriented to grow toward the base of the pit, and that the distribution of linker proteins around the endocytic pit is critical for this organization. Surprisingly, our model predicted that long actin filaments bend from their attachment sites in the coat to the base of the pit and store elastic energy that can be harnessed to drive endocytosis. This prediction was validated using cryo-electron tomography on cells, which revealed the presence of bent actin filaments along the endocytic site. Furthermore, we predict that under elevated membrane tension, the self-organized actin network directs more growing filaments toward the base of the pit, increasing actin nucleation and bending for increased force production. Thus, our study reveals that spatially constrained actin filament assembly utilizes an adaptive mechanism that enables endocytosis under varying physical constraints.
Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
Authors: Turner Matthew L. , Owens Sian E. , Sheldon I. Martin 
Published: June 2019

AbstractPathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.
Hepatitis E Virus infection and waste pickers: a case-control seroprevalence study
Authors: Alvarado-Esquivel Cosme , Gutierrez-Martinez Verónica Dayali , Ramírez-Valles Eda Guadalupe , Sifuentes-Alvarez Antonio 
Published: June 2019

AbstractWhether waste pickers are a risk group for hepatitis E virus (HEV) infection is largely unknown. Therefore, this study aimed to determine the association between HEV exposure and: 1) the occupation of waste picker; and 2) the work characteristics of waste pickers. An age-and gender-matched case-control seroprevalence study of 86 waste pickers (mean age: 35.45 ± 17.15 years) and 86 control subjects of the general population was performed. We determined anti-HEV IgG antibodies in sera of cases and controls using a commercially available enzyme-linked immunoassay. The McNemar’s test was used to assess the association between HEV seropositivity and the occupation of waste picker. The association between HEV seropositivity and work characteristics of waste pickers was assessed by bivariate and regression analyses. Anti-HEV IgG antibodies were detected in 14 (16.3%) of the 86 waste pickers and in 8 (9.3%) of the 86 control subjects (McNemar’s pair test: OR = 13.0; 95% CI: 0.73-230.77; P=0.02). Ill waste pickers had a higher HEV seroprevalence than those who were apparently healthy (6/15: 40% vs 8/71: 11.3%, respectively: P=0.01). Waste pickers with reflexes impairment had a higher HEV seroprevalence than those without this impairment (5/10: 50% and 9/76: 11.8%, respectively; P=0.009). Logistic regression analysis of sociodemographic, work, and behavioral characteristics of waste pickers showed that HEV seropositivity was associated with increasing age (OR = 6.52; 95% CI: 1.95-21.78; P=0.002) and raising pigs (OR = 12.01; 95% CI: 1.48-97.26; P=0.02). This is the first age- and gender-matched case-control study on the association between HEV infection and the occupation of waste picker. Waste pickers represent a risk group for HEV infection. Factors associated with HEV seropositivity found in this study may help in the design of optimal planning to avoid HEV infection.
Stochastic transcription in the p53-mediated response to DNA damage is modulated by burst frequency
Authors: Friedrich Dhana , Friedel Laura , Herrmann Andreas , Preibisch Stephan , Loewer Alexander 
Published: June 2019

ABSTRACTDiscontinuous transcription has been described for different mammalian cell lines and numerous promoters. However, our knowledge of how the activity of individual promoters is adjusted by dynamic signaling inputs from transcription factor is limited. To address this question, we characterized the activity of selected target genes that are regulated by pulsatile accumulation of the tumor suppressor p53 in response to ionizing radiation. We performed time resolved measurements of gene expression at the single cell level by smFISH and used the resulting data to inform a mathematical model of promoter activity. We found that p53 target promoters are regulated by frequency modulation of stochastic bursting and can be grouped along three archetypes of gene expression. The occurrence of these archetypes cannot solely be explained by nuclear p53 abundance or promoter binding of total p53. Instead, we provide evidence that the time-varying acetylation state of p53’s C-terminal lysine residues is critical for gene-specific regulation of stochastic bursting.
Determine the optimal capital structure of BOT projects using interval numbers with Tianjin Binhai New District Metro Z4 line in China as an example
Authors: Wang Yuning , Jin Xiaohua 
Published: June 2019

Purpose
Various factors may influence project finance when a multi-sourced debt financing strategy is used for financing capital investments, in general, and public infrastructure investments, in particular. Traditional indicators lack comprehensive consideration of the influences of many internal and external factors, such as investment structure, financing mode and credit guarantee structure, which exist in the financing decision making of BOT projects. An effective approach is, thus, desired. The paper aims to discuss these issues.

Design/methodology/approach
This paper develops a financial model that uses an interval number to represent the uncertain factors and, subsequently, conducts a standardization of the interval number. Decision makers determine the weight of each objective through the analytic hierarchy process. Through the optimization procedure, project investors and sponsors are provided with a strategy regarding the optimal amount of debt to be raised and the insight on the risk level based on the net present value, as well as the probability of bankruptcy for each different period of debt service.

Findings
By using an example infrastructure project in China and based on the comprehensive evaluation, comparison and ranking of the capital structures of urban public infrastructure projects using the interval number method, the final ranking can help investors to choose the optimal capital structure for investment. The calculation using the interval number method shows that X2 is the optimal capital structure plan for the BOT project of the first stage of Tianjin Binhai Rail Transit Z4 line. Therefore, investors should give priority to selecting a capital contribution ratio of 45 per cent for this investment.

Research limitations/implications
In this paper, some parameters, such as depreciation life, construction period and concession period, are assumed to be deterministic parameters, although the interval number model has been introduced to analyze the uncertainty indicators, such as total investment and passenger flow, of BOT rail transport projects. Therefore, more of the above deterministic parameters can be taken as uncertainty parameters in future research so that calculation results fit actual projects more closely.

Originality/value
This model can be used to make the optimal investment decision for a project by determining the impact of uncertainty factors on the profitability of the project in its lifecycle during the project financial feasibility analysis. Project sponsors can determine the optimal capital structure of a project through an analysis of the irregular fluctuation of the unpredictable factors in project construction such as construction investment, operating cost and passenger flow. The model can also be used to examine the effects of different capital investment ratios on indicators so that appropriate measures can be taken to reduce risks and maximize profit.