bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing RNA stability genome-wide through combined analysis of PRO-seq and RNA-seq data
Authors: Blumberg Amit , Zhao Yixin , Huang Yi-Fei , Dukler Noah , Rice Edward J. , Chivu Alexandra G. , Krumholz Katie , Danko Charles G. , Siepel Adam 
Published: July 2019

AbstractThe rate at which RNA molecules decay is a key determinant of cellular RNA concentrations, yet current approaches for measuring RNA half-lives are generally labor-intensive, limited in sensitivity, and/or disruptive to normal cellular processes. Here we introduce a simple method for estimating relative RNA half-lives that is based on two standard and widely available high-throughput assays: Precision Run-On and sequencing (PRO-seq) and RNA sequencing (RNA-seq). Our method treats PRO-seq as a measure of transcription rate and RNA-seq as a measure of RNA concentration, and estimates the rate of RNA decay required for a steady-state equilibrium. We show that this approach can be used to assay relative RNA half-lives genome-wide, with good accuracy and sensitivity for both coding and noncoding transcription units. Using a structural equation model (SEM), we test several features of transcription units, nearby DNA sequences, and nearby epigenomic marks for associations with RNA stability after controlling for their effects on transcription. We find that RNA splicing-related features are positively correlated with RNA stability, whereas features related to miRNA binding, DNA methylation, and G+C-richness are negatively correlated with RNA stability. Furthermore, we find that a measure based on U1-binding and polyadenylation sites distinguishes between unstable noncoding and stable coding transcripts but is not predictive of relative stability within the mRNA or lincRNA classes. We also identify several histone modifications that are associated with RNA stability. Together, our estimation method and systematic analysis shed light on the pervasive impacts of RNA stability on cellular RNA concentrations.
Genomic selection analyses reveal tradeoff between chestnut blight tolerance and genome inheritance from American chestnut (Castanea dentata) in (C. dentataxC. mollissima) xC. dentatabackcross populations
Authors: Westbrook Jared W. , Zhang Qian , Mandal Mihir K. , Jenkins Eric V. , Barth Laura E. , Jenkins Jerry W. , Grimwood Jane , Schmutz Jeremy , Holliday Jason A. 
Published: July 2019

AbstractAmerican chestnut was once a foundation species of eastern North American forests, but was rendered functionally extinct in the early 20th century by an exotic fungal blight (Cryphonectria parasitica). Over the past 30 years, The American Chestnut Foundation (TACF) has pursued backcross breeding to generate hybrids that combine the timber-type form of American chestnut with the blight tolerance of Chinese chestnut. The backcross strategy has been implemented based on the hypothesis that blight tolerance is conferred by few major effect alleles. We tested this hypothesis by developing genomic prediction models for five presence/absence blight phenotypes of 1,230 BC3F2selection candidates and average canker severity of their BC3F3progeny. We also genotyped pure Chinese and American chestnut reference panels to estimate the proportion of BC3F2genomes inherited from parent species. We found that genomic prediction from a method that assumes an infinitesimal model of inheritance (HBLUP) has a similar predictive ability to a method that tends to perform well for traits controlled by major genes (Bayes C). Furthermore, the proportion of BC3F2trees’ genomes inherited from American chestnut was negatively correlated with the blight tolerance of BC3F2trees and their progeny. On average, selected BC3F2trees inherited 83% of their genome from American chestnut and have blight-tolerance that is intermediate between F1hybrids and American chestnut. Results suggest polygenic rather than major gene inheritance for blight tolerance. The blight-tolerance of restoration populations will be enhanced by advancing additional sources of blight-tolerance through fewer backcross generations and by potentially by breeding with transgenic blight-tolerant trees.
Early life maturation of human visual system white matter is altered by monocular enucleation
Authors: Dunkley Benjamin T. , Vandewouw Marlee , Chakraborty Arijit , Taylor Margot J. , Gallie Brenda , McCulloch Daphne L. , Thompson Benjamin 
Published: July 2019

AbstractMonocular enucleation early in life and the resultant lack of binocular visual input during visual development results in functional and structural brain changes in adulthood, including alterations in white matter microstructure. However, the time courses of these neurodevelopmental changes are unknown. Here, we investigated whether structural brain changes were present at 8 to 12 years of age in a group of children with a history of monocular enucleation prior to 3 years of age (the ME group) relative to control participants with normal binocular vision (the BC group). Structural connectivity was measured using diffusion tensor imaging (DTI). Relative to the BC group, the ME group exhibited significantly increased radial and mean diffusivity in the optic radiation contralateral to the enucleated eye, the bidirectional interhemispheric V1 to V1 tracts and the V1 to MT tract ipsilateral to the enucleated eye. These changes indicate abnormal myelinization and reduced axonal density in subcortical and cortical visual pathway white matter structures following unilateral enucleation and loss of binocular vision. Our findings are broadly consistent with those recently reported for older uniocular individuals suggesting that these effects are present in childhood and persist into adulthood.
Dendritic plateau potentials can process spike sequences across multiple time-scales
Authors: Leugering Johannes , Nieters Pascal , Pipa Gordon 
Published: July 2019

AbstractThe brain constantly processes information encoded in temporal sequences of spiking activity. This sequential activity emerges from sensory inputs as well as from the brain’s own recurrent connectivity and spans multiple dynamically changing timescales. Decoding the temporal order of spiking activity across these varying timescales is a critical function of the brain, but we do not yet understand its neural implementation. The problem is, that the passive dynamics of neural membrane potentials occur on a short millisecond timescale, whereas many cognitive tasks require the integration of information across much slower behavioral timescales. However, actively generated dendritic plateau potentials do occur on such longer timescales, and their essential role for many aspects of cognition has been firmly established by recent experiments. Here, we build on these discoveries and propose a new model of neural computation that emerges from the interaction of localized plateau potentials across a functionally compartmentalized dendritic tree. We show how this interaction offers a robust solution to the timing invariant detection and processing of sequential spike patterns in single neurons. Stochastic synaptic transmission complements the deterministic all-or-none plateau process and improves information transmission by allowing ensembles of neurons to produce graded responses to continuous combinations of features. We found that networks of such neurons can solve highly complex sequence detection tasks by breaking down long inputs into sequences of shorter, random features that can be classified reliably. These results suggest that active dendritic processes are fundamental to neural computation.
ECHO: an Application for Detection and Analysis of Oscillators Identifies Metabolic Regulation on Genome-Wide Circadian Output
Authors: De los Santos Hannah , Collins Emily J. , Mann Catherine , Sagan April W. , Jankowski Meaghan S. , Bennett Kristin P. , Hurley Jennifer M. 
Published: July 2019

AbstractMotivationTime courses utilizing genome scale data are a common approach to identifying the biological pathways that are controlled by the circadian clock, an important regulator of organismal fitness. However, the methods used to detect circadian oscillations in these datasets are not able to accommodate changes in the amplitude of the oscillations over time, leading to an underestimation of the impact of the clock on biological systems.ResultsWe have created a program to efficaciously identify oscillations in large-scale datasets, called the Extended Circadian Harmonic Oscillator application, or ECHO. ECHO utilizes an extended solution of the fixed amplitude mass-spring oscillator that incorporates the amplitude change coefficient. Employing synthetic datasets, we determined that ECHO outperforms existing methods in detecting rhythms with decreasing oscillation amplitudes and recovering phase shift. Rhythms with changing amplitudes identified from published biological datasets revealed distinct functions from those oscillations that were harmonic, suggesting purposeful biologic regulation to create this subtype of circadian rhythms.AvailabilityECHO’s full interface is available athttps://github.com/delosh653/ECHO. An R package for this functionality, echo.find, can be downloaded athttps://CRAN.R-project.org/package=echo.find.Contacthurleyj2@rpi.eduSupplementary informationSupplementary data are available
Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes
Authors: Baldini Federico , Hertel Johannes , Sandt Estelle , Thinnes Cyrille C. , Neuberger-Castillo Lorieza , Pavelka Lukas , Betsou Fay , Krüger Rejko , Thiele Ines ,   on behalf of the NCER-PD Consortium
Published: July 2019

ABSTRACTParkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we first analysed the gut microbiome of patients and healthy controls by 16S rRNA gene sequencing of stool samples from the Luxembourg Parkinson’s study (n=147 typical PD cases, n=162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include: 1. eight genera and nine species changed significantly in their relative abundances between PD patients and healthy controls. 2. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. The relative abundances ofBilophilaandParaprevotellawere significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. In contrast, dopaminergic medication had no detectable effect on the PD microbiome composition. 3. Personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms and attributed to individual bacteria, such asAkkermansia muciniphilaandBilophila wardswarthia. Our results suggest that PD-associated alterations of gut microbiome could translate into functional differences affecting host metabolism and disease phenotype.
Y-chromosome haplotypes are associated with variation in size and age at maturity in male Chinook salmon
Authors: McKinney Garrett J. , Seeb James E , Pascal Carita E. , Schindler Daniel E. , Gilk-Baumer Sara E. , Seeb Lisa W. 
Published: July 2019

ABSTRACTVariation in size and age at maturity is an important component of life history that is influenced both by environmental and genetic factors. In salmonids, large size confers a direct reproductive advantage through increased fecundity and egg quality in females, while larger males gain a reproductive advantage by monopolizing access to females. In addition, variation in size and age at maturity in males can be associated with different reproductive strategies; younger smaller males may gain reproductive success by sneaking in among mating pairs. In both sexes there is a trade-off between older age and increased reproductive success and increased risk of mortality by delaying reproduction. We identified four Y-chromosome haplogroups that showed regional and population-specific variation in frequency using RADseq data for 21 populations of Alaska Chinook salmon. We then characterized the range-wide distribution of these haplogroups using GT-seq assays. These haplogroups exhibited associations with size at maturity in multiple populations suggesting that the lack of recombination between X and Y-chromosomes has allowed Y-chromosome haplogroups to capture different alleles that influence size at maturity. Ultimately, conservation of life history diversity in Chinook salmon may require conservation of Y-chromosome haplotype diversity.
A Mendelian randomization study of the role of lipoprotein subfractions in coronary artery disease
Authors: Zhao Qingyuan , Wang Jingshu , Miao Zhen , Zhang Nancy R , Hennessy Sean , Small Dylan S , Rader Daniel J 
Published: July 2019

AbstractRecent genetic data can offer important insights into the roles of lipoprotein subfractions and particle sizes in preventing coronary artery disease (CAD), as previous observational studies have often reported conflicting results. In this study, we first used the LD score regression to estimate the genetic correlation of 77 subfraction traits with traditional lipid profile and identified 27 traits that may involve distinct genetic mechanisms. We then used Mendelian randomization (MR) to estimate the causal effect of these traits on the risk of CAD. In univariable MR, the concentration and content of medium high-density lipoprotein (HDL) particles showed a protective effect against coronary artery disease. The effect was not attenuated in multivariable MR that adjusted for traditional lipid profile. The multivariable MR analyses also found that small HDL particles and smaller mean HDL particle diameter may have a protective effect. We identified four genetic markers for HDL particle size and CAD.
Unsupervised identification of the internal states that shape natural behavior
Authors: Calhoun Adam J. , Pillow Jonathan W. , Murthy Mala 
Published: July 2019

SummaryInternal states can shape stimulus responses and decision-making, but we lack methods to identify internal states and how they evolve over time. To address this gap, we have developed an unsupervised method to identify internal states from behavioral data, and have applied it to the study of a dynamic social interaction. During courtship, Drosophila melanogaster males pattern their songs using feedback cues from their partner. Our model uncovers three latent states underlying this behavior, and is able to predict the moment-to-moment variation in natural song patterning decisions. These distinct behavioral states correspond to different sensorimotor strategies, each of which is characterized by different mappings from feedback cues to song modes. Using the model, we show that a pair of neurons previously thought to be command neurons for song production are sufficient to drive switching between states. Our results reveal how animals compose behavior from previously unidentified internal states, a necessary step for quantitative descriptions of animal behavior that link environmental cues, internal needs, neuronal activity, and motor outputs.
Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma
Authors: Chen Kok-Siong , Bunt Jens , Bridges Caitlin R. , Lynton Zorana , Lim Jonathan W.C. , Stringer Brett W. , Rajagopal Revathi , Wong Kum-Thong , Ganesan Dharmendra , Ariffin Hany , Day Bryan W. , Richards Linda J. 
Published: July 2019

AbstractAstrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and are associated with a better prognosis. Therefore, inducing cellular differentiation may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation and therefore could be effectors of cellular differentiation in glioblastoma. We analysed expression of family membersNFIAandNFIBusing high-grade astrocytoma mRNA expression datasets, and with immunofluorescence co-staining. Their expression is reduced in glioblastomas and is associated with differentiated and mature astrocyte-like cells at a cellular level. Furthermore, induction of NFI expression is sufficient to promote cellular differentiation in patient-derived glioblastoma xenografts. Our findings indicate that NFI proteins may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal development. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.
Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and employ Mrc1a for cargo uptake
Authors: Padberg Yvonne , van Impel Andreas , van Lessen Max , Bussmann Jeroen , Schulte-Merker Stefan 
Published: July 2019

AbstractBrain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells within the meningeal layer of the zebrafish brain. We previously reported that BLECs efficiently endocytose extracellular cargo molecules (van Lessen et al., 2017), but how this is accomplished and controlled on the molecular level remains unclear. We here compare BLECs to scavenging endothelial cells (SECs) in the embryonic cardinal vein and find them to accept an identical set of substrate molecules. While there is redundancy in the type of scavenger receptors being used, the two cell populations rely for specific substrate molecules on different cell surface receptors to mediate their physiological role: Stab2 appears more critical within SECs in the cardinal vein, while BLECs depend more on the Mrc1a receptor for internalization of cargo. Given the striking similarities to the substrate specificity of cardinal vein SECs, we postulate that BLECs qualify functionally as SECs of the brain.
Are railways detrimental to bird populations? A BDACI study on the construction of the Bothnia Line Railway
Authors: de Jong Adriaan 
Published: July 2019

AbstractRailways, like roads, are commonly considered bad for birdlife, but supporting data are very scarce. We conducted a 14-year before-during-after control-impact (BDACI) study of birds in agricultural landscapes affected by the construction of the Bothnia Line Railway (BLR) in northern Sweden. The “during” phase was split into two phases, one for the true construction period and one for the years when the railway was ready but not trafficked. Avian biodiversity increased in impact sites (N=13), but not in control sites (N=6). The numbers of breeding territories decreased correspondingly in impact and control sites, but trends differed between species and sites. Developments in the Degernäs site demonstrated that mitigation could be successful. Finally, there was no support for a shying-away effect of the BLR. Territory midpoints moved closer rather than away from the railway, albeit with variable patterns for individual sites and species. Mixed effect models showed no differences in avian biodiversity between theConstruction,ReadyandTrafficphases compared withBefore, but relative increases in numbers of territories and decreases in territory midpoint distances to the BLR. The results do not support a general detrimental effect of railway construction on bird populations in terms of biodiversity loss, reduced abundances or shying-away from train traffic. More studies and the development of “Railway Ecology” are badly needed.
Formation of Phage Lysis Patterns and Implications on Co-Propagation of Phages and Motile Host Bacteria
Authors: Li Xiaochu , Gonzalez Floricel , Esteves Nathaniel , Scharf Birgit E. , Chen Jing 
Published: July 2019

AbstractCoexistence of bacteriophages, or phages, and their host bacteria plays an important role in maintaining the microbial communities. In natural environments with limited nutrients, motile bacteria can actively migrate towards locations of richer resources. Although phages are not motile themselves, they can infect motile bacterial hosts and spread in space via the hosts. Therefore, in a migrating microbial community coexistence of bacteria and phages implies their co-propagation in space. Here, we combine an experimental approach and mathematical modeling to explore how phages and their motile host bacteria coexist and co-propagate. When lytic phages encountered motile host bacteria in our experimental set up, a sector-shaped lysis zone formed. Our mathematical model indicates that local nutrient depletion and the resulting inhibition of proliferation and motility of bacteria and phages are the key to formation of the observed lysis pattern. The model further reveals the straight radial boundaries in the lysis pattern as a tell-tale sign for coexistence and co-propagation of bacteria and phages. Emergence of such a pattern, albeit insensitive to extrinsic factors, requires a balance between intrinsic biological properties of phages and bacteria, which likely results from co-evolution of phages and bacteria.Author summaryCoexistence of phages and their bacterial hosts is important for maintaining the microbial communities. In a migrating microbial community, coexistence between phages and host bacteria implies that they co-propagate in space. Here we report a novel phage lysis pattern that is indicative of this co-propagation. The corresponding mathematical model we developed highlights a crucial dependence of the lysis pattern and implied phage-bacteria co-propagation on intrinsic properties allowing proliferation and spreading of the microbes in space. Remarkably, extrinsic factors, such as overall nutrient level, do not influence phage-bacteria coexistence and co-propagation. Findings from this work have strong implications for dispersal of phages mediated by motile bacterial communities, which will provide scientific basis for the fast-growing applications of phages.
Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells
Authors: Weiss-Bilka Holly E. , Meagher Matthew J. , Gargac Joshua A. , Niebur Glen L. , Roeder Ryan K. , Wagner Diane R. 
Published: July 2019

AbstractCollagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate the use of these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model. Cell-seeded constructs were pre-treated with either control or osteogenic media. Cell-free and collagen-only groups were included, as was a clinically approved bone void filler as a control for the material. After 8 weeks implantation, cell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported bone formation and vascular invasion at comparable rates. HA-reinforcement allowed collagen constructs to maintain their implanted shape, provided for improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic induction medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs. Results suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.