bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs
Authors: Carlevaro-Fita Joana , Polidori Taisia , Das Monalisa , Navarro Carmen , Zoller Tatjana I. , Johnson Rory 
Published: September 2017

AbstractThe sequence domains underlying long noncoding RNA (lncRNA) activities, including their characteristic nuclear enrichment, remain largely unknown. It has been proposed that these domains can originate from neofunctionalised fragments of transposable elements (TEs), otherwise known as RIDLs (Repeat Insertion Domains of Long Noncoding RNA), although just a handful have been identified. It is challenging to distinguish functional RIDL instances against a numerous genomic background of neutrally-evolving TEs. We here show evidence that a subset of TE types experience evolutionary selection in the context of lncRNA exons. Together these comprise an enrichment group of 5374 TE fragments in 3566 loci. Their host lncRNAs tend to be functionally validated and associated with disease. This RIDL group was used to explore the relationship between TEs and lncRNA subcellular localisation. Using global localisation data from ten human cell lines, we uncover a dose-dependent relationship between nuclear/cytoplasmic distribution, and evolutionarily-conserved L2b, MIRb and MIRc elements. This is observed in multiple cell types, and is unaffected by confounders of transcript length or expression. Experimental validation with engineered transgenes shows that these TEs drive nuclear enrichment in a natural sequence context. Together these data reveal a role for TEs in regulating the subcellular localisation of lncRNAs.
The Role Of Circle Of Willis Anatomy Variations In Cardio-embolic Stroke - A Patient-specific Simulation Based Study
Authors: Mukherjee Debanjan , Jani Neel D. , Narvid Jared , Shadden Shawn C. 
Published: September 2017

AbstractWe describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.
Catecholaminergic modulation of the avoidance of cognitive control
Authors: Froböse Monja I. , Swart Jennifer C. , Cook Jennifer L. , Geurts Dirk E.M. , den Ouden Hanneke E.M. , Cools Roshan 
Published: September 2017

AbstractThe catecholamines have long been associated with cognitive control and value-based decision-making. More recently, we proposed that the catecholamines might modulate value-based decision-making about whether or not to engage in cognitive control. We test this hypothesis by assessing effects of a catecholamine challenge in a large sample of young, healthy adults (n = 100) on the avoidance of a cognitively demanding control process: task switching. Prolonging catecholamine transmission by blocking reuptake with methylphenidate altered the avoidance, but not the execution of cognitive control. Crucially, these effects could be isolated by taking into account individual differences in trait impulsivity, so that participants with higher trait impulsivity became more avoidant of cognitive control, despite faster task performance. One implication of these findings is that performance-enhancing effects of methylphenidate may be accompanied by an undermining effect on the willingness to exert cognitive control. Taken together, these findings integrate hitherto segregated literatures on catecholamines’ roles in value-based learning/choice and cognitive control.
High-Throughput Identification of Genetic Variation Impact on pre-mRNA Splicing Efficiency
Authors: Adamson Scott I. , Zhan Lijun , Graveley Brenton R. 
Published: September 2017

AbstractUnderstanding the functional impact of genomic variants is a major goal of modern genetics and personalized medicine. Although many synonymous and non-coding variants act through altering the efficiency of pre-mRNA splicing, it is difficult to predict how these variants impact pre-mRNA splicing. Here, we describe a massively parallel approach we used to test the impact of 2,059 human genetic variants spanning 110 alternative exons on pre-mRNA splicing. This method yields data that reinforces known mechanisms of pre-mRNA splicing, can rapidly identify genomic variants that impact pre-mRNA splicing, and will be useful for increasing our understanding of genome function.
Binge-like Acquisition of α-pyrrolidinopentiophenone (α-PVP) Self-Administration in Female Rats
Authors: Javadi-Paydar Mehrak , Harvey Eric L. , Grant Yanabel , Vandewater Sophia A. , Creehan Kevin M. , Nguyen Jacques D. , Dickerson Tobin J. , Taffe Michael A. 
Published: September 2017

AbstractThe synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with violent and/or bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a closely related drug, 3,4-methylenedioxypyrovalerone. The binge-like acquisition pattern appeared to be novel for rat IVSA, thus the present study was designed to determine if this effect generalizes to IVSA of α-PVP in female rats. Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers that contained an activity wheel. Groups of animals were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel-access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel-access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. This confirms the high reinforcer efficacy of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.
Lipid-Uptake Pathways and Lipid-Protein interactions in P-glycoprotein Revealed by Coarse-Grained Molecular Dynamics Simulations
Authors: Barreto-Ojeda E. , Corradi V. , Gu R.-X. , Tieleman D.P. 
Published: September 2017

AbstractP-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids and lipid-like molecules. Due to its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance (MDR). Although P-gp is one of the most studied members of ABC-transporters, the mechanism of how its substrates access the cavity remains unclear. In this work, we performed coarse-grained (CG) molecular dynamics (MD) simulations to explore possible pathways of lipid-uptake in the inward-facing conformation of P-gp embedded in bilayers with different PC:PE lipid ratios. Our results show that in the inward facing orientation only lipids from the lower leaflet are taken up by the transporter. We identify positively charged residues at the portals of P-gp that favor lipid entrance to the cavity, as well as lipid binding sites, in good agreement with previous experimental studies. Our results show no selectivity for PC vs. PE lipids. We offer several examples of lipid uptake-pathways for PC and PE lipids that help to elucidate the molecular mechanism of substrate-uptake in P-gp.
MEBS, a software platform to evaluate large (meta)genomic collections according to their metabolic machinery: unraveling the sulfur cycle
Authors: Anda Valerie De , Zapata-Peñasco Icoquih , Poot-Hernandez Augusto Cesar , Eguiarte Luis E. , Contreras-Moreira Bruno , Souza Valeria 
Published: September 2017

BACKGROUNDThe increasing number of metagenomic and genomic sequences has dramatically improved our understanding of microbial diversity, yet our ability to infer metabolic capabilities in such datasets remains challenging.FINDINGSWe describe the Multigenomic Entropy Based Score pipeline (MEBS), a software platform designed to evaluate, compare and infer complex metabolic pathways in large ‘omic’ datasets, including entire biogeochemical cycles. MEBS is open source and available throughhttps://github.com/eead-csic-compbio/metagenome_Pfam_score. To demonstrate its use we modeled the sulfur cycle by exhaustively curating the molecular and ecological elements involved (compounds, genes, metabolic pathways and microbial taxa). This information was reduced to a collection of 112 characteristic Pfam protein domains and a list of complete-sequenced sulfur genomes. Using the mathematical framework of relative entropy(H’),we quantitatively measured the enrichment of these domains among sulfur genomes. The entropy of each domain was used to both: build up a final score that indicates whether a (meta)genomic sample contains the metabolic machinery of interest and to propose marker domains in metagenomic sequences such as DsrC (PF04358). MEBS was benchmarked with a dataset of 2,107 non-redundant microbial genomes from RefSeq and 935 metagenomes from MG-RAST. Its performance, reproducibility, and robustness were evaluated using several approaches, including random sampling, linear regression models, Receiver Operator Characteristic plots and the Area Under the Curve metric (AUC). Our results support the broad applicability of this algorithm to accurately classify (AUC=0.985) hard to culture genomes (e.g.,Candidatus Desulforudis audaxviator),previously characterized ones and metagenomic environments such as hydrothermal vents, or deep-sea sediment.CONCLUSIONSOur benchmark indicates that an entropy-based score can capture the metabolic machinery of interest and be used to efficiently classify large genomic and metagenomic datasets, including uncultivated/unexplored taxa
Genetic diversity and mother-child overlap of the gut associated microbiota determined by reduced genome sequencing
Authors: Ravi Anuradha , Avershina Ekaterina , Angell Inga Leena , Ludvigsen Jane , Manohar Prashanth , Padmanaban Sumathi , Nachimuthu Ramesh , Rudi Knut 
Published: September 2017

ABSTRACTThe genetic diversity and sharing of the mother-child associated microbiota remain largely unexplored. This severely limits our functional understanding of gut microbiota transmission patterns. The aim of our work was therefore to use a novel reduced metagenome sequencing in combination with shotgun and 16S rRNA gene sequencing to determine both the metagenome genetic diversity and the mother-to-child sharing of the microbiota. For a cohort of 17 mother-child pairs we found an increase of the collective metagenome size from about 100 Mbp for 4-day-old children to about 500 Mbp for mothers. The 4-day-old children shared 7% of the metagenome sequences with the mothers, while the metagenome sequence sharing was more than 30% among the mothers. We found 15 genomes shared across more than 50% of the mothers, of which 10 belonged toClostridia. OnlyBacteroidesshowed a direct mother-child association, withB. vulgatusbeing abundant in both 4-day-old children and mothers. In conclusion, our results support a common pool of gut bacteria that are transmitted from adults to infants, with most of the bacteria being transmitted at a stage after delivery.
Lipid-protein interactions are unique fingerprints for membrane proteins
Authors: Corradi Valentina , Mendez-Villuendas Eduardo , Ingólfsson Helgi I. , Gu Ruo-Xu , Siuda Iwona , Melo Manuel N. , Moussatova Anastassiia , Degagné Christine , Sejdiu Besian I. , Singh Gurpreet , Wassenaar Tsjerk A. , Magnero Karelia Delgado , Marrink Siewert J. , Tieleman D. Peter 
Published: September 2017

ABSTRACTCell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.
Comprehensive analysis of central carbon metabolism reveals multiple connections between nutrients, biosynthetic capacity, and cell morphology inEscherichia coli
Authors: Westfall Corey S. , Levin Petra Anne 
Published: September 2017

AbstractBacterial morphology is a complex trait that is highly sensitive to changes in the environment. For heterotrophic organisms, such asEscherichia coli, increases in nutrient levels are frequently accompanied by several-fold increases in both size and growth rate. Despite the dramatic nature of these changes, how alterations in nutrient availability translate into changes in growth and morphology remains a largely open question. To understand the signaling networks coupling nutrient availability with size and shape, we examined the impact of deletions in the entirety of non-essential central carbon metabolic genes onE. coligrowth rate and cell size. Our data reveal the presence of multiple metabolic nodes that play important yet distinctive roles in shaping the cell. Consistent with recent work from our lab and others, although both are sensitive to nutrient availability, size and growth rate vary independently. Cell width and length also appear to be independent phenomena, influenced by different aspects of central carbon metabolism. These findings highlight the diversity of factors that can impact cell morphology and provide a foundation for further studies.Author summaryOften taken for granted, the shape of bacterial cells is a complex trait that is highly sensitive to environmental perturbations. Nutrients in particular, strongly impact bacterial morphology together with growth rate. The ubiquitous, rod-shaped bacteriaEscherichia coliincreases both length and width several fold upon a shift from nutrient poor to nutrient rich medium, a change accompanied by an equally dramatic increase in growth rate. Central carbon metabolism is an obvious site for the integration of nutrient dependent signals that dictate cell size and shape. To develop a clearer picture of the molecular mechanisms coupling nutrient assimilation with cell growth and morphology, we screened the entirety of nonessential carbon metabolic genes for their contribution to growth rate and cell shape. Our data reveal the presence of multiple regulatory circuits coordinating different metabolic pathways with specific aspects of cell growth and morphology. Together, these data firmly establish a role for central carbon metabolism as an environmentally sensitive sculptor of bacterial cells.
A Sequel to Sanger: Amplicon Sequencing That Scales
Authors: Hebert Paul DN , Braukmann Thomas WA , Prosser Sean WJ , Ratnasingham Sujeevan , deWaard Jeremy R , Ivanova Natalia V , Janzen Daniel H , Hallwachs Winnie , Naik Suresh , Sones Jayme E , Zakharov Evgeny V 
Published: September 2017

ABSTRACTAlthough high-throughput sequencers (HTS) have largely displaced their Sanger counterparts, the short read lengths and high error rates of most platforms constrain their utility for amplicon sequencing. The present study tests the capacity of single molecule, real-time (SMRT) sequencing implemented on the SEQUEL platform to overcome these limitations, employing 658 bp amplicons of the mitochondrial cytochromecoxidase I gene as a model system. By examining templates from more than 5,000 species and 20,000 specimens, the performance of SMRT sequencing was tested with amplicons showing wide variation in GC composition and varied sequence attributes. SMRT and Sanger sequences were very similar, but SMRT sequencing provided more complete coverage, especially for amplicons with homopolymer tracts. Because it can characterize amplicon pools from 10,000 DNA extracts in a single run, the SEQUEL reduces costs 40-fold from Sanger analysis. Reflecting the capacity of each instrument to recover sequences from more than five million DNA extracts a year, this platform facilitates massive amplicon characterization.
BioSankey: Visualizing microbial communities and gene expression data over time
Authors: Platzer Alexander , Polzin Julia , Han Ping Penny , Rembart Klaus , Nussbaumer Thomas 
Published: September 2017

AbstractMetagenomics, RNA-seq, WGS (Whole Genome Sequencing) and other types of next-generation sequencing techniques provide quantitative measurements for single strains and genes over time. To obtain a global overview of the experiment and to explore the full potential of a given dataset, intuitive and interactive visualization tools are needed. Therefore, we establishedBioSankey, which allows to visualize microbial species in microbiome studies and gene expression over time as a Sankey diagram. These diagrams are embedded into a project-specific HTML page, that contains all information as provided during the installation process.BioSankeycan be easily applied to analyse bacterial communities in time-series datasets. Furthermore, it can be used to analyse the fluctuations of differentially expressed genes (DEG). The output ofBioSankeyis a project-specific HTML page, which depends only on JavaScript to enable searches of interesting species or genes of interest without requiring a web server or connection to a database to exchange results among collaboration partners.BioSankeyis a tool to visualize different data elements from single and dual RNA-seq datasets as well as from metagenomes studies.
Impaired hippocampal representation of place in theFmr1-knockout mouse model of Fragile X syndrome
Authors: Arbab Tara , Pennartz Cyriel MA , Battaglia Francesco P 
Published: September 2017

AbstractFragile X syndrome (FXS) is an X-chromosome linked intellectual disability and the most common genetic cause of autism spectrum disorder (ASD). Building upon demonstrated deficits in neuronal plasticity and spatial memory in FXS, we investigated how spatial information processing is affectedin vivoin an FXS mouse model (Fmr1-KO). Healthy hippocampal neurons (so-called place cells) exhibit place-related activity during spatial exploration, and the stability of these spatial representations can be taken as an index of memory function. We find impaired stability and reduced specificity ofFmr1-KO spatial representations. This is a potential biomarker for the cognitive dysfunction observed in FXS, informative on the ability to integrate sensory information into an abstract representation and successfully retain this conceptual memory. Our results provide key insight into the biological mechanisms underlying cognitive disabilities in FXS and ASD, paving the way for a targeted approach to remedy these.
Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches
Authors: Ciernia Annie Vogel , Laufer Benjamin I. , Dunaway Keith W. , Mordaunt Charles E. , Coulson Rochelle L. , Totah Theresa S. , Stolzenberg Danielle S. , Frahm Jaime , Singh-Taylor Akanksha , Baram Tallie Z. , LaSalle Janine M. , Yasui Dag H. 
Published: September 2017

AbstractBackgroundMaternal care during early-life plays a crucial role in the sculpting of the mammalian brain. Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this potent phenotypic change commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood.MethodsHere, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression.ResultsA significant decrease in global DNA methylation was observed in offspring hypothalamus following a week of augmented maternal care, corresponding to differential methylation and expression of thousands of genes. Differentially methylated and expressed genes were enriched for functions in neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation, as well as known stress response genes. Twenty prioritized genes with three lines of evidence (methylation, expression, and altered miRNA target) were identified as highly relevant to the stress resiliency phenotype.ConclusionsThis combined unbiased approach enabled the discovery of novel genes and gene pathways that advance our understanding of the central epigenomic mechanisms underlying the profound effects of maternal care on the developing brain.
A Dynamic Bayesian Observer Model Reveals Origins of Bias in Visual Path Integration
Authors: Lakshminarasimhan Kaushik J , Petsalis Marina , Park Hyeshin , DeAngelis Gregory C , Pitkow Xaq , Angelaki Dora E 
Published: September 2017

ABSTRACTPath integration is a navigation strategy by which animals track their position by integrating their self-motion velocity over time. To identify the computational origins of bias in visual path integration, we asked human subjects to navigate in a virtual environment using optic flow, and found that they generally travelled beyond the goal location. Such a behaviour could stem from leaky integration of unbiased self-motion velocity estimates, or from a prior expectation favouring slower speeds that causes underestimation of velocity. We tested both alternatives using a probabilistic framework that maximizes expected reward, and found that subjects’ biases were better explained by a slow-speed prior than imperfect integration. When subjects integrate paths over long periods, this framework intriguingly predicts a distance-dependent bias reversal due to build-up of uncertainty, which we also confirmed experimentally. These results suggest that visual path integration performance is limited largely by biases in processing optic flow rather than by suboptimal signal integration.