bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Importance of Anti-Correlations in Graph Theory Based Classification of Autism Spectrum Disorder
Authors: Kazeminejad Amirali , Sotero Roberto C 
Published: February 2019

AbstractIn recent years, there has been a significant growth in the number of applications of machine learning (ML) techniques to the study and identification of neurological disorders. These methods rely heavily on what features are made available to the ML algorithm. Features such as graph theoretical metrics of resting-state fMRI-based brain networks have proven useful. However, the computation of functional brain networks relies on making an arbitrary choice about whether the obtained anti-correlations, representing the strengths of functional connections in the brain, should be discarded or not. In this study, we examine how this choice affects the performance of a support vector machine (SVM) model for classifying autism spectrum disorder. We extracted graph theoretical features using three different pipelines for constructing the functional network graph. These pipelines primarily used positive weights, negative weights (anti-correlations) and only the absolute value of weights of the correlation matrix derived from fMRI time-series. Our results suggest that in the presence of Global Signal Regression (GSR) the features extracted from anti-correlations play a major role in improving model performance. However, this does not undermine the importance of features from other pipelines.
Brassinosteroids Influence Arabidopsis Hypocotyl Graviresponses Through Changes In Mannans And Cellulose
Authors: Somssich Marc , Vandenbussche Filip , Ivakov Alexander , Funke Norma , Ruprecht Colin , Vissenberg Kris , Van Der Straeten Dominique , Persson Staffan , Suslov Dmitry 
Published: February 2019

AbstractThe force of gravity is a constant environmental factor. Plant shoots respond to gravity through negative gravitropism and gravity resistance. These responses are essential for plants to direct the growth of aerial organs away from the soil surface after germination and to keep an upright posture above ground. We took advantage of the effect of brassinosteroids on the two types of graviresponses inArabidopsis thalianahypocotyls to disentangle functions of cell wall polymers during etiolated shoot growth. The ability of etiolated Arabidopsis seedlings to grow upwards was suppressed in the presence of 24-epibrassinolide (EBL) but enhanced in the presence of brassinazole (BRZ), an inhibitor of brassinosteroid biosynthesis. These effects were accompanied by changes in cell wall mechanics and composition. Cell wall biochemical analyses and confocal microscopy of the cellulose-specific pontamine S4B dye revealed that the EBL and BRZ treatments correlated with changes in cellulose fibre organization and mannan content. Indeed, a longitudinal re-orientation of cellulose fibres supported upright growth whereas the presence of mannans reduced gravitropic bending. The negative effect of mannans on gravitropism is a new function for this class of hemicelluloses, highlighting evolutionary adaptations by which aquatic ancestors of terrestrial plants colonized land.
Short-term consumption of sucralose with, but not without, carbohydrate impairs neural and metabolic sensitivity to sugar
Authors: Dalenberg Jelle R. , Patel Barkha P. , Denis Raphael , Veldhuizen Maria G. , Nakamura Yuko , Vinke Petra C. , Luquet Serge , Small Dana M. 
Published: February 2019

SummaryThere is a general consensus that overconsumption of sugar sweetened beverages contributes to the prevalence of obesity and related comorbidities such as type 2 diabetes (T2D). Whether a similar relationship exists for no, or low-calorie “diet” drinks is a subject of intensive debate and controversy. Here, we show that metabolic dysfunction, coupled with reduced central sensitivity to sweet, but not sour, salty or bitter taste, occurs when sucralose is repeatedly consumed with, but not without, a carbohydrate over a two-week period in healthy humans. A similar exposure to sucralose, with, but not without, a carbohydrate altered substrate utilization in mice. More specifically, greater energy intake was required for the animals to shift from fatty acid to carbohydrate oxidation, indicating a reduced sensitivity to carbohydrate. These findings demonstrate that consumption of sucralose in the presence of a carbohydrate rapidly impairs glucose metabolism and may contribute to the rise in T2D.
Heart rate and its relationship with activity in free-ranging Cheloniidae sea turtles
Authors: Okuyama Junichi , Shiozawa Maika , Shiode Daisuke 
Published: February 2019

AbstractThe primary oxygen stores in Cheloniidae sea turtles are in the lungs. Therefore, management of blood oxygen transportation to peripheral tissues by cardiovascular adjustments while diving is crucial to maximize benefits from dives. However, heart rate, particularly cardiac response to exercise in free-ranging dives, has rarely been examined for sea turtles. In this study, heart rate and its relationship with the amount of activity were determined in six free-ranging green turtles using bio-logging techniques. Our results demonstrated that resting heart rate took 7–11 h to reduce to steady levels after turtles were released in the tank, indicating that turtles may not present normal physiological rates right after release. After heart rate reduction, resting heart rate of green turtles in free-ranging dives was generally low (10.9 ± 2.5 bpm), but they often presented arrhythmia (4–54 bpm) even in resting states. The amount of activity during a dive linearly increased heart rate, but maximum heart rates (39.0–69.8 bpm) were recorded during ventilation at surface. These results indicate that turtles have the capability of cardiac response to increased metabolic demands in their muscles while submerged, and also of cardiovascular adjustment for a rapid renewal of oxygen stores and removal of CO2during ventilation. Such well-organized cardiac adjustments may be because of characteristics of Cheloniidae sea turtles such as ectothermy and oxygen storage in lungs while submerged.Summary statementGreen sea turtles in free-ranging dive had generally lower heart rate compared to other air-breathing divers and it varied with the amount of exercise. Turtles often showed extreme arrhythmia.
Plasmid-based CRISPR-Cas9 gene editing in multipleCandidaspecies
Authors: Lombardi Lisa , Oliveira-Pacheco João , Butler Geraldine 
Published: February 2019

ABSTRACTManyCandidaspecies that cause infection have diploid genomes, and do not undergo classical meiosis. The application of CRISPR-Cas9 gene editing systems have therefore greatly facilitated the generation of gene disruptions, and the introduction of specific polymorphisms. However, CRISPR methods are not yet available for allCandidaspecies. We describe here an adaption of a previously developed CRISPR system inCandida parapsilosisthat uses an autonomously replicating plasmid. Guide RNAs can be introduced in a single cloning step, and are released by cleavage between a tRNA and a ribozyme. The plasmid also containsCAS9and a selectable nourseothricinSAT1marker. It can be used for markerless editing inC. parapsilosis, C. orthopsilosisandC. metapsilosis. We also show that CRISPR can easily be used to introduce molecular barcodes, and to reintroduce wild type sequences into edited strains. Heterozygous mutations can be generated, either by careful selection of the distance between the polymorphism and the Cas9 cut site, or by providing two different repair templates at the same time. In addition, we have constructed a different autonomously replicating plasmid for CRISPR-Cas9 editing inCandida tropicalis. We show that editing can easily be carried out in multipleC. tropicalisisolates. NHEJ repair occurs at a high level inC. metapsilosisandC. tropicalis.IMPORTANCECandidaspecies are a major cause of infection worldwide. The species associated with infection vary with geographical location, and patient population. Infection withCandida tropicalisis particularly common in South America and Asia, andCandida parapsilosisinfections are more common in the very young. Molecular methods for manipulating the genomes of these species are still lacking. We describe a simple and efficient CRISPR-based gene editing system that can be applied in theC. parapsilosisspecies group, including the sister speciesCandida orthopsilosisandCandida metapsilosis. We have also constructed a separate system for gene editing inC. tropicalis.
A comparison of three programming languages for a full-fledged next-generation sequencing tool
Authors: Pascal Costanza , Charlotte Herzeel , Wilfried Verachtert 
Published: February 2019

AbstractBackgroundelPrep is an established multi-threaded framework for preparing SAM and BAM files in sequencing pipelines. To achieve good performance, its software architecture makes only a single pass through a SAM/BAM file for multiple preparation steps, and keeps sequencing data as much as possible in main memory. Similar to other SAM/BAM tools, management of heap memory is a complex task in elPrep, and it became a serious productivity bottleneck in its original implementation language during recent further development of elPrep. We therefore investigated three alternative programming languages: Go and Java using a concurrent, parallel garbage collector on the one hand, and C++17 using reference counting on the other hand for handling large amounts of heap objects. We reimplemented elPrep in all three languages and benchmarked their runtime performance and memory use.ResultsThe Go implementation performs best, yielding the best balance between runtime performance and memory use. While the Java benchmarks report a somewhat faster runtime than the Go benchmarks, the memory use of the Java runs is significantly higher. The C++17 benchmarks run significantly slower than both Go and Java, while using somewhat more memory than the Go runs. Our analysis shows that concurrent, parallel garbage collection is better at managing a large heap of objects than reference counting in our case.ConclusionsBased on our benchmark results, we selected Go as our new implementation language for elPrep, and recommend considering Go as a good candidate for developing other bioinformatics tools for processing SAM/BAM data as well.
Single mRNP analysis by super-resolution microscopy and fluorescence correlation spectroscopy reveals that small mRNP granules represent mRNA singletons
Authors: Mateu-Regué Àngels , Christiansen Jan , Bagger Frederik Otzen , Hellriegel Christian , Nielsen Finn Cilius 
Published: February 2019

SummarySmall cytoplasmic mRNP granules are implicated in mRNA transport, translational control and decay. Employing Super-resolution Microscopy and Fluorescence Correlation Spectroscopy, we analyzed the molecular composition and dynamics of single cytoplasmic YBX1_IMP1 mRNP granules in live cells. Granules appeared elongated and branched with patches of IMP1 and YBX1 distributed along mRNA, reflecting the attachment of the two RNA-binding proteins incis. Particles form at the nuclear pore and are spatially segregated from translating ribosomes, so the mRNP is a repository for mRNAs awaiting translation. In agreement with the average number of mRNA-binding sites derived from CLIP analyses, individual mRNPs contain 5 to 15 molecules of YBX1 and IMP1 and a single poly(A) tail identified by PABPC1. Taken together, we conclude that small cytoplasmic mRNP granules are mRNA singletons, thus depicting the cellular transcriptome. Consequently, expression of functionally related mRNAs in RNA regulons is unlikely to result from coordinated assembly.
Pooled CRISPR Inverse PCR sequencing (PCIP-seq): simultaneous sequencing of retroviral insertion points and the associated provirus in thousands of cells with long reads
Authors: Artesi Maria , Hahaut Vincent , Ashrafi Fereshteh , Marçais Ambroise , Hermine Olivier , Griebel Philip , Arsic Natasa , van der Meer Frank , Burny Arsène , Bron Dominique , Charlier Carole , Georges Michel , Van den Broeke Anne , Durkin Keith 
Published: February 2019

AbstractRetroviral infections create a large population of cells, each defined by a unique proviral insertion site. Methods based on short-read high throughput sequencing can identify thousands of insertion sites, but the proviruses within remain unobserved. We have developed Pooled CRISPR Inverse PCR sequencing (PCIP-seq), a method that leverages long reads on the Oxford Nanopore MinION platform to sequence the insertion site and its associated provirus. We have applied the technique to three exogenous retroviruses, HTLV-1, HIV-1 and BLV, as well as endogenous retroviruses in both cattle and sheep. The long reads of PCIP-seq improved the accuracy of insertion site identification in repetitive regions of the genome. The high efficiency of the method facilitated the identification of tens of thousands of insertion sites in a single sample. We observed thousands of SNPs and dozens of structural variants within proviruses and uncovered evidence of viral hypermutation, recombination and recurrent selection.
ClassiPhages 2.0: Sequence-based classification of phages using Artificial Neural Networks
Authors: Chibani Cynthia Maria , Meinecke Florentin , Farr Anton , Dietrich Sascha , Liesegang Heiko 
Published: February 2019

AbstractBackground/ MotivationIn the era of affordable next generation sequencing technologies we are facing an exploding amount of new phage genome sequences. This requests high throughput phage classification tools that meet the standards of the International Committee on Taxonomy of Viruses (ICTV). However, an accurate prediction of phage taxonomic classification derived from phage sequences still poses a challenge due to the lack of performant taxonomic markers. Since machine learning methods have proved to be efficient for the classification of biological data we investigated how artificial neural networks perform on the task of phage taxonomy.ResultsIn this work, 5,920 constructed and refined profile Hidden Markov Models (HMMs), derived from 8,721 phage sequences classified into 12 well known phage families, were used to scan phage proteome datasets. The resulting Phage Family-proteome to Phage-derived-HMMs scoring matrix was used to develop and train an Artificial Neural Network (ANN) to find patterns for phage classification into one of the phage families. Results show that using the 100 fold cross-validation test, the proposed method achieved an overall accuracy of 84.18 %. The ANN was tested on a set of unclassified phages and resulted in a taxonomic prediction. The ANN prediction was benchmarked against the prediction resulting of multi-HMM hits, and showed that the ANN performance is dependent on the quality of the input matrix.ConclusionsWe believe that, as long as some phage families on public databases are underrepresented, multi-HMM hits can be used as a classification method to populate those phage families, which in turn will improve the performance and accuracy of the ANN. We believe that the proposed method is an effective and promising method for phage classification. The good performance of the ANN and HMM based predictor indicates the efficiency of the method for phage classification, where we foresee its improvement with an increasing number of sequenced viral genomes.
Evaluation of computational genotyping of Structural Variations for clinical diagnoses
Authors: Chander Varuna , Gibbs Richard A. , Sedlazeck Fritz J. 
Published: February 2019

AbstractBackgroundIn recent years, Structural Variation (SV) has been identified as having a pivotal role in causing genetic disease. Nevertheless, the discovery of SVs based on short DNA sequence reads from next-generation DNA sequence methods is still error-prone, suffering from low sensitivity and high false discovery. These shortcomings can be partially overcome with the use of long reads, but the current expense precludes their application for routine clinical diagnostics. Structural Variation genotyping, on the other hand, offers cost-effective application as diagnostic tool in the clinic, with potentially no false positives and low occurrence of false negatives.ResultsWe assess five state- of-the- art SV genotyping software methods that test short read sequence data. These methods are characterized based on their ability to genotype certain SV types and size ranges. Furthermore, we analyze their applicability to parse different VCF file sub-formats, or to rely on specific meta information that is not always at hand. We compare the SV genotyping methods across a range of simulated and real data including SVs that were not found with Illumina data alone. We assess their sensitivity and ability to filter out initial false discovery calls to assess their reliability.ConclusionOur results indicate that, although SV genotypers have superior performance to SV callers, there are performance limitations that suggest the need for further innovation.
A deconvolution algorithm for multiecho functional MRI: Multiecho Sparse Paradigm Free Mapping
Authors: Caballero-Gaudes César , Moia Stefano , Panwar Puja , Bandettini Peter A. , Gonzalez-Castillo Javier 
Published: February 2019

ABSTRACTThis work introduces a novel algorithm for deconvolution of the BOLD signal in multiecho fMRI data: Multiecho Sparse Paradigm Free Mapping (ME-SPFM). Assuming a linear dependence of the BOLD percent signal change on the echo time (TE) and using sparsity-promoting regularized least squares estimation, ME-SPFM yields voxelwise time-varying estimates of the changes in the transverse relaxationwithout prior knowledge of the timings of individual BOLD events. Our results in multi-echo fMRI data collected during a multi-task event-related paradigm at 3 Tesla demonstrate that the maps ofchanges obtained with ME-SPFM at the times of the stimulus trials show high spatial and temporal concordance with the activation maps and BOLD signals obtained with standard model-based analysis. This method yields estimates ofhaving physiologically plausible values. Owing to its ability to blindly detect events, ME-SPFM also enables us to mapassociated with spontaneous, transient BOLD responses occurring between trials. This framework is a step towards deciphering the dynamic nature of brain activity in naturalistic paradigms, resting-state or experimental paradigms with unknown timing of the BOLD events.
Mechanochemical coupling and junctional forces during collective cell migration
Authors: Bui J. , Conway D. E. , Heise R. L. , Weinberg S.H. 
Published: February 2019

ABSTRACTCell migration, a fundamental physiological process in which cells sense and move through their surrounding physical environment, plays a critical role in development and tissue formation, as well as pathological processes, such as cancer metastasis and wound healing. During cell migration, dynamics are governed by the bidirectional interplay between cell-generated mechanical forces and the activity of Rho GTPases, a family of small GTP-binding proteins that regulate actin cytoskeleton assembly and cellular contractility. These interactions are inherently more complex during the collective migration of mechanically coupled cells, due to the additional regulation of cell-cell junctional forces. In this study, we present a minimal modeling framework to simulate the interactions between mechanochemical signaling in individual cells and interactions with cell-cell junctional forces during collective cell migration. We find that migration of individual cells depends on the feedback between mechanical tension and Rho GTPase activity in a biphasic manner. During collective cell migration, waves of Rho GTPase activity mediate mechanical contraction/extension and thus synchronization throughout the tissue. Further, cell-cell junctional forces exhibit distinct spatial patterns during collective cell migration, with larger forces near the leading edge. Larger junctional force magnitudes are associated with faster collective cell migration and larger tissue size. Simulations of heterogeneous tissue migration exhibit a complex dependence on the properties of both leading and trailing cells. Computational predictions demonstrate that collective cell migration depends on both the emergent dynamics and interactions between cellular-level Rho GTPase activity and contractility, and multicellular-level junctional forces.
Precision-weighting of superior frontal cortex unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis
Authors: Haarsma J. , Fletcher P.C. , Griffin J.D. , Taverne H.J. , Ziauddeen H. , Spencer T.J. , Goodyer I. , Diederen K.M.J. , Murray G.K 
Published: February 2019

AbstractRecent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of cortical unsigned prediction error (i.e., surprise) signals plays a key role in learning and decision-making, to be controlled by dopamine, and to contribute to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation and in patients with early psychosis. Behavioural computational modelling indicated that precision-weighting of unsigned prediction errors benefits learning in health, and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors relative to their precision in bilateral superior frontal gyri and dorsal anterior cingulate, which was perturbed by dopaminergic modulation, impaired in psychosis, and associated with task performance and schizotypy. We conclude that precision-weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
A SMAD1/5-YAP signaling module drives radial glia self-amplification and growth of the developing cerebral cortex
Authors: Najas Sonia , Pijuan Isabel , Esteve-Codina Anna , Usieto Susana , Martinez Juan D. , Zwijsen An , Arbonés Maria L. , Martí Elisa , Le Dréau Gwenvael 
Published: February 2019

AbstractThe growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrain the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.