bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural depletion of H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation
Authors: He Shengbo , Vickers Martin , Zhang Jingyi , Feng Xiaoqi 
Published: October 2018

AbstractTransposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.
Novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide
Authors: Strawbridge Rona J. , Ward Joey , Ferguson Amy , Graham Nicholas , Shaw Richard J , Cullen Breda , Pearsall Robert , Lyall Laura M. , Johnston Keira J.A. , Niedzwiedz Claire L. , Pell Jill P. , Mackay Daniel , Martin Julie Langan , Lyall Donald M. , Bailey Mark E.S. , Smith Daniel J. 
Published: October 2018

Abstract:Background: Suicide is a major issue for global public health. ‘Suicidality’ describes a broad clinical spectrum of thoughts and behaviours, some of which are common in the general population.Methods: UK Biobank recruited ∼0·5 million middle age individuals from the UK, of whom 157,000 completed an assessment of suicidality. Mutually exclusive groups were assessed in an ordinal genome-wide association study of suicidality: ‘no suicidality’ controls (N=83,557); ‘thoughts that life was not worth living’ (N=21,063); ‘ever contemplated self-harm’ (N=13,038); ‘an act of deliberate self-harm in the past’ (N=2,498); and ‘a previous suicide attempt’ (N=2,666). Linkage of UK Biobank to death certification records identified a small sub-group of ‘completed suicide’ (N=137).Outcomes: We identified three novel genome-wide significant loci for suicidality (on Chromosomes 9, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). Higher polygenic risk scores for suicidality were associated with increased risk of completed suicide relative to controls in an independent sub-group (N=137 vs N=5,330, OR 1·23, 95%CI 1·06 to 1·41, p=0.03). Rs598046-G (chromosome 11) demonstrated a similar effect size and direction (p=0·05) within a Danish suicidality study.Interpretation: These findings have significant implications for our understanding of genetic vulnerability to suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level.Funding: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217).
Baseline corticosterone does not reflect iridescent plumage traits in female tree swallows
Authors: Sarpong Keneth , Madliger Christine L. , Harris Christopher M. , Love Oliver P. , Doucet Stéphanie M. , Bitton Pierre-Paul 
Published: October 2018

AbstractThe production of high quality secondary sexual traits can be constrained by trade-offs in the allocation of energy and nutrients with other metabolic activities, and is mediated by physiological processes. In birds, the factors influencing male plumage quality have been well studied; however, factors affecting female plumage quality are poorly understood. Furthermore, it remains uncertain which physiological traits mediate the relationship between body condition and ornaments. In this three-year study of after-second-year female tree swallows (Tachycineta bicolor), we investigated (1) the relationship between baseline corticosterone near the end of the brood-rearing period (CORTBR) and feather colour characteristics (hue, saturation, brightness) the following year, and (2) the relationship between baseline corticosterone measured during incubation (CORTI) and brood rearing (CORTBR), and feather colour in the same year. To control for reproductive effort, we included reproductive parameters as covariates in all analyses. In this first study between CORT and the plumage colour characteristics of a species bearing iridescent feathers, we did not find any relationship between CORTBRand the colour of subsequently-produced feathers, nor did we find any relationship between CORTIand the colour of feathers displayed during that breeding season. If CORT levels at the end of breeding carry over to influence the immediately subsequent moult period as we expect, our results generally indicate that structural plumage quality may not be as sensitive to circulating CORT levels compared to carotenoid-based colouration. Future studies, particularly those employing experimental manipulations of CORT during moult in species with iridescent traits, are necessary to fully determine the role glucocorticoids play in mediating the quality of secondary sexual characteristics.
Phytoplankton thermal responses adapt in the absence of hard thermodynamic constraints
Authors: Kontopoulos Dimitrios - Georgios , van Sebille Erik , Lange Michael , Yvon-Durocher Gabriel , Barraclough Timothy G. , Pawar Samraat 
Published: October 2018

AbstractTo better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related traits to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can—at least partly—overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curves of growth rate of phytoplankton—a globally important functional group—, controlling for environmental effects (habitat type and thermal regime). We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of maximum performance with the temperature at which the curve peaks, suggesting a weak “hotter-is-better” constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we find that all aspects of the thermal performance curve evolve along the phylogeny. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.
Topographical cuescontrol the morphology and dynamics of migrating cortical interneurons
Authors: Leclech Claire , Renner Marianne , Villard catherine , Métin Christine 
Published: October 2018

ABSTRACTIn mammalian embryos, cortical interneurons travel long distances among complex three-dimensional tissues before integrating into cortical circuits. Several molecular guiding cues involved in this migration process have been identified, but the influence of physical parameters remains poorly understood. In the present study, we have investigatedin vitrothe influence of the topography of the microenvironment on the migration of primary cortical interneurons released from mouse embryonic explants.We found that arrays of 10 μm-sized PDMS micro-pillars, either round or square, influenced both the morphology and the migratory behavior of interneurons. Strikingly, most interneurons exhibited a single and long leading process oriented along the diagonals of the square pillared array, whereas leading processes of interneurons migrating in-between round pillars were shorter, often branched and oriented in all available directions. Accordingly, dynamic studies revealed that growth cone divisions were twice more frequent in round than in square pillars. Both soma and leading process tips presented forward directed movements within square pillars, contrasting with the erratic trajectories and more dynamic movements observed among round pillars. In support of these observations, long interneurons migrating in square pillars displayed tight bundles of stable microtubules aligned in the direction of migration.Overall, our results show that micron-sized topography provides global spatial constraints promoting the establishment of two different morphological and migratory states. Remarkably, both states belong to the natural range of migratory behaviors of cortical interneurons, highlighting the potential importance of topographical cues in the guidance of these embryonic neurons, and more generally in brain development.
Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation
Authors: McAdams David , Waldetoft Kristofer Wollein , Tedijanto Christine , Lipsitch Marc , Brown Sam P. 
Published: October 2018

AbstractRapid point-of-care resistance diagnostics (POC-RD) are a key tool in the fight against antibiotic resistance. By tailoring drug choice to infection genotype, doctors can improve treatment efficacy while limiting costs of inappropriate antibiotic prescription. Here we combine epidemiological theory and data to assess the potential of RD innovations in a public health context, as a means to limit or even reverse selection for antibiotic resistance. POC-RD can be used to impose a non-biological fitness cost on resistant strains, by enabling diagnostic-informed treatment and targeted interventions that reduce resistant strains’ opportunities for transmission. We assess this diagnostic-imposed fitness cost in the context of a spectrum of bacterial population biologies, and find that the expected impact varies from selection against resistance for obligate pathogens to marginal public health improvements for opportunistic pathogens with high ‘bystander’ antibiotic exposure during asymptomatic carriage (e.g. the pneumococcus). We close by generalizing the notion of RD-informed strategies to incorporate carriage surveillance information, and illustrate that coupling transmission-control interventions to the discovery of resistant strains in carriage can potentially select against resistance in a broad range of opportunistic pathogens.
Hippocampal theta bursting and waveform shape reflect CA1 spiking patterns
Authors: Cole Scott , Voytek Bradley 
Published: October 2018

AbstractBrain rhythms are nearly always analyzed in the spectral domain in terms of their power, phase, and frequency. While this conventional approach has uncovered spike-field coupling, as well as correlations to normal behaviors and pathological states, emerging work has highlighted the physiological and behavioral importance of multiple novel oscillation features. Oscillatory bursts, for example, uniquely index a variety of cognitive states, and the nonsinusoidal shape of oscillations relate to physiological changes, including Parkinson’s disease. Open questions remain regarding how bursts and nonsinusoidal features relate to circuit-level processes, and how they interrelate. By analyzing unit and local field recordings in the rodent hippocampus, we uncover a number of significant relationships between oscillatory bursts, nonsinusoidal waveforms, and local inhibitory and excitatory spiking patterns. Bursts of theta oscillations are surprisingly related to a decrease in pyramidal neuron synchrony, and have no detectable effect on firing sequences, despite significant increases in neuronal firing rates during periods of theta bursting. Theta burst duration is predicted by the asymmetries of its first cycle, and cycle asymmetries relate to firing rate, synchrony, and sequences of pyramidal neurons and interneurons. These results provide compelling physiological evidence that time-domain features, of both nonsinusoidal hippocampal theta waveform and the theta bursting state, reflects local circuit properties. These results point to the possibility of inferring circuit states from local field potential features in the hippocampus and perhaps other brain regions with other rhythms.
Irregular chromatin: packing density, fiber width and occurrence of heterogeneous clusters
Authors: Bajpai Gaurav , Padinhateeri Ranjith 
Published: October 2018

AbstractHow chromatin is folded in the lengthscale of a gene is an open question. Recent experiments have suggested that, in vivo, chromatin is folded in an irregular manner and not as an ordered fiber with a width of 30 nm expected from theories of higher order packaging. Using computational methods, we examine how the interplay between DNA-bending non histone proteins, histone tails, intra-chromatin electrostatic and other interactions decide the nature of packaging of chromatin. We show that while the DNA-bending non histone proteins make the chromatin irregular, they may not alter the packing density and size of the fiber. We find that the length of the interacting region and intra-chromatin electrostatic interactions influence the packing density, clustering of nucleosomes, and the width of the chromatin fiber. Our results suggest that the actively maintained heterogeneity in the interaction pattern will play an an important role in deciding the nature of packaging of chromatin.
How non-veridical perception drives actions in healthy humans - Evidence from Synaesthesia
Authors: Luise Schreiter Marie , Chmielewski Witold X. , Ward Jamie , Beste Christian 
Published: October 2018

AbstractWe continually perform actions driven by our perception and it is commonly held that only objectively perceived changes within the ‘real’ world affect behaviour. Exceptions are usually only made for clinical conditions associated with hallucinations, where objectively non-existent percepts can influence behavior. Using synaesthesia as a model condition, we show that even in healthy populations irrelevant non-veridical precepts exert an effect on action. By non-veridical we refer to stimulus dimensions that are only subjectively perceived to be there. Applying electrophysiological (EEG) methods, we show that although these examined peculiarities are perceptual in nature, not primarily perceptual processes underlie the effects of irrelevant non-veridical perceptions on actions. Rather, high-order processes linking perceptions and motor control in medial frontal cortices reflect the underlying mechanism how irrelevant non-veridical perceptions modulate behaviour. Our results challenge assumptions about the determinants of healthy human behaviour but can be embedded within existing frameworks detailing perception action interactions.
SKA: Split Kmer Analysis Toolkit for Bacterial Genomic Epidemiology
Authors: Harris S. R. 
Published: October 2018

AbstractGenome sequencing is revolutionising infectious disease epidemiology, providing a huge step forward in sensitivity and specificity over more traditional molecular typing techniques. However, the complexity of genome data often means that its analysis and interpretation requires high-performance compute infrastructure and dedicated bioinformatics support. Furthermore, current methods have limitations that can differ between analyses and are often opaque to the user, and their reliance on multiple external dependencies makes reproducibility difficult. Here I introduce SKA, a toolkit for analysis of genome sequence data from closely-related, small, haploid genomes. SKA uses split kmers to rapidly identify variation between genome sequences, making it possible to analyse hundreds of genomes on a standard home computer. Tests on publicly available simulated and real-life data show that SKA is both faster and more efficient than the gold standard methods used today while retaining similar levels of accuracy for epidemiological purposes. SKA can take raw read data or genome assemblies as input and calculate pairwise distances, create single linkage clusters and align genomes to a reference genome or using a reference-free approach. SKA requires few decisions to be made by the user, which, along with its computational efficiency, allows genome analysis to become accessible to those with only basic bioinformatics training. The limitations of SKA are also far more transparent than for current approaches, and future improvements to mitigate these limitations are possible. Overall, SKA is a powerful addition to the armoury of the genomic epidemiologist. SKA source code is available from Github (https://github.com/simonrharris/SKA).
Predictive coding with neural transmission delays: a real-time temporal alignment hypothesis
Authors: Hogendoorn Hinze , Burkitt Anthony N 
Published: October 2018

AbstractHierarchical predictive coding is an influential model of cortical organization, in which sequential hierarchical layers are connected by feedback connections carrying predictions, as well as feedforward connections carrying prediction errors. To date, however, predictive coding models have neglected to take into account that neural transmission itself takes time. For a time-varying stimulus, such as a moving object, this means that feedback predictions become misaligned with new sensory input. We present an extended model implementing both feed-forward and feedback extrapolation mechanisms that realigns feedback predictions to minimize prediction error. This realignment has the consequence that neural representations across all hierarchical stages become aligned in real-time. Using visual motion as an example, we show that the model is neurally plausible, that it is consistent with evidence of extrapolation mechanisms throughout the visual hierarchy, that it predicts several known motion-position illusions, and that it provides a solution to the temporal binding problem.
Detection of low-density Plasmodium falciparum infections using amplicon deep sequencing
Authors: Early Angela M. , Daniels Rachel F. , Farrell Timothy M. , Grimsby Jonna , Volkman Sarah K. , Wirth Dyann F. , MacInnis Bronwyn L. , Neafsey Daniel E. 
Published: October 2018

AbstractBackgroundDeep sequencing of targeted genomic regions is becoming a common tool for understanding the dynamics and complexity of Plasmodium infections, but its lower limit of detection is currently unknown. Here, a new amplicon analysis tool, the Parallel Amplicon Sequencing Error Correction (PASEC) pipeline, is used to evaluate the performance of amplicon sequencing on low-density Plasmodium DNA samples. Illumina-based sequencing of two P. falciparum genomic regions (CSP and SERA2) was performed on two types of samples: in vitro DNA mixtures mimicking low-density infections (1-200 genomes/μl) and extracted blood spots from a combination of symptomatic and asymptomatic individuals (44-653,080 parasites/μl). Three additional analysis tools—DADA2, HaplotypR, and SeekDeep—were applied to both datasets and the precision and sensitivity of each tool were evaluated.ResultsAmplicon sequencing can contend with low-density samples, showing reasonable detection accuracy down to a concentration of 5 Plasmodium genomes/μl. Due to increased stochasticity and background noise, however, all four tools showed reduced sensitivity and precision on samples with very low parasitemia (<5 copies/μl) or low read count (<100 reads per amplicon). PASEC could distinguish major from minor haplotypes with an accuracy of 90% in samples with at least 30 Plasmodium genomes/μl, but only 61% at low Plasmodium concentrations (<5 genomes/μl) and 46% at very low read counts (<25 reads per amplicon). The four tools were additionally used on a panel of extracted parasite-positive blood spots from natural malaria infections. While all four identified concordant patterns of complexity of infection (COI) across four sub-Saharan African countries, the COI values obtained for individual samples differed in some cases.ConclusionsAmplicon deep sequencing can be used to determine the complexity and diversity of low-density Plasmodium infections. Despite differences in their approach, four state-of-the-art tools resolved known haplotype mixtures with similar sensitivity and precision. Researchers can therefore choose from multiple robust approaches for analyzing amplicon data, however, error filtration approaches should not be uniformly applied across samples of varying parasitemia. Samples with very low parasitemia and very low read count have higher false positive rates and call for read count thresholds that are higher than current recommendations.
HLA*PRG:LA – HLA typing from linearly projected graph alignments
Authors: Dilthey Alexander T , Mentzer Alexander J , Carapito Raphael , Cutland Clare , Cereb Nezih , Madhi Shabir A. , Rhie Arang , Koren Sergey , Bahram Seiamak , McVean Gil , Phillippy Adam M 
Published: October 2018

AbstractSummary:HLA*PRG:LA implements a new graph alignment model for HLA type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data); and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU hours per sample.Availability and Implementation:HLA*PRG:LA is implemented in C++ and Perl and freely available from https://github.com/DiltheyLab/HLA-PRG-LA (GPL v3).Contact:alexander.dilthey@med.uni-duesseldorf.deSupplementary informationSupplementary data are available online.
DNA motifs are not general predictors of recombination in twoDrosophilasister species
Authors: Howie James M. , Mazzucco Rupert , Taus Thomas , Nolte Viola , Schlötterer Christian 
Published: October 2018

ABSTRACTMeiotic recombination is crucial for chromosomal segregation, and facilitates the spread of beneficial and removal of deleterious mutations. Recombination rates frequently vary along chromosomes andDrosophila melanogasterexhibits a remarkable pattern. Recombination rates gradually decrease towards centromeres and telomeres, with dramatic impact on levels of variation in natural populations. Two close sister species,D. simulansandD. mauritianado not only have higher recombination rates, but also exhibit a much more homogeneous recombination rate that only drops sharply close to centromeres and telomeres. Because certain sequence motifs are associated with recombination rate variation inD. melanogaster, we tested whether the difference in recombination landscape betweenD. melanogasterandD. simulanscan be explained by the genomic distribution of recombination-rate associated sequence motifs. We constructed the first high resolution recombination map forD. simulans, and searched for motifs linked with high recombination in both sister species. We identified five consensus motifs, present in either species. While the association between motif density and recombination is strong and positive inD. melanogaster, the results are equivocal inD. simulans. Despite the strong association inD. melanogaster, we do not find a decreasing density of these repeat motifs towards centromeres and telomeres. We conclude that the density of recombination-associated repeat motifs cannot explain the large-scale recombination landscape inD. melanogaster, nor the differences toD. simulans. The strong association seen for the sequence motifs inD. melanogasterlikely reflects their impact influencing local differences in recombination rates along the genome.