bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring the average power of neural oscillations
Authors: Izhikevich Liz , Gao Richard , Peterson Erik , Voytek Bradley 
Published: October 2018

AbstractBackgroundNeural oscillations are often quantified as average power relative to a cognitive, perceptual, and/or behavioral task. This is commonly done using Fourier-based techniques, such as Welch’s method for estimating the power spectral density, and/or by estimating narrowband oscillatory power across trials, conditions, and/or groups. The core assumption underlying these approaches is that the mean is an appropriate measure of central tendency. Despite the importance of this assumption, it has not been rigorously tested.New methodWe introduce extensions of common approaches that are better suited for the physiological reality of how neural oscillations often manifest: as nonstationary, high-power bursts, rather than sustained rhythms. Log-transforming, or taking the median power, significantly reduces erroneously inflated power estimates.ResultsAnalyzing 101 participants’ worth of human electrophysiology, totaling 3,560 channels and over 40 hours data, we show that, in all cases examined, spectral power is not Gaussian distributed. This is true even when oscillations are prominent and sustained, such as visual cortical alpha. Power across time, at every frequency, is characterized by a substantial long tail, which implies that estimates of average power are skewed toward large, infrequent high-power oscillatory bursts.Comparison with existing methodsIn a simulated event-related experiment we show how introducing just a few high-power oscillatory bursts, as seen in real data, can, perhaps erroneously, cause significant differences between conditions using traditional methods. These erroneous effects are substantially reduced with our new methods.ConclusionsThese results call into question the validity of common statistical practices in neural oscillation research.HighlightsAnalyses of oscillatory power often assume power is normally distributed.Analyzing >40 hours of human M/EEG and ECoG, we show that in all cases it is not.This effect is demonstrated in simple simulation of an event-related task.Overinflated power estimates are reduced via log-transformation or median power.
In situ and high-resolution Cryo-EM structure of the Type VI secretion membrane complex
Authors: Rapisarda Chiara , Cherrak Yassine , Kooger Romain , Schmidt Victoria , Pellarin Riccardo , Logger Laureen , Cascales Eric , Pilhofer Martin , Durand Eric , Fronzes Rémi 
Published: October 2018

AbstractBacteria have evolved macromolecular machineries that secrete effectors and toxins to survive and thrive in diverse environments. The type VI secretion system (T6SS) is a contractile machine that is related to Myoviridae phages. The T6SS is composed of a baseplate that contains a spike onto which an inner tube is built, surrounded by a contractile sheath. Unlike phages that are released to and act in the extracellular medium, the T6SS is an intracellular machine inserted in the bacterial membranes by a trans-envelope complex. This membrane complex (MC) comprises three proteins: TssJ, TssL and TssM. We previously reported the low-resolution negative stain electron microscopy structure of the enteroaggregative Escherichia coli MC and proposed a rotational 5-fold symmetry with a TssJ:TssL:TssM stoichiometry of 2:2:2. Here, cryo-electron tomography analysis of the T6SS MC confirmed the 5-fold symmetry in situ and identified the regions of the structure that insert into the bacterial membranes. A high resolution model obtained by single particle cryo-electron microscopy reveals its global architecture and highlights new features: five additional copies of TssJ, yielding a TssJ:TssL:TssM stoichiometry of 3:2:2, a 11-residue loop in TssM, protruding inside the lumen of the MC and constituting a functionally important periplasmic gate, and hinge regions. Based on these data, we revisit the model on the mechanism of action of the MC during T6SS assembly and function.
Stochastic simulations show how passive immunization can influence the germinal centre reaction and optimize host humoral responses
Authors: Garg Amar K. , Desikan Rajat , Dixit Narendra M. 
Published: October 2018

AbstractPassive immunization with antigen-specific antibodies was shown recently to induce lasting improvements in endogenous antibody production, raising the prospect of using passive immunization as a tool to engineer host humoral responses. The mechanism with which administered antibodies alter endogenous antibody production remains unknown. B cells that produce antigen-specific antibodies evolve and get selected in germinal centres (GCs). This selection requires that B cells acquire antigen presented in GCs. We hypothesized that passive immunization biases this selection in favour of B cells with high affinities for antigen. Administered antibodies form immune complexes with antigen which only B cells with higher affinities than the administered antibodies for antigen can rupture and acquire antigen, thus increasing the selection stringency in GCs. With this mechanistic hypothesis, we constructed a stochastic simulation model of the GC reaction. The simulations recapitulated and synthesized several independent experimental observations, presenting strong evidence in support of our hypothesis. Further, the simulations revealed a quality-quantity trade-off constraining the GC response. As the selection stringency increased, surviving B cells had higher affinities for antigen but fewer B cells survived. Increasing antigen availability in the GC relaxed this constraint. The affinity of the administered antibodies and/or antigen availability could thus be tuned to maximize the GC output. Comprehensively spanning parameter space, we predict passive immunization protocols that exploit the quality-quantity trade-off and maximize the GC output. Our study thus presents a new conceptual understanding of the GC reaction and a computational framework for the rational optimization of passive immunization strategies.Significance statementWhen natural antibody production is inadequate, passive immunization with external antibodies can alleviate disease. Remarkably, passive immunization induced lasting improvements in natural antibody production in recent studies, suggesting that it could be deployed to engineer natural antibody responses. However, how administered antibodies alter natural antibody production remains unknown. B cells that produce antibodies targeting specific antigen evolve in germinal centres (GCs). We hypothesized that administered antibodies form complexes with antigen, preferentially allowing B cells with higher affinities to acquire antigen and be selected, thus altering antibody production. With this mechanistic hypothesis, we performed stochastic simulations of the GC reaction, which recapitulated experiments, unravelled a quality-quantity trade-off constraining the GC response, and predicted passive immunization protocols that maximized the GC output.
Root volatiles in plant-plant interactions I: Characterization of root sesquiterpene emissions from Centaurea stoebe and their effects on other plants
Authors: Gfeller Valentin , Huber Meret , Förster Christiane , Huang Wei , Köllner Tobias G. , Erb Matthias 
Published: October 2018

AbstractVolatile organic compounds (VOCs) emitted by plant leaves can influence the physiology of neighboring plants. In contrast to interactions above ground, little is known about the role of VOCs in belowground plant-plant interactions. Here, we characterize constitutive root volatile emissions of the spotted knapweed (Centaurea stoebe) and explore the impact of these volatiles on the germination and growth of different sympatric plant species. We show that C. stoebe roots emit high amounts of sesquiterpenes, with estimated release rates of (E)-β-caryophyllene above 3 μg g−1 dw h−1. Sesquiterpene emissions show little variation between different C. stoebe populations, but vary substantially between different Centaurea species. Through root transcriptome sequencing, we identify six root-expressed sesquiterpene synthases (TPSs). Two root-specific TPSs, CsTPS4 and CsTPS5, are sufficient to produce the full blend of emitted root sesquiterpenes. Volatile exposure experiments demonstrate that C. stoebe root volatiles have neutral to positive effects on the germination and growth of different sympatric neighbors. Thus, constitutive root sesquiterpenes produced by two C. stoebe TPSs are associated with facilitation of sympatric neighboring plants. The release of root VOCs may thus influence C. stoebe abundance and plant community structure in nature.
Fast Detection of Differential Chromatin Domains with SCIDDO
Authors: Ebert Peter , Schulz Marcel H. 
Published: October 2018

AbstractThe generation of genome-wide maps of histone modifications using chromatin immunoprecipitation sequencing (ChIP-seq) is a common approach to dissect the complexity of the epigenome. However, interpretation and differential analysis of histone ChIP-seq datasets remains challenging due to the genomic co-occurrence of several marks and their difference in genomic spread. Here we present SCIDDO, a fast statistical method for the detection of differential chromatin domains (DCDs) from chromatin state maps. DCD detection simplifies relevant tasks such as the characterization of chromatin changes in differentially expressed genes or the examination of chromatin dynamics at regulatory elements. SCIDDO is available at github.com/ptrebert/sciddo
Root volatiles in plant-plant interactions II: Root terpenes from Centaurea stoebe modify Taraxacum officinale root chemistry and root herbivore growth
Authors: Huang Wei , Gfeller Valentin , Erb Matthias 
Published: October 2018

AbstractVolatile organic compounds (VOCs) emitted by plant roots can influence the germination and growth of neighboring plants. However, little is known about the effects of root VOCs on plant-herbivore interactions. The spotted knapeed (Centaurea stoebe) constitutively releases high amounts of sesquiterpenes into the rhizosphere. Here, we examine the impact of C. stoebe root VOCs on primary and secondary metabolites of sympatric Taraxacum officinale plants and the resulting plant-mediated effects on a generalist root herbivore, the white grub Melolontha melolontha. We show that exposure of T. officinale to C. stoebe root VOCs does not affect the accumulation of defensive secondary metabolites, but modulates carbohydrate and total protein levels in T. officinale roots. Furthermore, VOC exposure increases M. melolontha growth on T. officinale plants. Exposure of T. officinale to a major C. stoebe root VOC, the sesquiterpene (E)-β-caryophyllene, partially mimics the effect of the full root VOC blend on M. melolontha growth. Thus, releasing root VOCs can modify plant-herbivore interactions of neighboring plants. The release of VOCs to increase the susceptibility of other plants may be a form of plant offense.
Modelling double strand break susceptibility to interrogate structural variation in cancer
Authors: Ballinger Tracy J. , Bouwman Britta , Mirzazadeh Reza , Garnerone Silvano , Crosetto Nicola , Semple Colin A. 
Published: October 2018

AbstractBackgroundStructural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge via errors in the repair processes following DNA double strand breaks (DSBs) and previous studies have experimentally measured DSB frequencies across the genome in cell lines.ResultsUsing these data we derive the first quantitative genome-wide models of DSB susceptibility, based upon underlying chromatin and sequence features. These models are accurate and provide novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type specific processes. Using model predictions as a proxy for susceptibility to DSBs in tumours, many SV enriched regions appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of these regions show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation, and are therefore credible targets of positive selection in tumours. These putatively positively selected SV hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel ‘coldspot’ regions appear to be subject to purifying selection in tumours and are enriched for active promoters and enhancers.ConclusionsWe conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumours.
Anthropogenic remediation of heavy metals selects against natural microbial remediation
Authors: Hesse Elze , Padfield Daniel , Bayer Florian , van Veen Eleanor M. , Bryan Christopher G. , Buckling Angus 
Published: October 2018

AbstractIn an era of unprecedented environmental change, there have been increasing ecological and global public health concerns associated with exposure to anthropogenic pollutants. While there is a pressing need to remediate polluted ecosystems, human intervention strategies might unwittingly oppose selection for natural detoxification, which is primarily carried out by microbes. We test this possibility in the context of a ubiquitous chemical remediation strategy aimed at targeting toxic metal pollution: the addition of lime-containing materials. Here we show that raising pH by liming decreased the availability of toxic metals in acidic mine-degraded soils, but as a consequence selected against microbial taxa that naturally remediate soil through the production of metal-scavenging siderophores. Understanding the ecological and evolutionary consequences of human intervention on key traits is crucial for the engineering of evolutionary resilient microbial communities, having important implications for human health and biotechnology.
Principles of Meiotic Chromosome Assembly
Authors: Schalbetter Stephanie A. , Fudenberg Geoffrey , Baxter Jonathan , Pollard Katherine S. , Neale Matthew J. 
Published: October 2018

AbstractDuring meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we elucidate how this elaborate three-dimensional chromosome organisation is underpinned by genomic sequence inSaccharomyces cerevisiae. Entering meiosis, strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion limited by barriers, yet are patterned by convergent transcription rather than binding of the mammalian interphase factor, CTCF, which is absent inS. cerevisiae—thereby both challenging and extending current paradigms of local chromosome organisation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process.
Combining transcriptomic and fitness data reveals additive and mostly adaptive plastic responses of gene expression to multiple stress in Tribolium castaneum
Authors: Koch Eva L. , Guillaume Frédéric 
Published: October 2018

AbstractGene expression is known to be highly responsive to the environment and to vary between species or populations under divergent selection. Yet, its contribution to the process of adaption is still controversial despite growing evidence that differences in gene regulation contribute to adaptive divergence. While most studies so far investigated evolved plasticity in already diverged populations, phenotypic selection acting on gene expression at the onset of adaptation to an environmental change has not been characterized. Here, we combined fitness and whole-transcriptome data in a large-scale experiment with Tribolium castaneum to investigate gene expression and fitness responses to drought, heat and their combination. Fitness was reduced by both stressors and their combined effects were nearly additive. Accordingly, expression data showed that both stressors were acting independently and did not interfere physiologically. With expression and fitness within the same individuals, we estimated selection on single gene expression levels. We found that variation in fitness can be attributed to gene expression variation. Selection intensities on expression levels differed between conditions and were opposite between control and stress conditions, showing evidence of evolutionary trade-offs. Plastic expression changes were mostly adaptive when affected by heat stress, and partially non-adaptive when affected by drought.
Differential immune gene expression associated with contemporary range expansion of two invasive rodents in Senegal
Authors: Charbonnel Nathalie , Galan Maxime , Tatard Caroline , Loiseau Anne , Diagne Christophe Amidi , Dalecky Ambroise , Parrinello Hugues , Rialle Stephanie , Severac Dany , Brouat Carine 
Published: October 2018

BackgroundBiological invasions are major anthropogenic changes associated with threats to biodiversity and health. What determines the successful establishment of introduced populations still remains unsolved. Here we explore the appealing assertion that invasion success relies on immune phenotypic traits that would be advantageous in recently invaded sites.ResultsWe compared gene expression profiles between anciently and recently established populations of two major invading species, the house mouse Mus musculus domesticus and the black rat Rattus rattus, in Senegal. Transcriptome analyses revealed respectively 364 and 83 differentially expressed genes along the mouse and rat invasion routes. Among them, 20.0% and 10.6% were annotated with functions related to immunity. All immune-related genes detected along the mouse invasion route were over-expressed in recently invaded sites. Genes of the complement activation pathway were over-represented. Results were less straightforward when considering the black rat as no particular immunological process was over-represented.ConclusionsWe revealed changes in transcriptome profiles along invasion routes. Patterns differed between both invasive species. These changes potentially be driven by increased infection risks in recently invaded sites for the house mouse and stochastic events associated with colonization history for the black rat. These results provide a first step in identifying the immune ecoevolutionary processes potentially involved in invasion success.
Alkaline ceramidase catalyzes the hydrolysis of ceramides via a catalytic mechanism shared by Zn2+-dependent amidases
Authors: Yi Jae Kyo , Xu Ruijuan , Obeid Lina M. , Hannun Yusuf A. , Airola Michael V. , Mao Cungui 
Published: October 2018

ABSTRACTHuman alkaline ceramidase 3 (ACER3) is one of three alkaline ceramidases (ACERs) that catalyze the conversion of ceramide to sphingosine. ACERs are the members of the CREST superfamily of integral-membrane lipid hydrolases, including the adiponectin receptors which play roles in energy metabolism. All CREST members conserve a set of three Histidine, one Aspartate, and one Serine residue. However, the structural and catalytic roles for these residues are unclear. Here, we use ACER3 as a prototype enzyme to gain insight into this unique class of enzymes. Recombinant ACER3 was expressed in yeast cells that lack endogenous ceramidase activity, and microsomes were used for biochemical characterization. Six point mutantions of the conserved CREST motif were developed that are predicted to form a Zn-dependent active site based on homology with the human adiponectin receptors, whose crystal structures were recently determined. Five mutations completely lost their activity, except for S77A, which showed a 600-fold decrease compared with the wild-type enzyme. The activity of S77C mutation was pH sensitive, with neutral pH partially recovering ACER3 activity. This suggested a role for S77 in stabilizing the oxyanion of the transition state and differs from the proposed role in Zinc coordination for the adiponectin receptors (Vasiliauskaité-Brooks et. al., Nature, 2017). Together, these data suggest ACER3 is a Zn2+-dependent amidase that uses a catalytic mechanism for ceramide hydrolysis that is similar to other soluble Zn-based amidases. Consistent with this mechanism, ACER3 was specifically inhibited by trichostatin A, an HDAC inhibitor, which is a strong chelator of Zinc.
The Flexiscope: a Low Cost, Flexible, Convertible, and Modular Microscope with Automated Scanning and Micromanipulation
Authors: Courtney Amy , Alvey Luke M. , Merces George O.T. , Pickering Mark 
Published: October 2018

AbstractWith technologies rapidly evolving, many research institutions are now opting to invest in costly, high-quality, specialised microscopes which are shared by many researchers. As a consequence, the user may not have the ability to adapt a microscope to their specific needs and limitations in experimental design are introduced. A flexible work-horse microscopy system is a valuable tool in any laboratory to meet the diverse needs of a research team and promote innovation in experimental design. We have developed the Flexiscope; a multi-functional, adaptable, efficient and high-performance microscopy/electrophysiology system for everyday applications in a neurobiology laboratory. The core optical components are relatively constant in the three configurations described here; an upright configuration, an inverted configuration and an upright/electrophysiology configuration. We have provided a comprehensive description of the Flexiscope. We show that this method is capable of oblique infrared illumination imaging, multi-channel fluorescent imaging, and automated 3D scanning of larger specimens. Image quality is conserved across the three configurations of the microscope, and conversion between configurations is possible quickly and easily, while the motion control system can be repurposed to allow sub-micron computer-controlled micromanipulation. The Flexiscope provides similar performance and usability to commercially available systems. However, as it can be easily reconfigured for multiple roles, it can remove the need to purchase multiple microscopes, giving significant cost savings. The modular re-configurable nature allows the user to customise the system to their specific needs and adapt/upgrade the system as challenges arise, without requiring specialised technical skills.