bluuebunny/crossref_metadata_2025 huggingface dataset:
Omnivory does not preclude strong trophic cascades
Authors: Fahimipour Ashkaan K. , Levin David A. , Anderson Kurt E.
Published: October 2018

Omnivory has been cited as an explanation for why trophic cascades are weak in many ecosystems, but empirical support for this prediction is equivocal. Compared to predators that feed only on herbivores, top omnivores — species that feed on both herbivores and primary producers — have been observed generating cascades ranging from strong, to moderate, null, and negative. To gain intuition about the sensitivity of cascades to omnivory, we analyzed models describing systems with top omnivores that display either fixed or flexible diets, two foraging strategies that are supported by empirical observations. We identified regions of parameter space wherein omnivores following a fixed foraging strategy, with herbivores and producers comprising a constant proportion of the diet, non-intuitively generate stronger cascades than predators that are otherwise demographically identical: (i) high productivity relative to herbivore mortality, and (ii) small discrepancies in producer versus herbivore reward create conditions in which cascades are stronger with moderate omnivory. In contrast, flexible omnivores that attempt to optimizeper capitagrowth rates during search never induce cascades that are stronger than the case of predators. Although we focus on simple models, the consistency of these general patterns together with prior empirical evidence suggests that omnivores should not be uniformly ruled out as agents of strong trophic cascades.
Nomenclature Errors in Public 16S rRNA Gene Reference Databases
Authors: Lesack Kyle , Birol Inanc
Published: October 2018

Background

Targeted gene surveys of the 16S rRNA gene have become a standard method for profiling the membership and biodiversity of microbial communities. These studies rely upon specialized databases that provide reference sequences and their corresponding taxonomic classifications, but few independent evaluations of the nomenclature used in the taxonomic classifications have been performed.

Results

Nomenclature data collected from the List of Prokaryotic names with Standing in Nomenclature, Prokaryotic Nomenclature Up-to-Date, and CyanoDB databases were used to validate the nomenclature contained in the taxonomic classifications in the Greengenes, RDP, and SILVA 16S rRNA gene reference databases. Between 82% and 97% of the genus annotations assigned to 16S rRNA gene reference sequences were deemed valid in the reference databases. Between 18% and 97% of the species annotations in Greengenes and SILVA were deemed valid. Misannotations included the use of metadata in place of taxonomic classifications, non-adherence to the binomial nomenclature, and sequences classified as eukaryote organelles or taxa.

Conclusions

The misannotations identified in public 16S rRNA gene databases call into question the reliability of research made using these resources. As targeted gene surveys depend on high quality marker gene databases, imed nomenclature accuracy will be necessary.
Multi-context blind source separation by error-gated Hebbian rule
Authors: Isomura Takuya , Toyoizumi Taro
Published: October 2018

Animals need to adjust their inferences according to the context they are in. This is required for the multi-context blind source separation (BSS) task, where an agent needs to infer hidden sources from their context-dependent mixtures. The agent is expected to invert this mixing process for all contexts. Here, we show that a neural network that implements the error-gated Hebbian rule (EGHR) with sufficiently redundant sensory inputs can successfully learn this task. After training, the network can perform the multi-context BSS without further updating synapses, by retaining memories of all experienced contexts. Finally, if there is a common feature shared across contexts, the EGHR can extract it and generalize the task to even inexperienced contexts. This demonstrates an attractive use of the EGHR for dimensionality reduction by extracting common sources across contexts. The results highlight the utility of the EGHR as a model for perceptual adaptation in animals.
Measuring the average power of neural oscillations
Authors: Izhikevich Liz , Gao Richard , Peterson Erik , Voytek Bradley
Published: October 2018

Background

Neural 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 method

We 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.

Results

Analyzing 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 methods

In 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.

Conclusions

These results call into question the validity of common statistical practices in neural oscillation research.

Highlights

Analyses 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

Bacteria 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

Passive 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 statement

When 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

Volatile 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

The 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

Volatile 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

Background

Structural 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.

Results

Using 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.

Conclusions

We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumours.
Spatial relationships between white matter degeneration, amyloid load and cortical volume in amnestic mild cognitive impairment
Authors: Jelescu Ileana O , Shepherd Timothy M , Novikov Dmitry S , Ding Yu-Shin , Ades-Aron Benjamin , Smith Jacqueline , Vahle Thomas , Babb James S , Friedman Kent P , de Leon Mony J , Golomb James B , Galvin James E , Fieremans Els
Published: October 2018

The spatial-temporal relationships between gray and white matter (WM) degeneration during preclinical and early symptomatic Alzheimer's disease are poorly understood. We characterized β-amyloid deposition, cortical volume and WM degeneration in 44 subjects including healthy control (N=23), amnestic mild cognitive impairment (aMCI) (N=19), and early Alzheimer's subjects (N=2). Integrated PET-MRI provided simultaneous measurement of 18F-Florbetapir uptake in cortical areas, regional brain volumes from structural MRI, and WM tract integrity metrics from diffusion MRI using biophysical modeling. Across the cohort of healthy control and aMCIs, cortical volumes correlated poorly with β-amyloid deposition in the same area (p < 0.05 only in the posterior cingulate and parietal lobe). WM degeneration correlated significantly with both amyloid and volume of connected cortical areas, but more strongly with volume. Diffusion MRI metrics for WM demyelination and/or axonal loss could therefore provide new biomarkers associated with clinical Alzheimer's conversion. These WM changes may represent sequential propagation of Alzheimer's neurodegeneration between functionally connected regions, and/or evidence of direct WM injury during the Alzheimer's pathology cascade.
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

In 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.
Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: Implications for in vivo dominance of the vaginal microbiota
Authors: van der Veer Charlotte , Hertzberger Rosanne , Bruisten Sylvia , Tytgat Hanne , Swanenburg Jorne , de Kat Angelino-Bart Alie , Schuren Frank , Molenaar Douwe , Reid Gregor , de Vries Henry , Kort Remco
Published: October 2018

Background: A vaginal microbiota dominated by lactobacilli (particularly Lactobacillus crispatus) is associated with vaginal health, whereas a vaginal microbiota not dominated by lactobacilli is considered dysbiotic. Here we investigated whether L. crispatus strains isolated from the vaginal tract of women with Lactobacillus-dominated vaginal microbiota (LVM) are pheno- or genotypically distinct from L. crispatus strains isolated from vaginal samples with dysbiotic vaginal microbiota (DVM).
Results: We studied 33 L. crispatus strains (n=16 from LVM; n=17 from DVM). Comparison of these two groups of strains showed that, although strain differences existed, both groups were heterofermentative, produced similar amounts of organic acids, inhibited Neisseria gonorrhoeae growth and did not produce biofilms. Comparative genomics analyses of 28 strains (n=12 LVM; n=16 DVM) revealed a novel, 3-fragmented glycosyltransferase gene that was more prevalent among strains isolated from DVM. Most L. crispatus strains showed growth on glycogen-supplemented growth media. Strains that showed less efficient (n=6) or no (n=1) growth on glycogen all carried N-terminal deletions (respectively, 29 and 37 amino acid-deletions) in a putative pullulanase type I gene.
Discussion: L. crispatus strains isolated from LVM were not phenotypically distinct from L. crispatus strains isolated from DVM, however, the finding that the latter were more likely to carry a 3-fragmented glycosyltransferase gene may indicate a role for cell surface glycoconjugates, which may shape vaginal microbiota-host interactions. Furthermore, the observation that variation in the pullulanase type I gene associated with growth on glycogen discourages previous claims that L. crispatus cannot directly utilize glycogen.
Principles of Meiotic Chromosome Assembly
Authors: Schalbetter Stephanie A. , Fudenberg Geoffrey , Baxter Jonathan , Pollard Katherine S. , Neale Matthew J.
Published: October 2018

During 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.
Spectral and topological analysis of the cortical representation of the head position: does hypnotizability matter?
Authors: Ibanez-Marcelo Esther , Campioni Lisa , Manzoni Diego , Santarcangelo Enrica L , Petri Giovanni
Published: October 2018

The aim of the study was to assess the EEG correlates of head positions, which have never been studied in humans, in participants with different psychophysiological characteristics, as encoded by their hypnotizability scores. This choice is motivated by earlier studies suggesting different processing of the vestibular/neck proprioceptive information in subjects with high (highs) and low (lows) hypnotizability scores maintaining their head rotated toward one side (RH). We analysed EEG signals recorded in 20 highs and 19 lows in basal conditions (head forward) and during RH, using spectral analysis, which captures changes localized to specific recording sites, and Topological Data Analysis (TDA), which instead describes large-scale differences in processing and representing sensorimotor information. Spectral analysis revealed significant differences related to the head position for alpha1, beta2, beta3, gamma bands, but not to hypnotizability. TDA instead revealed global hypnotizability-related differences in the strengths of the correlations among recording sites during RH. Significant changes were observed in lows on the left parieto-occipital side and in highs in right fronto-parietal region. Significant differences between the two groups were found in the occipital region, where changes were larger in lows than in highs. The study reports findings of the EEG correlates of the head posture for the first time, indicates that hypnotizability modulates its representation/processing on large-scale and that spectral and topological data analysis provide complementary results.
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

Gene 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

Background

Biological 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.

Results

We 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.

Conclusions

We 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

Human 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

With 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.
EZH2 influences mdDA neuronal differentiation, maintenance and survival
Authors: Wever Iris , von Oerthel Lars , Wagemans Cindy M.R.J. , Smidt Marten P.
Published: October 2018

Over the last decade several components have been identified to be differentially expressed in subsets of mesodiencephalic dopaminergic (mdDA) neurons. These differences in molecular profile have been implied to be involved in the selective degeneration of the SNc neurons in Parkinson’s disease. The emergence and maintenance of individual subsets is dependent on different transcriptional programs already present during development. In addition to the influence of transcription factors, recent studies have led to the hypothesis that modifications of histones might also influence the developmental program of neurons. In this study we focus on the histone methyltransferase EZH2 and its role in the development and maintenance of mdDA neurons. We generated two different conditional knock out (cKO) mice; an En1Cre driven cKO, for deletion of Ezh2 in mdDA progenitors and a Pitx3Cre driven cKO, to study the effect of post-mitotic deletion of Ezh2 on mdDA neurons maturation and neuronal survival. During development Ezh2 was found to be important for the generation of the proper amount of TH+ neurons. The loss of neurons primarily affected a rostrolateral population, which is also reflected in the analysis of the subset marks, Ahd2 and Cck. In contrast to early genetic ablation, post-mitotic deletion of Ezh2 did not lead to major developmental defects at E14.5. However, in 6 months old animals Cck was found ectopically in the rostral domain of mdDA neurons and Ahd2 expression was reduced in more mediocaudal positioned cells. In addition, Pitx3Cre driven deletion of Ezh2 led to a progressive loss of TH+ cells in the VTA and these animals display reduced climbing behavior. Together, our data demonstrates that Ezh2 is important for the generation of mdDA neurons during development and that during adult stages Ezh2 is important for the preservation of proper neuronal subset identity and survival.
Resting-State Brain Fluctuation and Functional Connectivity Dissociate Moral Injury from Posttraumatic Stress Disorder
Authors: Sun Delin , Phillips Rachel D. , Mulready Hannah L. , Zablonski Stephen T. , Turner Jessica A. , Turner Matthew D. , McClymond Kathryn , Nieuwsma Jason A. , Morey Rajendra A.
Published: October 2018

Moral injury is closely associated with posttraumatic stress disorder (PTSD) and is characterized by disturbances in social and moral cognition. Little is known about the neural underpinnings of moral injury, and whether the neural correlates are different between moral injury and PTSD.

A sample of 26 US military veterans (2 females; 28~55 years old) were investigated to determine how moral injury experiences and PTSD symptoms are differentially related to spontaneous fluctuations indexed by low frequency fluctuation (ALFF) as well as functional connectivity during resting-state functional magnetic resonance imaging (fMRI) scanning.

ALFF in the left inferior parietal lobule (L IPL) was positively associated with moral injury sub-scores of transgressions, negatively associated with sub-scores of betrayals, and not related with PTSD symptoms. Moreover, functional connectivity between the L IPL and bilateral precuneus was positively related with PTSD symptoms and negatively related with moral injury total scores.

Our results provide the first evidence that moral injury and PTSD have dissociable neural underpinnings, and behaviorally distinct sub-components of moral injury are different in neural responses. The findings increase our knowledge of the neural distinctions between moral injury and PTSD and may contribute to developing nosology and interventions for military veterans afflicted with moral injury.
Indirect effects on fitness between individuals that have never met via an extended phenotype
Authors: Fisher David N. , Haines Jessica A. , Boutin Stan , Dantzer Ben , Lane Jeffrey E. , Coltman David W. , McAdam Andrew G.
Published: October 2018

Interactions between organisms are ubiquitous and have important consequences for phenotypes and fitness. Individuals can even influence those they never meet, if they have extended phenotypes which mean the environments others experience are altered. North American red squirrels (Tamiasciurus hudsonicus) guard food hoards, an extended phenotype that typically outlives the individual and is almost always inherited by non relatives. Hoarding by previous owners can therefore influence subsequent owners. We found that red squirrels bred earlier and had higher lifetime fitness if the previous owner was a male. This was driven by hoarding behaviour, as males and mid-aged squirrels had the largest hoards, and these effects persisted across owners, such that if the previous owner was male or died in mid-age subsequent occupants had larger hoards. Individuals can, therefore, influence each other’s resource dependent traits and fitness without meeting via extended phenotypes, and so the past can influence contemporary population dynamics.
Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans
Authors: Schubert Jonathan T.W. , Buchholz Verena N. , Föcker Julia , Engel Andreas K. , Röder Brigitte , Heed Tobias
Published: October 2018

We investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.
Comparative Modeling of Transcranial Magnetic and Electric Stimulation in Mouse, Monkey, and Human
Authors: Alekseichuk Ivan , Mantell Kathleen , Shirinpour Sina , Opitz Alexander
Published: October 2018

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin monkey, and human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans.

HIGHLIGHTS

Translational research in brain stimulation should account for large differences in induced electric fields in different organisms

We simulate TMS and TES electric fields using anatomically realistic finite element models in three species: mouse, monkey, and human

TMS with a 70 mm figure-8 coil creates an approximately 2-times weaker electric field in a mouse brain than in monkey and human brains, where electric field strength is comparable

Two-electrode TES creates an approximately 100-times stronger electric field in a mouse brain and 3.5-times stronger electric field in a monkey brain than in a human brain
Supply and consumption of glucose 6-phosphate in the chloroplast stroma
Authors: Preiser Alyssa L. , Banerjee Aparajita , Fisher Nicholas , Sharkey Thomas D.
Published: October 2018

Fructose 6-phosphate is an intermediate in the Calvin-Benson cycle and can be acted on by phosphoglucoisomerase to make glucose 6-phosphate (G6P) for starch synthesis. A high concentration of G6P is favorable for starch synthesis but can also stimulate G6P dehydrogenase initiating the glucose-6-phosphate shunt an alternative pathway around the Calvin-Benson cycle. A low concentration of glucose 6-phosphate will limit this futile cycle. In order to understand the biochemical regulation of plastidic glucose 6-phosphate supply and consumption, we characterized biochemical parameters of two key enzymes, phosphoglucoisomerase (PGI) and G6P dehydrogenase (G6PDH). We have found that the plastidic PGI in has a higherKmfor G6P compared to that for fructose 6-phosphate. TheKmof G6PDH isoform 1 is increased under reducing conditions. The other two isoforms exhibit less redox regulation; isoform 2 is the most inhibited by NADPH. Our results support the conclusion that PGI restricts stromal G6P synthesis limiting futile cycling via G6PDH. It also acts like a one-way valve, allowing carbon to leave the Calvin-Benson cycle but not reenter. We found flexible redox regulation of G6PDH that could regulate the glucose-6-phosphate shunt.

Highlight

Glucose 6-phosphate stimulates glucose-6-phosphate dehydrogenase. This enzyme is less active during the day but retains significant activity that is very sensitive to the concentration of glucose 6-phopshate.
Removing Confounding Factors Associated Weights in Deep Neural Networks Improves the Prediction Accuracy for Healthcare Applications
Authors: Wang Haohan , Wu Zhenglin , Xing Eric P.
Published: October 2018

The proliferation of healthcare data has brought the opportunities of applying data-driven approaches, such as machine learning methods, to assist diagnosis. Recently, many deep learning methods have been shown with impressive successes in predicting disease status with raw input data. However, the “black-box” nature of deep learning and the high-reliability requirement of biomedical applications have created new challenges regarding the existence of confounding factors. In this paper, with a brief argument that inappropriate handling of confounding factors will lead to models’ sub-optimal performance in real-world applications, we present an efficient method that can remove the influences of confounding factors such as age or gender to improve the across-cohort prediction accuracy of neural networks. One distinct advantage of our method is that it only requires minimal changes of the baseline model’s architecture so that it can be plugged into most of the existing neu-ral networks. We conduct experiments across CT-scan, MRA, and EEG brain wave with convolutional neural networks and LSTM to verify the efficiency of our method.
Species composition and altitudinal distribution of bumble bees (Hymenoptera: Apidae: Bombus) in the East Himalaya, Arunachal Pradesh, India
Authors: Streinzer Martin , Chakravorty Jharna , Neumayer Johann , Megu Karsing , Narah Jaya , Schmitt Thomas , Bharti Himender , Spaethe Johannes , Brockmann Axel
Published: October 2018

The East Himalaya is one of the world’s most biodiverse ecosystems. Yet, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high altitude insects that fulfill an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Himalayan bumble bees have been studied systematically for a few decades now, with the main focus on the western region, while the eastern part of the mountain range received little attention and only a few species are genuinely reported. During a three-year survey, we collected more than 700 bumble bee specimens of 21 species in Arunachal Pradesh, the largest of the north-eastern states of India. We collected a range of species that were previously known from a very limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat and conservation. We observed clear altitudinal patterns of species diversity, which open important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya.
Entomopathogenic nematodes increase predation success by inducing specific cadaver volatiles that attract healthy herbivores
Authors: Zhang Xi , Machado Ricardo A. R. , Doan Cong Van , Arce Carla C. M. , Hu Lingfei , Robert Christelle A. M.
Published: October 2018

Herbivore natural enemies, including predators, parasitoids and parasites, protect plants by regulating herbivore populations. Some parasites can increase their transmission efficiency by manipulating host behavior. Whether natural enemies can manipulate herbivore behavior to increase top-down control, however, is unknown. Here, we investigate if and how the entomopathogenic nematodeHeterorhabditis bacteriophora,an important biocontrol agent, modulates the behavior of the western corn rootworm,Diabrotica virgifera virgifera,a major maize pest, and how these behavioral changes affect the capacity of the nematode to control the rootworm. We found that healthy rootworm larvae are attracted to nematode-infected cadavers shortly before the emergence of the next generation of nematodes. Nematode-infected rootworms release distinct volatile bouquets, including butylated hydroxytoluene (BHT), which attracts rootworms to infected cadavers. In a soil setting, BHT attracts rootworms and reduces nematode resistance, resulting in increased infection rates and rootworm mortality as well as increased nematode reproductive success. Five out of seven tested insect species were found to be attracted to nematode-infected conspecifics, suggesting that attraction of healthy hosts to nematode-infected cadavers is widespread. This study reveals a new facet of the biology of entomopathogenic nematodes that increases their capacity to control a major root pest by increasing the probability of host encounters.