bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoBRA: Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis - from differential peak calling to pathway analysis
Authors: Qiu Xintao , Feit Avery S. , Feiglin Ariel , Xie Yingtian , Kesten Nikolas , Taing Len , Perkins Joseph , Zhou Ningxuan , Gu Shengqing , Li Yihao , Cejas Paloma , Jeselsohn Rinath , Brown Myles , Liu X. Shirley , Long Henry W. 
Published: November 2020

AbstractChIP-seq and ATAC-seq have become essential technologies used as effective methods of measuring protein-DNA interactions and chromatin accessibility. However, there is a need for a scalable and reproducible pipeline that incorporates correct normalization between samples, adjustment of copy number variations, and integration of new downstream analysis tools. Here we present CoBRA, a modularized computational workflow which quantifies ChIP and ATAC-seq peak regions and performs unsupervised and supervised analysis. CoBRA provides a comprehensive state-of-the-art ChIP and ATAC-seq analysis pipeline that is usable by scientists with limited computational experience. This enables researchers to gain rapid insight into protein-DNA interactions and chromatin accessibility through sample clustering, differential peak calling, motif enrichment, comparison of sites to a reference DB and pathway analysis.Code availability:https://bitbucket.org/cfce/cobra
Implementing the precautionary approach into fisheries management: Making the case for probability-based harvest control rules
Authors: Mildenberger Tobias K. , Berg Casper W. , Kokkalis Alexandros , Hordyk Adrian R. , Wetzel Chantel , Jacobsen Nis S. , Punt André E. , Nielsen J. Rasmus 
Published: November 2020

AbstractThe precautionary approach to fisheries management advocates for risk-averse management strategies that include biological reference points as well as decision rules and account for scientific uncertainty. In this regard, two approaches have been recommended: (i) harvest control rules (HCRs) with threshold reference points to safeguard against low stock biomass, and (ii) theP* method, a ‘probability-based HCR’ that reduces the catch limit as a function of scientific uncertainty (i.e. process, model, and observation uncertainty). This study compares the effectiveness of these precautionary approaches in recovering over-exploited fish stocks with various life-history traits and under a wide range of levels of scientific uncertainty. We use management strategy evaluation based on a stochastic, age-based operating model with quarterly time steps and a stochastic surplus production model. The results show that the most effective HCR includes both a biomass threshold as well as theP* method, and leads to high and stable long-term yield with a decreased risk of low stock biomass. For highly dynamics stocks, management strategies that aim for higher biomass targets than the traditionally usedBMSYresult in higher long-term yield. This study makes the case for probability-based HCRs by demonstrating their benefit over deterministic HCRs and provides a list of recommendations regarding their definition and implementation.
Time-course in attractiveness of pheromone lure on the smaller tea tortrix moth: a generalized additive mixed model approach
Authors: Sudo Masaaki , Sato Yasushi , Yorozuya Hiroshi 
Published: November 2020

AbstractLong-term pest insect monitoring in agriculture and forestry has advanced population ecology. However, the discontinuation of research materials such as pheromone lure products jeopardizes data collection continuity, which constrains the utilization of the industrial datasets in ecology. Three pheromone lures against the smaller tea tortrix mothAdoxophyes honmaiYasuda (Lepidoptera; Tortricidae) were available but one was recently discontinued. Hence, a statistical method is required to convert data among records of moths captured with different lures. We developed several generalized additive mixed models (GAMM) separating temporal fluctuation in the background male density during trapping and attenuation of lure attractiveness due to aging or air exposure after settlement. We collected multisite trap data over four moth generations. The lures in each of these were unsealed at different times before trap settlement. We used cross-validation to select the model with the best generalization performance. The preferred GAMM had nonlinear density fluctuation terms and lure attractiveness decreased exponentially after unsealing. The attenuation rates varied among lures. A light trap dataset near the pheromone traps was a candidate for a male density predictor. Nevertheless, there was only a weak correlation between trap yields, suggesting the difficulty of data conversion between the traps differing in attraction mechanisms.
Function and regulation of chloroplast peroxiredoxin IIE
Authors: Dreyer Anna , Treffon Patrick , Basiry Daniel , Jozefowicz Anna Maria , Matros Andrea , Mock Hans-Peter , Dietz Karl-Josef 
Published: November 2020

AbstractPeroxiredoxins (PRX) are thiol peroxidases which are highly conserved throughout all biological kingdoms. Increasing evidence suggests that their high reactivity toward peroxides has a function not only in antioxidant defense but in particular in redox regulation of the cell. Peroxiredoxin IIE is one of three PRX types found in plastids and has previously been linked to pathogen defense and protection from protein nitration. However, its posttranslational regulation and its function in the chloroplast protein network remained to be explored. Using recombinant protein, it was shown that the peroxidatic Cys121 is subjected to multiple posttranslational modifications, namely disulfide formation, S-nitrosation, S-glutathionylation and hyperoxidation. Slightly oxidized glutathione fostered S-glutathionylation and inhibited activityin vitro. Immobilized recombinant PRX-IIE allowed trapping and subsequent identification of interaction partners by mass spectrometry. Interaction with the 14-3-3 ν protein was confirmedin vitroand was shown to be stimulated under oxidizing conditions. Interactions did not depend on phosphorylation as revealed by testing phospho-mimicry variants of PRX-IIE. Based on these data it is proposed that 14-3-3ν guides PRX-IIE to certain target proteins, possibly for redox regulation. These findings together with the other identified potential interaction partners of type II PRXs localized to plastids, mitochondria and cytosol provide a new perspective on the redox regulatory network of the cell.
Target-driven design of a coumarinyl chalcone scaffold based novel EF2 Kinase inhibitor suppresses breast cancer growthin vivo
Authors: Onder Ferah Comert , Kahraman Nermin , Atici Esen Bellur , Cagir Ali , Kandemir Hakan , Tatar Gizem , Tok Tugba Taskin , Karliga Bekir , Durdagi Serdar , Ay Mehmet , Ozpolat Bulent 
Published: November 2020

AbstractEukaryotic elongation factor 2 kinase (eEF-2K), an unusual alpha kinase, is involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is indicated as one of the critical drivers of breast cancer and associated with poor clinical prognosis, representing a potential molecular target. The crystal structure of eEF-2K is unknown and there is no potent and effective eEF-2K inhibitor reported for clinical applications. To meet this challenge, we designed and synthesized several generations of potential inhibitor compounds and performedin silicostudies. The effect of the inhibitors at the binding pocket of eEF-2K is analyzed after developing a 3D target model by homology modeling approaches using a domain of another α-kinase called myosin heavy-chain kinase A (MHCKA) that is closely resembling eEF-2K. Our results showed that compounds with coumarin-chalcone cores have a high predicted binding affinity for binding to eEF-2K. Followingin vitrostudies, we identified a compound that was highly effective in inhibiting eEF-2K activity at submicromolar concentrations and inhibited proliferation of various breast cancer cells with different features (BT20, MDA-MB-231, MDA-MB-436 and MCF-7) by induction of apoptosis while sparing normal cells.In vivosystemic administration of the the lead inhibitor encapsulated in single lipid-based nanoparticles twice a week significantly supressed growth of MDA-MB-231 tumors in orthotopic breast cancer models in nude mice. In conclusion, our study provides the firstin vivoeffective small molecule eEF-2K inhibitor that may be used for molecularly targeted precison medicine strategies in breast cancer or other eEF-2K-dependent tumors.
Microbiota-root-shoot axis modulation by MYC2 favoursArabidopsisgrowth over defence under suboptimal light
Authors: Hou Shiji , Thiergart Thorsten , Vannier Nathan , Mesny Fantin , Ziegler Jörg , Pickel Brigitte , Hacquard Stéphane 
Published: November 2020

ABSTRACTBidirectional root-shoot signalling is likely key in orchestrating stress responses and ensuring plant survival. Here we show thatArabidopsis thalianaresponses to microbial root commensals and light are interconnected along a microbiota-root-shoot axis. Microbiota and light manipulation experiments in a gnotobiotic system reveal that low photosynthetically active radiation (LP) perceived by leaves induce long-distance modulation of root bacterial, but not fungal or oomycetal communities. Reciprocally, bacterial root commensals and particularlyPseudomomasisolates are necessary for rescuing plant growth under LP. RNA-Seq, combined with leaf inoculation experiments with biotrophic and necrotrophic microbial pathogens indicate that microbiota-induced growth under LP coincides with transcriptional repression of immune responses, thereby increasing susceptibility to both pathogens. Inspection of a set ofA. thalianamutants demonstrates that orchestration of this light-dependent growth-defence trade-off requires the transcriptional regulator MYC2. Our work indicates that aboveground stress responses in plants can be governed by signals from microbial root commensals.
VTAM: A robust pipeline for validating metabarcoding data using internal controls
Authors: González Aitor , Dubut Vincent , Corse Emmanuel , Mekdad Reda , Dechatre Thomas , Meglécz Emese 
Published: November 2020

AbstractMetabarcoding studies should be carefully designed to minimize false positives and false negative occurrences. The use of internal controls, replicates, and several overlapping markers is expected to improve the bioinformatics data analysis.VTAM is a tool to perform all steps of data curation from raw fastq data to taxonomically assigned ASV (Amplicon Sequence Variant or simply variant) table. It addresses all known technical error types and includes other features rarely present in existing pipelines for validating metabarcoding data: Filtering parameters are obtained from internal control samples; cross-sample contamination and tag-jump are controlled; technical replicates are used to ensure repeatability; it handles data obtained from several overlapping markers.Two datasets were analysed by VTAM and the results were compared to those obtained with a pipeline based on DADA2. The false positive occurrences in samples were considerably higher when curated by DADA2, which is likely due to the lack of control for tag-jump and cross-sample contamination.VTAM is a robust tool to validate metabarcoding data and improve traceability, reproducibility, and comparability between runs and datasets.
Variant pathogenic prediction by locus variability, the importance of the last picture of evolution
Authors: Cabrera-Alarcon Jose Luis , Enriquez Jose Antonio , Martinez Jorge Garcia , Sánchez-Cabo Fátima 
Published: November 2020

ABSTRACTAccurate pathogenic detection for single nucleotide variants (SNVs) is a key problem to perform variant ranking in whole exome sequencing studies. Several in silico tools have been developed to identify deleterious variants. Locus variability, computed as Shannon entropy from gnomAD/helixMTdb variant allele frequencies can be used as pathogenic variants predictor. In this study we evaluate the use of Shannon entropy in non-coding mitochondrial DNA and also in coding regions with an additional selective pressure other than that imposed by the genetic code, as are splice-sites. To benchmark this functionality in non-coding mitochondrial variants, Shannon entropy was compared with HmtVar disease score, outperforming it in non-coding SNVs (AUCH=0.99 in ROC curve and PR-AUCH=1.00 in Precision-recall curve). In the same way, for splice-sites’ variants, Shannon entropy was compared against two state-of-the-art ensemble predictors ada score and rf score, matching their overall performance both in ROC curves (AUCH=0.95) and Precision-recall curves (PR-AUC=0.97). Therefore, locus variability could aid in variant ranking process for these specific types of SNVs.Contactjlcabreraa@cnic.es;fscabo@cnic.es
Epichloë festucaein mutualistic association withLolium perennesuppresses host apoplastic cysteine protease activity
Authors: Passarge Andrea , Demir Fatih , Green Kimberly , Depotter Jasper R.L. , Scott Barry , Huesgen Pitter F. , Doehlemann Gunther , Misas Villamil Johana C. 
Published: November 2020

AbstractPlants secrete various defence-related proteins into the apoplast, including proteases. Papain-like cysteine proteases (PLCPs) are central components of the plant immune system. To overcome plant immunity and successfully colonise their hosts, several plant pathogens secrete effector proteins inhibiting plant PLCPs. We hypothesized that not only pathogens but also mutualistic microorganisms interfere with PLCP-meditated plant defences to maintain endophytic colonisation with their hosts.Epichloë festucaeforms mutualist associations with cool season grasses and produces a range of secondary metabolites that protect the host against herbivores. In this study, we performed a genome wide identification ofLolium perennePLCPs, analysed their evolutionary relationship and classified them into nine PLCP subfamilies. Using activity-based protein profiling, we identified four active PLCPs in the apoplast ofL. perenneleaves that are inhibited during endophyte interactions. We characterized theL. perennecystatin LpCys1 for its inhibitory capacity against ryegrass PLCPs. LpCys1 inhibits LpCP2, indicating that LpCys1 might play a role in the suppression of PLCP activity during the interaction withE. festucae. However, since the activity of otherL. perennePLCPs is not sensitive to LpCys1 we propose that additional inhibitors are involved in the suppression of apoplastic PLCPs duringE. festucaeinfection.
Cortical representation of touchin silico
Authors: Huang Chao , Zeldenrust Fleur , Celikel Tansu 
Published: November 2020

AbstractWith its six layers and ~12000 neurons, a cortical column is a complex network whose function is plausibly greater than the sum of its constituents’. Functional characterization of its network components will require going beyond the brute-force modulation of the neural activity of a small group of neurons. Here we introduce an open-source, biologically inspired, computationally efficient network model of the somatosensory cortex’s granular and supragranular layers after reconstructing the barrel cortex in soma resolution. Comparisons of the network activity to empirical observations showed that thein siliconetwork replicates the known properties of touch representations and whisker deprivation-induced changes in synaptic strength inducedin vivo. Simulations show that the history of the membrane potential acts as a spatial filter that determines the presynaptic population of neurons contributing to a post-synaptic action potential; this spatial filtering might be critical for synaptic integration of top-down and bottom-up information.
Designer Scaffolds for Interfacial Bioengineering
Authors: Hickey Ryan J. , Latour Maxime Leblanc , Harden James L. , Pelling Andrew E. 
Published: November 2020

AbstractIn regenerative medicine, the healing of the interfacial zone between tissues is a major challenge, yet approaches for studying the complex microenvironment of this interface remain lacking. Here, we study these complex living interfaces by manufacturing modular “blocks” of naturally porous decellularized plant-derived scaffolds with a computer numerical controlled mill. We demonstrate how each scaffold can be seeded with different cell types and easily assembled in a manner akin to LEGO™ bricks to create an engineered tissue interface (ETI). Cells migrate across the interface formed between an empty scaffold and a scaffold pre-seeded with cells. However, when both scaffolds contain cells, only a shallow cross-over zone of cell infiltration forms at the interface. As a proof-of-concept study, we use ETIs to investigate the interaction between lab grown bone and connective tissues. Consistent with the above, a cross-over zone of the two distinct cell types forms at the interface between scaffolds, otherwise the populations remain distinct. Finally, we demonstrate how ETIs are biocompatible in vivo, becoming vascularized and integrated into surrounding tissue after implantation. This work creates new tissue design avenues for understanding biological processes or the development of synthetic artificial tissues.
Improved 7 Tesla Transmit Field Homogeneity with Reduced Electromagnetic Power Deposition Using Coupled Tic Tac Toe Antennas
Authors: Santini Tales , Wood Sossena , Krishnamurthy Narayanan , Martins Tiago , Aizenstein Howard J. , Ibrahim Tamer S. 
Published: November 2020

AbstractRecently cleared by the FDA, 7 Tesla (7T) MRI is a rapidly growing technology that can provide higher resolution and enhanced contrast in human MRI images. However, the increased operational frequency (~297 MHz) hinders its full potential since it causes inhomogeneities in the images and increases the power deposition in the tissues. This work describes the optimization of an innovative radiofrequency (RF) head coil coupled design, named Tic Tac Toe, currently used in large scale human MRI scanning at 7T; to date, this device was used in more than 1,300 patient/volunteer neuro 7T MRI scans. Electromagnetic simulations were performed for each of the coil’s antennas using the finite-difference time-domain method. Numerical optimizations were used to combine the calculated electromagnetic fields produced by these antennas, based on the superposition principle, and successfully produced homogeneous magnetic field distributions at low levels of power deposition in the tissues. The simulations were then successfully validated in-vivo using the Tic Tac Toe RF head coil system on a 7T MRI scanner.
First report in France ofCaenoplana decolorata, a recently described species of alien terrestrial flatworm (Platyhelminthes, Geoplanidae)
Authors: Justine Jean-Lou , Gey Delphine , Thévenot Jessica , Gouraud Clément , Winsor Leigh 
Published: November 2020

AbstractAlien land flatworms (family Geoplanidae) are invading many countries in the world. Some can easily be identified by their morphology and colour pattern, but some are more cryptic and necessitate a molecular approach.Caenoplana decolorataMateos et al., 2020 was recently described, from specimens found in Spain, as a sibling species toC. coeruleaMoseley, 1877. We found that one specimen collected in Nantes, France in 2014 had a 100% identity of its COI sequence with one specimen of the original description ofC. decolorata, and thus we record here the species for the first time in France.
Rapid compensatory evolution can rescue low fitness symbioses following partner-switching
Authors: Sørensen Megan E S , Wood A Jamie , Cameron Duncan D , Brockhurst Michael A 
Published: November 2020

AbstractPartner-switching plays an important role in the evolution of symbiosis, enabling local adaptation and recovery from the breakdown of symbiosis. Because of intergenomic epistasis, partner-switched symbioses may possess novel combinations of phenotypes but may also exhibit low fitness due to their lack of recent coevolutionary history. Here, we examine the structure and mechanisms of intergenomic epistasis in theParamecium-Chlorellasymbiosis and test if compensatory evolution can rescue initially low fitness partner-switched symbioses. Using partner-switch experiments coupled with metabolomics we show evidence for intergenomic epistasis wherein low fitness arose from mismatched photoprotection traits and the resulting light stress experienced by non-native symbionts when in high light environments. Experimental evolution under high light conditions revealed that an initially low fitness partner-switched non-native host-symbiont pairing rapidly adapted, gaining fitness equivalent to the native host symbiont pairing in less than 50 host generations. Compensatory evolution took two alternative routes: Either, hosts evolved higher symbiont loads to mitigate for their new algal symbiont’s poor performance, or the algal symbionts themselves evolved higher investment in photosynthesis and photoprotective traits to better mitigate light stress. These findings suggest that partner-switching combined with rapid compensatory evolution will enable the recovery and local adaptation of symbioses in response to changing environments.Significance statementSymbiosis enables the formation of new organisms through the merger of once independent species. Through symbiosis, species can acquire new functions, driving evolutionary innovation and underpinning important ecosystem processes. Symbioses that breakdown due to changing environmental conditions can reform by acquiring new symbionts in a process called partner-switching but may exhibit low fitness due to their lack of coadaptation. Using a microbial symbiosis between the single-celled eukaryoteParameciumand the green algaChlorellawe show that low fitness in partner-switched host-symbiont pairings arises from mismatched photoprotection traits. However, such low fitness partner-switched pairings can be rapidly rescued by adaptive evolution, regaining high fitness in less than 50 host generations. Partner-switching coupled with rapid compensatory evolution can enable symbioses to recover from breakdown.
Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk
Authors: Twigger Alecia-Jane , Engelbrecht Lisa K. , Bach Karsten , Schultz-Pernice Isabel , Petricca Stefania , Scheel Christina H. , Khaled Walid 
Published: November 2020

AbstractFindings from epidemiological studies suggest that breast cancer risk is influenced by parity in an age-dependent manner. However, human mammary tissue remodelling that takes place during pregnancy and lactation remain little understood due to the challenge of acquiring samples. Here, we present an approach to overcome this using single-cell RNA sequencing to examine viable primary mammary epithelial cells isolated from human milk compared to resting, non-lactating breast tissue. Thereby, we determined that separate to breast tissue, human milk largely contains epithelial cells belonging to the luminal lineage, as well as immune cells. Our data reveal the presence of two distinct secretory luminal cell clusters in milk which highly express luminal progenitor signatures akin to non-lactating breast tissue luminal cells. Taking advantage of the fact that both the resting and lactating mammary gland contain a luminal compartment, we focussed on comparing these transcriptomes and identified differences in mammary cell function and metabolism between these maturation states. These findings provide the basis to dissect human luminal differentiation and milk biosynthesis pathways that in the future, may be interrogated to determine how parity influences luminal cell metabolism and breast cancer risk.