bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARPEGGIO: Automated Reproducible Polyploid EpiGenetic GuIdance workflOw
Authors: Milosavljevic Stefan , Kuo Tony , Decarli Samuele , Mohn Lucas , Sese Jun , Shimizu Kentaro K. , Shimizu-Inatsugi Rie , Robinson Mark D. 
Published: July 2020

AbstractWhole genome duplication (WGD) events are common in the evolutionary history of many living organisms. For decades, researchers have been trying to understand the genetic and epigenetic impact of WGD and its underlying molecular mechanisms. Particular attention was given to allopolyploid study systems, species resulting from an hybridization event accompanied by WGD. Investigating the mechanisms behind the survival of a newly formed allopolyploid highlighted the key role of DNA methylation. With the improvement of high-throughput methods, such as whole genome bisulfite sequencing (WGBS), an opportunity opened to further understand the role of DNA methylation at a larger scale and higher resolution. However, only a few studies have applied WGBS to allopolyploids, which might be due to lack of genomic resources combined with a burdensome data analysis process. To overcome these problems, we developed the Automated Reproducible Polyploid EpiGenetic GuIdance workflOw (ARPEGGIO): the first workflow for the analysis of epigenetic data in polyploids. This workflow analyzes WGBS data from allopolyploid species via the genome assemblies of the allopolyploid’s parent species. ARPEGGIO utilizes an updated read classification algorithm (EAGLE-RC), to tackle the challenge of sequence similarity amongst parental genomes. ARPEGGIO offers automation, but more importantly, a complete set of analyses including spot checks starting from raw WGBS data: quality checks, trimming, alignment, methylation extraction, statistical analyses and downstream analyses. A full run of ARPEGGIO outputs a list of genes showing differential methylation. ARPEGGIO’s design focuses on ease of use and reproducibility. ARPEGGIO was made simple to set up, run and interpret, and its implementation includes both package management and containerization. Here we discuss all the steps, challenges and implementation strategies; example datasets are provided to show how to use ARPEGGIO. In addition, we also test EAGLE-RC with publicly available datasets given a ground truth, and we show that EAGLE-RC decreases the error rate by 3 to 4 times compared to standard approaches. The goal of ARPEGGIO is to promote, support and improve polyploid research with a reproducible and automated set of analyses in a convenient implementation.
Evolutionary history determines population spread rate in a stochastic, rather than in a deterministic way
Authors: Frederik Mortier , Stefano Masier , Dries Bonte 
Published: July 2020

AbstractFragmentation of natural landscapes results in habitat and connectedness loss, making it one of the most impactful avenues of anthropogenic environmental degradation. Populations living in a fragmented landscape can adapt to this context, as witnessed in changing dispersal strategies, levels of local adaptation and changing life-history traits. This evolution, however, can have ecological consequences beyond a fragmented range. Since invasive dynamics are driven by the same traits affected by fragmentation, the question arises whether fragmented populations evolve to be successful invaders.In this study we assess population spread during three generations of two-spotted spider mite (Tetranychus urticae) population in a replicated experiment. Experimental populations evolved independently in replicated experimental metapopulations differing only in the level of habitat connectedness as determined by the inter-patch distance.We find that habitat connectedness did not meaningfully explain variation in population spread rate. Rather, variation within experimental populations that shared the same level of connectedness during evolution was larger than the one across these levels. Therefore, we conclude that experimental populations evolved different population spread capacities as a result of their specific evolutionary background independent but of the connectedness of the landscape. While population spread capacities may be strongly affected by aspects of a population’s evolutionary history, predicting it from identifiable aspects of the evolutionary history may be hard to achieve.
Molecular and clinicopathological characterization of a prognostic immune gene signature associated with MGMT methylation in glioblastoma
Authors: Zhao Liang , Zhang Jiayue , Xuan Shurui , Liu Zhiyuan , Wang Yu , Zhao Peng 
Published: July 2020

AbstractBackgroundO6-methylguanine-DNA methyltransferase (MGMT) methylation status affects tumor chemo-resistance and the prognosis of glioblastoma (GBM) patients. We aimed to investigate the role of MGMT methylation in the regulation of GBM immunophenotype and discover an effective biomarker to improve prognosis prediction of GBM patients.MethodsA total of 769 GBM patients with clinical information from five independent cohorts were enrolled in the present study. Samples from the Cancer Genome Atlas (TCGA) dataset were used as the training set, whereas transcriptome data from the Chinese Glioma Genome Atlas (CGGA) RNA-seq, CGGA microarray, GSE16011, and the Repository for Molecular Brain Neoplasia (REMBRANDT) cohort were used for validation. A series of bioinformatics approaches were carried out to construct a prognostic signature based on immune-related genes, which were tightly related with the MGMT methylation status. The influence of the signature on immunosuppression and remodeling of the tumor microenvironment were comprehensively investigated. Then, the utility of this immune gene signature was analyzed by the development and evaluation of a nomogram.ResultsWe found that MGMT unmethylation was closely associated with immune-related biological processes in GBM. Sixty-five immune genes were more highly expressed in the MGMT unmethylated than the MGMT methylated group. An immune gene-based risk model was further established to divide patients into high and low-risk groups, and the prognostic value of this signature was validated in several GBM cohorts. Functional analyses manifested a universal up-regulation of immune-related pathways in the high-risk group as compared to the low-risk group. Furthermore, the risk score was highly correlated to the immune cell infiltration, immunosuppression, inflammatory activities, as well as the expression levels of immune checkpoints. Finally, a nomogram was developed for clinical application.ConclusionsMGMT methylation is strongly related to the immune responses in GBM. The immune gene-based signature we identified may have potential implications in predicting the prognosis of GBM patients and mechanisms underlying the role of MGMT methylation.
Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay
Authors: Kobow Katja , Jabari Samir , Pieper Tom , Kudernatsch Manfred , Polster Tilman , Woermann Friedrich G , Kalbhenn Thilo , Hamer Hajo , Rössler Karl , Mühlebner Angelika , Spliet Wim GM , Feucht Martha , Hou Yanghao , Stichel Damian , Korshunov Andrey , Sahm Felix , Coras Roland , Blümcke Ingmar , von Deimling Andreas 
Published: July 2020

AbstractPolymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration and abnormal cortical lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying PMG development are not yet understood. About 40 genes have been associated with PMG, and small copy number variations have also been described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here we analyzed 26 PMG patients employing array-based DNA-methylation profiling on formalin-fixed paraffin-embedded material. A series of 62 well-characterized non-PMG cortical malformations (focal cortical dysplasia type 2a/b and hemimegalencephaly), temporal lobe epilepsy, and non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction and hierarchical cluster analysis of DNA methylation profiles showed that PMG formed a distinct DNA methylation class. Copy number profiling from DNA methylation data identified a uniform duplication spanning the entire long arm of chromosome 1 in 7 out of 26 PMG patients, which was verified by additional fluorescence in situ hybridization analysis. In respective cases about 50% of nuclei in the center of the PMG lesion were 1q triploid. No chromosomal imbalance was seen in adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, PMG 1q patients presented with a unilateral frontal or hemispheric PMG without hemimegalencephaly, a severe form of intractable epilepsy with seizure onset in the first months of life, and severe developmental delay. Our results show that PMG can be classified among other structural brain lesions according to their DNA methylation profile. One subset of PMG with distinct clinical features exhibits a duplication of chromosomal arm 1q.
Behavioral effects of developmental exposure to JWH-018 in wild type and disrupted in schizophrenia 1 (disc1) mutant zebrafish
Authors: García-González Judit , de Quadros Bruno , Brock Alistair J. , Brennan Caroline H. 
Published: July 2020

AbstractSynthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene with important roles in neurodevelopment which has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to JWH-018 (a common psychoactive synthetic cannabinoid) and (2) whetherdisc1moderates the effects of JWH-018. As altered anxiety responses are seen in a several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae, and novel tank diving in adults. Compared to controls, developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli was unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function indisc1increased anxiety but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has behavioral impact in zebrafish, which is not moderated bydisc1.
CRISPR-Cas9-mediated editing ofmyb28impairs glucoraphanin accumulation ofBrassica oleraceain the field
Authors: Neequaye Mikhaela , Stavnstrup Sophia , Lawrenson Tom , Hundleby Penny , Troncoso-Rey Perla , Saha Shikha , Harwood Wendy , Traka Maria H , Mithen Richard , Østergaard Lars 
Published: July 2020

SummaryWe sought to quantify the role ofMYB28in the regulation of aliphatic glucosinolate biosynthesis and associated sulphur metabolism in field-grownB. oleraceawith the use of CRISPR-Cas9-mediated gene editing technology. We describe the first characterisedmyb28knockout mutant inB. oleracea, and the first UK field trial of CRISPR-Cas9-mediated gene edited plants under the European Court of Justice interpretation of the 2001/18 EU GMO directive. We report that knocking-outmyb28results in downregulation of aliphatic glucosinolate biosynthesis genes and reduction in accumulation of the methionine-derived glucosinolate, glucoraphanin, in leaves and florets of field-grownmyb28mutant broccoli plants. There were no significant changes to the accumulation of sulphate, S-methyl cysteine sulfoxide and indole glucosinolate in leaf and floret tissues.
Lack of redundancy between electrophysiological measures of long-range neuronal communication
Authors: Strahnen Daniel , Kapanaiah Sampath K.T. , Bygrave Alexei M. , Kätzel Dennis 
Published: July 2020

ABSTRACTCommunication between brain areas has been implicated in a wide range of cognitive and emotive functions and is impaired in numerous mental disorders. In rodent models, various functional connectivity metrics have been used to quantify inter-regional neuronal communication. However, in individual studies, typically only very few measures of coupling are reported and, hence, redundancy across such indicators is implicitly assumed. In order to test this assumption, we here comparatively assessed a broad range of directional and non-directional metrics like coherence, weighted Phase-Lag-Index (wPLI), Granger causality (GC), spike-phase coupling (SPC), cross-regional phase-amplitude coupling, amplitude cross-correlations, and others. We applied these analyses to simultaneous field recordings from the prefrontal cortex and the ventral and dorsal hippocampus in the schizophrenia-relatedGria1-knockout mouse model which displays a robust novelty-induced hyperconnectivity phenotype. We find that across such measures there is a considerable lack of functional redundancy. While coherence and GC yielded similar results, other measures, especially wPLI and SPC, often produced deviating conclusions. Bivariate correlations within animals revealed that virtually none of the metrics consistently co-varied with any of the other measures across the three connections and two genotypes analysed. Parametric GC showed the qualitatively highest degree of redundancy with other metrics and would be most suitable for connectivity analysis. We conclude that analysis of multiple metrics is necessary to characterise functional connectivity.
BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection
Authors: Evans Azia S. , Lennemann Nicholas J. , Coyne Carolyn B. 
Published: July 2020

AbstractAutophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3-regulated autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3-mediated non-canonical autophagy.Summary StatementBPIFB3 is a regulator of a non-canonical cellular autophagy pathway that impacts the replication of enteroviruses and flaviviruses. Here we define ARFGAP1 and TMED9 as essential components of this pathway.
Pathogen-driven coevolution across CBP60 plant immune regulator subfamilies confers resilience on the regulator module
Authors: Zheng Qi , Majsec Kristina , Katagiri Fumiaki 
Published: July 2020

ABSTRACTAmong eight Arabidopsis CaM-Binding Protein (CBP) 60 family members, AtCBP60g and AtSARD1 are partially functionally redundant, major positive immune regulators while AtCBP60a is a negative immune regulator. Phylogenetic analysis of CBP60 protein sequences of 247 diverse land plant species indicated that the CBP60a, CBP60g, and SARD1 immune regulator subfamilies diversified around the time of Angiosperm divergence. The immune regulator subfamilies, especially the CBP60g subfamily, have been evolving very fast, suggesting strong selection pressure from CBP60-targeting pathogen effectors. We closely examined this fast evolution of the immune regulator subfamilies using the subfamily protein sequences from 12 diverse Core Eudicot species. The fast evolution was caused by both high proportions of polymorphic sites and high evolution rates per polymorphic site, compared to the genomic norm. We developed an analytical platform for physical-chemical characteristics of amino acids, called Protein Evolution Analysis in Euclidean Space (PEAES). Using the pairwise distance rank on PEAES (PEAES-PDR), we detected signatures of significant coevolutionary interactions across the immune regulator subfamilies within the CBP60-conserved domain. The patterns of detected coevolutionary interactions were consistent with hypothetical coevolutionary mechanisms that protect the positive immune regulator function from targeting by pathogen effectors. The coevolutionary interactions across the subfamilies were largely specific to each species lineage, suggesting that the coevolution occurred through species lineage-specific histories of variable pathogen pressure. Thus, fast coevolution of the subfamilies with overlapping or opposing functions appears crucial to maintain resilience of the CBP60 immune regulator module against fast-evolving pathogen effectors.
Human-specific GAPDH RT-qPCR is an accurate and sensitive method of xenograft metastasis quantification
Authors: Dahn Margaret L , Dean Cheryl A , Jo Diana B , Coyle Krysta M , Marcato Paola 
Published: July 2020

AbstractMetastasis is the primary cause of cancer-related mortality. Having experimental models that accurately reflect changes in the metastatic burden is imperative for developing improved treatments and a better understanding of the disease. The murine xenograft tumor model mimics the human scenario and provides a platform forin vivoandex vivometastasis quantification analyses. Histological analysis of hematoxylin and eosin (H&E) stained thin sections has been the gold standard for quantifying metastasisex vivobut gaining favor for its ease and accuracy is reverse transcription-qualitative polymerase chain reaction (RT-qPCR). Herein we directly compare histological and RT-qPCR-based methods for quantifying lung metastasis in a murine xenograft tumor model. Furthermore, we have introduced a variation of the RT-qPCR method; human-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDH) RT-qPCR, which allows quantification of metastasis in xenograft models, without the requirement of overexpression of exogenous genes. Human-specific GAPDH RT-qPCR detected increased lung metastasis resulting from aldehyde dehydrogenase 1A3 (ALDH1A3) expression in MDA-MB-231 breast cancer cells orthotopically implanted in NOD/SCID mice. Further, in the xenograft tumor model, human-specific GAPDH RT-qPCR was more sensitive and cost-effective than quantification of lung metastasis by histological analysis of H&E stained fixed thin sections. The two assays were highly correlative in terms of determining relative metastatic burden, suggesting that the human-specific GAPDH RT-qPCR method could be used as a standard method for quantification of disseminated human cells in murine xenograft models.
Intrauterine growth restriction causes cellular, molecular, and behavioral deficits consistent with abnormal dentate gyrus neurogenesis in mice
Authors: Brown Ashley S. , Wieben Matthew , Murdock Shelby , Chang Jill , Dizon Maria , Dorsky Richard I. , Fung Camille M. 
Published: July 2020

AbstractBackgroundChildren born with intrauterine growth restriction (IUGR) are at increased risk for cognitive impairment including learning and memory deficits. Dentate gyrus (DG) granule neurons relay cortical information into the hippocampus proper for memory formation, and their production is highly dependent on environmental signals. However, it is unknown whether IUGR affects DG neurogenesis, and thus provides a potential mechanism underlying abnormal learning and memory function.MethodsUsing a hypertensive disease of pregnancy mouse model of IUGR, we assessed multiple behaviors, quantified neural stem and progenitor cells (NSPCs) and developing neurons in the DG, and characterized transcriptional effects on molecular pathways in the hippocampus.ResultsWe found that the predominant behavioral phenotype in IUGR offspring, short-term implicit learning and memory deficits, was associated with accelerated DG neurogenesis and NSPC depletion. Consistent with known molecular regulators of DG neurogenesis, we also found strong evidence for decreased Wnt pathway activity following IUGR.ConclusionWe have discovered that postnatal memory deficits are associated with accelerated NSPC differentiation following IUGR, a phenotype that could be explained by decreased Wnt signaling.
Diel Oxygen Changes in Closed Ecological Systems; Predictive of Lake Metabolism?
Authors: Taub Frieda B. , Bridges David J. 
Published: July 2020

AbstractThe net oxygen change over a 24-hour day/night cycle in a laboratory study showed strong consistent patterns of (1)gain, when nutrients and light were available; (2)maintain, with daytime gains being matched by nighttime losses; and (3)loss, over brief periods of time during intense zooplankton grazing on previously grown phytoplankton or over long durations without an external source of nutrients. These were simplified aquatic communities closed to the atmosphere, Closed Ecological Systems (CES). Natural lakes are much more complex. While temperate lakes, having a winter accumulation of nutrients followed by sequential algal and zooplankton blooms, may show similar patterns, tropical and flood lakes may exhibit different patterns. Examination of archived lake metabolic studies could yield new insights while looking for these patterns by examining net ecosystem production (NEP), often measured as changes in oxygen concentrations.
Heritable associations with microbial communities are essential for necrotrophic pathogen resistance
Authors: Pogoda Cloe S. , Reinert Stephan , Talukder Zahirul I. , Attia Ziv , Corwin Jason A. , Money Kennedy L. , Collier-zans Erin C.E. , Underwood William , Gulya Thomas J. , Quandt C. Alisha , Kane Nolan C. , Hulke Brent S. 
Published: July 2020

AbstractHost-microbe interactions are increasingly recognized as important drivers of organismal health, growth, longevity, and community-scale ecological processes. However, less is known about how genetic variation affects hosts’ associated microbiomes and downstream phenotypes. We demonstrate that sunflower (Helianthus annuus) harbors substantial, heritable variation in microbial communities under field conditions. We show that microbial communities explain up to 77.5% of the heritable variation in resistance to root infection caused by the necrotrophic pathogenSclerotinia sclerotiorum, and that plants grown in sterilized soil showed almost complete elimination of pathogen resistance. Association mapping revealed 69 genetic locations related to microbial abundance andSclerotiniaresistance. Although the genetic architecture is complex and quantitative, we have, in large part, elucidated previously unexplained genetic variation for resistance to this pathogen. This suggests new targets for plant breeding and demonstrates the potential for heritable microbial associations to play important roles in defense in natural and human-altered environments.