bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis
Authors: Tian Hui , Billings Timothy , Walker Michael , Petkova Pavlina M. , Baker Christopher L. , Petkov Petko M. 
Published: May 2018

AbstractMeiotic recombination in most mammals requires recombination hotspot activation through the action of the histone 3 lysine-4 and lysine-36 methyltransferase PRDM9 to ensure successful double-strand break initiation and repair. Here we show that EWSR1, a protein whose role in meiosis was not previously clarified in detail, binds to both PRDM9 and pREC8, a phosphorylated meiosis-specific cohesin, in male meiotic cells. We created aEwsr1conditional knockout mouse models to deplete EWSR1 before the onset of meiosis, and found that absence of EWSR1 causes meiotic arrest with decreased histone trimethylation at meiotic hotspots, impaired DNA double-strand break repair, and reduced crossover number. Our results demonstrate that EWSR1 is essential for promoting PRDM9-dependent histone methylation and normal meiotic progress, possibly by facilitating the linking between PRDM9-bound hotspots and the nascent chromosome axis.Author SummaryIn most mammals, including humans and mice, genetic recombination initiates when the meiosis-specific protein PRDM9 binds specific DNA sequences, known as hotspots, at the beginning of the extended prophase I of meiosis, and activates them by trimethylating histone 3 at lysine-4 and lysine-36 on nearby nucleosomes. Although this activation of hotspots is believed to occur on the chromatin loops, the subsequent double-strand break formation and repair occur on a proteinaceous structure known as the chromosome axis. We now show that Ewing sarcoma RNA binding protein 1 (EWSR1) is a key player in early recombination events, binding to PRDM9, promoting PRDM9-dependent histone methylation, and facilitating the linking between PRDM9-bound hotspots and the nascent chromosome axis through the meiosis-specific cohesion REC8. As a result of these activities, EWSR1 assures sufficient numbers of properly positioned crossovers in each meiosis.
A novel PCR method directly quantifies sequence features that block primer extension
Authors: Cawthon Richard M. 
Published: May 2018

AbstractMany quantitative polymerase chain reaction (qPCR) assays indirectly quantify a target of interest as a drop in amplification signal relative to a larger total signal. The targeted sequence features include: DNA strand breaks introduced by enzymes that cleave at specific sequences or modifications, or caused by ionizing radiation or other DNA-damaging agents; DNA damage that does not break the DNA but blocks the DNA polymerase; and deletions of various sizes that prevent one or both primers from annealing. All of these loss of signal (a.k.a. negative) assays share the drawback of low sensitivity, as compared to positive assays, which generate an amplification signal that directly reflects the copy numbers of the sequence feature. Here we present a novel qPCR strategy that converts all of the above negative assays into positive ones. A mixture of three primers is added to genomic DNA, one primer pair that targets a sequence for strand-specific PCR, and a third, longer primer that prevents initiation of that PCR, by annealing at high temperature and extending across the target sequence, rendering it doublestranded and inaccessible for priming. Any sequence feature that blocks the third primer’s annealing or extension, while leaving the target sequence intact, allows the PCR to proceed and quantify the copy number of the sequence feature. This Primer Extension Blockade Enabled qPCR (PEBE-qPCR) method will facilitate many high-throughput, low-cost qPCR-based investigations in biology and medicine. As a first example, we present direct qPCR of the unmethylated allele at a MspI/HpaII site in the promoter of the human 45S rDNA gene.
CellexalVR: A virtual reality platform to visualise and analyse single-cell data
Authors: Legetth Oscar , Rodhe Johan , Lang Stefan , Dhapola Parashar , Pålsson Joel , Wallergård Mattias , Soneji Shamit 
Published: May 2018

AbstractSingle-cell RNAseq is a routinely used technique to explore the composition of cell populations, and they are often visualised using dimension reduction methods where the cells are represented in two or three dimensional space. Many tools are available to do this but visualising and cross-comparing these representations can be challenging, especially when cells are projected onto three dimensions which can be more informative for complex datasets. Here we present CellexalVR (www.cellexalvr.med.lu.se), a feature-rich, fully interactive virtual reality environment for the visualisation and analysis of single-cell experiments that allows researchers to intuitively and collaboratively gain an understanding of their data.
Synchrony surfacing: epicortical recording of correlated action potentials
Authors: Bockhorst Tobias , Pieper Florian , Engler Gerhard , Stieglitz Thomas , Galindo-Leon Edgar , Engel Andreas K. 
Published: May 2018

AbstractSynchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high-density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduce a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 µm) and combined large-coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modeling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the subjacent cortex. As a result, responses to sensory stimulation were more robust and less noisy as compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly-coding beyond the informative value of subdural EEG or single-unit spiking, and be advantageous to real-time applications in brain-machine interfacing.Significance statementElectrocorticography allows chronic, low-noise recordings from the intact cortical surface - a prerequisite for investigations into brain network dynamics and brain-machine interfaces. Novel electrodes can capture spiking activity at the surface, which should boost precision in the spatial - and time domain, compared to conventional EEG-like measurements. To clarify how surface spiking relates to intracortically fired action potentials, we recorded both types of signal simultaneously from sensory cortices in anesthetized ferrets. Results suggest that mesoscale (250 µm) surface electrodes can selectively capture synchronized spiking from nearby cortical columns, which reduces contamination by non-representative, jittering spikes. Given the high relevance of neural synchrony for sensorimotor and cognitive processing, the novel methodology may improve signal decoding in brain-machine interface approaches.Author contributionsE.G.L., T.B. and A.K.E. conceptualized the research; E.G.L. and F.P. performed experiments; T.B. and E.G.L. wrote Matlab routines for data analysis; T.B. and E.G.L. analyzed the data; T.S. provided technical resources; T.B., E.G.L. and A.K.E. wrote the manuscript; G.E. administrated the project; A.K.E. acquired funding.
Is there a problem with methods skills in cognitive neuroscience? Evidence from an online survey
Authors: Hauk Olaf 
Published: May 2018

AbstractCognitive neuroscience increasingly relies on complex data analysis methods. Researchers in this field come from highly diverse scientific backgrounds, such as psychology, engineering and medicine. This poses challenges with respect to acquisition of appropriate scientific computing and data analysis skills, as well as communication among researchers with different knowledge and skills sets. Are researchers in cognitive neuroscience adequately equipped to address these challenges? Here, we present evidence from an online survey of methods skills. Respondents (n=305) mainly comprised students and post-doctoral researchers working in the cognitive neurosciences. Multiple choice questions addressed a variety of basic and fundamental aspects of neuroimaging data analysis, such as signal analysis, linear algebra, and statistics. We analysed performance with respect to the following factors: undergraduate degree (grouped into Psychology, Methods, Biology), current researcher status (undergraduate student, PhD student, post-doctoral researcher), gender, and self-rated expertise levels. Overall accuracy was 72%. Not surprisingly, the Methods group performed best (87%), followed by Biology (73%) and Psychology (66%). Accuracy increased from undergraduate (59%) to PhD (74%) level, but not from PhD to post-doctoral (74%) level. The difference in performance for the Methods versus non-methods (Psychology/Biology) groups was particularly striking for questions related to signal analysis and linear algebra, two areas especially relevant to neuroimaging research. Self-rated methods expertise was not strongly predictive of performance. The majority of respondents (93%) indicated they would like to receive at least some additional training on the topics covered in this survey. In conclusion, methods skills among junior researchers in cognitive neuroscience can be improved, researchers are aware of this, and there is strong demand for more skills-oriented training opportunities. We hope that this survey will provide an empirical basis for the development of bespoke skills-oriented training programmes in cognitive neuroscience institutions.
Pre-existing Technological Core and Roots for the CRISPR Breakthrough
Authors: Magee Christopher L. , Kleyn Patrick W. , monks Brendan M. , Betz Ulrich , Basnet Subarna 
Published: May 2018

AbstractThis paper applies objective methods to explore the technological origins of the widely acclaimed CRISPR breakthrough in the technological domain of genome engineering. Previously developed patent search techniques are first used to recover a set of patents that well-represent the genome editing domain before CRISPR. Main paths are then determined from the citation network associated with this patent set allowing identification of the three major knowledge trajectories. The most significant of these trajectories for CRISPR involves the core of genome editing with less significant trajectories involving cloning and endonuclease specific developments. The major patents on the core trajectory are consistent with qualitative expert knowledge of the topical area. A second set of patents that we call the CRISPR roots are obtained by finding the patents directly cited by the recent CRISPR patents along with patents cited by that set of patents. We find that the CRISPR roots contain 8 key patents from the genome engineering main path associated with restriction endonucleases and the expected strong connection of CRISPR to prior genome editing technology such as Zn finger nucleases. Nonetheless, analysis of the full CRISPR roots shows that a very wide array of technological knowledge beyond genome engineering has contributed to achieving the CRISPR breakthrough. Such breadth in origins is not surprising since “spillover” is generally perceived as important and previous qualitative studies of CRISPR have shown not only technological breadth in origins but scientific breadth as well. In addition, we find that the estimated rate of functional performance improvement of the CRISPR roots set is about 9% per year compared to the genome engineering set (˜4 % per year). These estimates indicate below average rates of improvement and may indicate that CRISPR (and perhaps yet undiscovered) genome engineering developments could evolve in effectiveness over an upcoming long rather than short time period.
Unperturbed Expression Bias of Imprinted Genes in Schizophrenia
Authors: Gulyás-Kovács Attila , Keydar Ifat , Xia Eva , Fromer Menachem , Hoffman Gabriel , Ruderfer Douglas ,   CommonMind Consortium, Lipska Barbara K , Devlin Bernie , Hahn Chang-Gyu , Lewis David A , Domenici Enrico , Schadt Eric , Shah Hardik R , Johnson Jessica S , Buxbaum Joseph D , Klei Lambertus L , Peters Mette A , Roussos Panos , Gur Raquel E , Sieberts Solveig K , Perumal Thanneer M , Haroutunian Vahram , Sachidanandam Ravi , Chess Andrew 
Published: May 2018

AbstractHow gene expression correlates with schizophrenia across individuals is beginning to be examined through analyses of RNA-seq from post-mortem brains of individuals with disease and control brains. Here we focus on variation in allele-specific expression, following up on the Common Mind Consortium (CMC) RNA-seq experiments of nearly 600 human dorsolateral prefrontal cortex (DLPFC) samples. Analyzing the extent of allelic expression bias—a hallmark of imprinting—we find that the number of imprinted human genes is consistent with lower estimates (≈0.5% of all genes) and thus contradicts much higher estimates. Moreover, the handful of putatively imprinted genes are all in close genomic proximity to known imprinted genes. Joint analysis of the imprinted genes across hundreds of individuals allowed us to establish how allelic bias depends on various factors. We find that age and genetic ancestry have gene-specific, differential effect on allelic bias. In contrast, allelic bias appears to be independent of schizophrenia.
Size-by-environment interactions: a neglected dimension of species’ responses to environmental variation
Authors: Tredennick Andrew T. , Teller Brittany J. , Adler Peter B. , Hooker Giles , Ellner Stephen P. 
Published: May 2018

AbstractIn both plant and animal systems, size can determine whether an individual survives and grows under different environmental conditions. However, it is less clear whether and when size-dependent responses to the environment affect population dynamics. Size-by-environment interactions create pathways for environmental fluctuations to influence population dynamics by allowing for negative covariation between sizes within vital rates (e.g., small and large individuals have negatively covarying survival rates) and/or size-dependent variability in a vital rate (e.g., survival of large individuals varies less than small individuals through time). Whether these phenomena affect population dynamics depends on how they are mediated by elasticities (they must affect the sizes and vital rates that matter) and their projected impacts will depend on model functional form (the impact of reduced variance depends on the relationship between the environment and vital rate). We demonstrate these ideas with an analysis of fifteen species from five semiarid plant communities. We find that size-by-environment interactions are common but do not impact long-term population dynamics. Size-by-environment interactions may yet be important for other species. Our approach can be applied to species in other ecosystems to determine if and how size-by-environment interactions allow them to cope with, or exploit, fluctuating environments.
Co-exposure to multipleRanavirustypes enhances viral infectivity and replication in a larval amphibian system
Authors: Mihaljevic Joseph R. , Hoverman Jason T. , Johnson Pieter T.J. 
Published: May 2018

AbstractMultiple pathogens commonly co-occur in animal populations, yet few studies demonstrate how co-exposure of individual hosts scales up to affect transmission. Although viruses in the genusRanavirusare globally widespread and multiple virus species or strains likely co-occur in nature, no studies have examined how co-exposure affects infection dynamics in larval amphibians. We exposed individualRana aurora(Northern red-legged frog) larvae toAmbystoma tigrinumvirus (ATV), frog virus 3 (FV3), or an FV3-like strain isolated from a frog-culturing facility in Georgia, USA (RCV-Z2). We compared single-virus to pairwise co-exposures, while experimentally accounting for dosage. Co-exposure to ATV and FV3-like strains resulted in almost twice as many infected individuals compared to single-virus exposures, suggesting an effect of co-exposure on viral infectivity. The viral load in infected individuals exposed to ATV and FV3 was also higher than the single-dose FV3 treatment, suggesting an effect of co-exposure on viral replication. In a follow-up experiment, we examined how the co-occurrence of ATV and FV3 affected epizootics in mesocosm populations of larvalPseudacris triseriata(Western chorus frog). Although ATV did not generally establish within host populations (<4% prevalence), when ATV and FV3 were both present, this co-exposure resulted in a larger epizootic of FV3. Our results emphasize the importance of multi-pathogen interactions in epizootic dynamics and have management implications for natural and commercial amphibian populations.
The African Bullfrog (Pyxicephalus adspersus) genome unites the two ancestral ingredients for making vertebrate sex chromosomes
Authors: Denton Robert D. , Kudra Randal S. , Malcom Jacob W. , Preez Louis Du , Malone John H. 
Published: May 2018

ABSTRACTHeteromorphic sex chromosomes have evolved repeatedly among vertebrate lineages despite largely deleterious reductions in gene dose. Understanding how this gene dose problem is overcome is hampered by the lack of genomic information at the base of tetrapods and comparisons across the evolutionary history of vertebrates. To address this problem, we produced a chromosome-level genome assembly for the African Bullfrog (Pyxicephalus adspersus)—an amphibian with heteromorphic ZW sex chromosomes—and discovered that the Bullfrog Z is surprisingly homologous to substantial portions of the human X. Using this new reference genome, we identified ancestral synteny among the sex chromosomes of major vertebrate lineages, showing that non-mammalian sex chromosomes are strongly associated with a single vertebrate ancestral chromosome, while mammals are associated with another that displays increased haploinsufficiency. The sex chromosomes of the African Bullfrog however, share genomic blocks with both humans and non-mammalian vertebrates, connecting the two ancestral chromosome sequences that repeatedly characterize vertebrate sex chromosomes. Our results highlight the consistency of sex-linked sequences despite sex determination system lability and reveal the repeated use of two major genomic sequence blocks during vertebrate sex chromosome evolution.
A heuristic method for fast and accurate phasing and imputation of single nucleotide polymorphism data in bi-parental plant populations
Authors: Gonen Serap , Wimmer Valentin , Gaynor R. Chris , Byrne Ed , Gorjanc Gregor , Hickey John M. 
Published: May 2018

AbstractThis paper presents a new heuristic method for phasing and imputation of genomic data in diploid plant species. Our method, called AlphaPlantImpute, explicitly leverages features of plant breeding programs to maximise the accuracy of imputation. The features are a small number of parents, which can be inbred and usually have high-density genomic data, and few recombinations separating parents and focal individuals genotyped at low-density (i.e. descendants that are the imputation targets). AlphaPlantImpute works roughly in three steps. First, it identifies informative low-density genotype markers in parents. Second, it tracks the inheritance of parental alleles and haplotypes to focal individuals at informative markers. Finally, it uses this low-density information as anchor points to impute focal individuals to high-density.We tested the imputation accuracy of AlphaPlantImpute in simulated bi-parental populations across different scenarios. We also compared its accuracy to existing software called PlantImpute. In general, AlphaPlantImpute had better or equal imputation accuracy as PlantImpute. The computational time and memory requirements of AlphaPlantImpute were tiny compared to PlantImpute. For example, accuracy of imputation was 0.96 for a scenario where both parents were inbred and genotyped at 25,000 markers per chromosome and a focal F2 individual was genotyped with 50 markers per chromosome. The maximum memory requirement for this scenario was 0.08 GB and took 37 seconds to complete.
Chloroplast competition is controlled by lipid biosynthesis in evening primroses
Authors: Sobanski Johanna , Giavalisco Patrick , Fischer Axel , Kreiner Julia , Walther Dirk , Schöttler Mark Aurel , Pellizzer Tommaso , Golczyk Hieronim , Obata Toshihiro , Bock Ralph , Sears Barbara B. , Greiner Stephan 
Published: May 2018

AbstractIn most eukaryotes, organellar genomes are transmitted preferentially by the mother, but molecular mechanisms and evolutionary forces underlying this fundamental biological principle are far from understood. It is believed that biparental inheritance promotes competition between the cytoplasmic organelles and allows the spread of so-called selfish cytoplasmic elements. Those can be, for example, fast replicating or aggressive chloroplasts (plastids) that are incompatible with the hybrid nuclear genome and therefore maladaptive. Here we show that the ability of plastids to compete against each other is a metabolic phenotype determined by extremely rapidly evolving genes in the plastid genome of the evening primroseOenothera. Repeats in the regulatory region ofaccD(the plastid-encoded subunit of the acetyl-CoA carboxylase, which catalyzes the first and rate limiting step of lipid biosynthesis), as well as inycf2(a giant reading frame of still unknown function), are responsible for the differences in competitive behavior of plastid genotypes. Polymorphisms in these genes influence lipid synthesis and most likely profiles of the plastid envelope membrane. These in turn determine plastid division and/or turn-over rates and hence competitiveness. This work uncovers cytoplasmic drive loci controlling the outcome of biparental chloroplast transmission. Here, they define the mode of chloroplast inheritance, since plastid competitiveness can result in uniparental inheritance (through elimination of the “weak” plastid) or biparental inheritance (when two similarly “strong” plastids are transmitted).Significance statementPlastids and mitochondria are usually uniparentally inherited, typically maternally. When the DNA-containing organelles are transmitted to the progeny by both parents, evolutionary theory predicts that the maternal and paternal organelles will compete in the hybrid. As their genomes do not undergo sexual recombination, one organelle will “try” to outcompete the other, thus favoring the evolution and spread of aggressive cytoplasms. The investigations described here in the evening primrose, a model species for biparental plastid transmission, have discovered that chloroplast competition is a metabolic phenotype. It is conferred by rapidly evolving genes that are encoded on the chloroplast genome and control lipid biosynthesis. Due to their high mutation rate these loci can evolve and become fixed in a population very quickly.