bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dark Control: Towards a Unified Account of Default Mode Function by Markov Decision Processes
Authors: Dohmatob Elvis , Dumas Guillaume , Bzdok Danilo 
Published: June 2017

AbstractThe default mode network (DMN) is believed to subserve the baseline mental activity in humans. Its highest energy consumption compared to other brain networks and its intimate coupling with conscious awareness are both pointing to an overarching function. Many research streams speak in favor of an evolutionarily adaptive role in envisioning experience to anticipate the future. In the present work, we propose aprocess modelthat tries to explainhowthe DMN may implement continuous evaluation and prediction of the environment to guide behavior. Specifically, we answer the question whether the neurobiological properties of the DMN collectively provide the computational building blocks necessary for a Markov Decision Process. We argue that our formal account of DMN function naturally accommodates as special cases previous interpretations based on (1) predictive coding, (2) semantic associations, and (3) a sentinel role. Moreover, this process model for the neural optimization of complex behavior in the DMN offers parsimonious explanations for recent experimental findings in animals and humans.
Replicating and cycling stores of information perpetuate life
Authors: Jose Antony M. 
Published: June 2017

AbstractLife is perpetuated through a single-cell bottleneck between generations in many organisms. Here, I highlight that this cell holds information in two distinct forms: in the linear DNA sequence that is replicated during cell divisions, and in the three-dimensional arrangement of molecules that can change during development but that is recreated at the start of each generation. These two interdependent stores of information – one replicating with each cell division and the other cycling with a period of one generation – coevolve while perpetuating an organism. Unlike the genome, the cycling arrangement of molecules, which could include RNAs, proteins, sugars, lipids, etc., is not well understood. Because this arrangement and the genome are together transmitted from one generation to the next, analysis of both is necessary to understand evolution, origins of inherited diseases, and consequences of genome engineering. Recent developments suggest that tools are in place to examine how all the information to build an organism is encoded within a single cell, and how this cell code is reproduced in every generation.
Research Synergy and Drug Development: Bright Stars in Neighboring Constellations
Authors: Keserci Samet , Livingston Eric B. , Wan Lingtian , Pico Alexander R. , Chacko George 
Published: June 2017

AbstractDrug discovery and subsequent availability of a new breakthrough therapeutic or ‘cure’ is a compelling example of societal benefit from research advances. These advances are invariably collaborative, involving the contributions of many scientists to a discovery network in which theory and experiment are built upon. To understand such scientific advances, data mining of public and commercial data sources coupled with network analysis can be used as a digital methodology to assemble and analyze component events in the history of a therapeutic. This methodology is extensible beyond the history of therapeutics and its use more generally supports (i) efficiency in exploring the scientific history of a research advance (ii) documenting and understanding collaboration (iii) portfolio analysis, planning and optimization (iv) communication of the societal value of research. As a proof of principle, we have conducted a case study of five anti-cancer therapeutics. We have linked the work of roughly 237,000 authors in 106,000 scientific publications that capture the research crucial for the development of these five therapeutics. We have enriched the content of networks of these therapeutics by annotating them with information on research awards as well as peer review that preceded these awards. Applying retrospective citation discovery, we have identified a core set of publications cited in the networks of all five therapeutics and additional intersections in combinations of networks as well as awards from the National Institutes of Health that supported this research. Lastly, we have mapped these awards to their cognate peer review panels, identifying another layer of collaborative scientific activity that influenced the research represented in these networks.
Approximate inference of gene regulatory network models from RNA-Seq time series data
Authors: Thorne Thomas 
Published: June 2017

AbstractInference of gene regulatory network structures from RNA-Seq data is challenging due to the nature of the data, as measurements take the form of counts of reads mapped to a given gene. Here we present a model for RNA-Seq time series data that applies a negative binomial distribution for the observations, and uses sparse regression with a horseshoe prior to learn a dynamic Bayesian network of interactions between genes. We use a variational inference scheme to learn approximate posterior distributions for the model parameters. The methodology is benchmarked on synthetic data designed to replicate the distribution of real world RNA-Seq data. We compare our method to other sparse regression approaches and information theoretic methods. We demonstrate an application of our method to a publicly available human neuronal stem cell differentiation RNA-Seq time series.
Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly
Authors: Aneichyk Tatsiana , Hendriks William.T. , Yadav Rachita , Shin David , Gao Dadi , Vaine Christine A. , Collins Ryan L. , Stortchevoi Alexei , Currall Benjamin , Brand Harrison , Hanscom Carrie , Antolik Caroline , Dy Marisela , Ragavendran Ashok , Acuña Patrick , Go Criscely , Sapir Yechiam , Wainger Brian J. , Henderson Daniel , Dhakal Jyotsna , Ito Naoto , Weisenfeld Neil , Jaffe David , Sharma Nutan , Breakefield Xandra O. , Ozelius Laurie J. , Bragg D. Cristopher , Talkowski Michael E. 
Published: June 2017

SummaryX-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease endemic to the Philippines. We integrated genome and transcriptome assembly with induced pluripotent stem cell-based modeling to identify the XDP causal locus and potential pathogenic mechanism. Genome sequencing identified novel variation that was shared by all probands and three recombination events that narrowed the causal locus to a genomic segment includingTAF1. Transcriptome assembly in neural derivative cells discovered novelTAF1transcripts, including a truncated transcript exclusively observed in probands that involved aberrant splicing and intron retention (IR) associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion. This IR correlated with decreased expression of the predominantTAF1transcript and altered expression of neurodevelopmental genes; both the IR and aberrantTAF1expression patterns were rescued by CRISPR/Cas9 excision of the SVA. These data suggest a unique genomic cause of XDP and may provide a roadmap for integrative genomic studies in other unsolved Mendelian disorders.HighlightsGenome assembly narrows the XDP causal locus to a segment includingTAF1XDP-specific SVA insertion induces intron retention and down-regulation ofTAF1CRISPR/Cas9 excision of SVA rescues aberrant splicing and cTAF1 expression in XDPGene networks perturbed in proband cells associate to synapse and neurodevelopment
Sparse coding and dimensionality reduction in cortex
Authors: Beyeler Michael , Rounds Emily , Carlson Kristofor D. , Dutt Nikil , Krichmar Jeffrey L. 
Published: June 2017

AbstractSupported by recent computational studies, sparse coding and dimensionality reduction are emerging as a ubiquitous coding strategy across brain regions and modalities, allowing neurons to achieve nonnegative sparse coding (NSC) by efficiently encoding high-dimensional stimulus spaces using a sparse and parts-based population code. Reducing the dimensionality of complex, multimodal sensory streams is critically important for metabolically constrained brain areas to represent the world. In this article, we provide an overview of NSC, summarize evidence for its role in neural computation in disparate regions of the brain, ranging from visual processing to spatial navigation, and speculate that specific forms of synaptic plasticity and homeostatic modulation may underlie its implementation. We suggest that NSC may be an organizing principle in the nervous system.
An extinct hummingbird species that never was: a cautionary tale about sampling issues in molecular phylogenetics
Authors: Pérez-Emán Jorge L. , Perdigón Ferreira Jhoniel , Gutiérrez-Pinto Natalia , Cuervo Andrés M. , Céspedes Laura N. , Witt Christopher C. , Cadena Carlos Daniel 
Published: June 2017

ABSTRACTThe Bogota Sunangel (Heliangelus zusii) was described based on a historical specimen lacking locality data as a striking–and potentially extinct– new species of hummingbird more than two decades ago. However, it was considered a dubious taxon by some researchers until a molecular study with strong species-level taxon sampling revealed its phylogenetic affinities and validated its status as a distinct species. We reanalysed existing mitochondrial DNA data together with a new data set sampling multiple populations of the Long-tailed Sylph (Aglaiocercus kingii), a species broadly distributed in the Andes of South America. In contrast to previous work, we found thatH. zusiishares a haplotype with specimens ofA. kingiifrom the Eastern Cordillera of Colombia, which is phylogenetically nested within a clade formed by populations ofA. kingiifrom the Colombian Andes. These results suggest thatH. zusiiis not a distinct species, but is most likely the result of hybridization between a femaleA. kingiiand a male of another hummingbird species. These findings highlight the importance of thorough taxonomic and geographic sampling when assessing the likelihood of hybrid origin of an organism, particularly in cases potentially involving wide-ranging species in areas where deep phylogeographic structure is likely.
Pericyte ontogeny: the use of chimeras to track a cell lineage of diverse germ line origins
Authors: Etchevers Heather C. 
Published: June 2017

AbstractThe goal of lineage tracing is to understand body formation over time by discovering which cells are the progeny of a specific, identified, ancestral progenitor. Subsidiary questions include unequivocal identification of what they have become, how many descendants develop, whether they live or die, and where they are located in the tissue or body at the end of the window examined. A classical approach in experimental embryology, lineage tracing continues to be used in developmental biology, stem cell and cancer research, wherever cellular potential and behavior need to be studied in multiple dimensions, of which one is time. Each technical approach has its advantages and drawbacks. This chapter, with some previously unpublished data, will concentrate non-exclusively on the use of interspecies chimeras to explore the origins of perivascular (or mural) cells, of which those adjacent to the vascular endothelium are termed pericytes for this purpose. These studies laid the groundwork for our understanding that pericytes derive from progenitor mesenchymal pools of multiple origins in the vertebrate embryo, some of which persist into adulthood. The results obtained through xenografting, like in the methodology described here, complement those obtained through genetic lineage tracing techniques within a given species.
High contiguityArabidopsis thalianagenome assembly with a single nanopore flow cell
Authors: Michael Todd P. , Jupe Florian , Bemm Felix , Timothy Motley S. , Sandoval Justin P. , Loudet Olivier , Weigel Detlef , Ecker Joseph R. 
Published: June 2017

AbstractWhile many evolutionary questions can be answered by short read re-sequencing, presence/absence polymorphisms of genes and/or transposons have been largely ignored in large-scale intraspecific evolutionary studies. To enable the rigorous analysis of such variants, multiple high quality and contiguous genome assemblies are essential. Similarly, while genome assemblies based on short reads have made genomics accessible for non-reference species, these assemblies have limitations due to low contiguity. Long-read sequencers and long-read technologies have ushered in a new era of genome sequencing where the lengths of reads exceed those of most repeats. However, because these technologies are not only costly, but also time and compute intensive, it has been unclear how scalable they are. Here we demonstrate a fast and cost effective reference assembly for anArabidopsis thalianaaccession using the USB-sized Oxford Nanopore MinION sequencer and typical consumer computing hardware (4 Cores, 16Gb RAM). We assemble the accession KBS-Mac-74 into 62 contigs with an N50 length of 12.3 Mb covering 100% (119 Mb) of the non-repetitive genome. We demonstrate that the polished KBS-Mac-74 assembly is highly contiguous with BioNano optical genome maps, and of high per-base quality against a likewise polished Pacific Biosciences long-read assembly. The approach we implemented took a total of four days at a cost of less than 1,000 USD for sequencing consumables including instrument depreciation.
EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment
Authors: Eva Richard , Koseki Hiroaki , Kanamarlapudi Venkateswarlu , Fawcett James W. 
Published: June 2017

AbstractIt is not clear why central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 positive carriers. We reasoned that this exclusion might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this hypothesis using laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 GEF EFA6. EFA6 exerts its effects from a previously unreported location within the axon initial segment (AIS). EFA6 does not localise here in DRG axons, and in these neurons, ARF activation is counteracted by an ARF-GAP which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whilst overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the axon initial segment, signalling and transport.Summary StatementWe identify a novel resident of the axon initial segment, EFA6. This functions to prevent growth-promoting molecules from entering mature CNS axons. Removing EFA6 elevates the axon’s regenerative potential.
Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA)
Authors: Michelmann Sebastian , Treder Matthias S. , Griffiths Benjamin , Kerrén Casper , Roux Frédéric , Wimber Maria , Rollings David , Sawlani Vijay , Chelvarajah Ramesh , Gollwitzer Stephanie , Kreiselmeyer Gernot , Hamer Hajo , Bowman Howard , Staresina Bernhard , Hanslmayr Simon 
Published: June 2017

AbstractIntracranial recordings from patients implanted with depth electrodes are a valuable source of information in cognitive neuroscience. They allow for the unique opportunity to record brain activity with a high spatial and temporal resolution. To extract the local signal of interest in stereotactic EEG (S-EEG) data, a common pre-processing choice is to re-reference the data with a bipolar montage.With bipolar reference, each channel is subtracted from its neighbour in order to reduce commonalities between channels and isolate activity that is spatially confined. We here challenge the assumption that bipolar reference can effectively perform this task. We argue that in order to extract local activity, the distribution of the signal source of interest, as well as the distribution of interfering distant signals and noise sources need to be considered. Those can have a variable spatial extent and are modulated by electrode spacing, location and anatomical characteristics. Those factors are not accounted for by a fixed referencing scheme and bipolar reference can therefore not only decrease the signal to noise ratio (SNR) of the data, but also lead to mislocalization of activity and consequently to misinterpretation of results.We promote the perspective of regarding referencing as a spatial filtering operation with fixed coefficients. As an alternative, we propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. We argue that ICA performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and can therefore be used to identify activity that is local. We first describe and demonstrate this procedure on human S-EEG recordings. In a simulation with real data, we then quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when it comes to revealing local time series from the superposition of neighbouring channels.
Ecophysiology of freshwater Verrucomicrobia inferred from metagenome-assembled genomes
Authors: He Shaomei , Stevens Sarah LR , Chan Leong-Keat , Bertilsson Stefan , del Rio Tijana Glavina , Tringe Susannah G , Malmstrom Rex R , McMahon Katherine D 
Published: June 2017

ABSTRACTMicrobes are critical in carbon and nutrient cycling in freshwater ecosystems. Members of the Verrucomicrobia are ubiquitous in such systems, yet their roles and ecophysiology are not well understood. In this study, we recovered 19 Verrucomicrobia draft genomes by sequencing 184 time-series metagenomes from a eutrophic lake and a humic bog that differ in carbon source and nutrient availabilities. These genomes span four of the seven previously defined Verrucomicrobia subdivisions, and greatly expand the known genomic diversity of freshwater Verrucomicrobia. Genome analysis revealed their potential role as (poly)saccharide-degraders in freshwater, uncovered interesting genomic features for this life style, and suggested their adaptation to nutrient availabilities in their environments. Between the two lakes, Verrucomicrobia populations differ significantly in glycoside hydrolase gene abundance and functional profiles, reflecting the autochthonous and terrestrially-derived allochthonous carbon sources of the two ecosystems respectively. Interestingly, a number of genomes recovered from the bog contained gene clusters that potentially encode a novel porin-multiheme cytochromeccomplex and might be involved in extracellular electron transfer in the anoxic humic-rich environment. Notably, most epilimnion genomes have large numbers of so-called “Planctomycete-specific” cytochromec-containing genes, which exhibited nearly opposite distribution patterns with glycoside hydrolase genes, probably associated with the different environmental oxygen availability and carbohydrate complexity between lakes/layers. Overall, the recovered genomes are a major step towards understanding the role, ecophysiology and distribution of Verrucomicrobia in freshwater.IMPORTANCEFreshwater Verrucomicrobia are cosmopolitan in lakes and rivers, yet their roles and ecophysiology are not well understood, as cultured freshwater Verrucomicrobia are restricted to one subdivision of this phylum. Here, we greatly expand the known genomic diversity of this freshwater lineage by recovering 19 Verrucomicrobia draft genomes from 184 metagenomes collected from a eutrophic lake and a humic bog across multiple years. Most of these genomes represent first freshwater representatives of several Verrucomicrobia subdivisions. Genomic analysis revealed Verrucomicrobia as potential (poly)saccharide-degraders, and suggested their adaptation to carbon source of different origins in the two contrasting ecosystems. We identified putative extracellular electron transfer genes and so-called “Planctomycete-specific” cytochromec-containing genes, and found their distinct distribution patterns between the lakes/layers. Overall, our analysis greatly advances the understanding of the function, ecophysiology and distribution of freshwater Verrucomicrobia, while highlighting their potential role in freshwater carbon cycling.
Maternal loading of a small heat shock protein increases embryo thermal tolerance inDrosophila melanogaster
Authors: Lockwood Brent L. , Julick Cole R. , Montooth Kristi L. 
Published: June 2017

ABSTRACTMaternal investment is likely to have direct effects on offspring survival. In oviparous animals whose embryos are exposed to the external environment, maternal provisioning of molecular factors like mRNAs and proteins may help embryos cope with sudden changes in the environment. Here we sought to modify the maternal mRNA contribution to offspring embryos and test for maternal effects on acute thermal tolerance in early embryos ofDrosophila melanogaster. We drove in vivo overexpression of a small heat shock protein gene (Hsp23) in female ovaries and measured the effects of acute thermal stress on offspring embryonic survival and larval development. We report that overexpression of theHsp23gene in female ovaries produced offspring embryos with increased thermal tolerance. We also found that brief heat stress in the early embryonic stage (0 to 1 hour-old) caused decreased larval performance later in life (5 to 10 days-old), as indexed by pupation height, as well as increased development time to pupation. Maternal overexpression ofHsp23protected embryos against these heat-induced larval defects. Our data demonstrate that transient products of single genes have large and lasting effects on whole-organism environmental tolerance. Further, our results suggest that maternal effects have a profound impact on offspring survival in the context of thermal variability.SUMMARY STATEMENTA gene-specific maternal effect confers thermal tolerance to offspring embryos in the fruit flyDrosophila melanogaster.
Leukocyte counts based on site-specific DNA methylation analysis
Authors: Frobel Joana , Božić Tanja , Lenz Michael , Uciechowski Peter , Han Yang , Herwartz Reinhild , Strathmann Klaus , Isfort Susanne , Panse Jens , Esser André , Birkhofer Carina , Gerstenmaier Uwe , Kraus Thomas , Rink Lothar , Koschmieder Steffen , Wagner Wolfgang 
Published: June 2017

AbstractThe composition of white blood cells is usually assessed by histomorphological parameters or flow cytometric measurements. Alternatively, leukocyte differential counts (LDCs) can be estimated by deconvolution algorithms for genome-wide DNA methylation (DNAm) profiles. We identified cell-type specific CG dinucleotides (CpGs) that facilitate relative quantification of leukocyte subsets. Site-specific analysis of DNAm levels by pyrosequencing provides similar precision of LDCs as conventional methods, whereas it is also applicable to frozen samples and requires only very small volumes of blood. Furthermore, we describe a new approach for absolute quantification of cell numbers based on a non-methylated reference DNA. Our “Epi-Blood-Count” facilitates robust and cost effective analysis of blood counts for clinical application.