bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of the EcoKMcrA N-terminal domain (NEco): recognition of modified cytosine bases without flipping
Authors: Slyvka Anton , Zagorskaitė Evelina , Czapinska Honorata , Sasnauskas Giedrius , Bochtler Matthias 
Published: October 2019

AbstractEcoKMcrA from Escherichia coli restricts CpG methylated or hydroxymethylated DNA, and may act as a barrier against host DNA. The enzyme consists of a novel N-terminal specificity domain that we term NEco, and a C-terminal catalytic HNH domain. Here, we report that NEco and full-length EcoKMcrA specificities are consistent. NEco affinity to DNA increases more from hemi- to full-methylation than from non- to hemi-methylation, indicating cooperative binding of the methyl groups. We determined the crystal structures of NEco in complex with fully modified DNA containing three variants of the Y5mCGR EcoKMcrA target sequence: C5mCGG, T5mCGA and T5hmCGA. The structures explain the specificity for the two central base pairs and one of the flanking pairs. As predicted based on earlier biochemical experiments, NEco does not flip any DNA bases. The proximal and distal methyl groups are accommodated in separate pockets. Changes to either pocket reduce DNA binding by NEco and restriction by EcoKMcrA, confirming the relevance of the crystallographically observed binding mode in solution.
PlantRegMap: charting functional regulatory maps in plants
Authors: Tian Feng , Yang De-Chang , Meng Yu-Qi , Jin Jinpu , Gao Ge 
Published: October 2019

AbstractWith the goal of charting plant transcriptional regulatory maps (i.e. transcription factors (TFs), cis-elements and interactions between them), we have upgraded the TF-centred database PlantTFDB (http://planttfdb.cbi.pku.edu.cn/) to a plant regulatory data and analysis platform PlantRegMap (http://plantregmap.cbi.pku.edu.cn/) over the past three years. In this version, we updated the annotations for the previously collected TFs and set up a new section, ‘extended TF repertoires’ (TFext), to allow users prompt access to the TF repertoires of newly sequenced species. In addition to our regular TF updates, we are dedicated to updating the data on cis-elements and functional interactions between TFs and cis-elements. We established genome-wide conservation landscapes for 63 representative plants and then developed an algorithm, FunTFBS, to screen for functional regulatory elements and interactions by coupling the base-varied binding affinities of TFs with the evolutionary footprints on their binding sites. Using the FunTFBS algorithm and the conservation landscapes, we further identified over 20 million functional TF binding sites (TFBSs) and two million functional interactions for 21 346 TFs, charting the functional regulatory maps of these 63 plants. These resources are publicly available at PlantRegMap (http://plantregmap.cbi.pku.edu.cn/) and a cloud-based mirror (http://plantregmap.gao-lab.org/), providing the plant research community with valuable resources for decoding plant transcriptional regulatory systems.
The reactome pathway knowledgebase
Authors: Jassal Bijay , Matthews Lisa , Viteri Guilherme , Gong Chuqiao , Lorente Pascual , Fabregat Antonio , Sidiropoulos Konstantinos , Cook Justin , Gillespie Marc , Haw Robin , Loney Fred , May Bruce , Milacic Marija , Rothfels Karen , Sevilla Cristoffer , Shamovsky Veronica , Shorser Solomon , Varusai Thawfeek , Weiser Joel , Wu Guanming , Stein Lincoln , Hermjakob Henning , D’Eustachio Peter 
Published: October 2019

Abstract
The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.
Mouse Phenome Database: a data repository and analysis suite for curated primary mouse phenotype data
Authors: Bogue Molly A , Philip Vivek M , Walton David O , Grubb Stephen C , Dunn Matthew H , Kolishovski Georgi , Emerson Jake , Mukherjee Gaurab , Stearns Timothy , He Hao , Sinha Vinita , Kadakkuzha Beena , Kunde-Ramamoorthy Govindarajan , Chesler Elissa J 
Published: October 2019

Abstract
The Mouse Phenome Database (MPD; https://phenome.jax.org) is a widely accessed and highly functional data repository housing primary phenotype data for the laboratory mouse accessible via APIs and providing tools to analyze and visualize those data. Data come from investigators around the world and represent a broad scope of phenotyping endpoints and disease-related traits in naïve mice and those exposed to drugs, environmental agents or other treatments. MPD houses rigorously curated per-animal data with detailed protocols. Public ontologies and controlled vocabularies are used for annotation. In addition to phenotype tools, genetic analysis tools enable users to integrate and interpret genome–phenome relations across the database. Strain types and populations include inbred, recombinant inbred, F1 hybrid, transgenic, targeted mutants, chromosome substitution, Collaborative Cross, Diversity Outbred and other mapping populations. Our new analysis tools allow users to apply selected data in an integrated fashion to address problems in trait associations, reproducibility, polygenic syndrome model selection and multi-trait modeling. As we refine these tools and approaches, we will continue to provide users a means to identify consistent, quality studies that have high translational relevance.
DDBJ Database updates and computational infrastructure enhancement
Authors: Ogasawara Osamu , Kodama Yuichi , Mashima Jun , Kosuge Takehide , Fujisawa Takatomo 
Published: October 2019

Abstract
The Bioinformation and DDBJ Center (https://www.ddbj.nig.ac.jp) in the National Institute of Genetics (NIG) maintains a primary nucleotide sequence database as a member of the International Nucleotide Sequence Database Collaboration (INSDC) in partnership with the US National Center for Biotechnology Information and the European Bioinformatics Institute. The NIG operates the NIG supercomputer as a computational basis for the construction of DDBJ databases and as a large-scale computational resource for Japanese biologists and medical researchers. In order to accommodate the rapidly growing amount of deoxyribonucleic acid (DNA) nucleotide sequence data, NIG replaced its supercomputer system, which is designed for big data analysis of genome data, in early 2019. The new system is equipped with 30 PB of DNA data archiving storage; large-scale parallel distributed file systems (13.8 PB in total) and 1.1 PFLOPS computation nodes and graphics processing units (GPUs). Moreover, as a starting point of developing multi-cloud infrastructure of bioinformatics, we have also installed an automatic file transfer system that allows users to prevent data lock-in and to achieve cost/performance balance by exploiting the most suitable environment from among the supercomputer and public clouds for different workloads.
TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration
Authors: Urán Landaburu Lionel , Berenstein Ariel J , Videla Santiago , Maru Parag , Shanmugam Dhanasekaran , Chernomoretz Ariel , Agüero Fernán 
Published: October 2019

Abstract
The volume of biological, chemical and functional data deposited in the public domain is growing rapidly, thanks to next generation sequencing and highly-automated screening technologies. These datasets represent invaluable resources for drug discovery, particularly for less studied neglected disease pathogens. To leverage these datasets, smart and intensive data integration is required to guide computational inferences across diverse organisms. The TDR Targets chemogenomics resource integrates genomic data from human pathogens and model organisms along with information on bioactive compounds and their annotated activities. This report highlights the latest updates on the available data and functionality in TDR Targets 6. Based on chemogenomic network models providing links between inhibitors and targets, the database now incorporates network-driven target prioritizations, and novel visualizations of network subgraphs displaying chemical- and target-similarity neighborhoods along with associated target-compound bioactivity links. Available data can be browsed and queried through a new user interface, that allow users to perform prioritizations of protein targets and chemical inhibitors. As such, TDR Targets now facilitates the investigation of drug repurposing against pathogen targets, which can potentially help in identifying candidate targets for bioactive compounds with previously unknown targets. TDR Targets is available at https://tdrtargets.org.
Rethinking the economics of rural water in Africa
Authors: Hope Rob , Thomson Patrick , Koehler Johanna , Foster Tim 
Published: October 2019

Abstract
Rural Africa lags behind global progress to provide safe drinking water to everyone. Decades of effort and billions of dollars of investment have yielded modest gains, with high but avoidable health and economic costs borne by over 300m people lacking basic water access. We explore why rural water is different for communities, schools, and healthcare facilities across characteristics of scale, institutions, demand, and finance. The findings conclude with policy recommendations to (i) network rural services at scale, (ii) unlock rural payments by creating value, and (iii) design and test performance-based funding models at national and regional scales, with an ambition to eliminate the need for future, sustainable development goals.
Reproductive performance of the Antarctic tardigrades, Acutuncus antarcticus (Eutardigrada: Hypsibiidae), revived after being frozen for over 30 years and of their offspring
Authors: Tsujimoto Megumu , Kagoshima Hiroshi , Kanda Hiroshi , Watanabe Kenichi , Imura Satoshi 
Published: October 2019

Abstract
Studies on the long-term survival of animals often focus on the specific instance of survival of animals only, and descriptions of subsequent reproduction are generally not reported. In this study, we recorded the reproductive performance of the first-generation offspring of the resuscitated individual (SB-1) and the hatchling of the resuscitated egg (SB-3) of the Antarctic tardigrade, Acutuncus antarcticus, after being frozen for 30.5 years. By providing further detailed description of the reproduction of SB-1 and SB-3 after revival, and then comparing the reproductive performance with that of their first-generation offspring, the possible indications of the damage accrued during the long-term preservation in SB-1 and SB-3 were more specifically detected. Additionally, the DNA analysis revealed two distinctively different mitochondrial genetic sequences of A. antarcticus between the SB strains and the LSW strain. The observed differences in some of the reproductive parameters between the two genetic types suggested a possible relationship between the life-history traits and genetic type in the species A. antarcticus. Further experiments using the SB-1 and SB-3 strains reared for a long period to exclude the instant effect of preservation are expected to improve our understanding of the mechanisms underlying the long-term survival of animals.
Deepening understanding of language through synaesthesia: a call to reform and expand
Authors: Mankin Jennifer L. 
Published: October 2019

In this paper, I present arguments and suggestions for the improvement of the scientific study of synaesthesia, and particularly grapheme-colour synaesthesia in relation to psycholinguistic research, although the principles I advocate can be easily adapted to any subfield of synaesthesia study. I postulate that the current state of research on synaesthesia in general, and on grapheme-colour synaesthesia in particular, suffers from a lack of exploratory evidence and essential groundwork upon which to build hypothesis-testing studies. In particular, I argue that synaesthesia research has been artificially bounded by assumptions about the nature of synaesthetic experiences, which constrain both the questions that researchers ask and the way in which they go about answering those questions. As a specific example, I detail how much of the current research on grapheme-colour synaesthesia is built to accommodate two major assumptions about the nature of colours for letters and for words—assumptions which I will contend are not universally true, and the exceptions to which point to a much richer and heterogeneous understanding of synaesthetic experience than current research practices capture. The top-down predetermination of what is important or meaningful to measure, and what is not, has subsequently impeded a full understanding of what synaesthesia is and how it works. I argue that these assumptions must be carefully addressed and evaluated, both for the particular case of grapheme-colour synaesthesia and for the field as a whole, to move towards a holistic and fruitful understanding of synaesthesia as a phenomenon and as a tool to study language, thought and perception. To that end, I propose specific recommendations for synaesthesia researchers to solidify and expand their understanding and to capture the actual experience of synaesthetes.This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
Synaesthesia: a distinct entity that is an emergent feature of adaptive neurocognitive differences
Authors: Ward Jamie 
Published: October 2019

In this article, I argue that synaesthesia is not on a continuum with neurotypical cognition. Synaesthesia is special: its phenomenology is different; it has distinct causal mechanisms; and is likely to be associated with a distinct neurocognitive profile. However, not all synaesthetes are the same, and there are quantifiable differences between them. In particular, the number of types of synaesthesia that a person possesses is a hitherto underappreciated variable that predicts cognitive differences along a number of dimensions (mental imagery, sensory sensitivity, attention to detail). Together with enhanced memory, this may constitute a common core of abilities that may go some way to explaining why synaesthesia might have evolved. I argue that the direct benefits of synaesthesia are generally limited (i.e. the synaesthetic associations do not convey novel information about the world) but, nevertheless, synaesthesia may develop due to other adaptive functions (e.g. perceptual ability, memory) that necessitate changes to design features of the brain. The article concludes by suggesting that synaesthesia forces us to reconsider what we mean by a ‘normal’ mind/brain. There may be multiple ‘normal’ neurodevelopmental trajectories that can sculpt very different ways of experiencing the world, of which synaesthesia is but one.
This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
Do synaesthesia and mental imagery tap into similar cross-modal processes?
Authors: O'Dowd Alan , Cooney Sarah M. , McGovern David P. , Newell Fiona N. 
Published: October 2019

Synaesthesia has previously been linked with imagery abilities, although an understanding of a causal role for mental imagery in broader synaesthetic experiences remains elusive. This can be partly attributed to our relatively poor understanding of imagery in sensory domains beyond vision. Investigations into the neural and behavioural underpinnings of mental imagery have nevertheless identified an important role for imagery in perception, particularly in mediating cross-modal interactions. However, the phenomenology of synaesthesia gives rise to the assumption that associated cross-modal interactions may be encapsulated and specific to synaesthesia. As such, evidence for a link between imagery and perception may not generalize to synaesthesia. Here, we present results that challenge this idea: first, we found enhanced somatosensory imagery evoked by visual stimuli of body parts in mirror-touch synaesthetes, relative to other synaesthetes or controls. Moreover, this enhanced imagery generalized to tactile object properties not directly linked to their synaesthetic associations. Second, we report evidence that concurrent experience evoked in grapheme—colour synaesthesia was sufficient to trigger visual-to-tactile correspondences that are common to all. Together, these findings show that enhanced mental imagery is a consistent hallmark of synaesthesia, and suggest the intriguing possibility that imagery may facilitate the cross-modal interactions that underpin synaesthesic experiences.
This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
How non-veridical perception drives actions in healthy humans: evidence from synaesthesia
Authors: Schreiter Marie Luise , Chmielewski Witold X. , Ward Jamie , Beste Christian 
Published: October 2019

We continually perform actions that are driven by our perception and it is a commonly held view that only objectively perceived changes within the ‘real’ world affect behaviour. Exceptions are generally only made for mental health disorders associated with delusions and hallucinations where behaviour may be triggered by the experience of objectively non-existent percepts. Here, we demonstrate, using synaesthesia as a model condition (inN= 19 grapheme-colour synaesthetes), how objectively non-existent (i.e. non-veridical) but still non-pathological perceptions affect actions in healthy humans. Using electroencephalography, we determine whether early-stage perceptual processes (reflected by P1 and N1 event-related potential (ERP) components), or late-stage-integration processes (reflected by N2 component), underlie the effects of non-veridical perceptions on action control. ERP analysis suggests that even though the examined peculiarities and experimental variations are perceptual in nature, it is not early-stage perceptual processes, but rather higher-order executive control processes linking perceptions to the appropriate motor response underlying this effect. Source localization analysis implicates activation within medial frontal cortices in the effect of how irrelevant non-veridical perceptions modulate behaviour. Our results challenge common conceptions about the determinants of human behaviour but can be explained by well-established theoretical frameworks detailing the link between perception and action.This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
Stochastic resonance model of synaesthesia
Authors: Lalwani Poortata , Brang David 
Published: October 2019

In synaesthesia, stimulation of one sensory modality evokes additional experiences in another modality (e.g. sounds evoking colours). Along with these cross-sensory experiences, there are several cognitive and perceptual differences between synaesthetes and non-synaesthetes. For example, synaesthetes demonstrate enhanced imagery, increased cortical excitability and greater perceptual sensitivity in the concurrent modality. Previous models suggest that synaesthesia results from increased connectivity between corresponding sensory regions or disinhibited feedback from higher cortical areas. While these models explain how one sense can evoke qualitative experiences in another, they fail to predict the broader phenotype of differences observed in synaesthetes. Here, we propose a novel model of synaesthesia based on the principles of stochastic resonance. Specifically, we hypothesize that synaesthetes have greater neural noise in sensory regions, which allows pre-existing multisensory pathways to elicit supra-threshold activation (i.e. synaesthetic experiences). The strengths of this model are (a) it predicts the broader cognitive and perceptual differences in synaesthetes, (b) it provides a unified framework linking developmental and induced synaesthesias, and (c) it explains why synaesthetic associations are inconsistent at onset but stabilize over time. We review research consistent with this model and propose future studies to test its limits.
This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
Neurophenomenology of induced and natural synaesthesia
Authors: Schwartzman David J. , Bor Daniel , Rothen Nicolas , Seth Anil K. 
Published: October 2019

People with synaesthesia have additional perceptual experiences, which are automatically and consistently triggered by specific inducing stimuli. Synaesthesia therefore offers a unique window into the neurocognitive mechanisms underlying conscious perception. A long-standing question in synaesthesia research is whether it is possible to artificially induce non-synaesthetic individuals to have synaesthesia-like experiences. Although synaesthesia is widely considered a congenital condition, increasing evidence points to the potential of a variety of approaches to induce synaesthesia-like experiences, even in adulthood. Here, we summarize a range of methods for artificially inducing synaesthesia-like experiences, comparing the resulting experiences to the key hallmarks of natural synaesthesia which include consistency, automaticity and a lack of ‘perceptual presence’. We conclude that a number of aspects of synaesthesia can be artificially induced in non-synaesthetes. These data suggest the involvement of developmental and/or learning components in the acquisition of synaesthesia, and they extend previous reports of perceptual plasticity leading to dramatic changes in perceptual phenomenology in adults.
This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.