bluuebunny/crossref_metadata_2025_split huggingface dataset:
AAK1 inhibits WNT signaling by promoting clathrin-mediated endocytosis of LRP6
Authors: Agajanian Megan J. , Walker Matthew P. , Axtman Alison D. , Ruela-de-Sousa Roberta R. , Rabinowitz Alex D. , Graham David M. , Ryan Meagan , Serafin D. Stephen , Bennett James M. , Couñago Rafael M. , Drewry David H. , Elkins Jonathan M. , Gileadi Carina , Gileadi Opher , Godoi Paulo H. , Kapadia Nirav , Müller Susanne , Santiago André S. , Sorrell Fiona J. , Wells Carrow I. , Fedorov Oleg , Willson Timothy M. , Zuercher William J. , Major Michael B. 
Published: February 2018

Abstractβ-catenin-dependent WNT signal transduction governs normal development and adult tissue homeostasis. Inappropriate pathway activity mediates a vast array of human diseases, including bone density disorders, neurodegeneration and cancer. Although several WNT-directed therapeutics are in clinical trials, new targets, compounds and strategies are needed. We performed a gain-of-function screen of the human kinome to identify new druggable regulators of β-catenin-dependent transcription. We found that over-expression of the AP2 Associated Kinase 1 (AAK1) strongly inhibited WNT signaling. Reciprocally, silencing of AAK1 expression or pharmacological inhibition of AAK1 kinase activity using a new, selective and potent small molecule inhibitor activated WNT signaling. This small molecule is a cell active dual AAK1/BMP2K inhibitor that represents the best available tool to study AAK1-dependent signaling pathways. We report that AAK1 and the WNT co-receptor LRP6 physically co-complex and that AAK1 promotes clathrin-mediated endocytosis of LRP6. Collectively, our data support a WNT-induced negative feedback loop mediated by AAK1-driven, clathrin-mediated endocytosis of LRP6.Summary StatementA gain-of-function screen of the human kinome revealed AAK1 as a negative regulator of WNT signaling. We show that AAK1 promotes clathrin-mediated endocytosis of LRP6, resulting in downregulation of WNT signaling. We use a new selective and potent AAK1/BMP2K small molecule probe to validate our findings.
Targeted enrichment outperforms other enrichment techniques and enables more multi-species RNA-Seq analyses
Authors: Chung Matthew , Teigen Laura , Liu Hong , Libro Silvia , Shetty Amol , Kumar Nikhil , Zhao Xuechu , Bromley Robin E. , Tallon Luke J. , Sadzewicz Lisa , Fraser Claire M. , Rasko David A. , Filler Scott G. , Foster Jeremy M. , Michalski Michelle L. , Bruno Vincent M. , Dunning Hotopp Julie C. 
Published: February 2018

AbstractEnrichment methodologies enable analysis of minor members in multi-species transcriptomic analyses. We compared standard enrichment of bacterial and eukaryotic mRNA to targeted enrichment with Agilent SureSelect (AgSS) capture for Brugia malayi, Aspergillus fumigatus, and the Wolbachia endosymbiont of B. malayi (wBm). Without introducing significant systematic bias, the AgSS quantitatively enriched samples, resulting in more reads mapping to the target organism. The AgSS-enriched libraries consistently had a positive linear correlation with its unenriched counterpart (r2=0.559-0.867). Up to a 2,242-fold enrichment of RNA from the target organism was obtained following a power law (r2=0.90), with the greatest fold enrichment achieved in samples with the largest ratio difference between the major and minor members. While using a single total library for prokaryote and eukaryote in a single sample could be beneficial for samples where RNA is limiting, we observed a decrease in reads mapping to protein coding genes and an increase of multi-mapping reads to rRNAs in AgSS enrichments from eukaryotic total RNA libraries as opposed to eukaryotic poly(A)-enriched libraries. Our results support a recommendation of using Agilent SureSelect targeted enrichment on poly(A)-enriched libraries for eukaryotic captures and total RNA libraries for prokaryotic captures to increase the robustness of multi-species transcriptomic studies.
Connecting conceptual and spatial search via a model of generalization
Authors: Wu Charley M. , Schulz Eric , Garvert Mona M. , Meder Björn , Schuck Nicolas W. 
Published: February 2018

AbstractThe idea of a “cognitive map” was originally developed to explain planning and generalization in spatial domains through a representation of inferred relationships between experiences. Recently, new research has suggested similar principles may also govern the representation of more abstract, conceptual knowledge in the brain. We test whether the search for rewards in conceptual spaces follows similar computational principles as in spatial environments. Using a within-subject design, participants searched for both spatially and conceptually correlated rewards in multi-armed bandit tasks. We use a Gaussian Process model combining generalization with an optimistic sampling strategy to capture human search decisions and judgments in both domains, and to simulate human-level performance when specified with participant parameter estimates. In line with the notion of a domain-general generalization mechanism, parameter estimates correlate across spatial and conceptual search, yet some differences also emerged, with participants generalizing less and exploiting more in the conceptual domain.
Sharing is not erring: Pseudo-reciprocity in collective search
Authors: Bouhlel Imen , Wu Charley M. , Hanaki Nobuyuki , Goldstone Robert L. 
Published: February 2018

AbstractInformation sharing in competitive environments may seem counterintuitive, yet it is widely observed in humans and other animals. For instance, the open-source software movement has led to new and valuable technologies being released publicly to facilitate broader collaboration and further innovation. What drives this behavior and under which conditions can it be beneficial for an individual? Using simulations in both static and dynamic environments, we show that sharing information can lead to individual benefits through the mechanisms of pseudo-reciprocity, whereby shared information leads to by-product benefits for an individual without the need for explicit reciprocation. Crucially, imitation with a certain level of innovation is required to avoid a tragedy of the commons, while the mechanism of a local visibility radius allows for the coordination of self-organizing collectives of agents. When these two mechanisms are present, we find robust evidence for the benefits of sharing—even when others do not reciprocate.
A Computational Synaptic Antibody Characterization and Screening Framework for Array Tomography
Authors: Simhal Anish K. , Gong Belvin , Trimmer James S. , Weinberg Richard J. , Smith Stephen J. , Sapiro Guillermo , Micheva Kristina D. 
Published: February 2018

ABSTRACTApplication-specific validation of antibodies is a critical prerequisite for their successful use. Here we introduce an automated framework for characterization and screening of antibodies against synaptic molecules for high-resolution immunofluorescence array tomography (AT). The proposed Synaptic Antibody Screening Tool (SACT), is designed to provide an automatic, robust, flexible, and efficient tool for antibody characterization at scale. By allowing the user to define the molecular composition and size of synapses expected to contain the antigen, the method detects and characterizes puncta and synapses, and outputs automatically computed characteristics such as synapse density and target specificity ratio, which reflect the sensitivity and specificity of immunolabeling with a given antibody. These measurements provide an objective way to characterize and compare the performance of different antibodies against the same target, and can be used to objectively select the antibodies best suited for AT and potentially for other immunolabeling applications.
Transfer learning for biomedical named entity recognition with neural networks
Authors: Giorgi John M , Bader Gary D 
Published: February 2018

AbstractMotivationThe explosive increase of biomedical literature has made information extraction an increasingly important tool for biomedical research. A fundamental task is the recognition of biomedical named entities in text (BNER) such as genes/proteins, diseases, and species. Recently, a domain-independent method based on deep learning and statistical word embeddings, called long short-term memory network-conditional random field (LSTM-CRF), has been shown to outperform state-of-the-art entity-specific BNER tools. However, this method is dependent on gold-standard corpora (GSCs) consisting of hand-labeled entities, which tend to be small but highly reliable. An alternative to GSCs are silver-standard corpora (SSCs), which are generated by harmonizing the annotations made by several automatic annotation systems. SSCs typically contain more noise than GSCs but have the advantage of containing many more training examples. Ideally, these corpora could be combined to achieve the benefits of both, which is an opportunity for transfer learning. In this work, we analyze to what extent transfer learning improves upon state-of-the-art results for BNER.ResultsWe demonstrate that transferring a deep neural network (DNN) trained on a large, noisy SSC to a smaller, but more reliable GSC significantly improves upon state-of-the-art results for BNER. Compared to a state-of-the-art baseline evaluated on 23 GSCs covering four different entity classes, transfer learning results in an average reduction in error of approximately 11%. We found transfer learning to be especially beneficial for target data sets with a small number of labels (approximately 6000 or less).Availability and implementationSource code for the LSTM-CRF is available athttps://github.com/Franck-Dernoncourt/NeuroNER/and links to the corpora are available athttps://github.com/BaderLab/Transfer-Learning-BNER-Bioinformatics-2018/.Contactjohn.giorgi@utoronto.caSupplementary informationSupplementary data are available atBioinformaticsonline.
Oscillations in working memory and neural binding: a mechanism for multiple memories and their interactions
Authors: Pina Jason E. , Bodner Mark , Ermentrout Bard 
Published: February 2018

AbstractNeural oscillations have been implicated in many different basic brain and cognitive processes. Oscillatory activity has been suggested to play a role in neural binding, and more recently in the maintenance of information in working memory. This latter work has focused primarily on oscillations in terms of providing a “code” in working memory. However, oscillations may additionally play a fundamental role in essential properties and behaviors that neuronal networks must exhibit in order to produce functional working memory. In the present work, we present a biologically plausible working memory model and demonstrate that specific types of stable oscillatory dynamics may play a critical role in facilitating properties of working memory, including transitions between different memory states and a multi-item working memory capacity. We also show these oscillatory dynamics may facilitate and provide an underlying mechanism to enable a range of different types of binding in the context of working memory.Author summaryWorking memory is a form of short-term memory that is limited in capacity to perhaps 3 – 5 items. Various studies have shown that ensembles of neurons oscillate during working memory retention, and cross-frequency coupling (between, e.g., theta and gamma frequencies) has been conjectured as underlying the observed limited capacity. Binding occurs when different objects or concepts are associated with each other and can persist as working memory representations; neuronal synchrony has been hypothesized as the neural correlate. We propose a novel computational model of a network of oscillatory neuronal populations that capture salient attributes of working memory and binding by allowing for both stable synchronous and asynchronous activity. The oscillatory dynamics we describe may provide a mechanism that can facilitate aspects of working memory, such as maintaining multiple items active at once, creating rich neural representations of memories via binding, and rapidly transitioning activtation patterns based on selective inputs.
State-Switching Probability Reveals Sleep-Related Biological Drives inDrosophila
Authors: Wiggin Timothy D. , Goodwin Patricia R. , Donelson Nathan C. , Liu Chang , Trinh Kien , Sanyal Subhabrata , Griffith Leslie C. 
Published: February 2018

ABSTRACTSleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters inDrosophila melanogasterhave low temporal resolution and/or require disrupting sleep. Here we report a novel analysis tool for high-resolution, non-invasive measurement of sleep pressure and depth from movement data. Probability of transitioning to an active state, P(Wake), measures sleep depth while probability of transitioning to an inactive state, P(Doze), measures sleep pressure.In vivoand computational analyses show that P(Wake) and P(Doze) are independent and control the amount of total sleep. Importantly, we demonstrate that these probabilities are tied to specific biological processes. Genetic and environmental perturbations demonstrate that a given amount of sleep can be produced by many combinations of underlying P(Wake) and P(Doze). We show that measuring sleep pressure and depth continuously, without disturbing on-going behavior, provides greater mechanistic insight into behavior than measuring the amount of sleep alone.
Holmes-ITS2: Consolidated ITS2 resources and search engines for plant DNA-based marker analyses
Authors: Li Hongjun , Bai Hong , Yu Shaojun , Han Maozhen , Ning Kang 
Published: February 2018

ABSTRACTPlants are valuable resources for a variety of products in modern societies. Plant species identification is an integral part of research and practical application on plants. In parallel with high-throughput sequencing technology, the high-throughput screening of species is in high demand. Highly accurate and efficient DNA-based marker identification is essential for the effective analysis of plant species or biological constituents of a mixture of plants as well. Therefore, it is of general interests and significance to generate a comprehensive and accurate DNA-based marker sequence resource, as well as to build efficient sequence search engines, for the accurate and fast identification of plant species.In this work, we have firstly established a high-quality ITS2 sequence database of plant species containing more than 150,000 entries, through the systematical collection and manually collation of the published ITS2 sequencing data of plant species, data quality control, as well as representative sequence refinement based on clustering method. Secondly, an accurate and efficient plant species identification system based on ITS2 sequence was constructed, which is the proper combination of sequence search algorithms including BLAST and Kraken. Through the deployment of high-performance and frequently updated web service, it’s expected to serve for a wide range of researchers involving the taxonomy classification of plant species, as well as for deciphering of plant mixed systems including herbal materials in TCM preparations.The Holmes-ITS2 web service is freely accessible at:http://its2.tcm.microbioinformatics.org/. The input of this web service could be multiple sequences in a single fasta format, to search for matching ITS2 biomarker sequences already annotated in the database. This sequence-based search is based on two engines: BLAST, and k-mer based Kraken. Alternatively, users can directly search for species name for the corresponding ITS2 biomarker sequences. The web service has been put to the test by more than 50 experts from China, Denmark and US, and the average running time for the search ranges from 3-30 seconds for up to 100 sequences as a batch query.
Centrality and the shortest path approach on the human interactome
Authors: Rubanova Natalia , Morozova Nadya 
Published: February 2018

AbstractA network is one of the most convenient way to represent interactions between biological entities in systems biology. A network of molecular interactions is a graph in which the vertices are biological component and the edges correspond to the interactions between them. Many notions and approaches for network analysis came to systems biology from the theory of graphs – a field of mathematics that study graphs. We focused on the study of the shortest path approach in this work. We investigated whether this approach yields valid molecular paths. To perform this, the shortest paths in the human interactome (derived from HPRD and HIPPIE databases) were found between all relevant combinations of proteins taken from eight well-studied highly conserved signaling pathways from the KEGG database (NF-kappa B, MAPK, Jak-STAT, mTOR, ErbB, Wnt, TGF-beta and the signaling part of the apoptotic process). Canonical paths were systematically compared with the shortest counterparts and centrality of vertices and paths in subnetworks induced by the shortest paths were analyzed. We found that the sets of the shortest paths contain the canonical counterparts only for very short canonical paths (length 2-3 interactions). We also found that high centrality vertices tend to belong to canonical counterparts, to less extent this can also be said about high centrality paths.
Mechanistic insight into the interactions of NAP1 with NDP52 and TAX1BP1 for the recruitment of TBK1
Authors: Fu Tao , Liu Jianping , Wang Yingli , Xie Xingqiao , Hu Shichen , Pan Lifeng 
Published: February 2018

AbstractNDP52 and TAX1BP1, two SKICH domain-containing autophagy recetpors, play crucial roles in selective autophagy. The autophagic functions of NDP52 and TAX1BP1 are regulated by TBK1, which can indirectly associate with them through the adaptor protein NAP1. However, the molecular mechanism governing the interactions of NAP1 with NDP52 and TAX1BP1 as well as the effects induced by TBK1-mediated phosphorylation of NDP52 and TAX1BP1 remain elusive. Here, we reported the first atomic structures of the SKICH regions of NDP52 and TAX1BP1 in complex with NAP1, which not only uncover the mechanismtic basis underpinning the specific interactions of NAP1 with NDP52 and TAX1BP1, but also reveal the first binding mode of a SKICH domain. Moreover, we demonstrated that the phosphorylation of TAX1BP1 SKICH mediated by TBK1 may regulate the interaction between TAX1BP1 and NAP1. In all, our findings provide mechanistic insights into the NAP1-mediated recruitments of TBK1 to NDP52 and TAX1BP1, and are valuable for further understanding the functions of these proteins in selective autophagy.
Bacterial division FtsZ forms liquid condensates with nucleoid-associated Z-ring inhibitor SlmA
Authors: Monterroso Begoña , Zorrilla Silvia , Sobrinos-Sanguino Marta , Robles-Ramos Miguel A. , López-Álvarez Marina , Keating Christine D. , Rivas Germán 
Published: February 2018

AbstractMacromolecular condensation resulting from biologically regulated liquid-liquid phase transitions is emerging as a mechanism to organize the intracellular space in eukaryotic systems, with broad implications in cell physiology and pathology. Here we show that FtsZ, central element of the division ring in most bacteria, forms condensates when in complex with SlmA, the protein preventing septal ring assembly nearby the chromosome in E. coli. The formation of condensates is promoted by crowding and enhanced by sequence-specific binding of SlmA to DNA. These structures are dynamic and FtsZ within them remains active for GTP-triggered fiber formation. Their location is sensitive to compartmentalization and to the presence of a membrane boundary in microfluidics-based cell mimetic systems, likely affecting their reactivity. We propose that reversible condensation may play a role in the modulation of FtsZ assembly and/or location by SlmA and, hence, in the regulation of ring stability, constituting a singular example of a prokaryotic nucleoprotein complex exhibiting this kind of phase transition.
Early mannitol-triggered changes in the Arabidopsis leaf (phospho)proteome
Authors: Nikonorova Natalia , Van den Broeck Lisa , Zhu Shanshuo , van de Cotte Brigitte , Dubois Marieke , Gevaert Kris , Inzé Dirk , Smet Ive De 
Published: February 2018

ABSTRACTDrought is one of the most detrimental environmental stresses to which plants are exposed. Especially mild drought is relevant to agriculture and significantly affects plant growth and development. In plant research, mannitol is often used to mimic drought stress and study the underlying responses. In growing leaf tissue of plants exposed to mannitol-induced stress, a highly-interconnected gene regulatory network is induced. However, early signaling and associated protein phosphorylation events that likely precede part of these transcriptional changes are largely unknown. Here, we performed a full proteome and phosphoproteome analysis on growing leaf tissue ofArabidopsisplants exposed to mild mannitol-induced stress and captured the fast (within the first half hour) events associated with this stress. Based on this in-depth data analysis, 167 and 172 differentially regulated proteins and phosphorylated sites were found back, respectively. Additionally, we identified H(+)-ATPASE 2 (AHA2) and CYSTEINE-RICH REPEAT SECRETORY PROTEIN 38 (CRRSP38) as novel regulators of shoot growth under osmotic stress.HighlightWe captured early changes in theArabidopsisleaf proteome and phosphoproteome upon mild mannitol stress and identified AHA2 and CRRSP38 as novel regulators of shoot growth under osmotic stress
Synthesis and crystal structures of (2E)-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione and (2E)-1,4-bis(4-bromophenyl)but-2-ene-1,4-dione
Authors: Lastovickova Dominika N. , La Scala John J. , Sausa Rosario C. 
Published: February 2018

The molecular structure of (2E)-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione [C16H10Cl2O2, (1)] is composed of twop-chlorophenyl rings, each bonded on opposite ends to a near planar 1,4-transenedione moiety [–C(=O)—CH=CH—(C=O)–] [r.m.s. deviation = 0.003 (1) Å]. (2E)-1,4-Bis(4-bromophenyl)but-2-ene-1,4-dione [C16H10Br2O2, (2)] has a similar structure to (1), but with twop-bromophenyl rings and a less planar enedione group [r.m.s. deviation = 0.011 (1) Å]. Both molecules sit on a center of inversion, thusZ′ = 0.5. The dihedral angles between the ring and the enedione group are 16.61 (8) and 15.58 (11)° for (1) and (2), respectively. In the crystal, molecules of (1) exhibit C—Cl...Cl type I interactions, whereas molecules of (2) present C—Br...Br type II interactions. van der Waals-type interactions contribute to the packing of both molecules, and the packing reveals face-to-face ring stacking with similar interplanar distances of approximately 3.53 Å.
Vigilant resilience: the possibilities for renewal through preparedness
Authors: Carlson Elizabeth 
Published: February 2018

Purpose
Post-crisis renewal discourse (Ulmer et al., 2007) is one form of communication that stakeholders may use as they attempt to organize for resilience. The purpose of this paper propose extending Discourse of Renewal Theory to explain how it could enact a different kind of resilience than scholars typically consider. Organizational resilience strategies often focus on the recovery or prevention stages of crisis management. Under conditions of persistent threat, it would be more productive for renewal discourse to emphasize greater preparedness.

Design/methodology/approach
To illustrate the need for this kind of theorizing, the author analyzes a case study that follows the public relations efforts of Canadian energy company Enbridge, Inc., in the aftermath of the 2010 Kalamazoo River oil spill.

Findings
By the criteria of Discourse of Renewal Theory, Enbridge attempted a renewal strategy, but it failed. By other criteria, however, it succeeded: it created the opportunity for richer dialogue among stakeholders about their interdependence and their competing interests.

Originality/value
By considering how elements of the resilience process may vary, this paper offers resources for more nuanced theory-building and theory-testing related to organizational and system-level resilience.