bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial specificity of auxin responses coordinates wood formation
Authors: Brackmann Klaus , Jouannet Virginie , Qi Jiyan , Schlamp Theresa , Grünwald Karin , Sanchez Pablo , Greb Thomas 
Published: May 2017

AbstractSpatial organization of signaling events of the phytohormone auxin is fundamental for maintaining a dynamic transition from plant stem cells to differentiated descendants. The cambium, the stem cell niche mediating wood formation, fundamentally depends on auxin signaling but its exact role and spatial organization is obscure. Here, we show that, while auxin signaling levels increase in differentiating cambium descendants, a moderate level of signaling in cambial stem cells is essential for cambium activity. We identify the auxin-dependent transcription factor ARF5/MONOPTEROS to cell-autonomously restrict the number of stem cells by attenuating the activity of the stem cell promotingWOX4gene. In contrast, ARF3 and ARF4 function as cambium activators in a redundant fashion from outside of WOX4-expressing cells. Our results reveal an influence of auxin signaling on distinct cambium features by specific signaling components and allow the conceptual integration of plant stem cell systems with distinct anatomies.
Optogenetic single-cell control of transcription achieves mRNA tunability and reduced variability
Authors: Rullan Marc , Benzinger Dirk , Schmidt Gregor W. , Gupta Ankit , Milias-Argeitis Andreas , Khammash Mustafa 
Published: May 2017

AbstractThe study of gene expression at the single-cell level has exposed the importance of stochasticity for the behavior of cellular systems. Research on cellular variability has mostly relied on observing expression either in response to natural stimuli or to constant gene regulators. However, the ability to probe cells individually can lead to a deeper understanding of the underlying process. Here, we propose an experimental platform for optogenetic feedback control of individual cells. It consists of a digital micromirror device that, coupled to a microscope, can target light-responsive cells with individualized illumination profiles, thereby exploiting the good spatial resolution of optogenetic induction. Together with an automated software pipeline for segmentation, quantification and tracking of single cells, the platform enables independent and real-time control of numerous cells. We demonstrate our platform by regulating transcription in over a hundred yeast cells simultaneously, while achieving tunability of mRNA abundance. Using a novel technique to measure extrinsic variation, we further show that single cell feedback regulation of this highly stochastic process achieves a 10-fold reduction of extrinsic variation in nascent mRNA over population control, with superior control loop properties. Our platform establishes a new, flexible method for studying transcriptional dynamics in single cells.
Predicting ligand-dependent tumors from multi-dimensional signaling features
Authors: Hass Helge , Masson Kristina , Wohlgemuth Sibylle , Paragas Violette , Allen John E , Sevecka Mark , Pace Emily , Timmer Jens , Stelling Joerg , MacBeath Gavin , Schoeberl Birgit , Raue Andreas 
Published: May 2017

AbstractTargeted therapies have shown significant patient benefit in about 5-10% of solid tumors that are addicted to a single oncogene. Here, we explore the idea of ligand addiction as a driver of tumor growth. High ligand levels in tumors have been shown to be associated with impaired patient survival, but targeted therapies have not yet shown great benefit in unselected patient populations. Using a novel approach of applying Bagged Decision Trees (BDT) to high-dimensional signaling features derived from a computational model, we can predict ligand dependent proliferation across a set of 58 cell lines. This mechanistic, multi-pathway model that features receptor heterodimerization, was trained on seven cancer cell lines and can predict signaling across two independent cell lines by adjusting only the receptor expression levels for each cell line. Interestingly, for patient samples the predicted tumor growth response correlates with high growth factor expression in the tumor microenvironment, which argues for a co-evolution of both factorsin vivo.SummaryPrediction of ligand-induced growth of cancer cell lines, which correlates with ligand-blocking antibody efficacy, could be significantly improved by learning from features of a mechanistic signaling model, and was applied to reveal a correlation between growth factor expression and predicted response in patient samples.
Vaxrank: A computational tool for designing personalized cancer vaccines
Authors: Rubinsteyn Alexander , Hodes Isaac , Kodysh Julia , Hammerbacher Jeffrey 
Published: May 2017

AbstractTherapeutic vaccines targeting mutant tumor antigens (“neoantigens”) are an increasingly popular form of personalized cancer immunotherapy. Vaxrank is a computational tool for selecting neoantigen vaccine peptides from tumor mutations, tumor RNA data, and patient HLA type. Vaxrank is freely available atwww.github.com/openvax/vaxrankunder the Apache 2.0 open source license and can also be installed from the Python Package Index.
Brain xQTL map: Integrating the genetic architecture of the human brain transcriptome and epigenome
Authors: Ng B , White CC , Klein H , Sieberts SK , McCabe C , Patrick E , Xu J , Yu L , Gaiteri C , Bennett DA , Mostafavi S , Jager PL De 
Published: May 2017

AbstractWe perform quantitative trait locus (xQTL) analyses on a multi-omic dataset, comprising RNA sequence, DNA methylation, and histone acetylation ChIP sequence data from the dorsolateral prefrontal cortex of 411 older adult individuals. We identify SNPs that are significantly associated with gene expression, DNA methylation, and histone modification levels. Many SNPs influence more than one type of molecular feature, and epigenetic features are shown to mediate eQTLs in a number of (9%) such loci. We illustrate the utility of our new resource,xQTL Serve, in prioritizing the cell type most affected by an xQTL and in enhancing genome wide association studies (GWAS) as we report 18 additional CNS disease susceptibility loci after re-analyzing published studies.
OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF
Authors: Sheinboim Danna , Maza Itay , Dror Iris , Parikh Shivang , Krupalnik Vladislav , Bell Rachel E , Zviran Asaf , Suita Yusuke , Hakim Ofir , Gutfreund Yael Mandel , Khaled Mehdi , Hanna Jacob H , Levy Carmit 
Published: May 2017

ABSTRACTEctopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has never been systemically examined. Here we discovered that amongst different developmental stages, embryonic stem cells (ESCs) were resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. We generated a transgenic system and found that in ESCs, the pluripotency master regulator, OCT4, counteracts pro-differentiation induced by MITF by physical interference with MITF transcriptional activity. We further found that ESCs must be released from OCT4-maintained pluripotency prior to ectopically induced differentiation. Moreover, OCT4 induction in various differentiated cells repressed their lineage identity in vivo. Alongside, chromatin architecture combined with ChIP-seq analysis suggested that OCT4 competes with various lineage master regulators for binding promoters and enhancers. Our analysis reveals pluripotency and transdifferentiation regulatory principles and could open new opportunities in the field of regenerative medicine.
Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons
Authors: Wang Ping , Zhao Dejian , Lachman Herbert M. , Zheng Deyou 
Published: May 2017

AbstractAutism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expressed module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons. In addition, we found that upregulated genes in multiple ASD cortex samples were also enriched with genes highly expressed in inhibitory neurons, suggesting a potential increase of inhibitory neurons and an imbalance in the ratio between excitatory and inhibitory neurons. Furthermore, the downstream targets of several ASD candidates, such asCHD8, EHMT1andSATB2,also displayed enriched expression in inhibitory neurons. Taken together, our analysis of single cell transcriptomic data suggest that inhibitory neurons may be the major neuron subtype affected by the disruption of ASD gene networks, providing single cell functional evidence to support the excitatory/inhibitory (E/I) imbalance hypothesis.
Forces driving cell sorting inHydra
Authors: Cochet-Escartin Olivier , Locke Tiffany T. , Shi Winnie H. , Steele Robert E. , Collins Eva-Maria S. 
Published: May 2017

AbstractCell sorting, whereby a heterogeneous cell mixture organizes into distinct tissues, is a fundamental patterning process in development. So far, most studies of cell sorting have relied either on 2-dimensional cellular aggregates,in vitrosituations that do not have a direct counterpartin vivo,or were focused on the properties of single cells. Here, we report the first multiscale experimental study on 3-dimensional regeneratingHydraaggregates, capable of reforming a full animal. By quantifying the kinematics of single cell and whole aggregate behaviors, we show that no differences in cell motility exist among cell types and that sorting dynamics follow a power law. Moreover, we measure the physical properties of separated tissues and determine their viscosities and surface tensions. Based on our experimental results and numerical simulations, we conclude that tissue interfacial tensions are sufficient to explainHydracell sorting. Doing so, we illustrate D’Arcy Thompson’s central idea that biological organization can be understood through physical principles, an idea which is currently re-shaping the field of developmental biology.Summary statementHydraregenerates after dissociation into single cells. We show how physical mechanisms can explain the first step of regeneration, whereby ectodermal and endodermal cells sort out to form distinct tissue layers.
Deep transcriptome annotation suggests that small and large proteins encoded in the same genes often cooperate
Authors: Samandi Sondos , Roy Annie V. , Delcourt Vivian , Lucier Jean-François , Gagnon Jules , Beaudoin Maxime C. , Vanderperre Benoît , Breton Marc-André , Motard Julie , Jacques Jean-François , Brunelle Mylène , Gagnon-Arsenault Isabelle , Fournier Isabelle , Ouangraoua Aida , Hunting Darel J. , Cohen Alan A. , Landry Christian R. , Scott Michelle S. , Roucou Xavier 
Published: May 2017

AbstractRecent studies in eukaryotes have demonstrated the translation of alternative open reading frames (altORFs) in addition to annotated protein coding sequences (CDSs). We show that a large number of small proteins could in fact be coded by altORFs. The putative alternative proteins translated from altORFs have orthologs in many species and evolutionary patterns indicate that altORFs are particularly constrained in CDSs that evolve slowly. Thousands of predicted alternative proteins are detected in proteomic datasets by reanalysis using a database containing predicted alternative proteins. Protein domains and co-conservation analyses suggest a potential functional relationship between small and large proteins encoded in the same genes. This is illustrated with specific examples, including altMiD51, a 70 amino acid mitochondrial fission-promoting protein encoded inMiD51/Mief1/SMCR7L, a gene encoding an annotated protein promoting mitochondrial fission. Our results suggest that many coding genes code for more than one protein that are often functionally related.
Rapid feedback responses are flexibly coordinated across arm muscles to support goal-directed reaching
Authors: Weiler Jeffrey , Gribble Paul L. , Pruszynski J. Andrew 
Published: May 2017

AbstractA transcortical pathway helps support goal-directed reaching by processing somatosensory information to produce rapid feedback responses across multiple joints and muscles. Here we tested whether such feedback responses can account for changes in arm configuration and for arbitrary visuomotor transformations – two manipulations that alter how muscles at the elbow and wrist need to be coordinated to achieve task success. Participants used a planar three degree-of-freedom exoskeleton robot to move a cursor to a target following a mechanical perturbation that flexed the elbow. In our first experiment, the cursor was mapped to the veridical position of the robot handle, but participants grasped the handle with two different hand orientations (thumb pointing upward or thumb point downward). We found that large rapid feedback responses were evoked in wrist extensor muscles when wrist extension helped move the cursor to the target (i.e., thumb upward), and in wrist flexor muscles when wrist flexion helped move the cursor to the target (i.e., thumb downward). In our second experiment, participants grasped the robot handle with their thumb pointing upward, but the cursor’s movement was either veridical, or was mirrored such that flexing the wrist moved the cursor as if the participant extended their wrist, and vice versa. After extensive practice, we found that rapid feedback responses were appropriately tuned to the wrist muscles that supported moving the cursor to the target when the cursor was mapped to the mirrored movement of the wrist, but were not tuned to the appropriate wrist muscles when the cursor was remapped to the wrist’s veridical movement.New and NoteworthyWe show that rapid feedback responses were evoked in different wrist muscles depending on the arm’s orientation, and this muscle activity was appropriate to generate the wrist motion that supported a reaching action. Notably, we also show that these rapid feedback responses can be evoked in wrist muscles that are detrimental to a reaching action if a non-veridical mapping between wrist and hand motion is extensively learned.
Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy
Authors: Zheng Xiaoyi , Soroush Fariborz , Long Jin , Hall Evan T. , Adishesha Puneeth K. , Bhattacharya Sanchita , Kiani Mohammad F. , Bhalla Vivek 
Published: May 2017

AbstractDiabetic nephropathy (DN) is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms which govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1), as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.
An Experiment in Learning the Language of Sequence Motifs: Sequence Logos vs. Finite-State Machines
Authors: Francisco Alexandre P , Gagie Travis , Kempa Dominik , Salmela Leena , Sverdlov Sophie , Toivonen Jarkko , Ukkonen Esko 
Published: May 2017

AbstractPosition weight matrices (PWMs) are the standard way to model binding site affinities in bioinformatics. However, they assume that symbol occurrences are position independent and, hence, they do not take into account symbols co-occurrence at different sequence positions. To address this problem, we propose to construct finite-state machines (FSMs) instead. A modified version of the Evidence-Driven State Merging (EDSM) heuristic is used to reduce the number of states as FSMs grow too quickly as a function of the number of sequences to reveal any useful structure. We tested our approach on sequence data for the transcription factor HNF4 and found out that the constructed FSMs provide small representations and an intuitive visualization. Furthermore, the FSM was better than PWMs at discriminating the positive and negative sequences in our data set.
OMSV enables accurate and comprehensive identification of large structural variations from nanochannel-based single-molecule optical maps
Authors: Li Le , Kwok Tsz-Piu , Leung Alden King-Yung , Lai Yvonne Y. Y. , Pang Iris K. , Chung Grace Tin-Yun , Mak Angel C. Y. , Poon Annie , Chu Catherine , Li Menglu , Wu Jacob J. K. , Lam Ernest T. , Cao Han , Lin Chin , Sibert Justin , Yiu Siu-Ming , Xiao Ming , Lo Kwok-Wai , Kwok Pui-Yan , Chan Ting-Fung , Yip Kevin Y. 
Published: May 2017

AbstractHuman genomes contain structural variations (SVs) that are associated with various phenotypic variations and diseases. SV detection by sequencing is incomplete due to limited read length. Nanochannel-based optical mapping (OM) allows direct observation of SVs up to hundreds of kilo-bases in size on individual DNA molecules, making it a promising alternative technology for identifying large SVs. SV detection from optical maps is non-trivial due to complex types of error present in OM data, and no existing methods can simultaneously handle all these complex errors and the wide spectrum of SV types. Here we present a novel method, OMSV, for accurate and comprehensive identification of SVs from optical maps. OMSV detects both homozygous and heterozygous SVs, SVs of various types and sizes, and SVs with and without creating/destroying restriction sites. In an extensive series of tests based on real and simulated data, OMSV achieved both high sensitivity and specificity, with clear performance gains over the latest existing method. Applying OMSV to a human cell line, we identified hundreds of SVs >2kbp, with 65% of them missed by sequencing-based callers. Independent experimental validations confirmed the high accuracy of these SVs. We also demonstrate how OMSV can incorporate sequencing data to determine precise SV break points and novel sequences in the SVs not contained in the reference. We provide OMSV as open-source software to facilitate systematic studies of large SVs.
Cell-accurate optical mapping across the entire developing heart
Authors: Weber Michael , Scherf Nico , Kohl Peter , Huisken Jan 
Published: May 2017

AbstractOrganogenesis depends on orchestrated interactions between individual cells and morphogenically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighbouring cells, which is established and fine-tuned during development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire heart during the looping stage in live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging,in vivostudies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.
Function of basal ganglia in tauG-guiding action
Authors: Lee David N. , Georgopoulos Apostolos P. , Pepping Gert-Jan 
Published: May 2017

AbstractNervous systems control purposeful movement, both within and outside the body, which is essential for the survival of an animal. The movement control functions of globus pallidus (GP), subthalamic nucleus (STN) and zona incerta (ZI) were analyzed in monkeys reaching for seen targets. Temporal profiles of the hand movements of monkeys and the synchronized flow of electrochemical energy through these basal ganglia were analyzed in terms of a theory of goal-directed movement. Theoretical and empirical analysis indicated: (i) the neural information for controlling movement is the relative-rate-of-change of flow of electrochemical energy in neurons rather than the flow itself; (ii) GP is involved in creatingprospectiveelectrochemical flow to guide movement; (iii) STN is involved in registering theperceptualelectrochemical flow monitoring the movement; (iv) ZI is involved in integrating the prospective and perceptual electrochemical flows to power the muscles and thence the movement. Possible implications for PD are discussed.
ANNOgesic: A Swiss army knife for the RNA-Seq based annotation of bacterial/archaeal genomes
Authors: Yu Sung-Huan , Vogel Jörg , Förstner Konrad U. 
Published: May 2017

AbstractTo understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or non-coding RNAs are harder to detect. RNA-Seq has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-Seq data in order to generate high-resolution annotations is challenging, time consuming and requires numerous different steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-Seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-Seq and dRNA-Seq, predicts and annotates numerous features, including small non-coding RNAs, with high precision. The software is available under an open source license (ISCL) athttps://pypi.org/project/ANNOgesic/.
Discovery of Drought-Responsive Transposable Element-Related Peach miRNAs
Authors: Pekmezci Asli Kurden , Karakülah Gökhan , Unver Turgay 
Published: May 2017

AbstractMicroRNAs (miRNA) are small non-coding regulatory RNAs that suppress their specific target transcripts either by cleavage or inhibition of translation. Transposable element related miRNAs (TE-miRNA) have been subjected to various studies so far, and some of them were found to be involved in stress response in plants. Here, small RNA (sRNA) sequencing libraries generated from drought stress treated peach tissues were utilized to identify TE-miRNAs. Our computational analysis led to the identification of 63 TE-miRNAs, which were either locating nearby of any TE (TE-related), or overlapping with a TE (TE-derived). Furthermore, 13 out of 63 TE-miRNAs were designated as drought-responsive. Expression pattern of the identified drought-responsive TE-miRNAs are observed as tissue-specific manner, and their specific target transcripts are mostly related to transcription factors and growth-associated genes. Our findings suggest that miRNAs in relation with transposable elements might be key molecular players in the regulation of drought response.