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bioRxiv (pronounced "bio-archive") is a free online archive and distribution service for unpublished preprints in the life sciences. It is operated by Cold Spring Harbor Laboratory, a not-for-profit research and educational institution. By posting preprints on bioRxiv, authors are able to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals.



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biorxiv
by Ashley P Ng; Maria Kauppi; Donald Metcalf; Craig D Hyland; Emma C Josefsson; Marion Lebois; Jian-Guo Zhang; Ladina Di Rago; Tracey Baldwin; Douglas J Hilton; Warren S Alexander
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Thrombopoietin (TPO) acting via its receptor Mpl is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets ( MplPF4cre/PF4cre . MplPF4cre/PF4cre mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential...
Topic: Cell Biology
Source: http://biorxiv.org/content/early/2014/03/19/003459
biorxiv
by Iosif Lazaridis; Nick Patterson; Alissa Mittnik; Gabriel Renaud; Swapan Mallick; Karola Kirsanow; Peter H. Sudmant; Joshua G. Schraiber; Sergi Castellano; Mark Lipson; Bonnie Berger; Tatijana Zemunik; Alan Cooper; Cristian Capelli; Mark G. Thomas; Andres Ruiz-Linares; Sarah A. Tishkoff; Lalji Singh; Kumarasamy Thangaraj; Richard Villems; David Comas; Christos Economou; Rem Sukernik; Mait Metspalu; Matthias Meyer; Evan E. Eichler; Joachim Burger; Montgomery Slatkin; Svante Pååbo; Janet Kelso;...
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We sequenced genomes from a ~7,000 year old early farmer from Stuttgart in Germany, an ~8,000 year old hunter-gatherer from Luxembourg, and seven ~8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/04/05/001552
biorxiv
by Kathryn G Turner; Christopher J Grassa
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New genomic tools are needed to elucidate the evolution of invasive, non-model organisms. Here we present the completed plastome assembly for the problematic invasive weed, Centaurea diffusa. This new tool represents a significant contribution to future studies of the ecological genomics of invasive plants, particularly this weedy genus, and studies of the Asteraceae in general.
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/11/005900
biorxiv
by Lior Nissim; Samuel D Perli; Alexandra Fridkin; Pablo Perez-Pinera; Timothy Lu
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RNA-based regulation, such as RNA interference, and CRISPR/Cas transcription factors (CRISPR-TFs), can enable scalable synthetic gene circuits and the modulation of endogenous networks but have yet to be integrated together. Here, we combined multiple mammalian RNA regulatory strategies, including RNA triple helix structures, introns, microRNAs, and ribozymes, with Cas9-based CRISPR-TFs and Cas6/Csy4-based RNA processing in human cells. We describe three complementary strategies for expressing...
Topic: Synthetic Biology
Source: http://biorxiv.org/content/early/2014/04/23/004432
biorxiv
by Mats Töpel; Maria Fernanda Calió; Alexander Zizka; Ruud Scharn; Daniele Silvestro; Alexandre Antonelli
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Understanding the patterns and processes underlying the uneven distribution of biodiversity across space and time constitutes a major scientific challenge in evolutionary biology. With rapidly accumulating species occurrence data, there is an increasing ne ed for making the process of coding species into operational units for biogeographic and evolutionary analyses faster, automated, transparent and reproducible. Here we present SpeciesGeoCoder, a free software package written in Python and R,...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/09/17/009274
biorxiv
by Jean-Philippe Fortin; Aurelie Labbe; Mathieu Lemire; Brent W. Zanke; Thomas J. Hudson; Elana J. Fertig; Celia M.T. Greenwood; Kasper D. Hansen
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We propose an extension to quantile normalization which removes unwanted technical variation using control probes. We adapt our algorithm, functional normalization, to the Illumina 450k methylation array and address the open problem of normalizing methylation data with global epigenetic changes, such as human cancers. Using datasets from The Cancer Genome Atlas and a large case-control study, we show that our algorithm outperforms all existing normalization methods with respect to replication...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/02/23/002956
biorxiv
by Prasad Patil; Peirre-Olivier Bachant-Winner; Benjamin Haibe-Kains; Jeffrey T Leek
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Background: Prior to applying genomic predictors to clinical samples, the genomic data must be properly normalized. The most effective normalization methods depend on the data from multiple patients. From a biomedical perspective this implies that predictions for a single patient may change depending on which other patient samples they are normalized with. This test set bias will occur when any cross-sample normalization is used before clinical prediction. Methods: We developed a new prediction...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/06/005983
biorxiv
by Thaddeus R Cybulski; Joshua I Glaser; Adam H Marblestone; Bradley M Zamft; Edward S Boyden; George M Church; Konrad P Kording
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A central issue in neural recording is that of distinguishing the activities of many neurons. Here, we develop a framework, based on Fisher information, to quantify how separable a neuron's activity is from the activities of nearby neurons. We (1) apply this framework to model information flow and spatial distinguishability for several electrical and optical neural recording methods, (2) provide analytic expressions for information content, and (3) demonstrate potential applications of the...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/02/21/002923
Lebers Hereditary Optic Neuropathy (LHON) appears as an enigmatic condition; affecting only certain families and often causing a severe loss of vision seemingly at random amongst family members. The first breakthrough came in 1988 with the linking of the condition to a mutation in the mitochondrial DNA (mtDNA). Now it is known that about 90% of cases are linked to 3 mutations. In this paper the hypothesis is suggested that a LHON mutation decreases the function of the mitochondrial enzyme,...
Topic: Genomics
Source: http://biorxiv.org/content/early/2013/11/25/000935
biorxiv
by Isabelle Busseau; Stephanie Pierson; Dany Severac; Christelle Dantec; Martine Simonelig
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Drosophila Orb, the homologue of vertebrate CPEB is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb has also an essential function during early oogenesis which has not been addressed at the molecular level. Here, we show that orb prevents cell death during early stages of oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy, by directly repressing, together with the CCR4...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/08/15/007971
biorxiv
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In a recent article entitled On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE , Graur et al. dismantle ENCODEs evidence and conclusion that 80% of the human genome is functional. However, the article by Graur et al. contains assumptions and statements that are questionable. Primarily, the authors limit their evaluation of DNAs biological functions to informational roles, sidestepping putative non-informational...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2013/11/18/000588
biorxiv
by Gholson J Lyon; Jason O'Rawe
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There are ~12 billion nucleotides in every cell of the human body, and there are ~25-100 trillion cells in each human body. Given somatic mosaicism, epigenetic changes and environmental differences, no two human beings are the same, particularly as there are only ~7 billion people on the planet. One of the next great challenges for studying human genetics will be to acknowledge and embrace complexity. Every human is unique, and the study of human disease phenotypes (and phenotypes in general)...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/06/22/000687
biorxiv
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Mycoplasmas are notorious contaminants of cell culture and can have profound effects on host cell biology by depriving cells of nutrients and inducing global changes in gene expression. Because they are small, they can escape filtration in culture media. Because they lack cell walls, they are resistant to commonly used antibiotics. Over the last two decades, sentinel testing has revealed wide-ranging contamination rates in mammalian culture. To obtain an unbiased assessment from hundreds of...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/11/007054
biorxiv
by Stephen E. Schauer; Teresa A. Golden; Delwin S. Merchant; Biranchi N. Patra; Jean D. Lang; Sumita Ray; Bulbul Chakravarti; Deb N. Chakravarti; Animesh Ray
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Abstract The ubiquity and importance of short duplex RNAs, termed microRNA (miRNA), for normal development in higher eukaryotes are becoming increasingly clear. We had previously shown that reduction-of-function mutations in Arabidopsis thaliana DCL1 (DICER-LIKE1) gene, affecting the nucleus-localized protein that produces 19-25 nucleotides long miRNA species from longer double stranded RNA precursors, cause a delay in flowering by prolonging the period of juvenile organ development. Here we...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2013/12/21/001438
biorxiv
by Michael A. McCarthy; Alana L. Moore; Jochen Krauss; John W Morgan; Christopher F. Clements
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Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/02/07/000760
biorxiv
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Activation of the NADPH oxidase (NOX2) of the phagocytic vacuole of neutrophils is essential for innate immunity. Sustained activity of the oxidase requires that charge movements across the membrane are balanced. A role for the proton channel, HVCN1, has been proposed but not proven. Using the ratiometric pH indicator SNARF, introduced into the cytosol and separately into the vacuole coupled to Candida , we used confocal microscopy to measure changes in pH in these two compartments in human and...
Topic: Cell Biology
Source: http://biorxiv.org/content/early/2014/03/27/003616
biorxiv
by Neil R Smalheiser; Giovanni Lugli
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Synaptosomes are a popular type of isolated synaptic fraction intensively used in neuroscience and cell biology. They are prepared by layering on density gradients and thought to consist largely of axonal endings with attached postsynaptic structures (Morgan, 1976), in contrast to synaptoneurosomes (Hollingsworth et al, 1985) which are prepared by filtration and are thought to consist largely of pinched-off dendritic spines with attached presynaptic structures. Although most studies of...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/06/24/006510
biorxiv
by Sebastian Gil Anthony Konietzny; Phillip Byron Pope; Aaron Weimann; Alice Carolyn McHardy
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Background: Efficient industrial processes for converting plant lignocellulosic materials into biofuels are a key challenge in global efforts to use alternative energy sources to fossil fuels. Novel cellulolytic enzymes have been discovered from microbial genomes and metagenomes of microbial communities. However, the identification of relevant genes without known homologs, and elucidation of the lignocellulolytic pathways and protein complexes for different microorganisms remain a challenge....
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/05/21/005355
biorxiv
by Alejandro Reyes; Carolin Blume; Vicent Pelechano; Petra Jakob; Lars M Steinmetz; Thorsten Zenz; Wolfgang Huber
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Background: Genome sequencing studies of chronic lympoid leukemia (CLL) have provided a comprehensive overview of recurrent somatic mutations in coding genes. One of the most intriguing discoveries has been the prevalence of mutations in the HEAT-repeat domain of the splicing factor SF3B1. A frequently observed variant is predicted to cause the substitution of a lysine with a glutamic acid at position 700 of the protein (K700E). However, the molecular consequences of the mutations are largely...
Topic: Cancer Biology
Source: http://biorxiv.org/content/early/2014/07/13/000992
biorxiv
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Presented here are the structures of three biologically important sweet sugars, based on the additivity of covalent atomic radii in bond lengths. The observed smaller carbon-oxygen distances involving the 'anomeric' carbons of the open chain hexoses are explained here, for the first time, as due to the smaller covalent double bond radii of carbon and oxygen than their single bond radii in the cyclic forms and in sucrose. The atomic structures of all the three carbohydrates, drawn to scale in...
Topic: Biochemistry
Source: http://biorxiv.org/content/early/2014/01/23/002022
biorxiv
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Temperature affects both the timing and outcome of animal development, but the detailed effects of temperature on the progress of early development have been poorly characterized. To determine the impact of temperature on the order and timing of events during Drosophila melanogaster embryogenesis, we used time-lapse imaging to track the progress of embryos from shortly after egg laying through hatching at seven precisely maintained temperatures between 17.5°C and 32.5°C. We employed a...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2013/11/11/000307
biorxiv
by Biranchi Patra; Yoshiko Kon; Gitanjali Yadav; Anthony Sevold; Jesse P Frumkin; Ravishankar R Vallabhajosyula; Arend Hintze; Bjørn Østman; Jory Schossau; Ashish Bhan; Bruz Marzolf; Jenna K Tamashiro; Amardeep Kaur; Nitin S Baliga; Elizabeth J Grayhack; Christoph Adami; David J Galas; Alpan Raval; Eric M Phizicky; Animesh Ray
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Mutational robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of mutational robustness in the budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high co-occurrence of mutant-suppressor pairs within...
Topic: Genomics
Source: http://biorxiv.org/content/early/2013/11/11/000265
biorxiv
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Background One of the most common goals of hierarchical clustering is finding those branches of a tree that form quantifiably distinct data subtypes. Achieving this goal in a statistically meaningful way requires (a) a measure of distinctness of a branch and (b) a test to determine the significance of the observed measure, applicable to all branches and across multiple scales of dissimilarity. Results We formulate a method termed Tree Branches Evaluated Statistically for Tightness (TBEST) for...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/06/05/002188
biorxiv
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Evolutionary theory is sufficiently well developed to allow for short-term prediction of evolutionary trajectories. In addition to the presence of heritable variation, prediction requires knowledge of the form of natural selection on relevant traits. While many studies estimate the form of natural selection, few examine the degree to which traits evolve in the predicted direction. In this study we examine the form of natural selection imposed by mantid predation on wing size and shape in the...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/05/19/005322
biorxiv
by Fillip Port; Hui-Min Chen; Tzumin Lee; Simon L Bullock
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The type II CRISPR/Cas system has recently emerged as a powerful method to manipulate the genomes of various organisms. Here, we report a novel toolbox for high efficiency genome engineering of Drosophila melanogaster consisting of transgenic Cas9 lines and versatile guide RNA (gRNA) expression plasmids. Systematic evaluation reveals Cas9 lines with ubiquitous or germline restricted patterns of activity. We also demonstrate differential activity of the same gRNA expressed from different U6...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/03/26/003541
biorxiv
by Michael Inouye; Harriet Dashnow; Lesley Raven; Mark B Schultz; Bernard J Pope; Takehiro Tomita; Justin Zobel; Kathryn E Holt
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Rapid molecular typing of bacterial pathogens is critical for public health epidemiology, surveillance and infection control, yet routine use of whole genome sequencing (WGS) for these purposes poses significant challenges. Here we present SRST2, a read mapping-based tool for fast and accurate detection of genes, alleles and multi-locus sequence types (MLST) from WGS data. Using >900 genomes from common pathogens, we show SRST2 is highly accurate and outperforms assembly-based methods in...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/28/006627
biorxiv
by Feng Zeng; Rui Jiang; Guoli Ji; Ting Chen
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The incorrect alignments are a severe problem in variant calling, and remain as a challenge computational issue in Bioinformatics field. Although there have been some methods utilizing the re-alignment approach to tackle the misalignments, a standalone re-alignment tool for long sequencing reads is lacking. Hence, we present a standalone tool to correct the misalignments, called ProbAlign. It can be integrated into the pipelines of not only variant calling but also other genomic applications....
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/09/02/008698
biorxiv
by Fang-Chieh Chou; Nathaniel Echols; Thomas C. Terwilliger; Rhiju Das
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The final step of RNA crystallography involves the fitting of coordinates into electron density maps. The large number of backbone atoms in RNA presents a difficult and tedious challenge, particularly when experimental density is poor. The ERRASER-Phenix pipeline can improve an initial set of RNA coordinates automatically based on a physically realistic model of atomic-level RNA interactions. The pipeline couples diffraction-based refinement in Phenix with the Rosetta-based real-space...
Topic: Biophysics
Source: http://biorxiv.org/content/early/2013/12/19/001461
biorxiv
by Guopeng Ren; Stephen S. Young; Lin Wang; Wei Wang; Yongcheng Long; Ruidong Wu; Junsheng Li; Jianguo Zhu; Douglas W. Yu
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There is profound interest in knowing the degree to which Chinas institutions are capable of protecting its natural forests and biodiversity in the face of economic and political change. Chinas two most important forest protection policies are its National Forest Protection Program (NFPP) and its National-level Nature Reserves (NNRs). The NFPP was implemented in 17 provinces starting in the year 2000 in response to deforestation-caused flooding. We used MODIS data (MOD13Q1) to estimate forest...
Topic: Ecology
Source: http://biorxiv.org/content/early/2013/11/25/000893
biorxiv
by Remco Stam; Graham Motion; Petra C. Boevink; Edgar Huitema
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Phytophthora spp. secrete vast arrays of effector molecules upon infection. A main class of intracellular effectors are the CRNs. They are translocated into the host cell and specifically localise to the nucleus where they are thought to perturb many different cellular processes. Although CRN proteins have been implicated as effectors, direct evidence of CRN mediated perturbation of host processes has been lacking. Here we show that a conserved CRN effector from P. capsici directly binds to...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2013/12/11/001248
biorxiv
by Yuval Elhanati; Anand Murugan; Curtis G Callan Jr.; Thierry Mora; Aleksandra Walczak
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The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ recombination, followed by functional selection of cells according to the interaction of their surface receptors with self and foreign antigenic peptides. To quantify the effect of selection on the highly variable elements of the receptor, we apply a...
Topic: Immunology
Source: http://biorxiv.org/content/early/2014/04/20/004341
biorxiv
by Vladimir Skornyakov; Maria Skornyakova; Antonina Shurygina; Pavel Skornyakov
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In this study Markov chain models of gene regulatory networks (GRN) are developed. These models gives the ability to apply the well known theory and tools of Markov chains to GRN analysis. We introduce a new kind of the finite graph of the interactions called the combinatorial net that formally represent a GRN and the transition graphs constructed from interaction graphs. System dynamics are defined as a random walk on the transition graph that is some Markovian chain. A novel concurrent...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/06/23/006361
biorxiv
by Guilherme Garcia; Rui Cerqueira; Erika Hingst-Zaher; Gabriel Marroig
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Patterns of genetic covariance between characters (represented by the covariance matrix G) play an important role in morphological evolution, since they interact with the evolutionary forces acting over populations. They are also expected to influence the patterns expressed in their phenotypic counterparts (P), because of limits imposed by multiple developmental and functional restrictions on the genotype/phenotype map. We have investigated genetic covariances in the skull and mandible of the...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/08/19/008151
biorxiv
by Ying-Wooi Wan; Claire Mach; Genevera I. Allen; Matthew Anderson; Zhandong Liu
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Dysregulated microRNA (miRNA) expression is a well-established feature of human cancer. However, the role of specific miRNAs in determining cancer outcomes remains unclear. Using Level 3 expression data from the Cancer Genome Atlas (TCGA), we identified 61 miRNAs that are associated with overall survival in 469 ovarian cancers profiled by microarray (p
Topic: Genomics
Source: http://biorxiv.org/content/early/2013/11/13/000315
biorxiv
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In vertebrates, the interferon (IFN) response is the primary form of innate antiviral defense. Previously (2005), a partial cDNA which could encode an interferon-like protein (IntlP) is reported in shrimp, later Rosa et al. (2008) argue that this partial cDNA should encode a portion of insect mitochondrial ATP synthase (MAS) B-chain. Recently (2009), it is demonstrated IntlP also possess antibacterial activity beside antiviral activity reported before. Lacking of a consensus opinion to the...
Topic: Immunology
Source: http://biorxiv.org/content/early/2013/11/16/000513
biorxiv
by Qiyun Zhu; Michael Kosoy; Kevin J Olival; Katharina Dittmar
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Bartonellae are mammalian pathogens vectored by blood-feeding arthropods. Although of increasing medical importance, little is known about their ecological past, and host associations are underexplored. Previous studies suggest an influence of horizontal gene transfers in ecological niche colonization by acquisition of host pathogenicity genes. We here expand these analyses to metabolic pathways of 28 Bartonella genomes, and experimentally explore the distribution of bartonellae in 21 species...
Topic: Microbiology
Source: http://biorxiv.org/content/early/2014/03/17/003350
biorxiv
by William Pitchers; Jason B. Wolf; Tom Tregenza; John Hunt; Ian Dworkin
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A fundamental question in evolutionary biology is the relative importance of selection and genetic architecture in determining evolutionary rates. Adaptive evolution can be described by the multivariate breeders' equation ( Δz = Gβ ), which predicts evolutionary change for a suite of phenotypic traits ( Δz ) as a product of directional selection acting on them ( β ) and the genetic variance-covariance matrix for those traits ( G ). Despite being empirically challenging to estimate, there...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/05/05/002683
biorxiv
by Nicola Fameli; Oluseye A. Ogunbayo; Cornelis van Breemen; A. Mark Evans
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We demonstrate how nanojunctions between lysosomes and sarcoplasmic reticulum (L-SR junctions) serve to couple lysosomal activation to regenerative, ryanodine receptor-mediated cellular calcium (Ca2+) waves. In pulmonary artery smooth muscle cells (PASMCs) nicotinic acid adenine dinucleotide phosphate (NAADP) may trigger increases in cytoplasmic Ca2+ via L-SR junctions, in a manner that requires initial Ca2+ release from lysosomes and subsequent Ca2+-induced Ca2+ release (CICR) via ryanodine...
Topic: Cell Biology
Source: http://biorxiv.org/content/early/2014/01/28/002196
biorxiv
by Kathrin Aprile von Hohenstaufen; Irina Puoti; Marisa Meloni; Barbara De Servi
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Background. The acute myeloid leukemia (AML) cell line OCI-AML3, carrying both NPM1 mutation A and the heterozygous DNMT3A R882C mutation, represents the model for in vitro studies on AML with mutated NPM1. AML with mutated NPM1 harbours a hypo-methylated profile distinct from those of the other AML subtypes. This characteristic is probably related to the inhibitory effect of the mutant DNMT3A on the wild type protein. S-adenosylmethionine (SAM) is a universal methyl donor acting as a coenzyme...
Topic: Pharmacology
Source: http://biorxiv.org/content/early/2014/05/08/004978
biorxiv
by Esther R. Berko; Masako Suzuki; Faygel Beren; Christophe Lemetre; Christine M. Alaimo; R. Brent Calder; Karen Ballaban-Gil; Batya Gounder; Kaylee Kampf; Jill Kirschen; Shahina B. Maqbool; Zeineen Momin; David M. Reynolds; Natalie Russo; Lisa Shulman; Edyta Stasiek; Jessica Tozour; Maria Valicenti-McDermott; Shenglong Wang; Brett S. Abrahams; Joseph Hargitai; Dov Inbar; Zhengdong Zhang; Joseph D. Buxbaum; Sophie Molholm; John J. Foxe; Robert W. Marion; Adam Auton; John Greally
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DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/05/06/004853
biorxiv
by Santiago Herrera; Paula H. Reyes-Herrera; Timothy M. Shank
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High-throughput sequencing of reduced representation libraries obtained through digestion with restriction enzymes–generally known as restriction-site associated DNA sequencing (RAD-seq)–is now one most commonly used strategies to generate single nucleotide polymorphism data in eukaryotes. The choice of restriction enzyme is critical for the design of any RAD-seq study as it determines the number of genetic markers that can be obtained for a given species, and ultimately the success of a...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/08/08/007781
biorxiv
by Emiliana Tognon; Nadine Wollscheid; Katia Cortese; Carlo Tacchetti; thomas vaccari
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Multivesicular endosome (MVE) sorting depends on proteins of the Endosomal Sorting Complex Required for Transport (ESCRT) family. These are organized in four complexes (ESCRT-0, -I, -II, -III) that act in a sequential fashion to deliver ubiquitylated cargoes into the internal luminal vesicles (ILVs) of the MVE. Drosophila genes encoding ESCRT-I, -II, -III components function in sorting signaling receptors, including Notch and the JAK/STAT signaling receptor Domeless. Loss of ESCRT-I, -II, -III...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/02/18/002790
biorxiv
by Ferran Galán; Mark R Baker; Kai Alter; Stuart N Baker
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A major assumption of brain-machine interface (BMI) research is that patients with disconnected neural pathways can still volitionally recall precise motor commands that could be decoded for naturalistic prosthetic control. However, the disconnected condition of these patients also blocks kinaesthetic feedback from the periphery, which has been shown to regulate centrally generated output responsible for accurate motor control. Here we tested how well motor commands are generated in the absence...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/05/06/004861
biorxiv
by Samir Suweis; Paolo D'Odorico
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A number of social-ecological systems exhibit complex behaviour associated with nonlinearities, bifurcations, and interaction with stochastic drivers. These systems are often prone to abrupt and unexpected instabilities and state shifts that emerge as a discontinuous response to gradual changes in environmental drivers. Predicting such behaviours is crucial to the prevention of or preparation for unwanted regime shifts. Recent research in ecology has investigated early warning signs that...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/06/16/003269
biorxiv
by Iker Vaquero-Alba; Andrew McGowan; Daniel Pincheira-Donoso; Matthew R. Evans; Sasha R.X. Dall
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The evolution of animal colouration is importantly driven by sexual selection operating on traits used to transmit information to rivals and potential mates, which therefore, have major impacts on fitness. Reflectance spectrometry has become a standard colour-measuring tool, especially after the discovery of tetrachromacy in birds and their ability to detect UV. Birds? plumage patterns may be invisible to humans, necessitating a reliable and objective way of assessing colouration not dependent...
Topic: Animal Behavior and Cognition
Source: http://biorxiv.org/content/early/2014/08/13/007914
biorxiv
by Jason Merkin*; Ping Chen*; Sampsa Hautaniemi; Christopher Burge
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Mammalian genes are typically broken into several protein-coding and non-coding exons, but the evolutionary origins and functions of new exons are not well understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from several mammals and one bird, identifying thousands of species- and lineage-specific exons. While exons conserved across mammals are mostly protein-coding and constitutively spliced, species-specific exons were mostly located in 5' untranslated regions...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/09/17/009282
biorxiv
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1. Understanding how landscape features affect functional connectivity among populations is a cornerstone of landscape genetic analyses. However, parameterization of resistance surfaces that best describe connectivity is largely a subjective process that explores a limited parameter space. 2. ResistanceGA is a new R package that utilizes a genetic algorithm to optimize resistance surfaces based on pairwise genetic distances and either CIRCUITSCAPE resistance distances or cost distances...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/07/29/007575
biorxiv
by Önder Kartal; Oliver Ebenhöh; Martin Steup
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Carbohydrate polymers are ubiquitous in biological systems and their roles are highly diverse, ranging from energy storage over mechanical stabilisation to mediating cell-cell or cell-protein interactions. The functional diversity is mirrored by a chemical diversity that results from the high flexibility of how different sugar monomers can be arranged into linear, branched or cyclic polymeric structures. Mathematical models describing biochemical processes on polymers are faced with various...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/09/01/008615
biorxiv
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Our understanding of macroevolutionary patterns of adaptive evolution has greatly increased with the advent of large-scale phylogenetic comparative methods. Widely used Ornstein-Uhlenbeck (OU) models can describe an adaptive process of divergence and selection. However, inference of the dynamics of adaptive landscapes from comparative data is complicated by interpretational difficulties, lack of identifiability among parameter values and the common requirement that adaptive hypotheses must be...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/04/23/004465
biorxiv
by Dennis Evangelista; Sharlene Cam; Tony Huynh; Austin Kwong; Homayun Mehrabani; Kyle Tse; Robert Dudley
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The capacity for aerial maneuvering shaped the evolution of flying animals. Here we evaluate consequences of aviaian morphology for aerial performance1,2 by quantifying static stability and control effectiveness of physical models3 for numerous taxa sampled from within the lineage leading to birds (Paraves4,5). Results of aerodynamic testing are mapped phylogenetically6-10 to examine how maneuvering characteristics correlate with tail shortening, fore- and hindwing elaboration, and other...
Topic: Biophysics
Source: http://biorxiv.org/content/early/2014/07/11/001750
biorxiv
by Chang-Jin Park; Min-Young Song; Chi-Yeol Kim; Jong-Seong Jeon; Pamela C. Ronald
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Plant innate immunity is mediated by pattern recognition receptors (PRRs) and intracellular NB-LRR (nucleotide-binding domain and leucine-rich repeat) proteins. Overexpression of the endoplasmic reticulum (ER) chaperone, luminal-binding protein 3 (BiP3) compromises resistance to Xanthomonas oryzae pv. oryzae (Xoo) mediated by the rice PRR XA21 (Park et al., PLoS ONE 5(2): e9262). Here we show that BiP3 overexpression also compromises resistance mediated by rice XA3, a PRR that provides...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2014/03/26/003533
biorxiv
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Understanding the mapping of genotypes into phenotypes is a central challenge of current biological research. Such mapping, conceptually represents a developmental mechanism through which phenotypic variation can be generated. Given the nongenetic character of developmental dynamics, phenotypic variation to a great extent has been neglected in the study of evolution. What is the relevance of considering this generative process in the study of evolution? How can we study its evolutionary...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/04/14/004218
biorxiv
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Correlations in neuronal spike times are thought to be key to processing in many neural systems. Many measures have been proposed to summarise these correlations and of these the correlation index is widely used and is the standard in studies of spontaneous retinal activity. We show that this measure has two undesirable properties: it is unbounded above and confounded by firing rate. We list properties needed for a measure to fairly quantify and compare correlations and we propose a novel...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/09/09/006635
biorxiv
by Timo Maarleveld; Bennet K NG; Herbert Sauro; Kyung Kim
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Biological organisms acclimatize to varying environmental conditions via active self-regulation of internal gene regulatory networks, metabolic networks, and protein signaling networks. While much work has been done to elucidate the topologies of individual networks in isolation, understanding of inter-network regulatory mechanisms remains limited. This shortcoming is of particular relevance to synthetic biology. Synthetic biological circuits tend to lose their engineered functionality over...
Topic: Bioengineering
Source: http://biorxiv.org/content/early/2014/08/05/007658
biorxiv
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The paradigm of competitive males vying to influence female mate choice has been repeatedly upheld, but, increasingly, studies also report competitive females and choosy males. One female trait that is commonly proposed to influence male mate choice is the exaggerated estrous swelling displayed by females of many Old World primate species. The reliable indicator hypothesis posits that females use the exaggerated swellings to compete for access to mates by advertising variation in female...
Topic: Animal Behavior and Cognition
Source: http://biorxiv.org/content/early/2014/07/21/007278
biorxiv
by Liangsheng Zhang; Zhenguo Zhang
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In this study, we retraced the origin of the reported avian influenza A H6N1 virus infecting a 20-year-old woman in Taiwan. As we know, this is the first reported case of human infection by the H6N1 virus, because this subtype virus usually circulates in birds and poultry. Therefore it is crucial to know how this virus attained the ability to infect humans. Using phylogenetic analysis, we found that this virus was derived from reassortments of multiple lineages of H6N1 viruses and H5N2 viruses....
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2013/11/14/000398
biorxiv
by Xubin Pan
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Sampling is a fundamental tool in ecology and critical for biodiversity measurement. However, basic principles of biodiversity sampling have been overlooked for many years. In this paper, I proposed and explored five principles of sampling for a specific area and biodiversity study. The first principle of sampling, species increasing with area, is that the number of species increases with the area. The second principle of sampling, individuals increasing with area, is that the number of...
Topic: Ecology
Source: http://biorxiv.org/content/early/2013/11/14/000364
Despite decades of research, thousands of studies and numerous advances, the etiologies of Alzheimers Disease (AD), Parkinsons Disease (PD), Huntingtons Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Lobar Degeneration (FTLD-U), Creutzfeldt-Jakob Disease (CJD), Reactive Systemic Amyloidosis (RSA) and many other neurodegenerative and systemic amyloid diseases have not been defined, nor have the pathogenic mechanisms leading to cellular death and disease. Moreover, the...
Topic: Immunology
Source: http://biorxiv.org/content/early/2013/11/18/000604
biorxiv
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The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model their ancestral relationship under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20-30 thousand years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The Multiple Sequentially Markovian Coalescent (MSMC)...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/05/23/005348
biorxiv
by Nuno A. Fonseca; Robert Petryszak; John Marioni; Alvis Brazma
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RNA-sequencing (RNA-Seq) has become the technology of choice for whole-transcriptome profiling. However, processing the millions of sequence reads generated requires considerable bioinformatics skills and computational resources. At each step of the processing pipeline many tools are available, each with specific advantages and disadvantages. While using a specific combination of tools might be desirable, integrating the different tools can be time consuming, often due to specificities in the...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/06/06/005991
biorxiv
by N. Ari Wijetunga; Fabien Delahaye; Yong Mei Zhao; Aaron Golden; Jessica C Mar; Francine H. Einstein; John M. Greally
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The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here, we purify human CD34+ hematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/08/01/007591
biorxiv
by Konstantin Berlin; Sergey Koren; Chen-Shan Chin; James Drake; Jane M Landolin; Adam M Phillippy
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We report reference-grade de novo assemblies of four model organisms and the human genome from single-molecule, real-time (SMRT) sequencing. Long-read SMRT sequencing is routinely used to finish microbial genomes, but the available assembly methods have not scaled well to larger genomes. Here we introduce the MinHash Alignment Process (MHAP) for efficient overlapping of noisy, long reads using probabilistic, locality-sensitive hashing. Together with Celera Assembler, MHAP was used to...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/08/14/008003
biorxiv
by Gregory A Moyerbrailean; Chris T Harvey; Cynthia A Kalita; Xiaoquan Wen; Francesca Luca; Roger Pique-Regi
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A detailed mechanistic understanding of the direct functional consequences of DNA variation on gene regulatory mechanism is critical for a complete understanding of complex trait genetics and evolution. Here, we present a novel approach that integrates sequence information and DNase I footprinting data to predict the impact of a sequence change on transcription factor binding. Applying this approach to 653 DNase-seq samples, we identified 3,831,862 regulatory variants predicted to affect active...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/29/007559
biorxiv
by Elizabeth A Williams; Markus Conzelmann; Gáspár Jékely
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During larval settlement and metamorphosis, marine invertebrates undergo changes in habitat, morphology, behavior and physiology. This change between life-cycle stages is often associated with a change in diet or a transition between a non-feeding and a feeding form. How larvae regulate changes in feeding during this life cycle transition is not well understood. Neuropeptides are known to regulate several aspects of feeding, such as food search, ingestion and digestion. The marine annelid...
Topic: Zoology
Source: http://biorxiv.org/content/early/2014/09/06/008854
Background: Comprehensive understanding of mechanisms of genome functions requires identification of molecules interacting with genomic regions of interest in vivo. We have developed the insertional chromatin immunoprecipitatin (iChIP) technology to isolate specific genomic regions retaining molecular interactions and identify their associated molecules. iChIP consists of locus-tagging and affinity purification. The recognition sequences of an exogenous DNA-binding protein such as LexA are...
Topic: Biochemistry
Source: http://biorxiv.org/content/early/2014/06/07/006080
biorxiv
by Katie Leach; Ruth Kelly; Alison Cameron; W.Ian Montgomery; Neil Reid
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Climate change during the last five decades has impacted on natural systems significantly and the rate of current climate change is of great concern among conservation biologists. Here, we assess the projected change in the bioclimatic envelopes of all 87 species in the mammalian order Lagomorpha under future climate using expertly validated species distribution models. Results suggest that climate change will impact more than two-thirds of Lagomorphs, with leporids (rabbits, hares and...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/01/14/001826
biorxiv
by Peter Acuña Combs; Michael B Eisen
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Recently, a number of protocols extending RNA-sequencing to the single-cell regime have been published. However, we were concerned that the additional steps to deal with such minute quantities of input sample would introduce serious biases that would make analysis of the data using existing approaches invalid. In this study, we performed a critical evaluation of several of these low-volume RNA-seq protocols, and found that they performed slightly less well in metrics of interest to us than a...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/10/006130
biorxiv
by Nikolai Slavov; David Botstein; Amy Caudy
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Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and cell division, we collected and analyzed DNA-content, gene-expression and physiological data, at...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/05/28/005629
biorxiv
by Enrique Carrillo de Santa Pau; Juliane Perner; David Juan; Simone Marsili; David Ochoa; Ho-Ryun Chung; Daniel Rico; Martin Vingron; Alfonso Valencia
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We have analyzed publicly available epigenomic data of mouse embryonic stem cells (ESCs) combining diverse next-generation sequencing (NGS) studies (139 experiments from 30 datasets with a total of 77 epigenomic features) into a homogeneous dataset comprising various cytosine modifications (5mC, 5hmC and 5fC), histone marks and Chromatin related Proteins (CrPs). We applied a set of newly developed statistical analysis methods with the goal of understanding the associations between chromatin...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/09/06/008821
biorxiv
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The debate over the ethnogenesis of Ashkenazi Jewry is longstanding, and has been hampered by a lack of Jewish historiographical work between the Biblical and the early Modern eras. Most historians, as well as geneticists, situate them as the descendants of Israelite tribes whose presence in Europe is owed to deportations during the Roman conquest of Palestine, as well as migration from Babylonia, and eventual settlement along the Rhine. By contrast, a few historians and other writers, most...
Topic: Genetics
Source: http://biorxiv.org/content/early/2013/12/12/001354
biorxiv
by Scott Brouilette; Samir Ounzain; Vinit Sawhney; Kenta Yashiro; Yasunori Shintani; Kunihiko Takahashi; Steven Coppen; Takuya Narita; Kelli Torsney; Martin Carrier; Niall Campbell; Ken Suzuki
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Telomeres comprise the distal ends of eukaryotic chromosomes, serve to maintain genomic integrity and are extended by the ribonucleoprotein telomerase. Recent evidence indicates that telomeres are transcribed to generate long non-coding RNAs (lncRNAs) and that these transcripts (TERRA) may inhibit telomerase activity. In this study we assessed telomerase activity and telomeric lncRNA expression in a mouse model of skeletal myogenesis. Using the C2C12 cell line we demonstrated decreased...
Topic: Molecular Biology
Source: http://biorxiv.org/content/early/2013/11/18/000679
biorxiv
by Oana Carja; Robert E Furrow; Marc W Feldman
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Stochastic switching is an example of phenotypic bet-hedging, where an individual can switch between different phenotypic states in a fluctuating environment. Although the evolution of stochastic switching has been studied when the environment varies temporally, there has been little theoretical work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here we use a population genetic model to explore the interaction of temporal and...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/03/19/003442-0
biorxiv
by R Daniel Kortschak; David L Adelson
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bíogo is a framework designed to ease development and maintenance of computationally intensive bioinformatics applications. The library is written in the Go programming language, a garbage-collected, strictly typed compiled language with built in support for concurrent processing, and performance comparable to C and Java. It provides a variety of data types and utility functions to facilitate manipulation and analysis of large scale genomic and other biological data. bíogo uses a concise and...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/05/12/005033
biorxiv
by Akihiro Shimokawa; Yuki Tonooka; Misato Matsumoto; Hironori Ara; Hiroshi Suzuki; Naoki Yamauchi; Masayoshi Shigyo
movies

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Because global climate change has made agricultural supply unstable, plant factories are expected to be a safe and stable means of food production. As the light source of a plant factory or controlled greenhouse, the light emitting diode (LED) is expected to solve cost problems and promote plant growth efficiently. In this study, we examined the light condition created by using monochromatic red and blue LEDs, to provide both simultaneous and alternating irradiation to leaf lettuce. The result...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2014/02/28/003103
biorxiv
by Mathieu Larocque; Thierry Chénard; Rafael Najmanovich
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Clostridium difficile is the leading cause of hospital-borne infections occurring when the natural intestinal flora is depleted following antibiotic treatment. We present i MLTC804cdf, an extensively curated reconstructed metabolic network for the C. difficile pathogenic strain 630. i MLTC804cdf contains 804 genes, 705 metabolites and 766 metabolic, 145 exchange and 118 transport reactions. i MLTC804cdf is the most complete and accurate metabolic reconstruction of a gram-positive anaerobic...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/07/25/006932