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A coordinated phosphorylation cascade initiated by MSK1 directs RAR alpha recruitment to target gene promoters Nature Precedings
Nathalie Bruck; Dominique Vitoux; Christine Ferry; Vanessa Duong; Annie Bauer; Hughes de The; Cecile Rochette-Egly.
The nuclear retinoic acid (RA) receptor alpha (RARα) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RARα-target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RARα at S369 located in the Ligand Binding Domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates Histone H3 at S10. Finally, the phosphorylation cascade...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/2107/version/1
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A Critical Evaluation of Clinical Trials in Cancer and Pharmacogenomics Nature Precedings
I. C. Baianu.
A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Developmental Biology; Genetics & Genomics; Immunology; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7052/version/1
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A Database for TSSs of Human MicroRNAs Nature Precedings
Malay Bhattacharyya; Sanghamitra Bandyopadhyay.
MicroRNAs (miRNAs) are small endogeneous non-coding RNAs of about 22nt length. These short RNAs regulate the expression of mRNAs by hybridizing with their 3'-UTRs or by translational repression. They have been shown to take crucial roles in many biological processes. Many of the current studies are focused over how mature miRNAs regulate mRNAs, even though there is very limited knowledge about their transcriptional loci. Primary miRNAs (pri-miRs) are first transcribed from the DNA, followed by the formation of precursor miRNA (pre-miR) by endonucleases activity, which finally produces mature miRNAs. Unfortunately, the identification of the loci of pri-miRs, and the associated information about transcription start sites (TSSs) and promoters is...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6832/version/1
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A database of naturally occurring human urinary peptides and proteins for use in clinical applications Nature Precedings
Petra Zürbig; Joshua Coon; Hartwig Bauer; Georg Behrens; Mohammed Dakna; Anna Dominiczak; Stephane Decramer; Jochen Ehrich; Danilo Fliser; Moritz Frommberger; Arnold Ganser; Mark Giolami; Igor Golovko; David Good; Wilfried Gwinner; Marion Haubitz; Stefan Herget-Rosenthal; Holger Jahn; George Jerums; Bruce Julian; Markus Kellmann; Volker Kliem; Walter Kolch; Andrzej Krolewski; Mario Luppi; Ziad Massy; Michael Melter; Christian Neusüss; Jan Novak; Karlheinz Peter; Kasper Rossing; Harald Rupprecht; Joost Schanstra; Eric Schiffer; Jens-Uwe Stolzenburg; Lise Tarnow; Dan Theodorescu; Visith Thongboonkerd; Raymond Vanholder; Eva Weissinger; Harald Mischak; Philippe Schmitt-Kopplin.
Owing to its availability, ease of collection and correlation with (patho-) physiology, urine is an attractive source for clinical proteomics. However, the lack of comparable datasets from large cohorts has greatly hindered development in this field. Here we report the establishment of a high resolution proteome database of naturally occurring human urinary peptides and proteins - ranging from 800-17,000 Da - from over 3,600 individual samples using capillary electrophoresis coupled to mass spectrometry, yielding an average of 1,500 peptides per sample. All processed data were deposited in an SQL database, currently containing 5,010 relevant unique urinary peptides that serve as classifiers for diagnosis and monitoring of diseases, including kidney and...
Tipo: Manuscript Palavras-chave: Biotechnology.
Ano: 2007 URL: http://precedings.nature.com/documents/1219/version/1
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A database of orthologous exons in primates for comparative analysis of RNA-seq data Nature Precedings
Ran Blekhman.
RNA-seq technology facilitates the study of gene expression at the level of individual exons and transcripts. Moreover, RNA-seq enables unbiased comparative analysis of expression levels across species. Such analyses typically start by mapping sequenced reads to the appropriate reference genome before comparing expression levels across species. However, this comparison requires prior knowledge of orthology at the exon level. With this in mind, I constructed a database of orthologous exons across three primate species (human, chimpanzee, and rhesus macaque). The database facilitates cross-species comparative analysis of exon- and transcript-level regulation. A web application allowing for an easy database query: http://giladlab.uchicago.edu/orthoExon/
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Bioinformatics; Evolutionary Biology.
Ano: 2012 URL: http://precedings.nature.com/documents/7054/version/1
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A decline in pollinator dependent vegetable crop productivity in India indicates pollination limitation and consequent agro-economic crises. Nature Precedings
Parthiba Basu; Ritam Bhattacharya; Pietro Ianetta.
Approximately 70% of the tropical crop species depend on pollinators for optimum yields (Roubik, 1995, Klein 2007). The economic value of such pollinated crops to India is $726 million and India is the world's second largest vegetable producer (Sidhu, 2005). This status has been underpinned by large-scale changes in land-use and pesticide dependency (Fazal, 2000; Shaw & Satish, 2007). A method (c.f. Aizen et al. 2008) that partitions crops into categories depending on their relative pollinator dependence (Index of pollinator dependence, DI) was applied to analysis of vegetable yields for India over 45 years (1963-2008) using FAO data. This has revealed that since 1993, relative yields of crop production has either flattened or declined,...
Tipo: Manuscript Palavras-chave: Ecology.
Ano: 2011 URL: http://precedings.nature.com/documents/6044/version/1
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A Discrete State Model for Kinesin-1 with Rate Constants Modulated by Neck Linker Tension Nature Precedings
Steven J. Koch; Lawrence J. Herskowitz.
Kinesin-1 is a homodimeric molecular motor protein that uses ATP and a hand-over-hand motion to transport cargo along microtubules. How kinesin converts chemical energy into directed motion is a question that has been actively studied since its discovery. Even at the most coarse-grained level of chemical kinetics, understanding is still lacking. Minimal kinetic models are often developed to both explain kinesin’s hand-over-hand forward-stepping behavior and to infer important kinetic rate constants from experimental data. These minimal models are often limited to a handful of two-headed states on a core cycle and have been essential for the current level of understanding. However, it is not always clear how to evolve these core-cycle models to...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/5038/version/1
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A Draft Sequence of the Puerto Rican Parrot Genome (Amazona vittata) – a Genome Project funded by a Local Community Effort Nature Precedings
Taras K. Oleksyk.
The genome of the Puerto Rican parrot (Amazona vittata) has been sequenced and assembled in an international collaboration supported by many individual donations from the people of Puerto Rico. This is a critically endangered endemic bird, the only surviving native parrot species in the territory of the United States, and the first parrot belonging to the large genus Amazona to have its genome sequenced and assembled. A genome of one A. vittata female was sequenced resulting in a total of almost 42.5 billion nucleotide bases equivalent to 26.89X average coverage depth. After filtering out the short fragments (<500bp), the assembly resulted in 259,423 short fragment library contigs, half of them (N50) of at least 6,983 bp in length, with a...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Bioinformatics; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6552/version/1
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A Drosophila systems model of withdrawal from chronic pentylenetetrazole relevant in post-epileptogenesis Nature Precedings
Priyanka Singh; Farhan Mohammad; Abhay Sharma.
Rodent kindling induced by pentylenetetrazole (PTZ) is an established model of epileptogenesis and antiepileptic drug (AED) testing. Recently, a Drosophila systems model has been described in which chronic PTZ causes a decreased climbing speed in adult males on 7th day. Some AEDs ameliorate development of this locomotor deficit. Time-series of microarray expression profiles of heads of flies treated with PTZ has been found to resemble transcriptomic alterations associated with epileptogenesis. In the fly model, withdrawal from seven day long PTZ treatment causes an increased climbing speed on 7th consequent day. Here, we present a systems model of the post-PTZ withdrawal regime. Unlike AED-untreated individuals, flies treated with any of the five AEDs...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3447/version/1
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A dynamical model of genetic networks describes cell differentiation Nature Precedings
Roberto Serra; Villani Marco; Alessia Barbieri.
Cell differentiation is a complex phenomenon whereby a stem cell becomes progressively more specialized and eventually gives rise to a specific cell type. Differentiation can be either stochastic or, when appropriate signals are present, it can be driven to take a specific route. Induced pluripotency has also been recently obtained by overexpressing some genes in a differentiated cell. Here we show that a stochastic dynamical model of genetic networks can satisfactorily describe all these important features of differentiation, and others. The model is based on the emergent properties of generic genetic networks, it does not refer to specific control circuits and it can therefore hold for a wide class of lineages. The model points to a peculiar role of...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4741/version/1
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A few remarks on the relationship between visuo-spatial attention deficits and dyslexia Nature Precedings
John Skoyles; Bernt C. Skottun.
Dyslexia and attentional problems are often comorbid. This raises the question whether reading deficits might etiologically follow from attentional difficulties, a hypothesis that has been proposed in regard to visuo-spatial attention deficits. This visuo-spatial attention deficit hypothesis would predict that attention deficits should be specific to dyslexia. However, it is here estimated that at the population level there are more non-dyslexic individuals than dyslexic individuals with visuo-spatial attention deficits. The reason for this is that in the overall population level there are far more individuals without dyslexia than with dyslexia. Thus, a relatively modest percentage presence of attention problems in the non-dyslexic population can result...
Tipo: Manuscript Palavras-chave: Neuroscience.
Ano: 2011 URL: http://precedings.nature.com/documents/5525/version/1
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A Formal Ontology of Sequences Nature Precedings
Robert Hoehndorf; Janet Kelso; Heinrich Herre.
The Sequence Ontology is an OBO Foundry ontology that provides categories of sequences and sequence features that are applied to the annotation of genomes. To facilitate interoperability with other domain ontologies and to provide a foundation for automated inference, we provide here an axiom system for the Sequence and Junction categories in first- and second-order predicate logics.
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3537/version/1
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A Fresh Look at Energy, Materials, and Labor in Agriculture Nature Precedings
Aaron W. Baum; Tadeusz Patzek; Martin Bender; Steve Renich; Wes Jackson.
An understanding of agriculture's energy, material, and labor requirements is essential for achieving economic and ecological sustainability, and for assessing the effectiveness of relevant policy decisions (biofuel subsidies, regulations, labeling, etc.). Previous studies of energy, materials, and labor use in farming have been based on either unverified voluntary reporting or test plots, rather than on the high-resolution measurements of mass and energy flows. Here we present a recursive analysis of 1.25 million data points describing in unprecedented detail the resource transactions on a 60 ha farm functioning for over 6 years. This analysis highlights the importance of accounting for all types of materials, as well as capital equipment,...
Tipo: Manuscript Palavras-chave: Ecology; Earth & Environment.
Ano: 2010 URL: http://precedings.nature.com/documents/4291/version/1
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A functional dissociation of conflict processing within anterior cingulate cortex Nature Precedings
Chobok Kim; James Kroger; Jeounghoon Kim.
Goal-directed behavior requires cognitive control to regulate neural processing when conflict is encountered. The dorsal anterior cingulate cortex (dACC) has been associated with detecting response conflict during conflict tasks. However, recent findings have indicated not only that two distinct subregions of dACC are involved in conflict processing but also that the conflict occurs at both perceptual and response levels. We clarified a functional dissociation of the caudal dACC (cdACC) and the rostral dACC (rdACC) in responding to different sources of conflict. The cdACC was selectively engaged in perceptual conflict whereas the rdACC was more active in response conflict. Further, the dorsolateral prefrontal cortex (DLPFC) was coactivated not with cdACC...
Tipo: Manuscript Palavras-chave: Neuroscience.
Ano: 2008 URL: http://precedings.nature.com/documents/2505/version/1
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A G4MP2 theoretical study on the gas phase enthalpies of formation for various polycyclic aromatic hydrocarbons (PAHs) and other C~10~ through C~20~ unsaturated hydrocarbons Nature Precedings
Sierra Rayne; Kaya Forest.
Gas phase enthalpies of formation at 298.15 and 1 atm (Δ~f~H~(g),298K~) were calculated using the atomization approach at the G4MP2 composite method level of theory for 86 polyaromatic hydrocarbons (PAHs) and other C~10~ through C~20~ unsaturated hydrocarbons. Where available, good agreement with prior experimental data and/or high level theoretical estimates was obtained. Linear regressions between semiempirical MNDO, MNDO-d, AM1, PM3, RM1, and PM6 estimated Δ~f~H~(g),298K~ and the corresponding G4MP2 values were employed to obtain G4MP2 corrected semiempirical Δ~f~H~(g),298K~ for a suite of 156 C~11~ through C~42~ unsaturated hydrocarbons and PAHs.
Tipo: Manuscript Palavras-chave: Chemistry.
Ano: 2011 URL: http://precedings.nature.com/documents/6450/version/1
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A G4/W1BD theoretical study into the gas phase enthalpies of formation for potential high energy materials Nature Precedings
Sierra Rayne; Kaya Forest.
Enthalpies of formation (Δ~f~H~(g)~) at 298.15 K and 0 K were calculated for various potential high energy materials (HEMs) using the high-level Gaussian-4 (G4) and W1BD methods with the atomization approach. Where prior high level estimates are available in the literature, the G4 and W1BD Δ~f~H~(g)~ are in good agreement. The results presented herein represent the highest level calculations performed to date on this suite of HEMs. These G4/W1BD enthalpies of formation should provide utility among the research community as a benchmark set of values against which to assess future experimental and/or theoretical data.
Tipo: Manuscript Palavras-chave: Chemistry.
Ano: 2011 URL: http://precedings.nature.com/documents/6461/version/1
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A Genome-Wide Analysis Reveals Significant Overlap of Transcription and DNA Repair in Stationary Phase Yeast Nature Precedings
Aviv de Morgan; Leonid Brodsky; Yefim Ronin; Eviatar Nevo; Abraham Korol; Yechezkel Kashi.
The association between transcription and DNA repair is acknowledged as a player in the generation of mutations in a non-random fashion in prokaryotes and eukaryotes. Previous studies demonstrated that the transcription complex is capable of directing DNA repair to sites of transcription. This process is especially important to growth-arrested cells, in which many DNA repair capacities are diminished; it may also lead to mutations preferentially in transcribed genes. Using microarray analysis of growth-arrested yeast cultures, we demonstrated on a genomic scale, the co-localization of a DNA-turnover marker, indicative of DNA-repair-associated DNA synthesis, with genes persistently transcribed during stationary phase. This may serve as a clue regarding the...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Evolutionary Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1543/version/1
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A Handy Script to Implement Genetic Models in R Nature Precedings
Wei Zhang.
Genome-wide associations between genotypic and phenotypic data often assume certain genetic models. A handy script in R was written to implement three commonly used genetic models: additive, dominant and recessive models. This script can be easily inserted into more complicated programs to facilitate high-throughput association studies.
Tipo: Manuscript Palavras-chave: Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1537/version/1
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A Handy Script to Implement Genetic Models in R Nature Precedings
Wei Zhang.
Genome-wide associations between genotypic and phenotypic data often assume certain genetic models. A handy script in R was written to implement three commonly used genetic models: additive, dominant and recessive models. This script can be easily inserted into more complicated programs to facilitate high-throughput association studies.
Tipo: Manuscript Palavras-chave: Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1537/version/2
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A Hyperstable Miniprotein: Additive Effects of D- and L-Ala Substitutions Nature Precedings
D. V. Williams; Bipasha Barua; Niels H. Andersen.
The effects of alanine substitutions in each helical segment of the structure, and Gly to D-Ala mutations at sites where glycines have positive phi angles in the Trp-cage miniprotein are reported. The effects of the stabilizing mutation were additive, yielding a 20-residue construct (Tm = 83^o^C). Gly to L-Ala substitutions were uniformly destabilizing ([DELTA][DELTA]G~F~ > 11 kJ/mol): the preference for a D-Ala can be as large as 16 kJ/mol. Glycine to D-Ala mutations are validated as a strategy for the design of hyperstable miniprotein scaffolds suitable for stereospecific pharmacophore display.
Tipo: Manuscript Palavras-chave: Chemistry.
Ano: 2008 URL: http://precedings.nature.com/documents/2074/version/1
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