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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 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 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 logistic regression model for microalbuminuria prediction in overweight male population Nature Precedings
BaoDe Chen; WeiYi Xu; Chen Yu; ZhenYun Ni; XueFen Li; DaWei Cui.
Background: Obesity promotes progression to microalbuminuria and increases the risk of chronic kidney disease. Current protocols of screening microalbuminuria are not recommended for the overweight or obese.

Design and Methods: A cross-sectional study was conducted. The relationship between metabolic risk factors and microalbuminuria was investigated. A regression model based on metabolic risk factors was developed and evaluated for predicting microalbuminuria in the overweight or obese.

Results: The prevalence of MA reached up to 17.6% in Chinese overweight men. Obesity, hypertension, hyperglycemia and hyperuricemia were the important risk factors for microalbuminuria in the overweight....
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Evolutionary Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/5372/version/1
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A Micropropagation, Molecular and Physiochemical Analysis of Canola Brassica napus L. From Seeds Nature Precedings
Israr Khan; Muhammad Shuaib; Sikandar Khan; Muhammad Amir Zia; Haji Akbar.
Canola is important for its oil, anticarcinogenic phytochemicals and low saturated fat content and has wide scope for further improvement through genetic transformations. Micropropagation is the practice of rapidly multiplying stock plant material to produce a large number of disease free progeny plants, using modern asceptic plant tissue culture methods and also to conserve germ plasm. A combination of auxin and cytikinin and a shock on growth regulator free medium is used for micropropagation. Molecular and physiochemical analysis done to know variation in seeds protein content and electric conductivity.
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Molecular Cell Biology; Plant Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4781/version/2
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A Modular Semantic Annotation Framework: CellML Metadata Specifications 2.0 Nature Precedings
Michael T. Cooling.
In the last decade or so, model encoding efforts such as CellML and SBML have greatly facilitated model availability. But, as the complexity of models increases, the utility of these models can vary. The addition of semantic information is crucial to transforming mathematical models from esoteric to informative resources. 

We have developed a metadata specification framework to better enable the annotation of CellML models with metadata. The framework consists of a core specification describing, in general terms, how annotations should be attached using RDF/XML, and satellite specifications covering several domains of immediate interest, using elements from the Dublin Core, FOAF (Friend-Of-A-Friend), BIBO (Bibliographic...
Tipo: Poster Palavras-chave: Molecular Cell Biology; Bioinformatics; Data Standards.
Ano: 2011 URL: http://precedings.nature.com/documents/6391/version/1
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A multiple-instance scoring method to predict tissue-specific cis-regulatory motifs and regions Nature Precedings
Jin Gu.
Transcription is the central process of gene regulation. In higher eukaryotes, the transcription of a gene is usually regulated by multiple cis-regulatory regions (CRRs). In different tissues, different transcription factors bind to their cis-regulatory motifs in these CRRs to drive tissue-specific expression patterns of their target genes. By combining the genome-wide gene expression data with the genomic sequence data, we proposed multiple-instance scoring (MIS) method to predict the tissue-specific motifs and the corresponding CRRs. The method is mainly based on the assumption that only a subset of CRRs of the expressed gene should function in the studied tissue. By testing on the simulated datasets and the fly muscle dataset, MIS can identify true...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/4038/version/1
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A normalization technique for next generation sequencing experiments Nature Precedings
Günter Klambauer; Karin Schwarzbauer; Andreas Mayr; Sepp Hochreiter.
Next generation sequencing (NGS) are these days one of the key technologies in biology. NGS' cost effectiveness and capability of finding the smallest variations in the genome makes them increasingly popular. For studies aiming at genome assembly, differences in read count statistics do not affect the outcome. However, these differences bias the outcome if the goal is to identify structural DNA characteristics like copy number variations (CNVs). Thus a normalization step must removed such random read count variations subsequently read counts from different experiments are comparable. Especially after normalization the commonly used assumption of Poisson read count distribution in windows on the chromosomes is more justified. Strong deviations of...
Tipo: Poster Palavras-chave: Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4710/version/2
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A normalization technique for next generation sequencing experiments Nature Precedings
Günter Klambauer; Karin Schwarzbauer; Andreas Mayr; Sepp Hochreiter.
Next generation sequencing (NGS) are these days one of the key technologies in biology. NGS' cost effectiveness and capability of finding the smallest variations in the genome makes them increasingly popular. For studies aiming at genome assembly, differences in read count statistics do not affect the outcome. However, these differences bias the outcome if the goal is to identify structural DNA characteristics like copy number variations (CNVs). Thus a normalization step must removed such random read count variations subsequently read counts from different experiments are comparable. Especially after normalization the commonly used assumption of Poisson read count distribution in windows on the chromosomes is more justified. Strong deviations of...
Tipo: Poster Palavras-chave: Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4710/version/1
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A novel alveolar Krebs cycle-triggered CO2 sensing mechanism regulates regional pulmonary ventilation. Nature Precedings
Rainer Kiefmann; Paula Keller; Oliver Tritt; Kai Heckel; Sascha Tank; Martina Kiefmann; Leoni Schulte-Uentrop; Alwin Goetz.
Pulmonary perfusion disorders provoke atelectasis in order to minimize ventilation/perfusion mismatch. However, the underlying mechanisms remain unknown. Because intraalveolar CO2 concentration ([CO2]iA) declines as a consequence of poor pulmonary perfusion we postulated the existence a novel alveolar CO2-sensing mechanism which adapts the ventilation to perfusion. Real-time fluorescence imaging of rat lungs revealed that low [CO2]iA decreased cytosolic and increased mitochondrial Ca2+ in alveolar epithelial cells (AEC), leading to reduction of surfactant secretion and alveolar ventilation. Mitochondrial inhibition by ruthenium red or rotenone blocked the hypocapnia-induced responses. In cultured Type 2 AEC hypocapnia decreased cytosolic Ca2+ independently...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6185/version/1
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A novel mathematical tool for generating highly conserved protein domain via different organismal genomic landscapes Nature Precedings
Arunava Goswami; Pabitra Pal Choudhury; Rajneesh Singh; Sk. Sarif Hassan.
Darwinian evolution hypothesizes that a short stretch of DNA was first constructed and then it expanded to give rise to a long strand. This long strand then produced a mix of exons, introns and repetitive DNA sequence. The order of production of above three kinds of DNA sequence is unknown. Reshuffling of stretches of DNA like above within organisms has given rise to different chromosomes. Till date it is not known how this process is governed. In this paper we show that starting with a sixteen base-pair human olfactory DNA sequence one can form a highly conserved protein domain. Once this domain is formed repetitive DNA sequences of a particular kind starts generating which signifies that this particular conserved protein domain will be unique in nature....
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4850/version/1
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A Novel NIR Spectroscopy Correlation Approach to Amino Acid Analysis of Soybean Proteins for Composition Improvements- (v.4) Nature Precedings
Valentin Prisecaru; I. C. Baianu.
Amino acid NIR calibrations were developed in our Physical Chemistry of Foods Laboratory of the University of Illinois at Urbana for three selected amino acid groups that include essential amino acids for identified soybean accessions. Conventional “wet chemistry” analytical methods are time-consuming and costly. As a result, soybean breeders and researchers have an imperative need to utilize faster and less expensive methods. NIR Spectroscopy is a rapid and inexpensive method for composition analysis for academia and industry. Recent advancements in instrumentation design, such as the application of the Diode Array (DA) technique and the Fourier Transform (FT) IR and NIR techniques, have significantly improved overall instrument...
Tipo: Presentation Palavras-chave: Biotechnology; Chemistry; Developmental Biology; Genetics & Genomics; Immunology; Molecular Cell Biology; Bioinformatics; Earth & Environment; Plant Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6231/version/4
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A novel predicted calcium-regulated kinase family implicated in neurological disorders Nature Precedings
Małgorzata Dudkiewicz; Anna Lenart; Krzysztof Pawłowski.
Protein kinases are essential effectors of cellular signaling. Surprisingly, using bioinformatics tools, we predicted protein kinase structure and function for proteins of unknown function (FAM69 family) coded by five related human genes and their Metazoan homologues. Analysis of three-dimensional structure models and conservation of the classic catalytic motifs of protein kinases in four of human FAM69 proteins suggests they might have retained catalytic phosphotransferase activity. The FAM69 genes, FAM69A, FAM69B, FAM69C, C3ORF58 and CXORF36, are by large uncharacterized molecularly, yet linked to several neurological disorders in genetics studies. An EF-hand Ca2+-binding domain in FAM69A and FAM69B proteins, inserted within the structure of the kinase...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7015/version/1
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A novel regulator of the p53-mediated mitochondrial apoptotic pathway Nature Precedings
Bo Young Ahn; Diane Trinh; Laura Zajchowski; Sung-Woo Kim.
The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal...
Tipo: Manuscript Palavras-chave: Cancer; Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1892/version/1
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A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability Nature Precedings
Eric Howlett; Curtis C. J. Lin; William Lavery; Michael Stern.
Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Neuroscience.
Ano: 2008 URL: http://precedings.nature.com/documents/1767/version/1
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A probabilistic model of plasmid replication regulation by a combination of handcuffing, iteron number and dimerization of RepA protein. Nature Precedings
Milind Watve; Gauri Tendulkar; Ketaki Ghate.
Plasmids are small circular DNA molecules in bacteria which replicate sharing the replication machinery with the bacterial chromosome. Since plasmids are much smaller than the chromosome, unless their replication is tightly regulated, their copy numbers can escalate quickly. A number of mechanisms of plasmid replication regulation are known in P1 plasmid of E. coli. Mechanisms such as autorepression of the replication initiator protein (RepA) and its dimerization are unable to explain copy number regulation by themselves. The number of RepA binding sites (iterons) is inversely related to copy numbers. Handcuffing of plasmids by RepA dimer is believed to be the main mechanism of arresting replication. We show here with a probabilistic model that for the...
Tipo: Poster Palavras-chave: Molecular Cell Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/5421/version/1
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A Rate Distortion approach to protein symmetry Nature Precedings
Rodrick Wallace.
A spontaneous symmetry breaking argument is applied to the problem of protein form, via a Rate Distortion analysis of the relation between genome coding and the final condensation of the protein 'molten globule'. The Rate Distortion Function, under coding constraints, serves as a temperature analog, so that low values act to drive proteins to simple symmetries. The Rate Distortion Function itself is significantly constrained by the availability of metabolic free energy. This work extends Tlusty's (2007) elegant exploration of the evolution of the genetic code, suggesting that rate distortion considerations may play a critical role across a broad spectrum of molecular expressions of evolutionary process.
Tipo: Manuscript Palavras-chave: Chemistry; Developmental Biology; Genetics & Genomics; Molecular Cell Biology; Bioinformatics; Earth & Environment; Evolutionary Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4280/version/1
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A Rate Distortion approach to protein symmetry Nature Precedings
Rodrick Wallace.
A spontaneous symmetry breaking argument is applied to the problem of protein folding, via a Rate Distortion analysis of the relation between genome coding and the final condensation of the protein molten globule. In the 'energy' picture, the average distortion between codon message and protein structure, under constraints driven by evolutionary selection, serves as a temperature analog, so that low values limit the possible distribution of protein forms, producing the canonical folding funnel. A dual 'developmental' perspective sees the rate distortion function itself as the temperature analog, and permits incorporation of chaperons or toxic exposures as catalysts, driving the system to different possible outcomes or...
Tipo: Manuscript Palavras-chave: Chemistry; Molecular Cell Biology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4280/version/2
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