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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 novel strategy for the targeted analysis of protein and peptide metabolites Nature Precedings
Nicholas A. Williamson; Charles Reilly; Chor-Teck Tan; Sri-Harsha Ramarathinam; Alun Jones; Christie L. Hunter; Francis R. Rooney; Anthony W. Purcell.
The detection and quantitation of exogenously administered biological macromolecules (e.g. vaccines, peptide and protein therapeutics) and their metabolites is frequently complicated by the presence of a complex endogenous mixture of closely related compounds. We describe a method that incorporates stable isotope labeling of the compound of interest allowing the selective screening of the intact molecule and all metabolites using a modified precursor ion scan. This method involves monitoring the low molecular weight fragment ions produced during MS/MS that distinguish isotopically labelled material from related endogenous compounds. All isotopically labelled substances can be selected using this scanning technique for further analysis whilst other...
Tipo: Manuscript Palavras-chave: Biotechnology; Immunology; Pharmacology.
Ano: 2009 URL: http://precedings.nature.com/documents/3812/version/1
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A novel superior factor widely controlling the rice grain quality Nature Precedings
Kao-Chih She; Hiroaki Kusano; Kazuyoshi Koizumi; Hiromoto Yamakawa; Makoto Hakata; Tomohiro Imamura; Masato Fukuda; Natsuka Naito; Yumi Tsurumaki; Ken'ichiro Matsumoto; Mari Kudoh; Eiko Itoh; Shoshi Kikuchi; Naoki Kishimoto; Junshi Yazaki; Tsuyu Ando; Masahiro Yano; Takashi Aoyama; Tadamasa Sasaki; Hikaru Satoh; Hiroaki Shimada.
Synthesis of storage starch and protein accumulation is the main action of endosperm organogenesis in term of the economic importance of rice. This event is strongly disturbed by abiotic stresses such as high temperature; thus, the upcoming global warming will cause a crisis with a great impact on food production^1,2^. The enzymes for the protein storage and starch synthesis pathway should work in concert to carry out the organogenesis of rice endosperm^3-5^, but the regulatory mechanism is largely unknown. Here we show that a novel regulatory factor, named OsCEO1, acts as the conductor of endosperm organogenesis during the rice grain filling stage. The physiological properties of _floury-endosperm-2_ (_flo2_) mutants showed many similarities to symptoms...
Tipo: Manuscript Palavras-chave: Plant Biology.
Ano: 2009 URL: http://precedings.nature.com/documents/3283/version/1
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A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1 Nature Precedings
Shi-He Liu; Donald Rao; John Nemunaitis; Neil Senzer; David Dawson; Marie-Claude Gingras; Zhaohui Wang; Richard Gibbs; Michael Norman; Nancy Templeton; Francesco DeMayo; Kelly Stehling; William Fisher; Charles Brunicardi.
Bi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA<sup>mousePDX-1</sup> or shRNA<sup>mousePDX-1</sup> lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2011 URL: http://precedings.nature.com/documents/6047/version/1
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A Novel Thermodynamic Method For Quantifying Ligand-Receptor Interactions: The IC (1/3) Standard Vs IC (50) Nature Precedings
Dr Sudarsan Prasad.
A method based on the Concentration Derivative Product (CDP) is proposed to analyze the thermodynamics of Drug-Receptor interactions. CDP is defined as the product of the fractional inhibition f and it’s concentration derivative. Assuming Michaelis-Menten kinetics, it is shown that for a number of drug-receptor systems (HIV protease, ACE, HMG-CoA, Opioid receptor inhibitors, etc.) f max = 0.333, irrespective of the nature of bonding interactions and Ki. The CDP max = [4 / ( 27 Ki ) ], and gives a measure of the drug potency directly. CDP also gives thermodynamic information about the ratio of the gradients of the inhibitor chemical potential in the free and bound states.
Tipo: Manuscript Palavras-chave: Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/6006/version/1
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A Paradigm for Biology's Next Revolution Nature Precedings
Fredric D. R. Young.
A recent essay on biology's next revolution described attributes of a future theory of biology that would replace post hoc modeling with an interplay between quantitative prediction and experimental test, more characteristic of the physical sciences1. The article suggested that flux from the environment whether it be energy, chemicals metabolites, or genes is a defining characteristic of life. The essay also suggests that an interdisciplinary approach to collective phenomena centered on statistical mechanics and dynamical systems theory will be required to make use of this perspective. Over the last 30 years we have developed an approach to drug discovery and translational research that is based on a paradigm for complex systems modeling that fits...
Tipo: Manuscript Palavras-chave: Biotechnology.
Ano: 2008 URL: http://precedings.nature.com/documents/1770/version/1
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A periodic pattern of SNPs in the human genome Nature Precedings
Bo Eskerod Madsen; Palle Villesen; Carsten Wiuf.
By surveying all validated SNPs in the human genome we have found that SNPs positioned 1, 2, 4, 6 or 8 bp apart are more frequent than SNPs 3, 5, 7 or 9 bp apart. This holds even when we correct for nucleotide frequencies and site dependencies in nucleotide usage in the genome. The observed pattern is not restricted to any of the genomic regions that might give sequencing or alignment errors; i.e. transposable elements (SINE, LINE and LTR), tandem repeats and large duplicated regions. However we can define periodic DNA, which virtually capture the entire pattern. Periodic DNA is defined as small DNA sequences (16.9 bp average length) with a high degree of periodicity in nucleotide usage. Periodic DNA is widely distributed in the genome, underrepresented in...
Tipo: Poster Palavras-chave: Genetics & Genomics.
Ano: 2007 URL: http://precedings.nature.com/documents/435/version/1
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A Physiological Role for Amyloid Beta Protein: Enhancement of Learning and Memory Nature Precedings
John Morley; Susan Farr; William Banks; Steven N. Johnson; Kelvin A. Yamada; Lin Xu.
Amyloid beta protein (A[beta]) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of A[beta] and its physiological role in non-disease states is not clear. In these studies, low doses of A[beta] enhanced memory retention in two memory tasks and enhanced acetylcholine production in the hippocampus _in vivo_. We then tested whether endogenous A[beta] has a role in learning and memory in young, cognitively intact mice by blocking endogenous A[beta] in healthy 2-month-old CD-1 mice. Blocking A[beta] with antibody to A[beta] or DFFVG (which blocks A[beta] binding) or decreasing A[beta] expression with an antisense directed at the A[beta] precursor APP all resulted in impaired...
Tipo: Manuscript Palavras-chave: Neuroscience.
Ano: 2008 URL: http://precedings.nature.com/documents/2119/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 population-based study of glutathione-S-transferase M1, T1 and P1 genotypes Nature Precedings
Monika Sivoňová; Iveta Waczulíková; Dušan Dobrota; Tatiana Matáková; Jozef Hatok; Peter Račay; Ján Kliment.
A retrospective study on healthy, unrelated subjects was conducted in order to estimate population glutathione-S-transferases (GST) genotype frequencies in Slovak population of men and compare our results with already published data (GSEC project)^1^. A further aim of the study was to evaluate frequencies of the _GST_ polymorphisms also in patients with prostate cancer in order to compare the evaluated proportions with those found in the control subjects. Analysis for the _GST_ gene polymorphisms was performed by PCR and PCR-RFLP. We found that the proportions are not significantly different from those estimated in a European multicentre study or from the results published by another group in Slovakia. We found significantly increased age-standardized...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2008 URL: http://precedings.nature.com/documents/2559/version/1
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A Possible Solution to the Etiological Paradox that Ties Anti-Social Personality Disorder to Major Depression Nature Precedings
Alvaro Machado Dias.
Abstract. Antisocial personality disorder (ASPD) is a pervasive condition among youngsters around the globe, which has particular pungency in countries where the socioeconomic context favors delinquency. Several behavioral genetics studies have linked the disorder to the presence of copies of a polymorphic variation of the MAO-A gene that leads to enzymatic hypofunction. An emerging tendency in this literature is to also associate it to the presence of short variations of the 5-HTTLPR polymorphism, which is well-known for its possible role in the vulnerability to major depression of individuals that were exposed to early-life stress. The current paper argues that the association of these findings introduce a theoretical problem that is not trivial...
Tipo: Manuscript Palavras-chave: Genetics & Genomics.
Ano: 2011 URL: http://precedings.nature.com/documents/6308/version/1
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A potential cyanobacterial ancestor of Viridiplantae chloroplasts Nature Precedings
Wriddhiman Ghosh; Prabir Haldar; Sabyasachi Bhattacharya; Jaideb Chatterjee; Prosenjit Pyne; Masrure Alam.
The theory envisaging the origin of plastids from endosymbiotic cyanobacteria is well-established but it is difficult to explain the evolution (spread) of plastids in phylogenetically diverse plant groups. It is widely believed that primordial endosymbiosis occurred in the last common ancestor of all algae^1^, which then diverged into the three primary photosynthetic eukaryotic lineages, viz. the Rhodophyta (red algae), Glaucocystophyta (cyanelle-containing algae) and Viridiplantae (green algae plus all land plants)^2^. Members of these three groups invariably have double membrane-bound plastids^3^, a property that endorses the primary endosymbiotic origin of the organelles. On the other hand, the three or four membrane-bound plastids of the evolutionary...
Tipo: Manuscript Palavras-chave: Microbiology; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6607/version/1
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A potential diagnostic biomarker: Proteasome LMP2/b1i-differential expression in human uterus neoplasm Nature Precedings
Takuma Hayashi; Akiko Horiuchi; Hiroyuki Aburatani; Nobuo Yaegashi; Susumu Tonegawa; Ikuo Konishi.
Uterine leiomyosarcoma (ULMS) develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine ULMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker which distinguishes malignant ULMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine ULMS, to establish a treatment method. Proteasome low-molecular mass polypeptide 2(LMP2)/b1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2012 URL: http://precedings.nature.com/documents/7082/version/1
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A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. Nature Precedings
Carl Gregory; Narae Lee; Angela Smolarz; Scott Olson; Odile David; Jacob Reiser; Robert Kutner; Najat Daw; Darwin Prockop; Edwin Horwitz.
Canonical Wnt signaling is an osteo-inductive signal that promotes bone repair through acceleration of osteogenic differentiation by progenitors. Dkk-1 is a secreted inhibitor of canonical Wnt signaling and thus inhibits osteogenesis. To examine a potential osteo-inhibitory role of Dkk-1 in osteosarcoma (OS), we measured serum Dkk-1 in pediatric patients with OS (median age, 13.4 years) and found it to be significantly elevated. We also found that Dkk-1 was maximally expressed by the OS cells at the tumor periphery and _in vitro_ Dkk-1 and RANKL are co-expressed by rapidly proliferating OS cells. Both Dkk-1 and conditioned media from OS cells reduces osteogenesis by human mesenchymal cells and by immuno-depletion of Dkk-1, or by adding a GSK3[beta]...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer.
Ano: 2007 URL: http://precedings.nature.com/documents/130/version/1
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A prelude report on molecular docking of HER2 protein towards comprehending anti-cancer properties of saponins from Solanum tuberosum Nature Precedings
Puneet K. Singh; Pratyoosh Shukla.
Saponins are extensively known for many biological activities e.g. antimicrobial, anti-palatability, anti-cancer and hemolytic. As cancer cells have a more cholesterol-like compound in their membrane structure the saponins bind cholesterol due to their natural affinity to bind cancer cell membrane. This prevents them from entering the body through the intestinal tract, where they have the ability to attach themselves to vital organs and grow. This study reports the effective use of lower dose saponins like immunotoxin so that they can inhibit the proliferation of cancerous pancreatic cells. The investigation of pancreatic cancer metabolic pathway it was found that proteins 3H3B produced by genes HER-2 are involved in the enhancement of this type of cancer....
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7147/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 Proposal of Genomic Analytical Workflow in a Bacterial Pathogen Outbreak Investigation Nature Precedings
Hoi Shan Kwan; Chun Hang Au; Chi Keung Cheng; Man Kit Cheung; Qianli Huang; Lei Li; Wenyan Nong; Man Chun Wong.
The German Escherichia coli O104:H4 outbreak causing Hemolytic Uremic Syndrome (HUS) started in early May 2011. Conventional typing methods including serotyping, multi-locus sequence typing (MLST) and pulse-field gel electrophoresis (PFGE) seemed to yield only limited information about the causative agent. The advantages of the Genome sequencing approach are apparent compared to conventional methods. Genome sequencing and analyses with an appropriate workflow would be the new paradigm in bacterial outbreak investigation.
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Microbiology.
Ano: 2011 URL: http://precedings.nature.com/documents/6663/version/1
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