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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 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 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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A Quality Evaluation Framework for Bio-Ontologies Nature Precedings
Jesualdo Tomas Fernandez-Breis; Mikel Egaña Aranguren; Robert Stevens.
Over the past few years the number of bio-ontologies has rapidly increased. The evaluation of ontologies has long been a problematic issue. The growing number of ontologies makes the need for a strategy for evaluating quality more urgent. We propose a framework for evaluating the quality of bio-ontologies. This framework is inspired by a well-known software quality standard, which has been adapted to the needs of ontology evaluation. An example of how to use the framework, comparing two versions of the Open Biomedical Ontologies' Cell Type Ontology, is included as an illustration.
Tipo: Manuscript Palavras-chave: Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3479/version/1
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A Quantitative Approach to Investigating the Hypothesis of Prokaryotic Intron Loss Nature Precedings
Robert M. Sinclair.
Using a novel method, we show that ordered triplets of motifs usually associated with spliceosomal intron recognition are underrepresented in the protein coding sequence of complete Thermotogae, archaeal and bacterial genomes. The underrepresentation observed does not extend to the noncoding strand, suggesting that the cause of the asymmetry is related to mRNA rather than DNA. Our data do not suggest that the underrepresentation is due to gene transfer from eukaryotes. We speculate that one possible explanation for these observations is that the protein coding sequence of Thermotogae, Archaea and Bacteria was at some time in the past subjected to selection against certain motifs appearing in an order which might initiate splicing in environments harboring...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Microbiology; Bioinformatics; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/5770/version/1
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A quantitative model for efficient construction of lentiviral vectors with a unique clone site Nature Precedings
Gang Zhang; Anurag Tandon.
Lentiviral vectors (LVs) were a powerful tool for transgene expression in vivo and in vitro. However, the construction of LVs is of low efficiency, due to the large sizes and lack of proper clone sites. Therefore, it is critical to develop efficient strategies for cloning LVs. Here, we reported a combinatorial strategy to efficiently construct LVs using EGFP, hPlk2 wild type (WT) and mutant genes as inserts. Firstly, site-directed mutagenesis (SDM) was performed to create BamH I site for the inserts; secondly, pWPI LV was dephosphorylated after BamH I digestion; finally, the amounts and ratios of the insert and vector DNA were optimized to increase monomeric ligation. Our results showed that the total percentage of positive clones was approximately...
Tipo: Manuscript Palavras-chave: Biotechnology.
Ano: 2012 URL: http://precedings.nature.com/documents/6876/version/1
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A Quantitative Model for Human Olfactory Receptors Nature Precedings
Sk. Sarif Hassan; Pabitra Pal Choudhury; Aritra Bose.
A wide variety of chemicals having distinct odors are smelled by humans. Odor perception initiates in the nose, where it is detected by a large family of olfactory receptors (ORs). Based on divergence of evolutionary model, a sequence of human ORs database has been proposed by D. Lancet et al (2000, 2006). It is quite impossible to infer whether a given sequence of nucleotides is a human OR or not, without any biological experimental validation. In our perspective, a proper quantitative understanding of these ORs is required to justify or nullify whether a given sequence is a human OR or not. In this paper, all human OR sequences have been quantified, and a set of clusters have been made using the quantitative results based on two different metrics. Using...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6967/version/2
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A Quantitative Model for Human Olfactory Receptors Nature Precedings
Sk. Sarif Hassan; Pabitra Pal Choudhury; Aritra Bose.
A wide variety of chemicals having distinct odors are smelled by humans. Odor perception initiates in the nose, where it is detected by a large family of olfactory receptors (ORs). Based on divergence of evolutionary model a sequence of human ORs database has been proposed by D. Lancet et al (2000, 2006). It is quite impossible to infer whether a given sequence of nucleotides is a human OR or not, without any biological experimental validation. In our perspective, a proper quantitative understanding of these ORs is required to justify or nullify whether a given sequence is a human OR or not. In this paper, all human OR sequences have been quantified, and a set of clusters have been made using the quantitative results based on two different metrics. Using...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6967/version/1
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A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness Nature Precedings
Louise Linsell; Lindsay J. L. Forbes; Marcia Kapari; Caroline Burgess; Lynne Omar; Lorraine Tucker; Amanda J. Ramirez.
There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We tested the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. We randomised 867 women aged 67 to 70 attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted ten-minute interaction with a radiographer plus a booklet; a booklet alone; or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk; and reported breast checking. At one...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2009 URL: http://precedings.nature.com/documents/3816/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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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 Reaction Route Approach to Flux Balance Analysis Nature Precedings
Ilie Fishtik.
Background: Flux balance and network-based pathway analyses are theoretical tools aimed to find optimal steady state flux distributions in a metabolic network subject to additional constraints on the rates of the reaction steps. Although these methods are mathematically accurate, there are several physicochemical and computational aspects that are questionable and misleading. In particular, it is well known that the flux balance analysis may result in multiple flux distributions for the same objective function. 

Results: The flux balance and network-based pathway analyses are reformulated in terms of reaction routes (RRs), a theoretical framework that has been developed by Horiuti over 50 years ago. Not only does the...
Tipo: Manuscript Palavras-chave: Biotechnology; Chemistry; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/2788/version/1
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A reassessment of the Carnot cycle and the concept of entropy Nature Precedings
Sosale Chandrasekhar.
It is argued that the Carnot cycle is a highly inaccurate representation of a steam engine, and that the net work obtained in its operation would be zero. This conclusion is also supported by an elementary mathematical approach, which re-examines the work done in the four individual steps of the cycle. An important consequence of this is that the concept of entropy, originally proposed on the basis of the Carnot theorem, may not be a fundamentally valid thermodynamic quantity. Also, the experimental approach generally adopted in the determination of entropy is questionable, and the importance of increasing randomness in natural processes not universally valid. In fact, a more viable basis, at least vis-à-vis chemical reactions, appears to be the...
Tipo: Manuscript Palavras-chave: Chemistry.
Ano: 2008 URL: http://precedings.nature.com/documents/1852/version/1
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