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Registros recuperados: 273
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Successful use of axonal transport for drug delivery by synthetic molecular vehicles Nature Precedings
Aaron G. Filler; Garth Whiteside; Mark Bacon; Martyn Frederickson; Franklyn A. Howe; Miri K. Rabinowitz; Alan J. Sokoloff; Terrence Deacon; Chris Abell; Raj Munglani; John R. Griffiths; B. Anthony Bell; Andrew Lever.
We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and...
Tipo: Manuscript Palavras-chave: Biotechnology; Chemistry; Molecular Cell Biology; Neuroscience; Pharmacology.
Ano: 2008 URL: http://precedings.nature.com/documents/2164/version/1
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_Drosophila_ and human transcriptomic data mining provides evidence for therapeutic mechanism of pentylenetetrazole in Down syndrome Nature Precedings
Abhay Sharma.
Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ’s therapeutic effect is however not clear. Microarray profiling has previously reported differential expression of genes in DS. No mammalian transcriptomic data on PTZ treatment however exists. Nevertheless, a _Drosophila_ model inspired by rodent models of PTZ induced kindling plasticity has recently been described. Microarray profiling has shown PTZ’s downregulatory effect on gene expression in fly heads. In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential mechanism of PTZ action in DS. I find that transcriptomic...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4330/version/1
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Gender differences in a Drosophila transcriptomic model of chronic pentylenetetrazole induced behavioral deficit Nature Precedings
Abhay Sharma; Farhan Mohammad; Priyanka Singh.
A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ), a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs) ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK,...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3460/version/1
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SNIPER SHOT PEGylation: TGase mediated site-specific conjugation of PEG to proteins Nature Precedings
Abhijeet Satwekar.
Commercially available recombinant protein drugs often cause immune reactions in the body which reduces their efficiency. Protein drugs can be PEGylated, (attachment of polyethylene glycol) to overcome this problem. PEGylation increases bioavailability by reduced immune reactions and decreased renal clearance [1]. So far the traditional approaches for PEGylation involve harsh reaction conditions which provide a heterogeneous product (PEG attached randomly to different sites) along with the formation of several byproducts. Due to heterogeneity, the PEGylated protein drug faces challenge for FDA approval. Therefore, there is an immense need to develop an approach which could generate a homogeneous PEGylated protein drug. 
The...
Tipo: Poster Palavras-chave: Biotechnology; Chemistry; Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/5671/version/1
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DNA expression microarrays may be the wrong tool to identify biological pathways Nature Precedings
Adrian Mondry; Marie Loh; Alessandro Giuliani.
DNA microarray expression signatures are expected to provide new insights into patho- physiological pathways. Numerous variant statistical methods have been described for each step of the signal analysis. We employed five similar statistical tests on the same data set at the level of gene selection. Inter-test agreement for the identification of biological pathways in BioCarta, KEGG and Reactome was calculated using Cohen’s k- score. The identification of specific biological pathways showed only moderate agreement (0.30 < k < 0.79) between the analysis methods used. Pathways identified by microarrays must be treated cautiously as they vary according to the statistical method used.
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2007 URL: http://precedings.nature.com/documents/1036/version/1
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Critical Concentration Gradient Model of Bacterial Cell Division Nature Precedings
Aijaz A. Rashid; Perminder P. Sing.
Critical concentration gradient model is helpful in understanding the mechanism of Z-ring formation. The distribution of positive and negative regulators of Z-ring formation in cell is not random but well programmed. The positive and negative regulators in cell lead to a critical concentration gradient from mid cell to the poles. The critical concentration of FtsZ required for Z-ring assembly at the centre of cell is less than that at the poles. So FtsZ starts polymerizing at cell centre and afterwards by cooperative association of more and more monomers leads to the Z-ring formation. Simultaneously during Z-ring formation the recruitment of other accessory proteins takes place, leading to the formation of a stable divisome complex.
Tipo: Manuscript Palavras-chave: Biotechnology; Microbiology; Pharmacology.
Ano: 2010 URL: http://precedings.nature.com/documents/4659/version/1
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Trans-Disciplinary Protein Binding Of Drug: Docking Approach Nature Precedings
Ajeet Ajeet.
The purpose of present work is to introduce the binding of existing drugs to the trans-disciplinary protein with the help of docking procedures. Docking procedures allows virtually screening a database of compounds and predict the strongest binder based on various scoring functions. This work has been performed with the help of Molegro Virtual docker, in which two drugs are docked with their corresponding and non-corresponding (trans-disciplinary) protein. Results reveals that the protein-ligand interaction energy, hydrogen bond energy and MolDock scores provided by molegro virtual docker, between legands (Levodopa and Acyclovir) and trans-disciplinary proteins have been equivalent or even better than that of between legands and corresponding proteins.
Tipo: Manuscript Palavras-chave: Pharmacology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6702/version/1
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QSAR & DOCKING APPROACH - POTENTIAL WAY TO NEW DRUG DEVELOPMENT Nature Precedings
Ajeet Ajeet.
With today's need for discovering and developing new drug molecules, it is necessary to accept ways to save time and wet lab essentials. To this end, the QSAR and molecular docking approach is used widely by us. This poster describes steps for developing a new or modified moiety of a drug molecule.

Tipo: Poster Palavras-chave: Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7071/version/1
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Inhibition of central insulin-receptor signaling by S961 causes hyperglycemia and glucose intolerance in rats Nature Precedings
Ajit Vikram; Gopabandhu Jena.
Genetic ablation studies confirmed the role of central insulin-receptor signaling (CIRS) in fuel metabolism. However, the need to examine the role of CIRS in glucose homeostasis under normal physiological condition is indispensable, as insulin affects the neuronal growth, differentiation and synaptic plasticity. Intracerebral administration of S961 induced hyperglycemia and glucose intolerance in normal rats, and provided direct evidence for the involvement of CIRS in the regulation of glucose homeostasis.
Tipo: Manuscript Palavras-chave: Neuroscience; Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/5701/version/1
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Predictive Models of Insulin Resistance Derived from Simple Morphometric and Metabolic Measurements Related to Obesity in Baboons. Nature Precedings
Alberto Chavez; Amalia Gastaldelli; Juan Carlos Lopez-Alvarenga; Rodolfo Guardado-Mendoza; Michelle Leland; M. Elizabeth Tejero; GianPio Sorice; Alberto Davalli; Raul Bastarrachea; Anthony Comuzzie; Ralph DeFronzo; Franco Folli.
Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and hemoglobin A1C). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. We characterized a population of obese nondiabetic, insulin resistant baboons using the euglycemic clamp technique and used a multivariate linear regression analysis (after adjustment for gender) to test three different predictive models for insulin sensitivity. In the first model, abdominal...
Tipo: Manuscript Palavras-chave: Pharmacology.
Ano: 2008 URL: http://precedings.nature.com/documents/2429/version/1
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Angiogenesis in Chronic Obstructive Pulmonary Disease Nature Precedings
Alessandro Matarese; Gaetano Santulli.
Angiogenesis is a crucial component of lung pathophysiology, not only in cancer but also in other disorders, such as chronic obstructive pulmonary disease (COPD). In COPD angiogenesis is definitely able to control and orchestrate the progression of airway remodeling. Herein, we provide several remarkable translational aspects of angiogenesis in COPD, exploring both basic and clinical research in this field. Indeed, we present a number of pro- and anti-angiogenic factors, which can be also used as potential biomarkers to monitor disease progression. 

This pre-print has subsequently been published at http://www.unisa.it/uploads/7100/06.pdf
Tipo: Manuscript Palavras-chave: Immunology; Molecular Cell Biology; Pharmacology.
Ano: 2012 URL: http://precedings.nature.com/documents/7112/version/1
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The universe of normal and cancer cell line responses to anticancer treatment: Lessons for cancer therapy Nature Precedings
Alexei Vazquez.
According to the Surveillance Epidemiology and End Results report, 1,479,350 men and women will be diagnosed with and 562,340 will die of cancer of all sites in 2009, indicating that about 40% of the cancer patients do not respond well to current anticancer therapies. Using tumor and normal tissue cell lines as a model, we show this high mortality rate is rooted in inherent features of anticancer
treatments. We obtain that, while on average anticancer treatments exhibit a two fold higher efficacy when applied to cancer cells, the response distribution of cancer and normal cells significantly overlap. Focusing on specific treatments, we provide evidence indicating that the therapeutic index is proportional to the fraction of cancer cell...
Tipo: Manuscript Palavras-chave: Cancer; Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/5785/version/1
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BBSRC Data Sharing Policy Nature Precedings
Amanda Collis; David McAllister; Michael Ball.
BBSRC recognizes the importance of contributing to the growing international efforts in data sharing. BBSRC is committed to getting the best value for the funds we invest and believes that making research data more readily available will reinforce open scientific inquiry and stimulate new investigations and analyses. BBSRC supports the view that data sharing should be led by the scientific community and driven by scientific need. It should also be cost effective and the data shared should be of the highest quality. Members of the community are expected and encouraged to practice and promote data sharing, determine standards and best practice, and create a scientific culture in which data sharing is embedded.
Tipo: Manuscript Palavras-chave: Biotechnology; Developmental Biology; Genetics & Genomics; Immunology; Microbiology; Molecular Cell Biology; Neuroscience; Pharmacology; Bioinformatics; Plant Biology; Evolutionary Biology; Data Standards.
Ano: 2011 URL: http://precedings.nature.com/documents/6015/version/1
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Neuronal plasticity: cell-based strategy for target identification and validation Nature Precedings
Ana Mingorance-Le Meur; Timothy P. O'Connor.
While growing neurites are relatively plastic during development, their plasticity levels drop rapidly as neurons mature and become integrated into neuronal networks. As a consequence, the central nervous system ability to reorganize itself in response to injury or disease is insufficient. One of the main limitations for the design of therapeutic strategies to enhance neurite sprouting following neurological diseases is our poor understanding of the mechanisms underlying neurite structural plasticity. 

To overcome this limitation, we have implemented a strategy to identify, characterize and validate the most therapeutically relevant drug targets to modulate neuronal plasticity. This strategy is based on the hypothesis...
Tipo: Poster Palavras-chave: Molecular Cell Biology; Neuroscience; Pharmacology.
Ano: 2009 URL: http://precedings.nature.com/documents/2780/version/1
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Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway Nature Precedings
Andrey Ptitsyn; Jeffrey Gimble.
*Background*
It has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences. 

*Results*
We report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2007 URL: http://precedings.nature.com/documents/858/version/1
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Computational system biology Nature Precedings
Ankit Geete.
Systems biology is a multi-disciplinary field that deals with mechanisms involved in complex biological processes by considering them as integrated systems of multiple interacting components. The huge amount of data involved in this study necessitates the use of computational tools.
Tipo: Presentation Palavras-chave: Biotechnology; Genetics & Genomics; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7104/version/1
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Antiviral activity of (E)-cinnamaldehyde revisited with nanoscience tools Nature Precedings
Arunava Goswami; Ayesha Rahman.
Contradictory results have been reported regarding the anti-viral activity of (E)-cinnamaldehyde, a major constituent (~69%) of cinnamon. Here we show that (E)-cinnamaldehyde alone has very low antiviral property contrary to the belief of commoners. There are early sporadic reports in ancient medicinal practices that fine sand was used for increasing the efficacy of antiviral drugs. Can we increase the efficacy of (E)-cinnamaldehyde marginally by using one of the major constituents of sand like silica? Yes, when nanosilica is used as a carrier during (E)-cinnamaldehyde administration, the antiviral efficacy of the resultant cocktail increases marginally. Therefore, (E)-cinnamaldehyde consumed for centuries in tribal therapy as well as in alternative...
Tipo: Manuscript Palavras-chave: Biotechnology; Pharmacology.
Ano: 2010 URL: http://precedings.nature.com/documents/5043/version/1
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Remote preconditioning by aortic constriction: affords cardioprotection as classical or other remote ischemic preconditioning? Role of iNOS Nature Precedings
Ashish Sharma; Arshee Munajjam; Bhawna Vaishnav; Richa Sharma; Kunal Kishore; Ashok Sharma; Akash Sharma; Divya Sharma; Rita Kumari; Ashish Tiwari; B.P. Srinivasan; Shyam Agarwal.
Dose remote preconditioning by aortic constriction (RPAC) affords cardioprotection similar to classical or other remote ischemic preconditioning stimulus? Moreover study was also designed to investigate role of inducible nitric oxide synthase in remote preconditioning by aortic constriction. There are sufficient evidences that "ischemic preconditioning" has surgical applications and afford clinically relevant cardioprotection. Transient occlusion of circumflex artery, renal artery, limb artery or mesenteric artery preconditions the myocardium against ischemia reperfusion injury in case of ischemic heart disease leading to myocardial infraction. Here abdominal aorta was selected to produce RPAC. Four episodes of Ischemia-reperfusion of 5...
Tipo: Manuscript Palavras-chave: Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/5494/version/1
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Study Of Phenothiazine On p53 Core Domain Mutant Y220C: Finding The Anti-tumor Activity Of Phenothiazine Nature Precedings
Asif Husain Naqvi; Hardik H. Sheth; Vijay Kumar; Suchindran H S; Vivek Gupta.
The tumor suppressor protein p53 is a transcription factor that plays a key role in the prevention of cancer development. The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to elucidate the extent of specificity of p53 cancer mutation Y220C towards different class of Phenothiazines (an anti-cancer agent). 

The 393 residue p53 tumor suppressor protein exists in a dynamic equilibrium to form homotetramers. Each chain comprises several functional domains. The N terminal part of the protein consists of the...
Tipo: Presentation Palavras-chave: Cancer; Pharmacology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6135/version/1
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Genome-wide transcription analysis of interaction between the human macrophage and Mycobacterium tuberculosis during concurrent drug administration by conventional and novel methods Nature Precedings
Awadh Bihari Yadav; Amit K. Singh; Amit Misra.
Targeted drug delivery to alveolar macrophages harboring Mycobacterium tuberculosis (Mtb) holds promise of high efficacy against pulmonary tuberculosis (TB). It was investigated whether inhalable microparticles (MP) can rescue macrophages from ‘alternative’ activation induced by pathogenic Mtb in addition to achieving targeted drug delivery. A genome-wide transcription analysis (Affymetrix HG-U133 Plus 2.0 DNA microarray) of THP-1 cell line derived macrophages was undertaken after exposing them to infection with 10 MOI of MTB H37Rv at 0, 12 and 24 hours post infection. The Molecular markers of macrophage bactericidal activity were assayed in THP-1- and primary human peripheral blood mononuclear cell (PBMC)-derived macrophages, in the...
Tipo: Poster Palavras-chave: Pharmacology.
Ano: 2008 URL: http://precedings.nature.com/documents/2453/version/1
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