G-quadruplex DNA aptamers and their ligands: Structure, function and application

Highly specific and tight-binding nucleic acid aptamers have been selected against a variety of molecular targets for over 20 years. A significant proportion of these oligonucleotides display G-quadruplex structures, particularly for DNA aptamers, that enable molecular recognition of their ligands. G-quadruplex structures couple a common scaffold to varying loop motifs that act in target recognition. Here, we review DNA G-quadruplex aptamers and their ligands from a structural and functional perspective. We compare the diversity of DNA G-quadruplex aptamers selected against multiple ligand targets, and consider structure with a particular focus on dissecting the thrombin binding aptamer - thrombin interaction. Therapeutic and analytical applications of DNA G-quadruplex aptamers are also discussed. Understanding DNA G-quadruplex aptamers carries implications not only for therapeutics and diagnostics, but also in the natural biochemistry of guanine-rich nucleic acids. © 2012 Bentham Science Publishers.postprin

Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1

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Impact of Environmental Parameters on Marathon Running Performance

PURPOSE: The objectives of this study were to describe the distribution of all runners' performances in the largest marathons worldwide and to determine which environmental parameters have the maximal impact. METHODS: We analysed the results of six European (Paris, London, Berlin) and American (Boston, Chicago, New York) marathon races from 2001 to 2010 through 1,791,972 participants' performances (all finishers per year and race). Four environmental factors were gathered for each of the 60 races: temperature (°C), humidity (%), dew point (°C), and the atmospheric pressure at sea level (hPA); as well as the concentrations of four atmospheric pollutants: NO(2)-SO(2)-O(3) and PM(10) (μg x m(-3)). RESULTS: All performances per year and race are normally distributed with distribution parameters (mean and standard deviation) that differ according to environmental factors. Air temperature and performance are significantly correlated through a quadratic model. The optimal temperatures for maximal mean speed of all runners vary depending on the performance level. When temperature increases above these optima, running speed decreases and withdrawal rates increase. Ozone also impacts performance but its effect might be linked to temperature. The other environmental parameters do not have any significant impact. CONCLUSIONS: The large amount of data analyzed and the model developed in this study highlight the major influence of air temperature above all other climatic parameter on human running capacity and adaptation to race conditions

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Inhibition of E3 ubiquitin ligase WWP1 with SELEX generated DNA aptamers

Poster Presentation - Theme 1: Reproduction and Development: 1.23The 15th Research Postgraduate Symposium (RPS 2010), the University of Hong Kong, Hong Kong, China, 1-2 December 2010

Discovery and application of DNA aptamers which specifically bind and inhibit WWP1 ubiquitin ligase in the osteoblast

Main Symposia and Workshops (SW): SW03 Mechanisms of Communication and Signaling: poster no. SW03.S15-18This journal suppl. entitled: Special Issue: 38th FEBS Congress ... 2013Conference Theme: Mechanisms in BiologyWWP1 ubiquitin ligase complexes with Schnurri3 to polyubiquitinate Runx2, the key transcriptional regulator of osteoblast destruction. Inhibition of WWP1 ubiquitin ligase may thus stimulate osteoblast differentiation as a therapeutic strategy in osteoporosis sufferers. Here, we present the discovery and application of DNA ...link_to_OA_fulltex