Topological Structure of the Space of Phenotypes: The Case of RNA Neutral Networks

The evolution and adaptation of molecular populations is constrained by the diversity accessible through mutational processes. RNA is a paradigmatic example of biopolymer where genotype (sequence) and phenotype (approximated by the secondary structure fold) are identified in a single molecule. The extreme redundancy of the genotype-phenotype map leads to large ensembles of RNA sequences that fold into the same secondary structure and can be connected through single-point mutations. These ensembles define neutral networks of phenotypes in sequence space. Here we analyze the topological properties of neutral networks formed by 12-nucleotides RNA sequences, obtained through the exhaustive folding of sequence space. A total of 412 sequences fragments into 645 subnetworks that correspond to 57 different secondary structures. The topological analysis reveals that each subnetwork is far from being random: it has a degree distribution with a well-defined average and a small dispersion, a high clustering coefficient, and an average shortest path between nodes close to its minimum possible value, i.e. the Hamming distance between sequences. RNA neutral networks are assortative due to the correlation in the composition of neighboring sequences, a feature that together with the symmetries inherent to the folding process explains the existence of communities. Several topological relationships can be analytically derived attending to structural restrictions and generic properties of the folding process. The average degree of these phenotypic networks grows logarithmically with their size, such that abundant phenotypes have the additional advantage of being more robust to mutations. This property prevents fragmentation of neutral networks and thus enhances the navigability of sequence space. In summary, RNA neutral networks show unique topological properties, unknown to other networks previously described

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP) : evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users

BACKGROUND: 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. METHODS: Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. RESULTS: Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (<100mcg/kg). Users make conscious and 'informed' decisions about DNP; are well-prepared for the side-effects and show nonchalant attitude toward self-experimentation with DNP. Steps are often taken to ensure that DNP is genuine. Personal experience with performance- and appearance enhancing substances appears to be a gateway to DNP. Advice on DNP and experiences are shared online. The significant discrepancy between the normative perception and the actual visibility suggests that DNP use is-contrary to the Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. CONCLUSION: Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements

Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells

BACKGROUND: The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles. METHODOLOGY/PRINCIPAL FINDINGS: to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes. CONCLUSIONS/SIGNIFICANCE: Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells

Aspectos clínicos y niveles de plomo en niños expuestos de manera paraocupacional en el proceso de reciclaje de baterías de automóviles en las localidades de Soacha y Bogotá, D.C.

Introducción. El plomo es un metal inocuo mientras no sea objeto de manipulación en procesos industriales. Aun cuando se ha eliminado la gasolina con plomo en muchos países, incluso en Colombia, el reciclaje informal de baterías sigue siendo una fuente potencial de exposición e intoxicación, tanto para los trabajadores como para sus familias, en los estratos bajos. Objetivo. Establecer hallazgos clínicos, niveles de plomo en sangre y frecuencia de intoxicación en niños expuestos de manera paraocupacional al reciclaje informal de baterías de automoviles. Materiales y métodos. Estudio descriptivo con selección por la exposición. La investigación se inició tras conocerse un caso índice de intoxicación en la población de Soacha, Cundinamarca. Se incluyeron consecutivamente a menores de edad, referidos por familiares, vecinos o conocidos, quienes se conocieran en exposición paraocupacional. Los menores fueron examinados y se tomaron muestras de sangre para determinación hematológica y dosificación de plomo. Resultados. Se examinaron 32 menores de 12 años, la mayoría en etapa escolar; todos presentaban altos niveles de plomo (dos a nueve veces el valor máximo aceptable) y dos tercios de ellos se encontraban con intoxicación grave. La serie de expuestos es significativamente sintomática en relación con los hallazgos sugestivos de intoxicación por plomo. Los niños con mayores niveles de plomo tenían la tendencia a presentar un mayor compromiso hematológico y a hacer manifiesto el ribete de Burton. Conclusión. Este trabajo descriptivo aporta un claro signo de alarma ante las autoridades sanitarias y de gobierno, a fin de tomar medidas tendientes a disminuir la exposición ocupacional, o paraocupacional de los niños, al reciclaje de baterías, mediante un programa de prevención y tamización en municipios y localidades del área metropolitana de Bogotá y Soacha