DNA methylation and chromatin structure: The puzzling CpG islands

DNA methylation is the epigenetic modification,which introduces 5mC as fifth base onto DNA. As for the distribution of 5rnCs, it is well known that they distribute themselves in a non-random fashion in genomic DNA so that methylation pattern is characterized by the presence of methylated cytosines on the bulk of DNA while the unmethylated ones are mainly located within particular regions termed CpG islands. These regions represent about 1% of genomic DNA and are generally found in the promoter region Of housekeeping genes. Their unmethylated state, which is an essential condition for the correct expression of correlated genes, is paradoxical if one considers that these regions are termed CpG islands because they are particularly rich in this dinucleotide, which is the best substrate for enzymes involved in DNA methylation. Anomalous insertion of methyl groups in these regions generally leads to the lack of transcription of correlated genes. An interesting scientific problem is to clarify the mechanism(s) whereby CpG islands, which remain protected from methylation in normal cells, are susceptible to methylation in tumour cells. How the CpG moieties in CpG islands become vulnerable or resistant to the action of DNA methyltransferases and can thus lose or maintain their characteristic pattern of methylation is still an open question. Our aim is to gather some mechanisms regarding this intriguing enigma, which, despite all energy spent, still remains all unresolved puzzle. (C) 2004 Wiley-Liss, Inc

Why is DNA methylation of Igf2 CpG island shore affected during ageing?

Comment on: Pirazzini C, Giuliani C, Bacalini MG, Boattini A, Capri M, Fontanesi E, Marasco E, Mantovani V, Pierini M, Pini E, Luiselli D, Franceschi C. Garagnani P. Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. AGING: V4, N7

Stable, Robust and Super Fast Reconstruction of Tensors Using Multi-Way Projections

In the framework of multidimensional Compressed Sensing (CS), we introduce an analytical reconstruction formula that allows one to recover an $N$th-order $(I_1\times I_2\times \cdots \times I_N)$ data tensor $\underline{\mathbf{X}}$ from a reduced set of multi-way compressive measurements by exploiting its low multilinear-rank structure. Moreover, we show that, an interesting property of multi-way measurements allows us to build the reconstruction based on compressive linear measurements taken only in two selected modes, independently of the tensor order $N$. In addition, it is proved that, in the matrix case and in a particular case with $3$rd-order tensors where the same 2D sensor operator is applied to all mode-3 slices, the proposed reconstruction $\underline{\mathbf{X}}_\tau$ is stable in the sense that the approximation error is comparable to the one provided by the best low-multilinear-rank approximation, where $\tau$ is a threshold parameter that controls the approximation error. Through the analysis of the upper bound of the approximation error we show that, in the 2D case, an optimal value for the threshold parameter $\tau=\tau_0 > 0$ exists, which is confirmed by our simulation results. On the other hand, our experiments on 3D datasets show that very good reconstructions are obtained using $\tau=0$, which means that this parameter does not need to be tuned. Our extensive simulation results demonstrate the stability and robustness of the method when it is applied to real-world 2D and 3D signals. A comparison with state-of-the-arts sparsity based CS methods specialized for multidimensional signals is also included. A very attractive characteristic of the proposed method is that it provides a direct computation, i.e. it is non-iterative in contrast to all existing sparsity based CS algorithms, thus providing super fast computations, even for large datasets.Comment: Submitted to IEEE Transactions on Signal Processin

Structural response of transport airplanes in crash situations

This report highlights the results of contractural studies of transport accident data undertaken in a joint research program sponsored by the FAA and NASA. From these accident data studies it was concluded that the greatest potential for improved transport crashworthiness is in the reduction of fire related fatalities. Accident data pertaining to fuselage integrity, main landing gear collapse, fuel tank rupture, wing breaks, tearing of tank lower surfaces, and engine pod scrubbing are discussed. In those accidents where the energy absorbing protective capability of the fuselage structure is expended and the airplane experiences major structural damage, trauma caused fatalities are also discussed. The dynamic performance of current seat/restraint systems are examined but it is concluded that the accident data does not adequately define the relationship between occupant response and the dynamic interaction with the seat, floor and fuselage structure

5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme

5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP-1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins

Induction-coil transducers for measuring transversal field harmonics in accelerator magnets

The following thesis deals with the mathematical development, the numerical validation, the design, and the metrological characterization of an innovative sensor for magnetic measurements based on rotating coils. The developed mathematical model, linking experimental data and the field description in the aperture of magnets for accelerator, was numerically validated using simulated data. The validation results made it possible to check the correlation between measurements and the mathematical model itself. Furthermore, the numerical validation allowed to satisfy the constraints for the design and manufacturing tolerances of the sensor. The sensor that is required to perform local field distribution measurements along the magnet axis, must be not sensitive to the $z$-field component (namely to the field in the direction of beam travelling in the particle accelerator magnet). For this reason, the coil design is based on a certain number of loops placed on the same radius. This particular geometry has been called "Iso-perimetric". The sensor production, the transducer design, an innovative methodology for the sensitivity coefficients calculations and for the calibration procedure were carried out. Finally, the experimental results of the proof of principle of the first prototype, the design of the second prototype, and the measurements results are reported

Information needs along the journey chain: users’ perspective about bus system

Buses constitute the main public transport mode in most cities of the world. Accessible Bus Systems are defined as systems that are easy to use. However accessible the infrastructure may be, it is unlikely to provide access if people cannot know about it. Therefore it is essential to have comprehensive and accessible information systems which describe the bus systems during all the stages of the journey. There is a widespread understanding amongst researchers that Information Systems can increase the efficiency of the system and that they should be oriented to meet bus users’ needs. However, existing information systems largely ignore the user’s point of view, in special the requirement of the disabled users. This thesis describes a methodology developed to investigate the problem of using information during a journey by bus in real conditions taking into account the (un)familiarity of the area in study and the individual’s previous knowledge of information system. Two main aspects are identified — the “Required Environment Capability” (the physical, social and psychological environment conditions) and the “Individual Capability Provided” (the individual ability in physical, sensorial and cognitive terms) to plan and execute a journey by bus in an unfamiliar environment. Because of the multidisciplinary aspect of the theme this study uses approaches from different fields of research to construct a methodology to understand individual information use. Based on the principles of Single Case Analysis adapted by adding the concept of the Capabilities Model (CM) (which explores interactions between individual and environment), the combined SCA/CM approach was employed to construct the INFOChain experiment. A set of information pieces were developed for the experiment, delivering Accessibility- Issues (AI-type) information in order to help older people to plan and execute different bus journeys in two different cities: London/UK and Brasilia/BR. General results have shown that although the AI-Type of information is considered important by older people, it needs more than simple expositions to actually take advantages of the information and be able to help disabled users

DNA methylation dynamics in aging: How far are we from understanding the mechanisms?

DNA methylation is currently the most promising molecular marker for monitoring aging and predicting life expectancy. However, the mechanisms underlying age-related DNA methylation changes remain mostly undiscovered.Here we discuss the current knowledge of the dynamic nature of DNA epigenome landscape in mammals, and propose putative molecular mechanisms for aging-associated DNA epigenetic changes. Specifically, we describe age-related variations of methylcytosine and its oxidative derivatives in relation to the dynamics of chromatin structure, histone post-translational modifications and their modulators.Finally, we are proposing a conceptual framework that could explain the complex nature of the effects of age on DNA methylation patterns. This combines the accumulation of DNA methylation noise and also all of the predictable, site-specific DNA methylation changes.Gathering information in this area would pave the way for future investigation aimed at establishing a possible causative role of epigenetic mechanisms in aging

Magnitude and drivers of greenhouse gas emission from ant nests

Greenhouse gas (GHG) emission is a worldwide concern, making the identification of emission sources and their magnitude an urgent issue. Ants release large amounts of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) from their nests. Beyond the already known anthropogenic sources of CO2 emissions, such as fossil fuel combustion in the power generation, industrial, residential, and transport sectors, the evaluation of GHG emissions from ant nests is a current research target. However, there are still gaps regarding the real impact of ant nests on GHG emission, primarily because most surveys were conducted excluding anthropogenic areas. In the present study, we aimed to fill part of these gaps by evaluating the magnitude and drivers of GHG emission from ant nests. Our results were organized over three chapters. First, chapter I discussed the current scenario and highlighted the methodological issues of the studies on GHG emissions from ant nests using a systematic review as methodology. We present a scientometry of available publications, which revealed the lack of investigations of ant nests emission in anthropogenic areas and on countries that are higher sources of anthropogenic GHG. Second, in Chapter II, we’ve made a methodology test related to the closed chamber method, guided by some warnings which stood out in the systematic review. Results revealed a dilution effect of the soil surface over the CO2 measurements when using chambers whose diameters are significantly larger than the nest hole. Finally, in Chapter III, we’ve made field measurements of CO2 emissions from Acromyrmex subterraneus nests in urban areas, considering the effect of features of the nest. This investigation revealed an association of CO2 flux with the function of the nest hole, a component of ant nests not yet investigated. Obtained results also showed that ant nests are on a par with recognized anthropogenic CO2 sources, adding one more point to consider in the context of climate change, considering the facility of installation of some ant species in urban and disturbed areas. We hope that these results contribute to expanding knowledge regarding the role of ant nests in CO2 emissions and could even guide the next steps for future investigations.A emissão de gases de efeito estufa (GEE) é uma preocupação mundial, tornando urgente a identificação das fontes de emissão e sua magnitude. As formigas liberam grandes quantidades de dióxido de carbono (CO2), metano (CH4) e óxido nitroso (N2O) de seus ninhos. Além das já conhecidas fontes antropogênicas de emissões de CO2, como a queima de combustíveis fósseis nos setores de geração de energia, industrial, residencial e de transporte, a avaliação das emissões de GEE por ninhos de formigas é um alvo atual de pesquisa. No entanto, ainda existem lacunas em relação ao real impacto dos ninhos de formigas na emissão de GEE, principalmente porque a maioria dos estudos foram feitos em áreas naturais, não incluindo as áreas antrópicas. No presente estudo, nosso objetivo foi preencher parte dessas lacunas avaliando a magnitude e os drivers da emissão de GEE por ninhos de formigas. Nossos resultados foram organizados em três capítulos. Primeiramente, o capítulo I, através de uma revisão sistemática como metodologia, discutiu o cenário atual e destacou as questões metodológicas dos estudos sobre emissões de GEE por ninhos de formigas. Apresentamos uma cienciometria das publicações disponíveis, que revelou a falta de investigações sobre a emissão de formigueiros em áreas antropogênicas e em países que são maiores fontes de GEE antrópicos. Em segundo lugar, no Capítulo II, norteados pela lacuna encontrada na revisão sistemática, fizemos um teste de metodologia relacionado ao método de câmara fechada. Os resultados revelaram um efeito de diluição da superfície do solo sobre as medições de CO2 ao usar câmaras cujos diâmetros são significativamente maiores do que o buraco do ninho. Por fim, no Capítulo III, fizemos medições em campo das emissões de CO2 de ninhos de Acromyrmex subterraneus em áreas urbanas, considerando o efeito das características do ninho. Essa investigação revelou uma associação do fluxo de CO2 com a função do olheiro, um componente dos ninhos de formigas ainda não investigado nesse contexto. Os resultados obtidos também mostraram que os ninhos de formigas se equiparam a importantes fontes antrópicas de CO2, acrescentando mais um ponto a se considerar no contexto das mudanças climáticas, levando em conta a facilidade de instalação de algumas espécies de formigas em áreas urbanas e perturbadas. Esperamos que esses resultados contribuam para ampliar o conhecimento sobre o papel dos formigueiros nas emissões de CO2 e possam orientar os próximos passos para futuras investigações.CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológic

On the conditions for valid objective functions in blind separation of independent and dependent sources

It is well known that independent sources can be blindly detected and separated, one by one, from linear mixtures by identifying local extrema of certain objective functions (contrasts), like negentropy, Non-Gaussianity measures, kurtosis, etc. It was also suggested in [1], and verified in practice in [2,4], that some of these measures remain useful for particular cases with dependent sources, but not much work has been done in this respect and a rigorous theoretical ground still lacks. In this paper, it is shown that, if a specific type of pairwise dependence among sources exists, called Linear Conditional Expectation (LCE) law, then a family of objective functions are valid for their separation. Interestingly, this particular type of dependence arises in modeling material abundances in the spectral unmixing problem of remote sensed images. In this work, a theoretical novel approach is used to analyze Shannon entropy (SE), Non-Gaussianity (NG) measure and absolute moments of arbitrarily order, i.e. Generic Absolute (GA) moments for the separation of sources allowing them to be dependent. We provide theoretical results that show the conditions under which sources are isolated by searching for a maximum or a minimum. Also, simple and efficient algorithms based on Parzen windows estimations of probability density functions (pdfs) and Newton-Raphson iterations are proposed for the separation of dependent or independent sources. A set of simulation results on synthetic data and an application to the blind spectral unmixing problem are provided in order to validate our theoretical results and compare these algorithms against FastICA and a very recently proposed algorithm for dependent sources, the Bounded Component Analysis algorithm (BCA). It is shown that, for dependent sources verifying the LCE law, the NG measure provides the best separation results.Fil: Caiafa, Cesar Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Argentino de Radioastronomia (i); Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; Argentin