Superstructure Detection in Nucleosome Distribution Shows Common Pattern within a Chromosome and within the Genome.

Nucleosome positioning plays an important role in crucial biological processes such as replication, transcription, and gene regulation. It has been widely used to predict the genome's function and chromatin organisation. So far, the studies of patterns in nucleosome positioning have been limited to transcription start sites, CTCFs binding sites, and some promoter and loci regions. The genome-wide organisational pattern remains unknown. We have developed a theoretical model to coarse-grain nucleosome positioning data in order to obtain patterns in their distribution. Using hierarchical clustering on the auto-correlation function of this coarse-grained nucleosome positioning data, a genome-wide clustering is obtained for Candida albicans. The clustering shows the existence beyond hetero- and eu-chromatin inside the chromosomes. These non-trivial clusterings correspond to different nucleosome distributions and gene densities governing differential gene expression patterns. Moreover, these distribution patterns inside the chromosome appeared to be conserved throughout the genome and within species. The pipeline of the coarse grain nucleosome positioning sequence to identify underlying genomic organisation used in our study is novel, and the classifications obtained are unique and consistent.

Inter-nucleosomal potentials from nucleosomal positioning data.

No systematic method exists to derive inter-nucleosomal potentials between nucleosomes along a chromosome consistently across a given genome. Such potentials can yield information on nucleosomal ordering, thermal as well as mechanical properties of chromosomes. Thus, indirectly, they shed light on a possible mechanical genomic code along a chromosome. To develop a method yielding effective inter-nucleosomal potentials between nucleosomes, a generalized Lennard-Jones potential for the parameterization is developed based on nucleosomal positioning data. This approach eliminates some of the problems that the underlying nucleosomal positioning data have, rendering the extraction difficult on the individual nucleosomal level. Furthermore, patterns on which to base a classification along a chromosome appear on larger domains, such as hetero- and euchromatin. An intuitive selection strategy for the noisy optimization problem is employed to derive effective exponents for the generalized potential. The method is tested on the Candida albicans genome. Applying k-means clustering based on potential parameters and thermodynamic compressibilities, a genome-wide clustering of nucleosome sequences is obtained for C. albicans. This clustering shows that a chromosome beyond the classical dichotomic categories of hetero- and euchromatin is more feature-rich.

Prediction and comparative analysis of CTCF binding sites based on a first principle approach.

We calculated the patterns for the CCCTC transcription factor (CTCF) binding sites across many genomes on a first principle approach. The validation of the first principle method was done on the human as well as on the mouse genome. The predicted human CTCF binding sites are consistent with the consensus sequence, ChIP-seq data for the K562 cell, nucleosome positions for IMR90 cell as well as the CTCF binding sites in the mouse HOXA gene. The analysis ofHomo sapiens,Mus musculus,Sus scrofa,Capra hircusandDrosophila melanogasterwhole genomes shows: binding sites are organized in cluster-like groups, where two consecutive sites obey a power-law with coefficient ranging from 0.3292 ± 0.0068 to 0.5409 ± 0.0064; the distance between these groups varies from 18.08 ± 0.52 kbp to 42.1 ± 2.0 kbp. The genome ofAedes aegyptidoes not show a power law, but 19.9% of binding sites are 144 ± 4 and 287 ± 5 bp distant of each other. We run negative tests, confirming the under-representation of CTCF binding sites inCaenorhabditis elegans, Plasmodium falciparum andArabidopsis thalianacomplete genomes.

Pharmacokinetics, electrophysiological, and morphological effects of the intravitreal injection of mycophenolic acid in rabbits.

PURPOSE: To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA. METHODS: Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 µg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy. RESULTS: MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 µg and higher on day 30, while eyes injected with 100 µg presented the same changes already from day 15. No morphological change was found. CONCLUSIONS: MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 µg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 µg may be safe for intravitreal use in rabbits.

Espaço de cores / Color space

O artigo apresenta definições para os termos espaço de cores e sistemas de cores; classifica, de acordo com David Brainard (2003), os sistemas de cores em dois grupos: aparência de cores e diferenças de cores. Dentre os diversos sistemas de cores existentes, o artigo descreve dois deles: o sistema de cores Munsell – um dos mais utilizados entre os sistemas de aparência de cores – e a descrição do sistema de cores CIE 1931 – um dos mais utilizados dentre os sistemas de diferença de cores. Faz-se uma retrospectiva histórica da busca por espaços de cores que representem a percepção de cores humana assim como as diversas reconstruções de espaços de cores por métodos eletrofisiológicos ou psicofísicos. Muitas dessas reconstruções utilizam a escala multidimensional (mds). O artigo também introduz a possibilidade da reconstrução dos espaços de cores de pacientes com discromatopsia adquirida como uma distorção do espaço de indivíduos tricromatas normais (AU)

Espaço de cores / Color space

O artigo apresenta definições para os termos espaço de cores e sistemas de cores; classifica, de acordo com David Brainard (2003), os sistemas de cores em dois grupos: aparência de cores e diferenças de cores. Dentre os diversos sistemas de cores existentes, o artigo descreve dois deles: o sistema de cores Munsell – um dos mais utilizados entre os sistemas de aparência de cores – e a descrição do sistema de cores CIE 1931 – um dos mais utilizados dentre os sistemas de diferença de cores. Faz-se uma retrospectiva histórica da busca por espaços de cores que representem a percepção de cores humana assim como as diversas reconstruções de espaços de cores por métodos eletrofisiológicos ou psicofísicos. Muitas dessas reconstruções utilizam a escala multidimensional (mds). O artigo também introduz a possibilidade da reconstrução dos espaços de cores de pacientes com discromatopsia adquirida como uma distorção do espaço de indivíduos tricromatas normais

On the analysis of large-scale genomic structures.

We apply methods from statistical physics (histograms, correlation functions, fractal dimensions, and singularity spectra) to characterize large-scale structure of the distribution of nucleotides along genomic sequences. We discuss the role of the extension of noncoding segments ("junk DNA") for the genomic organization, and the connection between the coding segment distribution and the high-eukaryotic chromatin condensation. The following sequences taken from GenBank were analyzed: complete genome of Xanthomonas campestri, complete genome of yeast, chromosome V of Caenorhabditis elegans, and human chromosome XVII around gene BRCA1. The results are compared with the random and periodic sequences and those generated by simple and generalized fractal Cantor sets.