A linear domain decomposition method for two-phase flow in porous media

This article is a follow up of our submitted paper [11] in which a decomposition of the Richards equation along two soil layers was discussed. A decomposed problem was formulated and a decoupling and linearisation technique was presented to solve the problem in each time step in a fixed point type iteration. This article extends these ideas to the case of two-phase in porous media and the convergence of the proposed domain decomposition method is rigorously shown.Comment: 8 page

Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach

MicroRNAs (miRNAs) are short (∼22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ∼11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs in vivo is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs in vivo. Our findings underscore the complexities of miRNA-mediated regulation in vivo and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized

LTR retrotransposons and the evolution of dosage compensation in Drosophila

© 2008 Matyunina et al; licensee BioMed Central Ltd. The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2199/9/55DOI:10.1186/1471-2199-9-55Background: Dosage compensation in Drosophila is the epigenetic process by which the expression of genes located on the single X-chromosome of males is elevated to equal the expression of X-linked genes in females where there are two copies of the X-chromosome. While epigenetic mechanisms are hypothesized to have evolved originally to silence transposable elements, a connection between transposable elements and the evolution of dosage compensation has yet to be demonstrated. Results: We show that transcription of the Drosophila melanogaster copia LTR (long terminal repeat) retrotransposon is significantly down regulated when in the hemizygous state. DNA digestion and chromatin immunoprecipitation (ChIP) analyses demonstrate that this down regulation is associated with changes in chromatin structure mediated by the histone acetyltransferase, MOF. MOF has previously been shown to play a central role in the Drosophila dosage compensation complex by binding to the hemizygous X-chromosome in males. Conclusion: Our results are consistent with the hypothesis that MOF originally functioned to silence retrotransposons and, over evolutionary time, was co-opted to play an essential role in dosage compensation in Drosophila

Overlap among differentially expressed (DE) genes in HEY cells after ectopic expression of miRNAs with different seed region sequences.

<p>An overlap of 85% in differentially expressed genes was observed among 3 replicate experiments in which miR-429 was ectopically expressed in HEY cells (C). A single nucleotide change in the seed region of miR-429 (M12, M14) resulted is a significant reduction (56% vs 85%) in the overlap among differentially expressed genes (A, B). Differences in the position of this single nucleotide difference (M12, position 2 vs M14, position 4) did not have a significant effect on degree of overlap (A vs. B). Five nucleotide differences in the seed region of miR-429 (M5) also resulted in a significant reduction in overlap (56% vs. 85%) among differentially expressed genes (D vs. C) but not significantly different from miRNAs differing by only 1 nucleotide difference from miR-429 (D vs. A; D vs B).</p

Mouse and human miRNAs share sequentially identical seed regions but regulate highly divergent groups of target genes.

<p>A) Sequence alignment between human (has-miR-429/200b) and mouse (mmu-miR-429/200b) miR-429 and miR-200b miRNAs. Despite the substantial evolutionary distances between these two species, the respective seed regions are sequentially identical indicative of strong stabilizing selection. B) Venn diagrams showing the % overlap in predicted miR-429 and miR-200b target genes between human and mouse orthologs. C) The average percent overlap of genes predicted to be targeted by all 249 sequentially conserved mouse and human miRNAs is <30%. The results are consistent with a model of miRNA regulatory evolution whereby miRNA seed region sequences are selectively conserved while target genes may rapidly re-position themselves under novel miRNA regulatory control(s).</p

Functional and Evolutionary Significance of Human MicroRNA Seed Region Mutations

<div><p>MicroRNAs have emerged in recent years as important regulators of cell function in both normal and diseased cells. MiRNAs coordinately regulate large suites of target genes by mRNA degradation and/or translational inhibition. The mRNA target specificities of miRNAs in animals are primarily encoded within a 7 nt “seed region” mapping to positions 2–8 at the molecule's 5′ end. We here combine computational analyses with experimental studies to explore the functional significance of sequence variation within the seed region of human miRNAs. The results indicate that a substitution of even a single nucleotide within the seed region changes the spectrum of mRNA targets by >50%. The high functional cost of even single nucleotide changes within seed regions is consistent with their high sequence conservation among miRNA families both within and between species and suggests processes that may underlie the evolution of miRNA regulatory control.</p></div