miRNAs link metabolic reprogramming to oncogenesis

The most profound biochemical phenotype of cancer cells is their ability to metabolize glucose to lactate, even under aerobic conditions. This alternative metabolic circuitry is sufficient to support the biosynthetic and energy requirements for cancer cell proliferation and metastasis. Alterations in oncogenes and tumor suppressor genes are involved in the metabolic switch of cancer cells to aerobic glycolysis, increased glutaminolysis and fatty acid biosynthesis. MiRNAs mediate fine-tuning of genes involved directly or indirectly in cancer metabolism. In this review, we discuss the regulatory role of miRNAs on enzymes, signaling pathways and transcription factors involved in glucose and lipid metabolism. We further consider the therapeutic potential of metabolism-related miRNAs in cancer

Systems biology in inflammatory bowel diseases

Purpose of review: Ulcerative colitis (UC) and Crohn’s Disease (CD) are the two predominant types of inflammatory bowel disease (IBD), affecting over 1.4 million individuals in the US. IBD results from complex interactions between pathogenic components, including genetic and epigenetic factors, the immune response and the microbiome through an unknown sequence of events. The purpose of this review is to describe a system biology approach to IBD as a novel and exciting methodology aiming at developing novel IBD therapeutics based on the integration of molecular and cellular "omics" data. Recent Findings: Recent evidence suggested the presence of genetic, epigenetic, transcriptomic, proteomic and metabolomic alterations in IBD patients. Furthermore, several studies have shown that different cell types, including fibroblasts, epithelial, immune and endothelial cells together with the intestinal microbiota are involved in IBD pathogenesis. Novel computational methodologies have been developed aiming to integrate high - throughput molecular data. Summary: A systems biology approach could potentially identify the central regulators (hubs) in the IBD interactome and improve our understanding of the molecular mechanisms involved in IBD pathogenesis. The future IBD therapeutics should be developed on the basis of targeting the central hubs in the IBD network

Several approaches for optical data storage in thin organic films

Date du colloque : 12/2012International audienc

Covering Problems for Partial Words and for Indeterminate Strings

We consider the problem of computing a shortest solid cover of an indeterminate string. An indeterminate string may contain non-solid symbols, each of which specifies a subset of the alphabet that could be present at the corresponding position. We also consider covering partial words, which are a special case of indeterminate strings where each non-solid symbol is a don't care symbol. We prove that indeterminate string covering problem and partial word covering problem are NP-complete for binary alphabet and show that both problems are fixed-parameter tractable with respect to $k$, the number of non-solid symbols. For the indeterminate string covering problem we obtain a $2^{O(k \log k)} + n k^{O(1)}$-time algorithm. For the partial word covering problem we obtain a $2^{O(\sqrt{k}\log k)} + nk^{O(1)}$-time algorithm. We prove that, unless the Exponential Time Hypothesis is false, no $2^{o(\sqrt{k})} n^{O(1)}$-time solution exists for either problem, which shows that our algorithm for this case is close to optimal. We also present an algorithm for both problems which is feasible in practice.Comment: full version (simplified and corrected); preliminary version appeared at ISAAC 2014; 14 pages, 4 figure

Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. Methods: MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. Results: A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3’UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3’UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Conclusions: Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis

Reversible recording medium based on optical storage of information, method of reversible recording on such a medium.

A reversible recording medium based on optical storage of at least one item ofinformation within a support material, includes at least one layer of support material having: base molecules able to take, in a local zone, a first collective state of molecules able to generate a first signal of second harmonic characteristic of this first collective state of molecules when excited by electromagnetic reading radiation; the base molecules having the first collective state of molecules able to transform, at least in part, into transformed molecules so as to pass to a second collective state of molecules when excited by electromagnetic writing radiation, the molecules having the second collective state of molecules able to generate a second signal of second harmonic characteristic of this second collective state of molecules when excited by the electromagnetic reading radiation. The molecules exhibit a molecular structure based on a coumarin skeleton of Formula (I)

Reversible Two-Photon Optical Data Storage in Coumarin-Based Copolymers

A functionalized polymer film allowing for a complete and straightforward second-harmonic generation (SHG)-assisted high-contrast writing?reading?erasing?writing sequence is proposed. The whole process is supported by the reversible photoinduced dimerization of a coumarin chromophore and enables efficient optical data storage that can be detected only by SHG imaging

Spectral action in matrix form

Quantization of the noncommutative geometric spectral action has so far been performed on the final component form of the action where all traces over the Dirac matrices and symmetry algebra are carried out. In this work, in order to preserve the noncommutative geometric structure of the formalism, we derive the quantization rules for propagators and vertices in matrix form. We show that the results in the case of a product of a four-dimensional Euclidean manifold by a finite space, could be cast in the form of that of a Yang-Mills theory. We illustrate the procedure for the toy electroweak model.Comment: 16 pages, 2 figures, changed equation numberin