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

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

Influence Costs in Agribusiness Cooperatives: Evidence from Case Studies

This article addresses the influence costs problem in the governance structure ‘agribusiness cooperative.’ Influence costs are higher in cooperatives than in investor-oriented firms due to the unique governance structure of the former. Hypotheses are formulated and tested regarding the relationship between influence costs and seven variables: membership size, member heterogeneity, average member age, singleness of purpose, managerial power over members, level of managerial compensation, and professional versus inside management. The main results are that heterogeneous member preferences, older average member age, and investment in multiple product lines all contribute to higher influence costs. At the same time, cooperatives with well-paid, powerful and professional managers incur lower influence costs. The impact of membership size on the level of influence costs is undetermined

A NEW LATE PLEISTOCENE MAMMAL LOCALITY FROM WESTERN CRETE

During the last five years systematic explorations of the Natural History Museum of Crete have added more than 20 Pleistocene fossil localities around Crete to the catalogue of the over 70 already known on the Island. The new localities are distributed in all four prefectures of Crete. The most important of these is the newly discovered site of Koutalas at Cape Drepano in Western Crete. The fossil remains are found in two levels and in red cemented clays of a collapsed cave. In the upper level a rich assemblage of micromammal, bird and large mammal remains has been discovered. The large mammals consist of dwarf hippopotamus (Hippopotamus creutzburgi) and elephants (Elephas sp.). A partly articulated skeleton (vertebral column, mandible and few long bones) of a dwarf hippo has been found next to a deciduous molar of an elephantid, indicating that the two taxa probably coexisted. The micromammal remains belong to the giant Cretan mouse Kritimys catreus. Therefore, the age of the assemblage is dated to the Kritimys catreus zone and thus to the late Middle Pleistocene. In the lower level scattered remains of deers, birds and micromammals have been identified, and their age is most likely younger than that of the upper level