5'-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans.
Authors: Ahmadi M, Roy R Abstract AMP-activated protein kinase (AMPK) is one of the central regulators of cellular and organismal metabolism in eukaryotes. Once activated by decreased energy levels, it induces ATP production by promoting catabolic pathways while conserving ATP by inhibiting anabolic pathways. AMPK plays a crucial role in various aspects of cellular function such as regulating growth, reprogramming metabolism, autophagy, and cell polarity. In this chapter, we focus on how recent breakthroughs made using the model organism Caenorhabditis elegans have contributed to our understanding of AMPK ...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

The Role of AMPK in Drosophila melanogaster.
Authors: Sinnett SE, Brenman JE Abstract In the fruit fly, Drosophila melanogaster, mono-allelic expression of AMPK-α, -β, and -γ yields a single heterotrimeric energy sensor that regulates cellular and whole-body energetic homeostasis. The genetic simplicity of Drosophila, with only a single gene for each subunit, makes the fruit fly an appealing organism for elucidating the effects of AMPK mutations on signaling pathways and phenotypes. In addition, Drosophila presents researchers with an opportunity to use straightforward genetic approaches to elucidate metabolic signaling pathways that contain a lev...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

Plant SnRK1 Kinases: Structure, Regulation, and Function.
Authors: Margalha L, Valerio C, Baena-González E Abstract SnRK1 is an evolutionarily conserved protein kinase complex that regulates energy homeostasis in plants. In doing so, it promotes tolerance to adverse environmental conditions and influences a large array of growth and developmental processes. SnRK1 shares clear structural and functional similarities with its orthologs, yeast SNF1 and mammalian AMPK, but has evolved unique features that presumably provide a better adaptation to an autotrophic lifestyle. In this chapter, we review current knowledge on SnRK1, an atypical member of the SNF1/AMPK famil...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

Animal Models to Study AMPK.
Authors: Viollet B, Foretz M Abstract AMPK is an evolutionary conserved energy sensor involved in the regulation of energy metabolism. Based on biochemical studies, AMPK has brought much of interest in recent years due to its potential impact on metabolic disorders. Suitable animal models are therefore essential to promote our understanding of the molecular and functional roles of AMPK but also to bring novel information for the development of novel therapeutic strategies. The organism systems include pig (Sus scrofa), mouse (Mus musculus), fly (Drosophila melanogaster), worm (Caenorhabditis elegans), and ...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

In Vitro Methods to Study AMPK.
Authors: Zhu X, Voncken JW, Neumann D Abstract AMPK studies in cell-free and cellular systems have significantly contributed to recent progress in the AMPK field. Biochemical characterization, structure determination and elucidation of AMPK-dependent signalling events benefit from application of state-of-the-art tools and methodology. This chapter provides a synopsis of recombinant protein expression systems and biochemical and cell-based study methods. We summarize three different expression systems for AMPK production: bacteria, insect cells and mammalian cells. In addition, kinase activity measurement, ...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

Genetically Encoded Fluorescent Biosensors to Explore AMPK Signaling and Energy Metabolism.
Authors: Pelosse M, Cottet-Rousselle C, Grichine A, Berger I, Schlattner U Abstract Maintenance of energy homeostasis is a basic requirement for cell survival. Different mechanisms have evolved to cope with spatial and temporal mismatch between energy-providing and -consuming processes. Among these, signaling by AMP-activated protein kinase (AMPK) is one of the key players, regulated by and itself regulating cellular adenylate levels. Further understanding its complex cellular function requires deeper insight into its activation patterns in space and time at a single cell level. This may become possible wi...
Source: EXS - November 6, 2016 Category: Research Tags: EXS Source Type: research

Introduction to microRNAs: Biogenesis, Action, Relevance of Tissue microRNAs in Disease Pathogenesis, Diagnosis and Therapy-The Concept of Circulating microRNAs.
Authors: Nagy Z, Igaz P Abstract MicroRNAs as the endogenous mediators of RNA interference have principal roles in gene expression regulation. Since their discovery in the early 1990s, their number has steadily grown to approximately 2500 known microRNAs at present in humans. MicroRNAs encoded by distinct genes regulate the expression of about 30-60 % of human protein coding genes by targeting their messenger RNAs (mRNAs) and induce mostly posttranscriptional inhibition, or in some cases enhancement. MicroRNAs, as fine regulators of the gene expression, have important roles in development, the physiologic...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Extracellular microRNAs in Membrane Vesicles and Non-vesicular Carriers.
Authors: Coenen-Stass AM, Mäger I, Wood MJ Abstract Great excitement has surrounded the finding that small RNAs are stable in various biofluids and carry specific signatures reflecting physiological and pathological states. In this chapter, we briefly describe the impact of this revolutionary discovery and introduce different subclasses of circulating microRNAs based on their mode of transport. Subsequently, we review the current state-of-the art knowledge on microRNA selection for export, secretion and possible uptake mechanisms and their potential function in circulation. Furthermore, we give an overvie...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Technical Aspects Related to the Analysis of Circulating microRNAs.
Authors: Butz H, Patócs A Abstract Specific and sensitive noninvasive biofluid-based biomarkers are always needed in the laboratory diagnosis of diseases. Biomarkers are applied not only for diagnostic purposes but for stratifying a disease and for assessing the therapy response or disease progression. MicroRNAs (miRNAs) are short noncoding RNA molecules regulating gene expression posttranscriptionally. They are frequently dysregulated in many physiological and pathophysiological conditions. miRNAs are present in the circulation and in other biofluids that are common matrices for clinical laboratory testi...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating Blood-Borne microRNAs as Biomarkers in Solid Tumors.
Authors: Vychytilova-Faltejskova P, Slaby O Abstract One of the major challenges in cancer research is the identification of stable biomarkers that could be routinely measured in easily accessible samples. Human blood and other body fluids represent rich sources for the identification of novel biomarkers. It is apparent that the availability of these biomarkers would improve an early detection of asymptomatic disease and the clinical management of cancer. MicroRNAs have been described to be present in various types of body fluids including cell-free serum and plasma. These days, the involvement of microRNA...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating microRNA as Biomarkers in Hematological Malignancies.
Authors: Stankova M, Kubaczkova V, Sedlarikova L, Sevcikova S Abstract Hematopoiesis is a highly regulated process controlled by a complex network of molecular mechanisms that simultaneously regulate differentiation, proliferation, and apoptosis of hematopoietic stem cells. Aberrant microRNA (miRNA) expression could affect normal hematopoiesis, leading to the development of hematological malignancies. Hematologic cancers, which are caused by malignant transformation of cells of the bone marrow and the lymphatic system, are usually divided into three major groups: leukemias, lymphomas, and monoclonal gammop...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating microRNAs as Biomarkers in Cardiovascular Diseases.
Authors: De Rosa S, Indolfi C Abstract MicroRNAs, key regulators of biological processes, are involved in the pathophysiological mechanisms underlying human diseases, including cardiovascular diseases. Their recent discovery revealed a previously unknown layer of pathophysiologic regulators, which also play a key role in the regulation of several aspects of cardiovascular diseases. More recently, it was demonstrated that circulating microRNAs can be measured in the blood. Hence, the potential use of microRNAs as disease biomarkers attracted many research groups. Indeed, their unusual stability in the blood...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating microRNAs in Neurodegenerative Diseases.
Authors: Grasso M, Piscopo P, Crestini A, Confaloni A, Denti MA Abstract Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by a combination of events that impair normal neuronal function. Although they are considered different disorders, there are overlapping features among them from the clinical, pathological, and genetic points of view. Synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities such as axonal transport defects normally precede the neuronal loss that is a relatively ...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating Extracellular microRNA in Systemic Autoimmunity.
Authors: Heegaard NH, Carlsen AL, Skovgaard K, Heegaard PM Abstract MicroRNAs (miRNAs) are differentially regulated in healthy, activated, inflamed, neoplastic, or otherwise pathological cells and tissues. While their main functions are executed intracellularly, many miRNAs can reproducibly be detected extracellularly in plasma and serum. This circulating, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using cir...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research

Circulating microRNAs in Inflammatory Bowel Diseases.
Authors: Gazouli M Abstract Inflammatory bowel diseases (IBD) are chronic, idiopathic, polygenic diseases with significant genetic heterogeneity. The two major types of IBD are Crohn's disease (CD) and ulcerative colitis (UlC). It is well known that chronic intestinal inflammation results from the interplay of genetic, immunologic, and environmental factors, so the failure to properly downregulate nonspecific inflammation started by an environmental trigger may lead to the development of IBD. Recent studies indicate several microRNAs (miRNAs) as regulators of important pathways of the immune response and i...
Source: EXS - July 21, 2016 Category: Research Tags: EXS Source Type: research