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Targeting PI3K/mTOR signaling in cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192441 Year: Pages: 93 DOI: 10.3389/978-2-88919-244-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Medicine (General) --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. Rapamycin and its analogs targeting mTOR are effective in many preclinical cancer models. Although rapalogs are approved for the treatment of some cancers, their efficacy in clinical trials remains the subject of debate. Due to the complexity of the PI3K/mTOR signaling pathway, developing an effective anti-cancer therapy remains a challenge. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments.

Current challenges in photosynthesis: From natural to artificial

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192861 Year: Pages: 102 DOI: 10.3389/978-2-88919-286-1 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Botany --- Science (General)
Added to DOAB on : 2015-12-10 11:59:07
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Jules Verne (1828-1905), author of Around the World in Eighty Days (1873) and Journey to the Center of the Earth (1864), wrote in 1875:"I believe that water will one day be used as a fuel, because the hydrogen and oxygen which constitute it, used separately or together, will furnish an inexhaustible source of heat and light. I therefore believe that, when coal (oil) deposits are oxidised, we will heat ourselves by means of water. Water is the fuel of the future". Solar energy is the only renewable energy source that has sufficient capacity for the global energy need; it is the only one that can address the issues of energy crisis and global climate change. A vast amount of solar energy is harvested and stored via photosynthesis in plants, algae, and cyanobacteria since over 3 billion years. Today, it is estimated that photosynthesis produces more than 100 billion tons of dry biomass annually, which would be equivalent to a hundred times the weight of the total human population on our planet at the present time, and equal to a global energy storage rate of about 100 TW. The solar power is the most abundant source of renewable energy, and oxygenic photosynthesis uses this energy to power the planet using the amazing reaction of water splitting. During water splitting, driven ultimately by sunlight, oxygen is released into the atmosphere, and this, along with food production by photosynthesis, supports life on our earth. The other product of water oxidation is “hydrogen” (proton and electron). This ‘hydrogen’ is not normally released into the atmosphere as hydrogen gas but combined with carbon dioxide to make high energy containing organic molecules. When we burn fuels we combine these organic molecules with oxygen. The design of new solar energy systems must adhere to the same principle as that of natural photosynthesis. For us to manipulate it to our benefit, it is imperative that we completely understand the basic processes of natural photosynthesis, and chemical conversion, such as light harvesting, excitation energy transfer, electron transfer, ion transport, and carbon fixation. Equally important, we must exploit application of this knowledge to the development of fully synthetic and/or hybrid devices. Understanding of photosynthetic reactions is not only a satisfying intellectual pursuit, but it is important for improving agricultural yields and for developing new solar technologies. Today, we have considerable knowledge of the working of photosynthesis and its photosystems, including the water oxidation reaction. Recent advances towards the understanding of the structure and the mechanism of the natural photosynthetic systems are being made at the molecular level. To mimic natural photosynthesis, inorganic chemists, organic chemists, electrochemists, material scientists, biochemists, biophysicists, and plant biologists must work together and only then significant progress in harnessing energy via “artificial photosynthesis” will be possible. This Research Topic provides recent advances of our understanding of photosynthesis, gives to our readers recent information on photosynthesis research, and summarizes the characteristics of the natural system from the standpoint of what we could learn from it to produce an efficient artificial system, i.e., from the natural to the artificial. This topic is intended to include exciting breakthroughs, possible limitations, and open questions in the frontiers in photosynthesis research.

Regulation of immune system cell functions by protein kinase C

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193264 Year: Pages: 129 DOI: 10.3389/978-2-88919-326-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:32
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Members of the protein kinase C (PKC) family of Ser/Thr kinases are encoded by nine distinct but closely related genes, which give rise to more than 12 different protein isoforms via a mechanism of alternative RNA splicing. Most PKC proteins are ubiquitously expressed and participate in a plethora of functions in most cell types. A majority of PKC isoforms is also expressed in cells of the immune system in which they are involved in signal transduction downstream of a range of surface receptors, including the antigen receptors on T and B lymphocytes. PKC proteins are central to signal initiation and propagation, and to the regulation of processes leading to immune cell proliferation, differentiation, homing and survival. As a result, PKC proteins directly impact on the quality and quantity of immune responses and indirectly on the host resistance to pathogens and tendency to develop immune deficiencies and autoimmune diseases. A significant progress was made in recent years in understanding the regulation of PKC enzymes, their mechanism of action and their role in determining immunocyte behavior This volume reviews the most significant contributions made in the field of immune cell regulation by PKC enzymes. Several manuscripts are devoted to the role of distinct PKC isoforms in the regulation of selected immunocyte responses. Additional manuscripts review more general mechanisms of regulation of PKC enzymes, either by post-translational modifications, such as phosphorylation or controlled proteolysis, or by interaction with different binding proteins that may alter the conformation, activity and subcellular location of PKC. Both types of mechanisms can introduce conformational changes in the molecule, which may affect its ability to interact with cofactors, ATP, or substrates. This topic will be followed by a discussion on the positive and negative impact of individual PKC isoforms on cell cycle regulation. A second section of this volume concentrates on selected topics relevant to role of the novel PKC isoform, PKC-theta, in T lymphocyte function. PKC-theta plays important and some non-redundant roles in T cell activation and is a key isoform that recruits to the immunological synapse - the surface membrane area in T cells that comes in direct contact with antigen presenting cells. The immunological synapse is formed in T cells within seconds following the engagement of the TCR by a peptide-bound MHC molecule on the surface of antigen-presenting cells. It serves as a platform for receptors, adaptor proteins, and effector molecules, which assemble into multimolecular activation complexes required for signal transduction. The unique ability of PKC-theta to activate the NF-kB, AP-1 and NF-AT transcription factors is well established, and recent studies contributed essential information on the mechanisms involved in the recruitment of PKC-theta to the center of the immunological synapse and the nature of its substrates and the role of their phosphorylated forms in signal transduction. Additional review manuscripts will describe the unique behavior of PKC-theta in regulatory T cells and its role in the regulation of other cell populations, including those of the innate immune response. This volume brings together leading experts from different disciplines that review the most recent discoveries and offer new perspectives on the contributions of PKC isoforms to biochemical processes and signaling events in different immune cell populations and their impact on the overall host immune response.

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