Download or read book A Genome wide SiRNA Screen Identifies a Novel 7 Transmembrane Protein that Mediates Amino Acid Signaling to MTORC1 written by Lin Gan and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cells have an evolutionarily conserved mechanism to sense and integrate nutrient information for optimal growth and survival. The signaling network that is central to receiving nutritional inputs and translating them to effects on anabolic and catabolic activities of the cell consists of a large serine/threonine kinase known as mTOR. mTOR signaling is crucial for many important cellular processes such metabolism, growth, proliferation and differentiation. It is able to integrate diverse inputs including growth factors, cytokines, energy, oxygen and stress in addition to nutrients and regulate diverse outputs including translation, ribosome biogenesis, lipid biogenesis and autophagy. It is also an important therapeutic target and its inhibitor Rapamycin is currently being used or tested for a wide range of diseases including cancers and neurodegenerative diseases. Amino acids are arguably the most important regulators of mTOR and a long standing mystery in the field is the identity of the amino acid sensor and the mechanism of sensing. Using RNAi, we systematically screened through the human genome for candidate genes regulating amino acid signaling. We confirm that the mitochondria and the lysosomes are the two key sensing organelles, with amino acid metabolism and the RagGTPases being important for signal transduction. We identify a novel lysosomal 7 transmembrane protein that mediates signals upstream the RagGTPases and binds mTORC1-RagA in an amino-acid dependent manner. We also demonstrate that increasing levels of this protein enables cells to recruit mTOR to lysosomes and activate its kinase activity in the absence of amino acids. We show that GPR137B, mTORC1 and RagA form an amino acid sensitive, high-affinity binding complex at the lysosome. We propose a model of sensing where the 7-transmembrane protein, which we renamed to MORTOR, forms a tight complex with mTORC1-RagA in the presence of amino acids, resulting in the persistent lysosomal recruitment and activation of mTORC1. In addition to identifying novel regulators, this systematic study has also generated testable hypotheses about systems level properties of mTORC1 signaling, thus providing the foundation to understand mTOR signaling as a network. The discovery of the novel 7 transmembrane protein and its GPCR-like characteristics also has the potential to lead to new classes of therapeutics and targets for this important pathway.
Download or read book The Epstein Barr Virus written by M. A. Epstein and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Epstein-Barr virus was discovered 15 years ago. Since that time an immense body of information has been accumu lated on this agent which has come to assume great signifi cance in many different fields of biological science. Thus, the virus has very special relevance in human medicine and oncology, in tumor virology, in immunology, and in mole cular virology, since it is the cause of infectious mononu cleosis and also the first human cancer virus, etiologically related to endemic Burkitt's lymphoma and probably to nasopharyngeal carcinoma. In addition, continuous human lymphoid cell lines initiated and maintained by the transform ing function of the virus genome provide a laboratory tool with wide and ever-growing applications. Innumerable papers on the Epstein-Barr virus have ap peared over recent years and reports of work with this agent now constitute a veritable flood. The present book provides the first and only comprehensive, authoritative over-view of all aspects of the virus by authors who have been the original and major contributors in their particular disciplines. A complete and up-to-date survey of this unique and important agent is thus provided which should be of great interest to experts, teachers, and students engaged in cancer research, virology, immunology, molecular biology, epide miology, and cell culture. Where topics have been dealt with from more than one of these viewpoints, some inevitable overlap and duplication has resulted; although this has been kept to a minimum, it has been retained in some places because of positive usefulness.
Download or read book Membrane Protein Cytoskeleton Interactions written by and published by Academic Press. This book was released on 1996-11-21 with total page 449 pages. Available in PDF, EPUB and Kindle. Book excerpt: The plasma membrane acts as both a boundary and a site of exchange between the outside and the inside of a cell. The cytoskeleton plays essential roles in delineating membrane protein distributions, in defining structural and functional domains in the plasma membrane, and in regulating membrane protein, and ultimately, cell function. This volume reviews the regulation of membrane protein distribution, organization, and function at the plasma membrane by the cytoskeleton. Discussions also include the roles of cytoskeleton in the structural and functional organization of membranes and membrane proteins with emphasis on key problems, the current status of understanding, experimental approaches, and future directions.
Download or read book The Surfaceome written by Kenneth R. Boheler and published by Humana Press. This book was released on 2017-12-20 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides readers with the latest techniques and tools to assess modifications and functions of the surfaceome. The chapters in this book are divided into 4 sections: discovery-based approaches to surfaceome content; targeted approaches for surfaceome content; cell-based function analyses related to surfaceome content; and computational approaches in surfaceome studies. Section 1 focuses on discovery-based approaches for cataloging surfaceome content that analyses the surfaceome of bacteria, avian embryos, and mammalian systems. Section 2 discusses methods that over-express specific targets in Sf9 cells and generate bi-specific antibodies for targeting cancer and somatic cells. Section 3 explores voltage dependent sodium channels and high-content electrophysiological analyses. The final section looks at the new web-based platform known as targets-search. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and thorough, Surfaceome: Methods and Protocols assists in the study of cell surface protein biology and function. It is a valuable resource for all researchers interested in this field.
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Download or read book Therapeutic Oligonucleotides written by Jens Kurreck and published by Royal Society of Chemistry. This book was released on 2008 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compelling overall update on current status of RNA interference
Download or read book Protein Phosphorylation in Human Health written by Cai Huang and published by BoD – Books on Demand. This book was released on 2012-09-06 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: 15 chapters on protein phosphorylation and human health written by expert scientists. Covers most important research hot points, such as Akt, AMPK and mTOR. Bridges the basic protein phosphorylation pathways with human health and diseases. Detailed and comprehensive text with excellent figure illustration.
Download or read book Angiogenesis Assays written by Carolyn A. Staton and published by John Wiley & Sons. This book was released on 2007-01-11 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.
Download or read book Autophagosome and Phagosome written by Vojo Deretic and published by Humana Press. This book was released on 2008-04-24 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy and phagocytosis are distinct yet partially morphologically similar processes. Understanding them is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. This book presents autophagosome and phagosome methods for novices and advanced researchers alike. Comprehensive and forward-thinking, the book offers a valuable guide to both cellular processes while inciting researchers to explore their potentially important connections.
Download or read book Autophagy Cancer Other Pathologies Inflammation Immunity Infection and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2016-12-28 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Download or read book Manganese in Health and Disease written by Lucio G Costa and published by Royal Society of Chemistry. This book was released on 2014-11-27 with total page 655 pages. Available in PDF, EPUB and Kindle. Book excerpt: Manganese in the diet is nutritionally essential for normal physiologic functioning. However, excessive exposure to manganese has been associated with developmental, neurodegenerative and other disorders. The book comprehensively covers the toxicology of manganese. Leading investigators provide perspectives from toxicology, neuroscience, nutrition, molecular biology and risk assessment disciplines and chapters cover the toxicokinetics, toxicodynamic interactions and health effects of manganese, as well as its potential role in neurodegenerative diseases. A large section devoted to health effects presents the latest research that associates manganese exposure to potential human diseases. Any scientists, health professional or regulator involved with metal exposure and toxicology should find this volume essential reading. Students and researchers in neurotoxicology will also find this book a useful reference.
Download or read book Interrelations between Essential Metal Ions and Human Diseases written by Astrid Sigel and published by Springer Science & Business Media. This book was released on 2014-01-27 with total page 603 pages. Available in PDF, EPUB and Kindle. Book excerpt: MILS-13 provides an up-to-date review on the relationships between essential metals and human diseases, covering 13 metals and 3 metalloids: The bulk metals sodium, potassium, magnesium, and calcium, plus the trace elements manganese, iron, cobalt, copper, zinc, molybdenum, and selenium, all of which are essential for life. Also covered are chromium, vanadium, nickel, silicon, and arsenic, which have been proposed as being essential for humans in the 2nd half of the last century. However, if at all, they are needed only in ultra-trace amounts, and because of their prevalence in the environment, it has been difficult to prove whether or not they are required. In any case, all these elements are toxic in higher concentrations and therefore, transport and cellular concentrations of at least the essential ones, are tightly controlled; hence, their homeostasis and role for life, including deficiency or overload, and their links to illnesses, including cancer and neurological disorders, are thoroughly discussed. Indeed, it is an old wisdom that metals are indispensable for life. Therefore, Volume 13 provides in an authoritative and timely manner in 16 stimulating chapters, written by 29 internationally recognized experts from 7 nations, and supported by more than 2750 references, and over 20 tables and 80 illustrations, many in color, a most up-to-date view on the vibrant research area of the Interrelations between Essential Metal Ions and Human Diseases.
Download or read book Non Canonical Autophagy written by Giulia Petroni and published by Academic Press. This book was released on 2021-04-21 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: Non-canonical Autophagy: Mechanisms and Pathophysiological Implications outlines the differences between 'canonical' and 'non-canonical' forms of autophagy, highlighting the discoveries concerning the molecular mechanisms underlying these unconventional forms of autophagy and the advancements in pathophysiological features of 'non-canonical' autophagy. The book discusses all forms of 'non-canonical' autophagy and the complexity of autophagy-dependent cell death. Readers will gain a better understanding of mechanisms underlying 'non-canonical' autophagy so that they can interpret the biological effects of autophagy correctly and identify reliable, novel and effective treatment strategies. - Presents the most advanced information surrounding the molecular mechanisms underlying non-canonical autophagy - Outlines the increasing evidence regarding the involvement of non-canonical autophagy in multiple physiological and pathological processes - Discusses the therapeutic potential of autophagy modulators and the obstacles that have limited their development
Download or read book New Prognostic and Predictive Markers in Cancer Progression written by Susan Costantini Alfredo Budillon and published by MDPI. This book was released on 2021-02-12 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomarkers are of critical medical importance for oncologists, allowing them to predict and detect disease and to determine the best course of action for cancer patient care. Prognostic markers are used to evaluate a patient’s outcome and cancer recurrence probability after initial interventions such as surgery or drug treatments and, hence, to select follow-up and further treatment strategies. On the other hand, predictive markers are increasingly being used to evaluate the probability of benefit from clinical intervention(s), driving personalized medicine. Evolving technologies and the increasing availability of “multiomics” data are leading to the selection of numerous potential biomarkers, based on DNA, RNA, miRNA, protein, and metabolic alterations within cancer cells or tumor microenvironment, that may be combined with clinical and pathological data to greatly improve the prediction of both cancer progression and therapeutic treatment responses. However, in recent years, few biomarkers have progressed from discovery to become validated tools to be used in clinical practice. This Special Issue comprises eight review articles and five original studies on novel potential prognostic and predictive markers for different cancer types.
Download or read book Concepts and Principles of Pharmacology written by James E. Barrett and published by Springer Nature. This book was released on 2019-12-24 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
Download or read book Autophagy written by Nicholas Ktistakis and published by Humana Press. This book was released on 2019-01-05 with total page 741 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details a comprehensive and extensive set of protocols for the study of autophagy in vitro and in vivo. Chapters focus on mammals, various model organisms, and provide protocols for the study of autophagy-related processes outside of the canonical autophagy pathways. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Autophagy: Methods and Protocols aims to ensure successful results in the further study of this vital field.
Download or read book MicroRNAs written by Krishnarao Appasani and published by Cambridge University Press. This book was released on 2009-08-20 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development. Forewords by: Sidney Altman, Yale University, Winner of the Nobel Prize in Chemistry, 1989 and Victor R. Ambros, Dartmouth Medical School, Co-discoverer of MicroRNAs
