Download or read book Blmp 1 is a Ras cooperating Tumor Suppressor Gene in Caenorhabditis Elegans written by Nattha Wannissorn and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: While hypermorphic Ras mutations are found in approximately 35% of colorectal, 45% of lung and 90% of pancreatic cancers, activated Ras alone is not sufficient to transform normal cells into cancerous tumors. Additional driver mutations or epigenetic alterations are required to cooperate with the activating Ras mutations in tumorigenesis. In C. elegans, worms homozygous for activated Ras mutations have 60 - 80% penetrant visible multivulval (Muv) phenotype. Several suppressors and enhancers of this phenotype have been shown to be orthologous to Ras-cooperating proto-oncogenes and tumor-suppressor genes, respectively. Because several epigenetic regulators are now targets of cancer treatments and many cancer genomes exhibit changes in epigenetic regulation, I sought to systematically identify chromatin regulators that cooperate with activated Ras using RNAi screening in C. elegans. After screening 215 C. elegans chromatin remodeling factors and 193 C. elegans orthologs of known driver genes from Tumor Sequencing Project, I identified several attenuators of Ras signaling. By generating double mutants, I was able to confirm that loss of PRDM1/Blimp1 homolog blmp-1 served as a strong enhancer of the let-60(n1046) Muv phenotype. In addition, blmp-1(tm548) mutant worms are not Muv. I chose to investigate one of these genes, called blmp-1, in great detail because of known roles of its mammalian ortholog PRDM1/Blimp1 in cancer. PRDM1/Blimp1 is a known tumor suppressor gene in activated-B cell diffuse large B-cell lymphoma (ABC-DLBCL). Whether PRDM1/Blimp1 cooperates with activated Ras is unknown. Therefore, I further sought to understand how BLMP-1 attenuates Ras signaling in C. elegans. blmp-1 mutants have mildly elevated Ras signaling in the vulval cells. In addition, blmp-1(RNAi) and null mutant blmp-1(tm548) are strong enhancers of let-60(n1046) Muv phenotype, resulting in nearly 100% penetrance Muv. blmp-1 expression is downregulated in response to vulval induction, and this downregulation is important for correct vulval induction. However, bypassing this downregulation reduced, but did not abolish vulval induction, suggesting that blmp-1 functions late in vulval development. In addition, I also identified distinct key regions within the blmp-1 promoter which are necessary and sufficient for the regulation of blmp-1 expression in the gut, seam cells, hypodermal cells and the vulva cells. In conclusion, this is the first characterization of blmp-1 as a putative Ras-cooperating tumor suppressor gene as blmp-1 enhances the activated Ras phenotype through a novel mechanism. These results may shed light into our understanding of ABC-DCLBL as a Ras pathway-driven cancer, and PRDM1/Blimp1 as a Ras-cooperating tumor suppressor genes.
Download or read book Identification of Novel Candidate Tumor Suppressor Genes Using C Elegans as a Model written by Paul Sternberg and published by . This book was released on 1997 with total page 26 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular genetic analysis of the model organism Caenorhabditis elegans was used to identify and study mechanisms of action of negative regulators of tyrosine kinase/ras mediated signal transduction that are candidate tumor suppressors. A homolog of the proto oncogene cbl, SLI-1, inhibits Ras activation by the epidermal growth factor receptor homolog LET-23. The domain of human c-cbl most highly conserved functions in C. elegans when substituted for the homologous region of SLI-1. Proteins that interact with this region of SLI-1 have been identified by a "two-hybrid" screen in yeast. ROK-1, a novel tyrosine kinase, has been characterize. Both SLI-1 and ROK-1 have proline-rich domains that are necessary for their function. New screens for additional negative regulators have identified at least three genes that are now being analyzed. Human homologs of ROK-1 are now being sought.
Download or read book HSF1 and Molecular Chaperones in Biology and Cancer written by Marc Laurence Mendillo and published by Springer Nature. This book was released on 2020-04-15 with total page 185 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Download or read book Pathogenesis and Treatment of Acne and Rosacea written by Christos C. Zouboulis and published by Springer. This book was released on 2014-07-28 with total page 729 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by experts from across the world, provides comprehensive coverage of acne and rosacea, focusing in particular on pathogenesis and treatment but also considering clinical aspects, prognostic factors, and impacts on quality of life. Both standard knowledge and important, clinically relevant insights that have emerged over the past decade are presented with the goal of assisting the reader in understanding these diseases and improving treatment outcome. It is explained how high-level research has recently given rise to a variety of new concepts in etiology and treatment, and emerging trends are also discussed. The book is in a reader-friendly format that highlights core messages with a very practical and clinical focus. Pathogenesis and Treatment of Acne and Rosacea will be an indispensable reference for all physicians who care for patients with acne or rosacea and for scientists working in the field.
Download or read book Tryptophan Metabolism Implications for Biological Processes Health and Disease written by Atilla Engin and published by Humana Press. This book was released on 2015-04-28 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the relationship between cellular immunity and tryptophan metabolism, as well as its products, serotonin and melatonin, in the development of several diseases and reappraises the common signal transduction pathways of the neurodegenerative diseases, carcinogenesis, immune tolerance, inflammation, hypersensitivity reactions, neuropsychiatric disorders, in addition to bacterial tryptophan biosynthesis and novel antimicrobials. Tryptophan Metabolism: Implications for Biological Processes, Health and Disease presents fundamental information on tryptophan related metabolic pathways and metabolites, implications of these products for specific biological processes, diseases and conditions. This book focuses on effects of tryptophan metabolites on human health and will appeal to researchers, clinicians and students within this field.
Download or read book Molecular Signaling in Spermatogenesis and Male Infertility written by Rajender Singh and published by CRC Press. This book was released on 2019-11-06 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: Spermatogenesis involves the coordination of a number of signaling pathways, which culminate into production of sperm. Its failure results in male factor infertility, which can be due to hormonal, environmental, genetic or other unknown factors. This book includes chapters on most of the signaling pathways known to contribute to spermatogenesis. Latest research in germ cell signaling like the role of small RNAs in spermatogenesis is also discussed. This book aims to serve as a reference for both clinicians and researchers, explaining possible causes of infertility and exploring various treatment methods for management through the basic understanding of the role of molecular signaling. Key Features Discusses the signaling pathways that contribute to successful spermatogenesis Covers comprehensive information about Spermatogenesis at one place Explores the vital aspects of male fertility and infertility Explains the epigenetic regulation of germ cell development and fertility Highlights the translational opportunities in molecular signaling in testis
Download or read book Emerging Model Organisms written by and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Zinc Signaling written by Toshiyuki Fukada and published by Springer Nature. This book was released on 2019-12-13 with total page 412 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes, autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.
Download or read book Waldenstr m s Macroglobulinemia written by Véronique Leblond and published by Springer. This book was released on 2016-10-06 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book sheds new light on clinical, biological and therapeutic data on the rare disease Waldenström’s Macroglobulinemia (WM) with the participation of widely-recognized experts, involved in this field. It represents the efforts of physicians, scientists and patients, all around the world, to better understand and cure this rare disease. Considerable advances in the diagnosis, treatment indications, response criteria, prognostic factors and treatment options have been made since Dr Jan Waldenström first reported this “new syndrome“ 70 years ago. Particularly instrumental in advancing of our understanding of WM have been the eight international workshops devoted to this disease. New, exciting molecular data have recently been reported, allowing us to revisit the oncogenic events leading to WM B-cell proliferation and to use newly available compounds targeting oncogenic pathways.
Download or read book Yeast Genetics written by Jeffrey S. Smith and published by Humana. This book was released on 2016-09-17 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Yeast Genetics: Methods and Protocols is a collection of methods to best study and manipulate Saccharomyces cerevisiae, a truly genetic powerhouse. The simple nature of a single cell eukaryotic organism, the relative ease of manipulating its genome and the ability to interchangeably exist in both haploid and diploid states have always made it an attractive model organism. Genes can be deleted, mutated, engineered and tagged at will. Saccharomyces cerevisiae has played a major role in the elucidation of multiple conserved cellular processes including MAP kinase signaling, splicing, transcription and many others. Written in the 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 protocols and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Yeast Genetics: Methods and Protocols will provide a balanced blend of classic and more modern genetic methods relevant to a wide range of research areas and should be widely used as a reference in yeast labs.
Download or read book Systems Genetics written by Florian Markowetz and published by Cambridge University Press. This book was released on 2015-07-02 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: Whereas genetic studies have traditionally focused on explaining heritance of single traits and their phenotypes, recent technological advances have made it possible to comprehensively dissect the genetic architecture of complex traits and quantify how genes interact to shape phenotypes. This exciting new area has been termed systems genetics and is born out of a synthesis of multiple fields, integrating a range of approaches and exploiting our increased ability to obtain quantitative and detailed measurements on a broad spectrum of phenotypes. Gathering the contributions of leading scientists, both computational and experimental, this book shows how experimental perturbations can help us to understand the link between genotype and phenotype. A snapshot of current research activity and state-of-the-art approaches to systems genetics are provided, including work from model organisms such as Saccharomyces cerevisiae and Drosophila melanogaster, as well as from human studies.
Download or read book Gene and Cell Therapy Biology and Applications written by Giridhara R. Jayandharan and published by Springer. This book was released on 2018-09-12 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in stem cell biology, nanotechnology and gene therapy have opened new avenues for therapeutics. The availability of molecular therapeutics that rely on the delivery of DNA, RNA or proteins, harnessing enhanced delivery with nanoparticles, and the regenerative potential of stem cells (adult, embryonic or induced pluripotent stem cells) has had a tremendous impact on translational medicine. The chapters in this book cover a range of strategies for molecular and cellular therapies for human disease, their advantages, and central challenges to their widespread application. Potential solutions to these issues are also discussed in detail. Further, the book addresses numerous advances in the field of molecular therapeutics that will be of interest to the general scientific community. Lastly, the book provides specific examples of disease conditions for which these strategies have been transferred to the clinic. As such, it will be extremely useful for all students, researchers and clinicians working in the field of translational medicine and molecular therapeutics.
Download or read book Microbial Pathogenesis Infection and Immunity written by Uday Kishore and published by Springer. This book was released on 2013-12-04 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book starts with dissecting mechanisms underlying viral immune evasion via exploiting the host complement system by vaccinia virus, and by modulating the type 1 interferon response by RNA viruses. Yet another chapter looks into how viroporins expressed by different families of viruses causing influenza A virus, SARS, hepatitis C and HIV interact with several cellular pathways. Understanding of these mechanisms can aid the development of novel potential anti‐viral targets. The chapter on tuberculosis discusses the emerging importance of the innate immune mechanisms against Mycobacterium tuberculosis infection and latency. This book has a strong focus on fungal pathogenesis and immunity, starting with virulence and host factors that attain great importance in candidiasis and associated escape tricks of seriously opportunistic fungi. Two chapters on Aspergillus fumigatus elaborate on the pathogenic mechanisms: first discussing A. fumigatus‐airway epithelium interaction, followed by fungal and host factors that are paramount in the development of allergic and invasive aspergillosis. In the subsequent chapter, there is a general discussion on the innate and adaptive immune responses against primary and opportunistic fungal pathogens.
Download or read book The Physical Basis of Heredity written by Thomas Hunt Morgan and published by . This book was released on 1919 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Endoplasmic Reticulum Stress in Health and Disease written by Patrizia Agostinis and published by Springer Science & Business Media. This book was released on 2012-08-13 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.
Download or read book Essential Aspects of Immunometabolism in Health and Disease written by Niels Olsen Saraiva Camara and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunometabolism has emerged as an intersectional crossroad between metabolism and immune response. Over the past decade, it has become clear that most - if not all - immune cell functions are not separated from cellular metabolism. Although seminal works have addressed the metabolic fate of immune cells during differentiation and function, the physiological status of a given tissue is also dependent on the cell metabolism. The dialogue between immune cells and their microenvironment can also modulate cellular metabolism, which can trigger the onset and progression of a multitude of inflammation-mediated diseases. Thus, uncovering the specific characteristics of the metabolism in different immune cells types and in different conditions, can shed light into the molecular mechanisms of disease and help develop new drugs and therapeutic strategies to treat immune diseases. The edited volume Essentials aspects of Immunometabolism will give the readers a broad view on how metabolic pathways can influence many types of immune cells during activation, differentiation and function, in health and disease. Of note, the structure of the book was created thinking not only on the experienced immunologist but also on undergraduate and graduate students, physicians, and all members of the scientific community interested in this exciting field of research.
Download or read book Index Medicus written by and published by . This book was released on 2002 with total page 1404 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
