Cytokine molecular

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  • Cytokine receptors are crucial for the maintenance, regulation and growth of cells in multicellular organisms. As a common theme in cytokine signal-ling, single-span receptor chains are assembled in the cell membrane by a ligand enabling cross-activation of the aligned cytoplasmic receptor domains.

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  • Mycobacteria are endowed with mechanisms through which they can evade the onslaught ofhost defense response. These mechanisms are discussed including diminishing the ability ofantigen presenting cells to present antigens to CD4+ T cells; production of suppressive cytokines;escape from fused phagosomes and inducing T cell apoptosis.

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  • Erythropoietin (Epo) is a hematopoietic cytokine that is crucial for the differentiation and proliferation of erythroid progenitor cells. Epo acts on its target cells by inducing homodimerization of the erythropoietin receptor (EpoR), thereby triggering intracellular signaling cascades. The EpoR encompasses eight tyrosine motifs on its cytoplasmic tail that have been shown to recruit a number of regulatory proteins.

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  • The protein arginine methyltransferase (PRMT) family of enzymes cata-lyzes the transfer of methyl groups from S-adenosylmethionine to the gua-nidino nitrogen atom of peptidylarginine to form monomethylarginine or dimethylarginine. We created several less polar analogs of the specific PRMT inhibitor arginine methylation inhibitor-1, and one such compound was found to have improved PRMT inhibitory activity over the parent molecule.

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  • Staphylococcus aureusand Streptococcus pyogenes(group A streptococci) are Gram-positive pathogens capable of producing a variety of bacterial exo-toxins known as superantigens. Superantigens interact with antigen-present-ing cells (APCs) and T cells to induce T cell proliferation and massive cytokine production, which leads to fever, rash, capillary leak and subse-quent hypotension, the major symptoms of toxic shock syndrome.

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  • Developing thymocytes and T cells express the Tec kinases Itk, Rlk⁄Txk and Tec, which are critical modulators of T-cell receptor signaling, required for full activation of phospholipase Cc, and downstream Ca 2+ and ERK-mediated signaling pathways.

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  • Stress-activated protein kinase (SAPK) signaling plays essential roles in eliciting adequate cellular responses to stresses and proinflammatory cytokines. SAPK pathways are composed of three successive protein kinase reactions. The phosphorylation of SAPK signaling components on Ser/Thr or Thr/Tyr residues suggests the involvement of various protein phosphatases in the negative regulation of these systems.

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  • Cancer, although a dreadful disease, is at the same time a fascinating biological phenotype. Around 1980, cancer was first attributed to malfunctioning genes and, subsequently, cancer research has become a major area of scientific research supporting the foundations of modern biology to a great extent. To unravel the human genome sequence was one of those extraordinary tasks, which has largely been fuelled by cancer research, and many of the fascinating insights into the genetic circuits that regulate developmental processes have also emerged from research on cancer....

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  • The cystine-knot motif, made up of three intertwined disulfide bridges, is a unique feature of several toxins, cyclotides and growth factors, and occurs in a variety of species, including fungi, insects, molluscs and mammals. Growth factor molecules containing the cystine-knot motif serve as ligands for a diverse range of receptors and play an important role in extracellular signalling.

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  • Tumour necrosis factor-a(TNF-a) is a cytokine that is involved in many functions, including the inflammatory response, immunity and apoptosis. Some of the responses of TNF-a are mediated by caspase-1, which is involved in the production of the pro-inflammatory cytokines interleukin-1b, interleukin-18 and interleukin-33.

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  • Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction, and the expression of growth factors, cytokines, neuropeptides, and other secreted molecules involved in cell-to-cell communication promoting regen-eration and neurite outgrowth.

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  • The ultimate goal of cancer research is the development of effective anticancer therapy. During the last several decades, the discovery of oncogenes, tumor suppressors, growth factors, signal transduction pathways has dramatically escalated our understanding of cancer cell biology and mechanisms of cell transformation.1-3 Hundreds of cellular proteins and pathways have been logically considered as molecular targets in a mechanism-based approaches of anticancer drug development.4-6 Yet, the progress in cancer treatment has not paralleled these dramatic achievements in basic research.

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  • Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin diseases, allergies and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential.

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  • The molecular definition of tumor antigens, costimulatory signals, and the possibility to genetically engineer tumor cells as well as simple protocols for efficient isolation and preparation of dendritic cells (DC) renew the interest in tumor immunotherapy and vaccination, in particular. Engineering of tumor cells with the gene of a particular cytokine is a way of releasing that cytokine at the tumor site. In contrast to bolus administration, it provides a constant supply of cytokine.

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  • This book has been made possible by the contributions of leading scientists and clinicians from upcoming and interdisciplinary fields of research concerning the molecular and clinical features of insulin resistance. Multiple metabolic disturbances associated with Insulin Resistance include inflammatory cytokines, adipokines, endothelial dysfunction, tissue-specific defects in insulin action and signaling, oxidative stress, ectopic lipid deposition, and disordered neuroregulation.

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  • Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis....

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  • Subunits (a, b and c) of the interleukin-2 receptor complex (IL-2R) are involved in both proliferative and activationinduced cell death (AICD) signaling of T cells. In addition, the signaling b and c chains are shared by other cytokines (e.g. IL-7, IL-9, IL-15). However, the molecular mechanisms responsible for recruiting/sorting the a chains to the signaling chains at the cell surface are not clear.

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  • The proliferation of smooth muscle cells (SMC) is a key event in the development of atherosclerosis. In addition to growth factors or cytokines, we have shown previously that n-3 polyunsaturated fatty acids (PUFAs) act in opposition to n-6 PUFAs by modulating various steps of the inflam-matory process. We have investigated the molecular mech-anisms by which the incorporation of the n-6 PUFA, arachidonic acid, increases the proliferation of rat SMC treated with interleukin-1b, while the n-3 PUFAs eicosa-pentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit nomitogenic response. ...

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