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Immune tolerance ensures that the immune system responds to foreign molecules and not to self-molecules. When tolerance breaks down, severe, self-destructive diseases such as rheumatoid arthritis, lupus, and multiple sclerosis may develop. Understanding the mechanisms involved in establishing and maintaining immune tolerance is essential for effectively treating these autoimmune diseases. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology reviews how self- tolerant T- and B-cell populations are produced. The contributors discuss the elimination of autoreactive lymphocytes during their development in the thymus and bone marrow, the suppression of autoreactive cells by regulatory T cells in the periphery, and intrinsic mechanisms that produce clonal anergy. The roles of dendritic cells in antigen presentation and mechanisms that prevent autoreactivity in natural killer cells are also covered. Including discussions of autoimmune diseases, their genetic bases, and therapeutic strategies, this volume is a valuable reference for all immunologists and clinicians wishing to understand or develop treatments for autoimmune diseases.

The synthesis of proteins by ribosomes is a fundamental cellular process. Cells must tightly control protein synthesis to maintain homeostasis and regulate proliferation, growth, differentiation, and development. Indeed, aberrant translational control is associated with cancer, several neurologic syndromes, and genetic disorders including "ribosomopathies." Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers our current understanding of protein synthesis and its control, from the genomic level to single- molecule analysis and single-cell imaging. The contributors describe the fundamental steps in protein synthesis (initiation, elongation, and termination), the factors involved, and high- resolution structures of the translational machinery. They review the targets of translational control (e.g., initiation factors and mRNAs) and how signaling pathways modulate this machinery. The roles of the endoplasmic reticulum, the unfolded protein response, processing bodies (P-bodies), stress granules, and small RNAs (including microRNAs) are also covered. This volume includes discussion of translational deregulation in cancer and the development of therapeutic agents that target translation initiation. Thus, it is an essential reference for cell and molecular biologists, as well as developmental and neurobiologists, oncologists, virologists, and all those investigating human diseases associated with translation dysfunction.

The endoplasmic reticulum (ER) is an extensive network of membranes that folds, modifies, and transports proteins in eukaryotic cells. It also manufactures lipids and interacts extensively with other organelles, playing essential roles in cell growth and homeostasis. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of ER morphology and function, as well as its interactions with the nucleus, Golgi, and mitochondria. Contributors examine how proteins translocate across the ER membrane, the processes that occur inside the ER lumen (e.g., folding, glycosylation, and disulfide bond formation), and how the proteins are packaged into vesicles and transported to the Golgi. They also review quality-control mechanisms that are employed by the ER to detect and eliminate misfolded or unassembled proteins. Lipid synthesis and transport are also discussed. This volume covers not only the biochemistry and cell biology of the ER, but also ER stress, metabolism, and the role of the ER in viral replication. Thus, it is an essential reference for cell biologists, physiologists, and pathologists interested in understanding the numerous functions of the ER.

Receptor tyrosine kinases are cell-surface receptors that respond to numerous hormones and growth factors, including insulin, insulin-like growth factors, epidermal growth factor, and nerve growth factor. They activate highly conserved intracellular signaling pathways that regulate cell proliferation, differentiation, and metabolism, playing essential roles in developing and adult animals. This book examines the nature of these receptors and their ligands, the molecular mechanisms that they regulate within cells, and the roles of the receptors in normal physiology and control of embryogenesis. It also discusses how dysfunction of these mechanisms can contribute to cancer and other diseases.

During endocytosis, extracellular molecules and plasma membrane components are selectively internalized by cells. This fundamental process of "cellular ingestion" is required for diverse activities such as nutrient uptake, cell adhesion and migration, signal transduction, cytokinesis, neurotransmission, and antigen presentation. Pathogens (e.g., HIV) exploit endocytic pathways to gain entry into cells, and defects in the endocytic machinery can lead to diseases such as cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all of the major pathways of endocytosis and post-endocytic trafficking, and how they regulate cellular and organismal physiology. Contributors describe how cargo enters the cell via clathrin-mediated and clathrin-independent pathways, including caveolar endocytosis, micropinocytosis, cholesterol-sensitive endocytosis, phagocytosis, and the CLIC/GEEC pathway. They review the numerous machineries (e.g., Rab GTPases, tethering factors, and retromer) that transport cargo through endosomes and deliver it to lysosomes or recycle it back to the cell surface, and the signals and mechanisms governing these sorting decisions. Topics such as lysosomal dynamics, the biophysical challenges of bending membranes, and the evolution of endocytic systems are also covered. This volume also includes substantial discussion of the roles of endocytic trafficking in organismal development, physiology, and disease. It is thus an indispensable reference for cell biologists, but also neuroscientists, immunologists, developmental biologists, microbiologists, and others concerned with the physiological and therapeutic implications of this key cellular process.