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This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.
This thoroughly revised second edition is an up-to-date overview of the current knowledge of Notch and Notch signaling in embryology and cancer. It discusses this topic from Notch’s role in the development of the embryo to the Notch signaling pathway’s role in the development of a number of cancers, including breast cancer, malignant melanoma, Non-melanoma skin cancer, intestinal cancer and others. In the years since the previous edition, there have been numerous developments and insights within this rapidly moving field, making this new edition urgently needed. This volume also features discussions of current insights on Notch’s role in senescence, the regulation of Notch signaling by...
This volume in the series "Documentary History of the Jews in Italy" illustrates the history of the Jews in Sicily from 1478 to 1489. It is the sequel to the first six volumes and covers the events during the first years of the rule of King Ferdinand II. These include the prelude to the expulsion, which witnessed a further deterioration in the position of the Jews on the island. At the same time, the Jewish community on the island reached the points of its greatest expansion in population as well as economic prosperity. Some 900 documents--many of them published here for the first time--record the fortunes of the Jews and their relationship with the authorities and their Christian neighbours...
Drawing on the authors' extensive research in the analysis of categorical longitudinal data, this book focuses on the formulation of latent Markov models and the practical use of these models. It demonstrates how to use the models in three types of analysis, with numerous examples illustrating how latent Markov models are used in economics, education, sociology, and other fields. The R and MATLAB routines used for the examples are available on the authors' website.
This book describes transcription factors in the context of hematopoietic development and reveal mechanistic insights how they orchestrate specific gene expression patterns. Several examples from lymphoid and myeloid lineages are given as well as particular examples of leukemia fusion proteins that contain a part of a transcription factor. In the given chapters covering each one particular example, the function of transcription factors is characterized in normal as well as leukemic contexts. New technologies such as ChIP-Seq or RNA-Seq, that make use of genome-wide sequencing, have shown that such master regulators of blood cell development often work in combinatorial fashion and, when dysregulated, results in leukemogenesis. This book is not only intended for experts but it should also be a useful resource for younger scientists or scientists from other disciplines, who may use this book as a stimulating starting point for further discoveries and/ or translational endeavors.
This volume contains cutting-edge techniques to study the function of enhancers and promoters in depth. Chapters are divided into six sections and describe enhancer-promoter transcripts, nucleosome occupancy, DNA accessibility, chromatin interactions, protein-DNA interactions, functional analyses, and DNA methylation assays. Written in the Methods in Molecular Biology series format, chapters include comprehensive introductions, lists of the necessary materials and reagents, step-by-step laboratory protocols, and useful suggestions for troubleshooting. Authoritative and cutting-edge, Enhancers and Promoters: Methods and Protocols is a useful guide for future experiments. Chapters 4 and 11 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com