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Munc13-3 is Required for the Developmental Localization of Ca 2+ Channels to Active Zones and the Nanopositioning of Ca V 2.1 Near Release Sensors
Abstract: Spatial relationships between Cav channels and release sensors at active zones (AZs) are a major determinant of synaptic fidelity. They are regulated developmentally, but the underlying molecular mechanisms are largely unclear. Here, we show that Munc13-3 regulates the density of Cav2.1 and Cav2.2 channels, alters the localization of Cav2.1, and is required for the development of tight, nanodomain coupling at parallel-fiber AZs. We combined EGTA application and Ca2+-channel pharmacology in electrophysiological and two-photon Ca2+ imaging experiments with quantitative freeze-fracture immunoelectron microscopy and mathematical modeling. We found that a normally occurring developmental shift from release being dominated by Ca2+ influx through Cav2.1 and Cav2.2 channels with domain overlap and loose coupling (microdomains) to a nanodomain Cav2.1 to sensor coupling is impaired in Munc13-3-deficient synapses. Thus, at AZs lacking Munc13-3, release remained triggered by Cav2.1 and Cav2.2 microdomains, suggesting a critical role of Munc13-3 in the formation of release sites with calcium channel nanodomains
Germans to America
Title of the first 10 volumes of the series is Germans to America : lists of passengers arriving at U.S. ports 1850-1855.
Frontiers of Complexity
"SCIENCE JOURNALISM AT ITS BEST. . . An impeccably researched, amazingly up-to-date, crisply written and well-illustrated survey." --Nature At the cutting edge of the sciences, a dynamic new concept is emerging: complexity. In this groundbreaking new book, Peter Coveney and Roger Highfield explore how complexity in mathematics, physics, biology, chemistry, and even the social sciences is transforming not only the way we think about the universe, but also the very assumptions that underlie conventional science. Complexity is a watchword for a new way of thinking about the behavior of interacting units, whether they are atoms, ants in a colony, or neurons firing in a human brain. The rise of t...
Karl-Valentin-Abend
None
Principles of Safety Pharmacology
This book illustrates, in a comprehensive manner, the most current areas of importance to Safety Pharmacology, a burgeoning unique pharmacological discipline with important ties to academia, industry and regulatory authorities. It provides readers with a definitive collection of topics containing essential information on the latest industry guidelines and overviews current and breakthrough topics in both functional and molecular pharmacology. An additional novelty of the book is that it constitutes academic, pharmaceutical and biotechnology perspectives for Safety Pharmacology issues. Each chapter is written by an expert in the area and includes not only a fundamental background regarding the topic but also detailed descriptions of currently accepted, validated models and methods as well as innovative methodologies used in drug discovery.
A Basis for Scientific and Engineering Translation
Annotation This handbook and the accompanying e-book attack many of the most crucial difficulties encountered by both native and non-native English speakers when translating scientific and engineering material from German. The e-book is like a miniature encyclopaedia dealing with the fundamental conceptual basis of science, engineering and mathematics, with particular regard to terminology. It provides didactically organised dictionaries, thesauri and a wide range of microglossaries highlighting polysemy, homonymy, hyponymy, context, collocation, usage as well as grammatical, lexical and semantic considerations essential to accurate translation. It also supplies a wide variety of reference m...
Geosynthetics: Leading the Way to a Resilient Planet
This volume contains the proceedings of the 12th International Conference on Geosynthetics (12 ICG), held in Roma, Italy, 17-21 September 2023. About 750 Authors - Academics, Researchers, Students, Practitioners, Contractors and Manufacturers – contributed to the peer-reviewed papers of this volume, which includes the Giroud lecture, the Bathurst lecture, the Rowe lecture, four keynote lectures and 296 technical papers. The content of these proceedings illustrates the sustainable use of geosynthetics in a variety of innovative as well as consolidated applications. After the sustainability implications in the correct use of geosynthetics, the ability to overcome the natural events effects, ...
Changing Hearts: Performing Jesuit Emotions between Europe, Asia, and the Americas
This volume of essays contributes to our understanding of the ways in which the Jesuits employed emotions to “change hearts”—that is, convert or reform—both in Europe and in the overseas missions.
