Julian Nida-Rümelin

Contents of Volume II

Zermelo 1896a Introductory note to 1896a, 1896b, and Boltzmann 1896, 1897, by Jos Uffink. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 Ueber einen Satz der Dynamik und die mechanische Wärmetheorie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 On a theorem of dynamics and the mechanical heat theory . . . . . . . . . 215

Preface to Volume I

The extracellular matrix is complex in its composition, wide ranging in its deposition, and diverse in how it shapes cell behavior and tissue organization. Critical to matrix function is the balance between deposition and turnover of its many, varied protein components. Indeed, the spatially and temporally precise removal and remodeling of connective tissue is critical to several developmental, homeostatic, and reparative processes. However, if matrix turnover and degradation are excessive and unregulated, as occur in many inflammatory conditions, bad things can happen. Because of the marked chemical diversity of matrix proteins – inclusive of glycoproteins, proteoglycans, and insoluble hydrophobic polymers, among other components – it is not surprising that the endopeptidases implicated in matrix turnover are equally diverse, both in their makeup and function. For example, the large and physiologically important serine proteinase family, which includes leukocyte elastase, plasminogen, and its activators, among many others enzymes, mediates a variety of activities, from clot dissolution to tissue destruction. Matrix metalloproteinases (MMPs), which compose a large subfamily within the even larger metalloproteinase family, have a specialized function in turnover of some extracellular matrix proteins, but as is discussed in more than one chapter in this volume, these enzymes are also effectors in other functions, particularly repair and immunity. Essentially, all proteins transition through inactive, active, and finally deactivated states, and various posttranslational modifications mediate these changes. Proteolysis is one of several posttranslational mechanisms that regulate protein activity, and it is the principal way for ending a protein’s time and recycling its amino acids for reuse. Evolution has provided us with six families of proteinases, defined by the amino acid or cofactor that catalyzes the nucleophilic attack on the peptide backbone of substrate proteins. Proteinases are found and operate both inside and outside of the cell. Many members of the cysteine, serine, and metalloprotienase families function extracellularly, and thus members of these three families have been implicated or demonstrated to function in turnover and degradation of the matrix. Hence, this volume focuses on these groups of enzymes.