A huge variety of proteins are able to form fibrillar structures, especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand. Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal and carboxy-terminal domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation initiated by changes in ionic composition and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation. However, despite recent structural data, little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.

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SUMMARY The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was hiffected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean ± 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract.The main site for the absorption of drugs in man is considered to be the small intestine, with its high effective surface area.' Little, if any, drug absorption occurs from the stomach, although some drugs are thought to be absorbed to a limited extent from the large intestine. As a general rule, therefore, drugs should be formulated so that they can be largely absorbed from the small intestine.Ho, Higuchi, and colleagues2 3 have introduced the concept of the 'reserve length' for drug absorption. This is defined as the anatomical length over which absorption of drug can occur, less the length at which absorption is complete. The reserve length is dependent on physiological factors, however, such as bulk flow rate, spreading of the dosage form in the small intestine and the permeability of the drug through the intestinal mucosa.In the pharmaceutical field, the length of time a dosage form can remain in the small intestine tends to have been overestimated4; particularly when consideration is given to controlled release systems designed to provide 24 hour dosage. In some cases insufficient attention has been paid to the influence of gastric emptying, or to the implications of the studies on the nature and function of the migrating myoelectric complex,5 and the consequent differ-

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A sacrificial templating process using lithographically printed minimal surface structures allows complex de novo geo-metries of delicate hydrogel materials. The hydrogel scaffolds based on cellulose and chitin nanofibrils show differences in terms of attachment of human mesenchymal stem cells, and allow their differentiation into osteogenic outcomes. The approach here serves as a first example toward designer hydrogel scaffolds viable for biomimetic tissue engineering.