Structure of astacin and implications for activation of astacins and zinc-ligation of collagenases.

Astacin, a digestive zinc-endopeptidase from the crayfish Astacus astacus L., is the prototype for the 'astacin family', which includes mammalian metallo-endopeptidases and developmentally regulated proteins of man, fruitfly, frog and sea urchin. Here we report the X-ray crystal structure of astacin, which reveals a deep active-site cleft, with the zinc at its bottom ligated by three histidines, a water molecule and a more remote tyrosine. The third histidine (His 102) forms part of a consensus sequence, shared not only by the members of the astacin family, but also by otherwise sequentially unrelated proteinases, such as vertebrate collagenases. It may therefore represent the elusive 'third' zinc ligand in these enzymes. The amino terminus of astacin is buried forming an internal salt-bridge with Glu 103, adjacent to His 102. Astacin pro-forms extended at the N terminus, as observed for some 'latent' mammalian astacin homologues, did not exhibit this 'active' conformation, indicating an activation mechanism reminiscent of trypsin-like serine proteinases.     

An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ～ 50 seconds) and those that are also burning helium (period spacing ～ 100 to 300 seconds).     

Einfluss von angiotensin auf das argentaffine system des meerschweinchens

Summary The duodenum of guinea-pigs were dissected immediately after death and incubated for 10 min at 37 °C in a solution of Krebs-Ringer-Bicarbonate buffer, in which Hypertensin (CIBA) was added. The result was that the argentaffine cells were more numerous after the incubation period, as compared with the controls. The 2 controls were pieces placed into the solutions of Formalin and blank Krebs-Ringer-Bicarbonate buffer.     

Structure and function of desmosomal proteins and their role in development and disease

Desmosomes represent major intercellular adhesive junctions at basolateral membranes of epithelial cells and in other tissues. They mediate direct cell-cell contacts and provide anchorage sites for intermediate filaments important for the maintenance of tissue architecture. There is increasing evidence now that desmosomes in addition to a simple structural function have new roles in tissue morphogenesis and differentiation. Transmembrane glycoproteins of the cadherin superfamily of Ca²⁺-dependent cell-cell adhesion molecules which mediate direct intercellular interactions in desmosomes appear to be of central importance in this respect. The complex network of proteins forming the desmosomal plaque associated with the cytoplasmic domain of the desmosomal cadherins, however, is also involved in junction assembly and regulation of adhesive strength. This re-view summarizes the structural features of these desmosomal proteins, their function during desmosome assembly and maintenance, and their role in development and disease.Received 5 February 2003; received after revision 14 March 2003; accepted 1 April 2003     

Über optische Untersuchungen an Deckschichten auf Aluminium

Summary The double refraction of oxide films on Al conditioned by an electrolytic treatment of the metal in oxalic acid, sulphuric acid and so on (Eloxal-layers) is due only to the disperse structure of the film (Formdoppel-brechung), since the substances the film consists of are optically isotropic.The optical properties depend, excepting the formation conditions, in a very characteristic manner on the crystallographic orientation of the metallic surface.     

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice.

T cells that recognize self antigen are clonally deleted in the thymus--a maturation process that occurs in the context of histocompatibility molecules and the T-cell receptor. The minor lymphocyte stimulation antigens (Mls) effect these deletions through interactions with the V beta portion of the T-cell receptor, thus mimicking bacterial 'superantigens'. Intrigued by the fact that each known Mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (Mtv), we reevaluated the linkage relationships between the two gene families. Here we report perfect concordance in inbred and recombinant inbred mice between the presence of four Mtv proviruses with the expression of Mls gene products. These data suggest a general model in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immunological repertoire of common laboratory mice.