A novel low wearing differential hardness, ceramic-on-metal hip joint prosthesis

Osteolysis and loosening of artificial joints caused by polyethylene wear debris has prompted renewed interest in alternative bearing materials for hip prosthesis designs. Lower wearing metal-on-metal (MOM) and ceramic-on-ceramic prostheses are being used more extensively, and there is considerable interest in further improving on their performance. This study investigated the wear properties and debris morphology of a novel differential hardness ceramic-on-metal (COM) prosthesis, in comparison with MOM articulations in a physiological anatomical hip joint simulator.The COM pairings were found to have wear rates approximately 100-fold lower than the MOM pairings. The MOM pairings showed a higher "bedding in" wear rate (3.09+/-0.46mm(3)/10(6) cycles) in the first million cycles, which then reduced to a steady state wear rate of 1.23+/-0.5mm(3)/10(6) cycles. The wear rate of the COM pairings over the duration of the test was approximately 0.01mm(3)/10(6) cycles with very little wear detected on the surface of the prosthesis components.The wear particles from both articulations were oval to round in shape and in the nanometer size range. After one million cycles the mean maximum diameter of the MOM and COM wear particles were 30+/-2.25 and 17.57+/-1.37nm, respectively. After five million cycles the wear particles were statistically significantly smaller than at one million cycles, 13.9+/-0.72nm for the MOM pairings and 6.11+/-0.40nm for the COM pairings.The wear rates of the MOM prostheses were representative of clinical values. The use of differential hardness COM pairings dramatically reduced the wear rate compared to MOM hip prostheses. The wear particles from the MOM articulation were similar to particles found in retrieved tissues from around MOM prostheses. The extremely low wearing differential hardness COM bearings presented in this study produced far smaller volumetric particle loads compared to MOM prostheses currently used clinically.     

The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase

B cell antigen receptor (BCR) signaling causes tyrosine phosphorylation of the Gab1 docking protein. This allows phosphatidylinositol 3-kinase (PI3K) and the SHP2 tyrosine phosphatase to bind to Gab1. In this report, we tested the hypothesis that Gab1 acts as an amplifier of PI3K- and SHP2-dependent signaling in B lymphocytes. By overexpressing Gab1 in the WEHI-231 B cell line, we found that Gab1 can potentiate BCR-induced phosphorylation of Akt, a PI3K-dependent response. Gab1 expression also increased BCR-induced tyrosine phosphorylation of SHP2 as well as the binding of Grb2 to SHP2. We show that the pleckstrin homology (PH) domain of Gab1 is required for BCR-induced phosphorylation of Gab1 and for Gab1 participation in BCR signaling. Moreover, using confocal microscopy, we show that BCR ligation can induce the translocation of Gab1 from the cytosol to the plasma membrane and that this requires the Gab1 PH domain as well as PI3K activity. These findings are consistent with a model in which the binding of the Gab1 PH domain to PI3K-derived lipids brings Gab1 to the plasma membrane, where it can be tyrosine-phosphorylated and then act as an amplifier of BCR signaling.     

Conversion of fibrinogen to fibrin: mechanism of exposure of tPA- and plasminogen-binding sites

Conversion of fibrinogen into fibrin results in the exposure of cryptic interaction sites and modulation of various activities. To elucidate the mechanism of this exposure, we tested the accessibility of the Aalpha148-160 and gamma312-324 fibrin-specific epitopes that are involved in binding of plasminogen and its activator tPA, in several fragments derived from fibrinogen (fragment D and its subfragments) and fibrin (cross-linked D-D fragment and its noncovalent complex with the E(1) fragment, D-D. E(1)). Neither D nor D-D bound tPA, plasminogen, or anti-Aalpha148-160 and anti-gamma312-324 monoclonal antibodies, indicating that their fibrin-specific epitopes were inaccessible. The Aalpha148-160 epitope became exposed only upon proteolytic removal of the beta- and gamma-modules from D. At the same time, both epitopes were accessible in the D-D.E(1) complex, indicating that the DD.E interaction resulted in their exposure. This exposure was reversible since the dissociation of the D-D.E(1) complex made the sites unavailable, while reconstitution of the complex made them exposed. The results indicate that upon fibrin assembly, driven primarily by the interaction between complementary sites of the D and E regions, the D regions undergo conformational changes that cause the exposure of their plasminogen- and tPA-binding sites. These changes may be involved in the regulation of fibrin assembly and fibrinolysis.     

A multi-platform flow device for microbial (co-) cultivation and microscopic analysis

Novel microbial cultivation platforms are of increasing interest to researchers in academia and industry. The development of materials with specialized chemical and geometric properties has opened up new possibilities in the study of previously unculturable microorganisms and has facilitated the design of elegant, high-throughput experimental set-ups. Within the context of the international Genetically Engineered Machine (iGEM) competition, we set out to design, manufacture, and implement a flow device that can accommodate multiple growth platforms, that is, a silicon nitride based microsieve and a porous aluminium oxide based microdish. It provides control over (co-)culturing conditions similar to a chemostat, while allowing organisms to be observed microscopically. The device was designed to be affordable, reusable, and above all, versatile. To test its functionality and general utility, we performed multiple experiments with Escherichia coli cells harboring synthetic gene circuits and were able to quantitatively study emerging expression dynamics in real-time via fluorescence microscopy. Furthermore, we demonstrated that the device provides a unique environment for the cultivation of nematodes, suggesting that the device could also prove useful in microscopy studies of multicellular microorganisms.     

Sdf1a patterns zebrafish melanophores and links the somite and melanophore pattern defects in choker mutants

Pigment pattern formation in zebrafish presents a tractable model system for studying the morphogenesis of neural crest derivatives. Embryos mutant for choker manifest a unique pigment pattern phenotype that combines a loss of lateral stripe melanophores with an ectopic melanophore ;collar' at the head-trunk border. We find that defects in neural crest migration are largely restricted to the lateral migration pathway, affecting both xanthophores (lost) and melanophores (gained) in choker mutants. Double mutant and timelapse analyses demonstrate that these defects are likely to be driven independently, the collar being formed by invasion of melanophores from the dorsal and ventral stripes. Using tissue transplantation, we show that melanophore patterning depends upon the underlying somitic cells, the myotomal derivatives of which--both slow--and fast-twitch muscle fibres--are themselves significantly disorganised in the region of the ectopic collar. In addition, we uncover an aberrant pattern of expression of the gene encoding the chemokine Sdf1a in choker mutant homozygotes that correlates with each aspect of the melanophore pattern defect. Using morpholino knock-down and ectopic expression experiments, we provide evidence to suggest that Sdf1a drives melanophore invasion in the choker mutant collar and normally plays an essential role in patterning the lateral stripe. We thus identify Sdf1 as a key molecule in pigment pattern formation, adding to the growing inventory of its roles in embryonic development.     

The mycorrhizal colonization of six wetland plant species at sites differing in land use history

 Five wetland prairie sites and six native plant species in western Oregon were examined to determine patterns of vesicular-arbuscular mycorrhizal fungal (VAMF) colonization. The sites differed in type and intensity of past land use. VAMF colonization was tested in situ on seedlings from both field-sown seeds and from transplants. Colonization was measured as the percentage of root length with arbuscles or vesicles. All species (Deschampsia cespitosa, Downingia elegans, Eriophyllum lanatum, Hordeum brachyantherum, Microseris laciniata, and Plagiobothrys figuratus) became colonized by VAMF during the study. This is the first report of mycorrhizal colonization of these important native species. All sites supported mycorrhizal colonization of some of the experimental species. Average VAMF colonization ranged from 58% to 92% but was unrelated to subjective rankings of land use intensity. These results suggest that VAMF inoculum at all sites was sufficient to support revegetation by at least some species of native plants. Accepted: 16 September 1999