Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid beta-galactosidase (beta-gal). The disease manifests itself either as an infantile, juvenile or adult form and is primarily a neurological disorder with progressive brain dysfunction. A mouse model lacking a functional beta-gal gene has been generated by homologous recombination and embryonic stem cell technology. Tissues from affected mice are devoid of beta-gal mRNA and totally deficient in GM1-ganglioside-hydrolyzing capacity. Storage material was already conspicuous in the brain at 3 weeks. By 5 weeks, extensive storage of periodic acid Schiff-positive material was observed in neurons throughout the brain and spinal cord. Consistent with the neuropathology, abnormal accumulation of GM1-ganglioside in the brain progressed from twice to almost five times the normal amount during the period from 3 weeks to 3.5 months. Despite the accumulation of brain GM1-ganglioside at the level equal to or exceeding that seen in gravely ill human patients, these mice show no overt clinical phenotype up to 4-5 months. However, tremor, ataxia and abnormal gait become apparent in older mice. Thus, the beta-gal-deficient mice appear to mimic closely the pathological, biochemical and clinical abnormalities of the human disease.

We propose and demonstrate a "bottom-up" approach to constructing photonic structures for photon manipulation. Supermonodispersive polymer microspheres are used as building blocks and a size uniformity better than 0.05% could be obtained by sorting the spheres using spectroscopic methods. The spheres are positioned in a V groove on a silicon substrate and form a photonic chain with resonant coupling of the optical whispering-gallery modes. Photonic band modes are clearly observed in fluorescence and resonant scattering spectra, and an excellent agreement with a tight-binding model calculation is found. Heavy photon states and a group index as high as 40 are obtained.

Bacillus subtilis produces a 35-kDa cell wall hydrolase, CwlF, during vegetative growth. The CwlF protein was extracted from B. subtilis cwlB sigD mutant cells and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-terminal amino acid sequencing revealed that its sequence is completely identical to that of the internal region of thepapQ gene product. Disruption of the papQ gene in the B. subtilis chromosome led to the complete loss of CwlF, indicating that papQ is identical tocwlF. CwlF exhibits high sequence similarity to the p60 proteins of Listeria species, NlpC proteins ofEscherichia coli and Haemophilus influenzae, and Enp2 protein of Bacillus sphaericus. The β-galactosidase activity of the cwlF-lacZ transcriptional fusion and Northern blot analysis of the cwlF gene indicated that the gene is expressed as a monocistronic operon during the exponential growth phase, and primer extension analysis suggested that the cwlF gene is transcribed mainly by EςA RNA polymerase and weakly by EςH RNA polymerase. While the cells of the cwlF-deficient mutant were about twice as long as those of the wild-type strain, the cwlF sigD double mutant cells exhibited extraordinary microfiber formation, in contrast to the filamentation of the sigD mutant. The CwlF production was not affected by the pleiotropic mutationsflaD1 and degU32(Hy), which endow cells with the ability of extensive filamentation.

Lasing at resonantly coupled whispering-gallery mode frequencies is observed in photonic molecules consisting of bispheres of 4.2 and 5.1 microm in diameter placed in a silicon V-groove. We examine spatial profiles of photonic molecule modes by use of frequency-resolved imaging and reveal bonding and antibonding mode features. From the lasing threshold characteristics, we quantitatively measure the quality factor and the spontaneous-emission coupling ratio of the photonic molecule modes and confirm that strong coherent coupling leads to photonic molecule modes.

These results indicate the important contribution of visceral fat accumulation to the development of hyperinsulinemia, regardless of sex. Accordingly, it is suggested that evaluating Pmax by ultrasonography may be the most sensitive and reliable method of predicting insulin resistance-associated metabolic derangements in children, compared with other conventional indices of obesity.

Thiocyanate hydrolase (SCNase) is a cobalt-containing enzyme with a post-translationally modified cysteine ligand, cCys131-SO 2 H. When the SCNase a, b and c subunits were expressed in Escherichia coli, the subunits assembled to form a hetero-dodecamer, (abc) 4 , like native SCNase but exhibited no catalytic activity. Metal analysis indicated that SCNase was expressed as an apo-form irrespective of the presence of cobalt in the medium. On the contrary, SCNase co-expressed with P15K, encoded just downstream of SCNase genes, in cobalt-enriched medium under the optimized condition (SCNase (+P15K) ) possessed 0.86 Co atom/abc trimer and exhibited 78% of the activity of native SCNase. SCNase (+P15K) showed a UV-Vis absorption peak characteristic of the SCNase cobalt center. About 70% of SCNase (+P15K) had the cCys131-SO 2 H modification. These results indicate that SCNase (+P15K) is the active holo-SCNase. P15K is likely to promote the functional expression of SCNase probably by assisting the incorporation of cobalt ion.

Cell-free and concentrated ascites reinfusion therapy (CART) is frequently used to treat refractory ascites in Japan. However, its efficacy remains unclear. This controlled cohort study verified the serum albumin elevating effect of CART by comparisons with simple paracentesis. Ascites patients receiving CART (N = 88) or paracentesis (N = 108) at our hospital were assessed for the primary outcome of change in serum albumin level within 3 days before and after treatment. A significantly larger volume of ascites was drained in the CART group. The change in serum albumin level was +0.08 ± 0.25 g/dL in the CART group and −0.10 ± 0.30 g/dL in the paracentesis group (P < 0.001). The CART – paracentesis difference was +0.26 g/dL (95%CI +0.18 to +0.33, P < 0.001) after adjusting for potential confounders by multivariate analysis. The adjusted difference increased with drainage volume. In the CART group, serum total protein, dietary intake, and urine volume were significantly increased, while hemoglobin and body weight was significantly decreased, versus paracentesis. More frequent adverse events, particularly fever, were recorded for CART, although the period until re-drainage was significantly longer. This study is the first demonstrating that CART can significantly increase serum albumin level as compared with simple paracentesis. CART represents a useful strategy to manage patients requiring ascites drainage.

These results demonstrate that residual aldosterone has a significant impact on target-organ damage in hypertension, even during chronic administration of an ARB. The addition of an aldosterone antagonist has an advantage in facilitating the cardioprotective effects of ARBs.