CTLA-4Ig Improves Hyperalgesia in a Mouse Model of Osteoporosis

This study aimed to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effects of cytotoxic T lymphocyte-associated antigen-4Ig (CTLA-4Ig) administration in ovariectomized (OVX) mice. Eight-week-old female ddY mice were assigned to three groups: sham-operated mice (SHAM) treated with vehicle, OVX mice treated with vehicle (OVX), and OVX mice treated with CTLA-4Ig (CTLA-4Ig). Vehicle or CTLA-4Ig was injected intraperitoneally, starting immediately after surgery. After 4 weeks of treatment, mechanical sensitivity was examined, and the bilateral hind limbs were removed and evaluated by micro-computed tomography, immunohistochemical analyses, and messenger RNA expression analysis. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs. CTLA-4Ig treatment prevented bone loss in the hindlimbs compared to vehicle administration in the OVX group. Moreover, mechanical hyperalgesia was significantly decreased in the CTLA-4Ig treatment group in comparison to the OVX group. The expression levels of tumor necrosis factor-α (TNF-α) and sclerostin (SOST), as well as the number of osteoclasts, were increased, and the expression level of Wnt-10b was decreased in the OVX group compared with the SHAM group, whereas these parameters were improved in the CTLA-4Ig group compared with the OVX group. The novelty of this research is that CTLA-4Ig administration prevented bone loss and mechanical hyperalgesia induced by ovariectomy in the hindlimbs.     

Involvement of β-Alkylation Machinery and Two Sets of Ketosynthase-Chain-Length Factors in the Biosynthesis of Fogacin Polyketides in Actinoplanes missouriensis

Fogacin and two novel fogacin derivatives, fogacins B and C, were isolated from the rare actinomycete Actinoplanes missouriensis. Biosynthesis of fogacin C apparently requires β alkylation of a polyketide chain. The fogacin biosynthetic type II polyketide synthase (PKS) gene cluster contains a hydroxymethylglutaryl-coenzyme A synthase (HCS) cassette, which is usually responsible for β alkylation in the type I PKS system. Another characteristic of the fog cluster is that it encodes two sets of ketosynthase (KS) and chain-length factor (CLF). Inactivation of either of the two KS genes in A. missouriensis and heterologous expression of the HCS cassette with either of the two KS-CLF genes in Streptomyces albus indicated that each KS-CLF had a different starter substrate specificity: one preferred an unusual β-alkylated starter and the other preferred a normal acetyl starter. This study expands knowledge of HCS cassette-dependent β alkylation into the type II PKS system and provides a natural example of combinatorial biosynthesis for producing diverse polyketides from different starter substrates.     

Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitro

Because of their useful chemical and physical properties, nanomaterials are widely used around the world - for example, as additives in food and medicines - and such uses are expected to become more prevalent in the future. Therefore, collecting information about the effects of nanomaterials on metabolic enzymes is important. Here, we examined the effects of amorphous silica particles with various sizes and surface modifications on cytochrome P450 3A4 (CYP3A4) activity by means of two different in vitro assays. Silica nanoparticles with diameters of 30 and 70 nm (nSP30 and nSP70, respectively) tended to inhibit CYP3A4 activity in human liver microsomes (HLMs), but the inhibitory activity of both types of nanoparticles was decreased by carboxyl modification. In contrast, amine-modified nSP70 activated CYP3A4 activity. In HepG2 cells, nSP30 inhibited CYP3A4 activity more strongly than the larger silica particles did. Taken together, these results suggest that the size and surface characteristics of the silica particles determined their effects on CYP3A4 activity and that it may be possible to develop silica particles that do not have undesirable effects on metabolic enzymes by altering their size and surface characteristics.     

Synthesis of ultrafine nano-polycrystalline cubic boron nitride by direct transformation under ultrahigh pressure

Using a turbostratic pyrolytic boron nitride as a starting material, we synthesized a variety of ultrahard polycrystalline cubic boron nitride (PcBN) as a function of the heating duration changing from 1 to 60?min under a constant temperature and pressure conditions (1950?°C and 25?GPa) using a multi-anvil apparatus. When the heating duration was less than 13?min, ultrafine nano-polycrystalline cBN (U-NPcBN) with the mean grain size of <50?nm was produced. Among these U-NPcBNs those synthesized with 11–13?min were found to have a uniform texture composed purely of cBN (i.e. with no wurzite BN residue) and a Knoop hardness of >53?GPa, which is 20% higher than that of the hardest conventional binderless PcBN in practical use. Furthermore, the PcBNs synthesized with 18–20?min showed a unique nanocrystalline texture composed of relatively coarse grains dispersed in a fine grained matrix and even higher Knoop hardness (54.5–55.2?GPa).     

Structural phase transition in the perovskite-type tantalum oxynitrides, Ca1−xEuxTa(O,N)3

Pure Ca_1−xEu_xTa(O,N)₃ were successfully synthesized in the whole range of Ca/Eu compositions by means of ammonia nitridation via a citrate precursor route. As-nitrided products with x < 0.4 were apparently orthorhombic, while those with x ≥ 0.4 crystallized in a cubic structure. The anionic composition was found to be essentially O₂N and independent of Eu content (x). The as-nitrided EuTaO₂N possessed a cubic perovskite-type structure, while high-temperature post-annealing led to a tetragonal EuTaO₂N phase with better crystallinity. The re-nitridation transformed the post-annealed product into the original cubic lattice, which might be an average of the tetragonal micro-domains.     

Design method for a new control system for an autonomous underwater vehicle using linear matrix inequalities

The independent administrative corporation Japan Agency for Marine–Earth Science and Technology (JAMSTEC) has developed a small light autonomous underwater vehicle (AUV) named marine robot experimental 1 (MR-X1).¹ The motion control of MR-X1 is considered in this article. Since the dynamics of MR-X1 mainly depends on its own speed, the motion control is a nonlinear control system. We propose a new controller design method for this system using linear matrix inequalities (LMIs). This algorithm gives a solution as a linear matrix inequality, and can be adapted to solve many LMIs simultaneously. LMIs can be obtained by substituting several speeds into the dynamics of the MR-X1. The proposed controller, which can be derived from the solution of the LMIs, was adapted to MR-X1 and showed good performance in experiments. This work was presented in part at the 11th International Symposium on Artificial Life and Robotics, Oita, Japan, January 23–25, 2006     

On the dynamic version of the minimum hand jerk criterion

This paper is concerned with the problem of trajectory formation of humanlike reaching movements. First, we review conventional criteria of optimality adopted in robotics and computational neuroscience for the prediction of reaching movements and formulate a dynamic version of the minimum hand jerk criteria. We call it a minimum driving force change criterion and check its performance for the free‐space movements. Next, we test the performance of the new criterion for the movements where the human hand is geometrically constrained by the external environment, and for the movements with flexible objects. The main feature of these movements is that the hand velocity profiles are not always bell shaped. Our simulations and initial experimental results show that the minimum driving force change criterion can roughly capture this feature and, therefore, can be a reasonable candidate for modeling of humanlike reaching movements. © 2005 Wiley Periodicals, Inc.