Combination effect of phospholipids and n-3 polyunsaturated fatty acids on rat cholesterol metabolism

This study evaluated phospholipids (PLs) containing n-3 polyunsaturated fatty acids (n-3 PUFAs) for their specific inherent effects and effects due to a combination of the presence of glycerophosphate structure and n-3 PUFAs on cholesterol metabolism in rats. Rats were fed a diet of AIN-93G containing soybean oil (SO, 7%), SO (5.8%)+fish oil (1.2%), SO (5.2%)+soybean PLs (1.8%), SO (5.2%)+PLs containing n-3 PUFAs (1.8%), and SO (4.0%)+fish oil (1.2%)+soybean PLs (1.8%). Diets with PLs containing n-3 PUFAs, and soybean PLs in combination with fish oil, resulted in decreased serum and liver cholesterol levels through enhancement of fecal cholesterol excretion and suppression of liver sterol regulatory element binding protein-2 mRNA expression compared with the diet containing soybean oil alone. This study shows that soybean PLs with added triacylglycerol that included n-3 PUFAs have the same effects on cholesterol metabolism as PLs containing n-3 PUFAs, and that these could be of benefit to people.     

Site-directed mutagenesis study of the antibody 2D7 which catalyzes a reaction for insertion of Cu2+ into mesoporphyrin

Monoclonal antibody 2D7 generated against a transition-state analog N-methyl mesoporphyrin catalyzes a reaction for insertion of a cupric ion into mesoporphyrin. To investigate amino acid residues responsible for the catalytic activity, site-directed mutagenesis of the amino acid residues in the third complementarity determining region of the heavy chain (CDRH3) was performed on the antigen-binding fragment (Fab) of the antibody. Recombinant Fab mutants, in which Arg95 is replaced with Ala (R95A), Asp96 with Asn (D96N) and Met97 with Gly (M97G), were examined in terms of the catalytic efficiency of the reaction (k/K(S)) and the dissociation constant for N-methyl mesoporphyrin binding (K(d)) and these values were compared with those of the wild type. The k/K(S) values of the R95A and D96N mutants were 0.96% and 1.0% of that of the wild type, respectively, whereas the M97G mutant had no detectable catalytic activity. The K(d) values of the R95A and D96N mutants were 165 and 69 times that of the wild type, respectively, while that of the M97G mutant was similar to that of the wild type. The relationship between the k/K(S) and 1/K(d) values in the wild type and the R95A and D96N mutants suggests that Arg95 and Asp96 are responsible for stabilizing the transition-state in the catalytic reaction. The results of the M97G mutant allow us to propose that Met97 plays an important role in the catalytic activity probably due to a subtle and specific conformation of the antibody.     

Porcine hemoglobin promotes lipid excretion to feces more strongly than globin protein in rats

In an effort to clarify whether the lipid-lowering effect of hemoglobin is due to globin protein or heme, this study investigated the effects of dietary porcine hemoglobin (PH) and porcine globin (PG) on lipids contents of serum, liver, and feces in rats. Five-week-old male Wistar rats were divided into 3 dietary groups of 7 rats each, with one group receiving a control diet and the other groups receiving diets containing 1.25% (w/w) PH or 1.18% (w/w) PG for 4 weeks. The PH diet decreased triacylglycerol content in serum and cholesterol in serum and liver, whereas the PG diet reduced triacylglycerol content in serum and cholesterol in liver. Fecal lipid excretion in the PH group was significantly higher than in the PG group. Therefore, PH affected lipid excretion to feces due to globin protein as well as heme.     

Molecular structure of La3+-induced methanol dehydrogenase-like protein in Methylobacterium radiotolerans

La(3+) and not Ca(2+) increases methanol dehydrogenase (MDH) activity in Methylobacterium radiotolerans NBRC15690. La(3+)- and Ca(2+)-MDH-like proteins were found to be homodimeric (α(2)) and heterotetrameric (α(2)β(2)), respectively. N-terminal amino acid sequences of these proteins revealed that La(3+)- and Ca(2+)-MDH-like proteins were encoded by xoxF and mxaFI, respectively.     

Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats

Effects of reduction of the number of primordial follicles on follicular development and concentrations of circulating hormones were examined in immature female rat offspring of dams given busulfan intraperitoneally on day 14 of gestation. The offspring of dams treated with 5 mg busulfan kg(-1) showed vaginal opening at an age comparable with the offspring of dams treated with 2.5 mg busulfan kg(-1) or with corn oil as a control, although they exhibited an irregular oestrous cycle until week 14 after birth. The serum concentrations of immunoreactive inhibin and FSH on day 26 after birth of the offspring treated with 5 mg busulfan kg(-1) were similar to those of age-matched controls. On day 15 after birth, however, the concentration of their immunoreactive inhibin was markedly lower than that of controls, whereas the concentration of their FSH was increased inversely. Comparison of the numbers of ovarian follicles in the controls and groups treated with 2.5 mg busulfan kg(-1) and 5 mg busulfan kg(-1) revealed that prenatal treatment with busulfan reduced the number of follicles in the primordial or primary phase and in the preantral phase on day 7 after birth. Although the increase of the ratio of the number of preantral follicles during days 7-13 after birth tended to vary with the prenatal dose of busulfan, the number of preantral follicles in the group treated with 5 mg busulfan kg(-1) was still smaller than in the controls. The concentration of serum immunoreactive inhibin of the offspring treated with busulfan was reduced on day 7 after birth without alteration of the concentration of gonadotrophin. On day 13 after birth, the concentration of serum immunoreactive inhibin was reduced only in the offspring treated with 5 mg busulfan kg(-1), and the concentration of serum FSH of the offspring was increased inversely as found on day 15 after birth. These results indicate that a reduction in the number of primordial follicles decreases the number of follicles that enter the growing phase, a major source of circulating inhibin in the neonatal and infantile ovary, and that consequently increased circulating FSH may accelerate follicular development to achieve puberty.     

The Role of Podoplanin in Skin Diseases

Podoplanin is a sialomucin-like type I transmembrane receptor glycoprotein that is expressed specifically in lymphatic vessels, sebaceous glands, and hair follicles in normal skin. However, under pathological conditions podoplanin expression is upregulated in various cells, such as keratinocytes, fibroblasts, tumor cells, and inflammatory cells, and plays pivotal roles in different diseases. In psoriasis, podoplanin expression is induced in basal keratinocytes via the JAK-STAT pathway and contributes toward epidermal hyperproliferation. Podoplanin expression on keratinocytes can also promote IL-17 secretion from lymphocytes, promoting chronic inflammation. During wound healing, the podoplanin/CLEC-2 interaction between keratinocytes and platelets regulates re-epithelialization at the wound edge. In skin cancers, podoplanin expresses on tumor cells and promotes their migration and epithelial-mesenchymal transition, thereby accelerating invasion and metastasis. Podoplanin is also expressed in normal peritumoral cells, such as cancer-associated fibroblasts in melanoma and keratinocytes in extramammary Paget’s disease, which promote tumor progression and predict aggressive behavior and poor prognosis. This review provides an overview of our current understanding of the mechanisms via which podoplanin mediates these pathological skin conditions.     

Prolonged Aftereffect of Visuomotor Adaptation to Gradually Distorted Reality Displayed on a See-Through Head-Mounted Device

Growing evidence suggests that the gradual transformation of visuomotor association drives a distinct learning process from abrupt transformation in humans. In the current study, we developed a novel omnidirectional visuomotor transformation paradigm to study details of such difference in more realistic environment than conventional experimental systems. Participants were asked to perform a repetitive three-dimensional (3D) arm-reaching task to a target on a front touch panel, wearing a video see-through head-mounted device that displayed a rotating view of surrounding images. In the abrupt condition, the images were rotated by 20°; in the gradual condition, the rotation was increased in a stepwise-manner from 0° to 20°. In both conditions, pointing errors were decreased after adaptation. Further, although the aftereffect of adaptation was not different between conditions, the speed of decay of the aftereffect, which was quantified by an exponential fit, was slower in the gradual condition, suggesting longer-lasting aftereffects for the gradual shift.     

Examination of pin-by-pin fission rate distribution in large geometry evaluated by the Monte-Carlo method

Accuracy and reliability of pin-by-pin fission rate distribution in large geometries calculated by the multi-group Monte-Carlo method is examined through comparison with a deterministic transport code based on the method of characteristics. Various calculation geometries from a single assembly to a PWR full core are used for comparison of pin-by-pin fission rate distribution. An integral parameter, i.e., k-effective, can be accurately calculated by the Monte-Carlo method with a practical number of neutron histories (10⁶–10⁷) regardless of the size of the calculation geometry. On the other hand, comparison with the deterministic calculation shows that the estimated statistical errors for pin-by-pin fission rate distribution obtained by a Monte-Carlo calculation are somewhat underestimated in a large geometry, e.g., a PWR full core, under the present calculation conditions. Such underestimation of the statistical uncertainty of a local parameter should be carefully considered when the Monte-Carlo method is used as a reference tool for verification of a deterministic code, especially in large geometries.