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(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 μM (IC50 of alendronate, 3.7 μM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 μM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 μM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.

The ethanolic extract obtained from the stems of Glycosmis pentaphylla was found to suppress antigen-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. Four new geranylated 2-quinolone alkaloids, named glycopentanolones A–D (1–4), and 12 known metabolites (5–16) were isolated from the ethanolic extract from the stems of G. pentaphylla using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, and HRESI-MS. The inhibitory effects of the isolated constituents on β-hexosaminidase release from RBL-2H3 cells were examined, and compounds 1, 5, 8 and 11 exhibited potent inhibitory activity with IC50 values between 0.05 and 4.28 μM.

We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer’s disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC50 of 29.6, 16.2 and 48.1 µM, respectively. The Ki values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC50 values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure−activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (Pe) of 60.3×10−6 cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of Aβ peptides from neuroblastoma cells that overexpressed human β-amyloid precursor protein at 500 μM. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics., Alzheimer’s disease: Promising therapeutic compounds found in plants Compounds extracted from bracken fern block the activity of three enzymes associated with Alzheimer’s disease (AD). Because AD is a complex and multifactorial disease, a multitarget-directed approach is an attractive strategy for the development of disease-modifying therapeutics. A study led by Gil Hong Park, Korea University, Seoul, and Nam Sook Kang, Chungnam National University, Daejon, revealed that pterosin derivatives could reduce the activity of β-site amyloid precursor protein cleaving enzyme 1, acetylcholinesterase and butyrylcholinesterase in a concentration-dependent manner. Furthermore, the fern-extracted compounds did not cause cellular toxicity and were able to cross the blood–brain barrier, which is impermeable to most drugs, to reach the brain. Future studies will determine whether they can be developed into drugs to simultaneously engage various AD targets in animal models of the disease.

Bioassay-guided fractionation of the ethanolic extract from the whole plants of Pteridium aquilinum has resulted in the isolation of a new pterosin glycoside, (‒)-pteroside N (1), and a new seco-illudoid sesquiterpene, pterosinone (2). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for the anti-Alzheimer disease (anti-AD) activity through enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). (‒)-Pteroside N (1) showed moderate BACE1 inhibitory activity (IC50 value: 30.6 μM), but exhibited potent inhibitory activity against AChE and BChE (IC50 values: 4.47 and 7.39 μM, respectively). On the other hand, pterosinone (2) showed mild AChE and BChE inhibitory activity (IC50 value: 87.7 and 72.9 μM), but exhibited potent inhibitory activity against BACE1 (IC50 value: 19.4 μM). The results of the present study demonstrate that sesquiterpenoids from P. aquilinum might be beneficial in the treatment of AD.

Cross-sectional transmission electron microscopy (TEM) was employed to study the effect of the additive oxygen gas on the microstructure of boron nitride (BN) films especially focusing on the intervening turbostratic BN (tBN) layer's behavior. Films in this study were deposited on diamond coated Si substrates, which were biased with negative voltages, using an unbalanced magnetron sputtering method with a boron carbide target. Various amounts of oxygen were added into argon‑nitrogen mixed sputtering gas. TEM showed that the tBN intervening layer was also observed to form prior to cubic BN (cBN) layer formation for all films, irrespective of oxygen addition. The tBN layer thickness increased with increasing oxygen content. This thickness increase implied that the addition of oxygen delayed cBN phase nucleation. On the other hand, the alignment of the hexagonal BN planes in the tBN layer, estimated from FTIR spectra, was observed to be enhanced with increasing oxygen content. Such alignment enhancement is considered as a result of oxygen adsorption on the tBN layer surface, which suppresses breaking sp2 bonds caused by Ar ion bombardments. The suppression of the sp2 bond breakage, consequently, causes the difficulty of forming sp3 bonds and delays the cBN phase nucleation.

Microalgae have gained considerable attention due to their high-value biomolecules and potential applications in the pharmaceutical, food, medical and cosmeceutical field. However, the conventional biorefinery process of microalgae are costly, energy-intensive, and time-consuming. Aqueous two-phase system (ATPS) has emerged as a potential technique for the separation and fractionation of biomolecules in the biorefinery field. This study proposed the application of ionic liquid (IL) based ATPS for the fractionation of high-value phycocyanin and carbohydrates from a crude extract of Spirulina platensis.The biomass was first lysed by a high-speed homogenization with a solid to liquid ratio (S/L) of 1:10 and an operation time of 5 min to achieve optimum yields of multiple products. Next, the feasibility of several IL-based ATPS with phosphate/citrate buffer was evaluated by investigating the effects of cation, anion, and alkyl chain’s length of ILs. Among the IL-based ATPS, the system comprising of 1-butyl-1-methylpyrrolidinium dicyanamide and citrate buffer demonstrated the optimum phycocyanin extraction efficiency of 83.26 ± 0.05% at the top phase and a concurrent recovery of 73.89±0.06% carbohydrate at the bottom phase. In this work, the IL-based ATPS performed better than conventional polymer-based ATPS. This work suggests that IL-based ATPS allows efficient fractionation of phycocyanin and carbohydrates.

Oxygen partial pressure at the boundary between external oxidation layer and steel matrix was determined by characterisation of internal oxidation in Si-containing low-carbon steels oxidised under atmospheric condition. The oxygen partial pressure calculated from the rate equation of the internal oxidation matches with the equilibrium value between Fe and FeO. From the oxygen partial pressure between external oxidation layer and steel matrix, the evolution of internal oxidation zone and the diffusion profile of solute Si were numerically simulated. The calculated depth of internal oxidation and solute Si profile accords to the measured ones from the EPMA, which implies that the numerical simulation captures reasonably the evolution of the internal oxidation in the Si-containing steels.

Background Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research. Objectives To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects. Methods The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM). Results Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin. Conclusions This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.

Coix lachryma-jobi L. var. ma-yuen has been a source of food and traditional folk medicine in some parts of Asia for thousands of years; however, the roots of this plant have not been phytochemically investigated. Herein, we report the isolation of a new benzoxazinoid glycoside, coixlachryside B (1), along with ten known compounds (2–11), from the roots of C. lachryma-jobi var. ma-yuen using a variety of chromatographic methods. Among the known compounds, the absolute configuration of compound 4 was determined. The structures of all compounds were elucidated by interpreting NMR spectroscopic data, and experimental and calculated electronic circular dichroism spectra.

Objective Organophosphate poisoning is a serious clinical entity and of considerable morbidity and mortality. Several factors have been identified to predict outcomes of organophosphate poisoning. This investigation aims to identify the relationship between the dynamics of serum cholinesterase (SChE) activity and mortality. Methods In this retrospective study, medical records of all patients with acute organophosphate poisoning were reviewed from January 2001 to December 2009. Clinical features, SChE activity, Glasgow Coma Scale, laboratory findings, electrocardiogram finding, management and their outcomes were examined. Results A total of 169 patients were included in this study. A total of 55 patients were enrolled. Deceased patients were 8 in number. Absence of an increase in SChE activity was related with mortality in organophosphate poisoned patients (p value=0.036; odds ratio, 5.445; 95% confidence interval, 1.121-26.551). Conclusions The absence of an increase in SChE activity is associated with higher mortality in organophosphate poisoning. The SChE dynamic activity can provide a guide to physicians in the evaluation and management of organophosphate poisoned patients.

We report for the first time the direct conversion of raw grape berry biomass to hydroxymethylfurfural (HMF) using ionic liquid solvents with metal chloride catalysts. Exploiting raw plant biomass as a biorefinery feedstock is innovative for sustainable chemical industry. The use of the raw biomass to synthesize compounds can indeed lead to less energy consumption and less CO2 emissions. Using raw plant biomass skips pretreatment steps that are required to produce biomaterials such as carbohydrates or cellulosic biomass. Here, grape berry biomass was used as a raw chemical feedstock for the production of hydroxymethylfurfural, a key platform intermediate for syntheses of future renewable biofuels. We examined 3 ionic liquid solvents, 3 reaction temperatures, 5 chloride catalysts, and 5 concentrations of HCl. We found an increasing HMF yields depending on reaction conditions. 1-octyl-3-methylimidazolium chloride was most effective for HMF synthesis. Addition of HCl or metal chlorides alone showed little improvement. The highest HMF yield of about 100 mg HMF per mL of grape biomass extract was obtained using 0.3 M HCl, [OMIM]Cl, and CrCl2 at 100°C for 3 h. Our study provides a model system of sustainable production of valuable compounds from raw plant biomass.

The whole body concentration ratio (CR) of 137 Cs, 85 Sr and 65 Zn for Chinese minnow (P. oxycephalus ) and earthworm (E. andrei ) were experimentally measured in a laboratory. The mean CR (Bq/kg fresh per Bq/l) of Chinese minnow was 3.5 for 137 Cs, 11.0 for 85 Sr, and 9.8 for 65 Zn, respectively. The mean CR (Bq/kg fresh per Bq/kg) of earthworm was 4.4 × 10−4 for 137 Cs, 1.7 × 10−3 for 85 Sr, and 1.4 × 10−3 for 65 Zn, respectively.

Oltipraz is a potential candidate drug for the treatment of liver fibrosis (LF) and liver cirrhosis (LC). The pharmacokinetics of oltipraz and its major rearranged metabolite (7-methyl-6,8-bis(methylthio)H-pyrrolo[1,2-a]pyrazine (RM)) were evaluated after single-dose (30-90 mg) and multiple-dose (60 mg b.i.d. or 90 mg q.d. for 24 weeks) oral administration of oltipraz to patients with LF or LC. Oltipraz was safe and well tolerated in both studies. In the single-dose study, the area under the plasma concentration-time curve (AUC), peak plasma concentration (C(max)), and terminal half-life (t(1/2)) of oltipraz as well as the AUC of its RM were dose dependent. Oltipraz was rapidly absorbed; the time to reach C(max) (T(max)) was 2-4 h. The conversion of oltipraz to RM was also rapid and substantial (AUC of RM from time 0 to the last measured concentration (AUC(last, RM))/AUC(last, oltipraz), 42-61%). In the multiple-dose study, the level of transforming growth factor-beta1 (TGF-beta1) (a blood fibrosis marker) was suppressed at steady-state plasma concentrations of approximately 20-60 ng/ml of oltipraz or of approximately 60-140 ng/ml of oltipraz plus RM. Overall, the pharmacokinetics, safety, and efficacy of oltipraz suggest that it may be helpful in the treatment of patients with LF or LC, at an optimal dosing regimen.

In this study, 2 myofibrillar protein extraction methods were compared for the preparation of chicken surimi using spent hen breast muscle. One method involved 1 washing with 0.1, 0.5, or 1% sodium chloride solution followed by 2 washings with distilled water, with homogenization and centrifugation of the breast muscle after each washing (new method; NM). The other method used only distilled water for the extraction, and washing was repeated 3 times followed by homogenization and centrifugation of the breast muscle after each washing (conventional method; CM). The redness values of the batter as well as the cooked gel were significantly lower (P ≤ 0.05) by NM as compared with CM. In addition, the SDS-PAGE of NM sarcoplasmic protein fractions showed phosphorylase bands with increased staining intensity as compared with CM, indicating that brightness was related to the sarcoplasmic protein fractions. Overall, the data implied that sodium chloride solution was more appropriate for the myofibrillar protein extraction of spent hen breast muscle than the commonly used distilled water method.

L ab o rtyfA n im l Nu ,G d eS ch B g sU vABSTRACT This work was conducted to evaluate the effects of induced-molting methods on visceral organs and blood stress indicators in laying hens. One hundred fifty of 63-wk-old White Leghorn hens, with over 85% of egg production and 1.7±0.4 kg of average weight, were used in this study. Treatments were control (non-molt treatment), feeding molt treatment (FM), and starving molt treatment (SM). There were 5 replicates of 10 hens for each treatment. All treatment groups were fed basal diet (15% CP and 2,700 kal/kg of ME) for two weeks as adaptation period. Heart weights were 8.2, 7.9 and 7.5 g in control, FM and SM, respectively. Liver and oviduct weights were decreased in both molting treatments compared with control (P

The effect of phytohormones on the breaking of dormancy of axillary buds in Salix pseudolasiogyne and their subsequent proliferation from nodal explants were examined. Nodal explants obtained from a 20–year-old S. pseudolasiogyne tree were cultured either on woody plant basal medium (WPM) or WPM supplemented with benzyladenine (BA, 2.2/4.4 μM), zeatin (1.1/2.2 μM), gibberillic acid (GA3, 2.9 and 14.5 μM), and GA3 + BA (2.9 + 4.4 μM). Although axillary shoots developed in all the media, a higher percentage bud break occurred on BA supplemented media. To corroborate the results, endogenous levels of cytokinins [Cks, N 6-isopentenyladenine (iP), zeatin riboside (t-ZR), dihydrozeatinriboside (DHZR)] and abscisic acid (ABA) were determined. On BA supplemented media, the levels of zeatin type (Z-type) of Cks were higher than those of isopentenyladenine type of Ck in the explants, while the ABA level was low. Axillary shoots did not grow well and became necrotic upon subculture to fresh basal WPM. In order to improve shoot growth, they were subcultured twice at a 4-week interval on to WPM supplemented with BA (2.2/4.4 μM), GA3 (1.4 μM), or GA3 + BA (1.4 + 4.4/2.9 + 4.4 μM). Maximal shoot growth (93%) was achieved on WPM supplemented with 2.2 μM BA. Comparative analyses of endogenous Cks revealed that higher Cks (Z-type Cks) were present in actively growing shoots. Rooting was readily achieved when the shoots were subcultured to WPM without phytohormones. The rooted plants were acclimatized well upon transplantation.

Purpose: To investigate the mechanism by which pinitol inhibits tumor necrosis factor-α (TNF-α)- induced expression of matrix metalloproteinase-9 (MMP-9) and invasion of prostate cancer LNCaP cells. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) together with Western blot analysis was used to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, in TNF-α- treated LNCaP cells, while 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and DNA fragmentation were used to evaluate cell viability and apoptosis. MMP-9 activity and invasion were measured by gelatin zymography and matrigel invasion assay, respectively. DNA-binding activity of NF-κB and AP-1 was determined by electrophoretic mobility shift assay and luciferase activity. Results: MMP-9 activity significantly increased in response to TNF-α; however, pinitol reduced TNF-α- induced MMP-9 activity without cytotoxicity. Matrigel invasion assay showed that pinitol reduced TNF-α-induced invasion of prostate cancer LNCaP cells. Further, it downregulated the expression of MMP-9 gene induced by TNF-α-treatment. Pinitol suppressed TNF-α-induced NF-κB activity by suppressing nuclear translocation of the NF-κB subunits, p65 and p50. Conclusion: The results indicate that pinitol is a potential anti-invasive agent and acts by suppressing TNF-α-induced cancer cell invasion and specifically inhibiting NF-κB as well as downstream target genes such as MMP-9.

Takagi, T., Choi, Y-H., Tachibana, T., Denbow, D.M. and Furuse, M. 2005. Effect of intracerebroventricular injection of L-pipecolic acid on GABA concentrations in brain sites of neonatal chicks. J. Appl. Anim. Res., 28: 9–13. L-pipecolic acid (L-PA) is a major metabolic intermediate of L-lysine in the mammalian and chicken brain, which enhances y-amino butyric acid (GABA) release and inhibits GABA re-uptake. Our previous study showed that intracerebroventricular (i.c.v.) injection of L-PA suppressed feeding and induced sleep-like behavior in neonatal chicks. These behaviors which are associated with the GABA system, suggest a link between L-PA and GABA. The present study was designed to determine GABA concentrations in several chick brain sites after i.c.v. injection of L-PA. Unexpectedly, L-PA tended to decrease GABA concentrations in all brain sites tested except for the pons-medulla oblongata and the decrease was largest in the optic lobe. These results, taken together with previous findings, ...

High energy neutron radiation causes the embrittlement of reactor pressure vessel (RPV) materials. Magnetic parameter changes were measured by ferromagnetic resonance (FMR) and impedance spectroscopy for steel surveillance specimens of a Mn-Mo-Ni low alloy high copper weld which were irradiated for 5.08 and 15.49 effective full power years in a commercial light water reactor (LWR), respectively. Their dose levels were in the range of 1.23 x 10 19 to 3.94 × 10 19 n/cm 2 . The resonance field of FMR signal increased as the neutron dose is increased. Linewidth (ΔH) increased predominantly in the neutron irradiation. In the complex susceptibility spectra, the initial permeability decreased and the relaxation frequency of the permeability μ shifted to higher frequencies with an increase of the dose levels. Both magnetic methods show consistent results with each other for the assessment of radiation embrittlement.

A trial was conducted to investigate the effects of dietary energy levels and β-mannanase supplementation on egg production performance, nutrient retention and blood metabolites of laying hens. Hy-Line Brown layers (n=240, 68 wk-old) were randomly allotted to 6 treatments on the basis of laying performance. Each treatment had 8 replicates with 5 birds. Laying hens were fed three energy levels (2650, 2750 and 2850 kcal/kg) and 0 and 0.4 g β-mannanase/kg diet in a 2×3 factorial arrangement for 56d. Laying hens fed diets supplemented with β-mannanase or high energy (2750 and 2850 kcal) had greater overall egg production. Addition with either high energy diet or β-mannanase improved the egg mass in the second production phase as well as overall egg mass. Feed intake was decreased in laying hens fed the highest (2850 kcal) dietary energy level. Moreover, laying hens fed the highest energy diets had a greater feed conversion ratio. Laying hens fed diets with β-mannanase had greater retention of DM, GE and CP than hens fed diets without β-mannanase. Retention of mannose was greater in laying hens fed diets supplemented with β-mannanase or high energy diets. The results obtained indicate that a high energy content in diets had positive effect on the performance of laying hens and that dietary supplementation with β-mannanase has the potential to improve laying hen performance and nutrient retention.

Interception, loss and translocation of 85 Sr, 103 Ru and 134 Cs in rice plants were investigated through a greenhouse experiment in which the whole aboveground plant parts were exposed to radioactive spray at 6 different growth stages. Showing little difference among radionuclides, the interception factor tended to increase as the plant grew to maturity. The highest observed factor was 0.94. The fractions of the intercepted activity that remained in rice plants at harvest were 0.19~0.42 for 85 Sr, 0.23~0.62 for 103 Ru and 0.11~0.69 for 134 Cs, depending on application times. The translocation factors for hulled seeds were in the range of 5.8x10-4 ~3.2x10-2 for 85 Sr, 1.6x10-4 ~7.6x10-3 for 103 Ru and 3.2x10-2 ~2.0x10-1 for 134 Cs indicating the highest mobility of 134 Cs. The greatest translocation factor of every radionuclide came when plants were contaminated at the active seed growth stage. It was indicated that weathering loss and translocation would not greatly depend on the rain frequency if it differs by a factor of less than 2. Based on the experimental results, the concentrations of 85 Sr, 90 Sr, 103 Ru, 106 Ru, 134 Cs and, 137 Cs in hulled rice seeds at harvest were estimated for their deposition at different growth stages.

Bungo, T., Choi, Y.-H. and Furuse, M. 2001. Chronic inhibition of the sympathetic nervous system with guanethidine: Effects on body and organ weights and food intake of chicks given a phenylalanine excess diet. J. Appl. Anim. Res., 19: 97–106. To investigate the effect of chronic inhibition of the sympathetic nervous system on food intake in the chicken, guanethidine (GTD, 0 or 50 mg/kg body weight/d), an adrenergic blocker, was subcutaneously administered to chicks for 4 weeks starting at 10 days of age in experiment 1. Chronic GTD decreased body weight gain and brain weight, but not heart and adrenal gland weights. In the second experiment, effects of chronic GTD and dietary excess phenylalanine (Phe) on daily food, intake were investigated at one week interval for 4 weeks. At each week, food intake was determined at 1, 2, 4, 6, 12 and 24 h after feeding. Significant dietary effects of excess Phe were found at several times in every week, but chronic GTD administration did not alter intake of P...

Bungo. T., Choi. Y.-H., Shimojo, M., Masuda. Y., Denbow, D.M. and Furuse, M. 2000. A nitric oxide synthase inhibitor attenuates neuropeptide Y- and clonidine- induced feeding in the neonatal chick. J. Appl. Anim. Res., 17: 257–264. It is reported that inhibition of nitric oxide (NO) synthase (NOS) decreased food intake in mammalian and avian species. On the other hand, central administration of α2-agonists stimulated, food, intake in both species. Similarly, neuropeptide Y (NPY) has the orcxigenic effect mediated by α2 receptors. The present study was done to determine whether central injection of NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, in the neonatal chick modulates the increase in food intake induced by NPY- and clonidine (CLON, a specific α2-agonist)-induced food intake. Both NPY (2.5 μg)- and CLON (50 ng)-induced food intake of neonatal chicks was significantly attenuated by co-administration with the higher doses of L-NAME (0, 0.2, 0.4 and 0.8 mg). Our results suggest th...

To clarify the relationship between neuropeptide Y (NPY) and the α2-adrenergic system on ingestive behavior of the young chick, NPY receptor and α2-adrenoceptor were stimulated by intracerebroventricular injection of NPY and clonidine (CLON), α2-receptor agonist, respectively. Central injection of NPY (1, 2.5 or 5μg) significantly increased food intake in a dose-dependent manner in Experiment 1. No additive or synergistic effect was observed when NPY (1μg) and CLON (50ng) were co-administered. However, a significant interaction between NPY (2.5μg) and CLON (50ng) was observed in food intake, implying that an enhanced food intake by NPY was attenuated by co-injection with CLON. These results indicate that α2-adrenoceptors and NPY may interact and regulate food intake within the central nervous system in the young chick, depending their concentrations.

Proteolysis of hemoglobin provides an essential nutrient source for the malaria parasite Plasmodium falciparum during the intraerythrocytic stage of the parasite's lifecycle. Detoxification of the liberated heme occurs through a unique heme polymerization pathway, leading to the formation of hemozoin. Heme polymerization has been demonstrated in the presence of P. falciparum histidine-rich protein 2 (PfHRP2) [Sullivan, D. J., Gluzman, I. Y., and Goldberg, D. E. (1996) Science 271, 219-221]; however, the molecular role that PfHRP2 plays in this polymerization is currently unknown. PfHRP2 is a 30 kDa protein composed of several His-His-Ala-His-His-Ala-Ala-Asp repeats and is present in the parasite food vacuole, the site of hemoglobin degradation and heme polymerization. We found that, at pH 7.0, PfHRP2 forms a saturable complex with heme, with a PfHRP2 to heme stoichiometry of 1:50. Spectroscopic characterization of heme binding by electronic absorption, resonance Raman, and EPR has shown that bound hemes share remarkably similar heme environments as >95% of all bound hemes are six-coordinate, low-spin, and bis-histidyl ligated. The PfHRP2-ferric heme complex at pH 5.5 (pH of the food vacuole) has the same heme spin state and coordination as observed at pH 7.0; however, polymerization occurs as heme saturation is approached. Therefore, formation of a PfHRP2-heme complex appears to be a requisite step in the formation of hemozoin.

To clarify noradrenergic systems on food intake of the neonatal chicks, we examined the effects of i.c.v injection of clonidine (CLON), an alpha2-receptor agonist, and fusaric (5-butylpicolinic) acid (FA), a dopamine (DA)-beta-hydroxylase (DBH) inhibitor. Although a high dose (250 ng) of CLON induced a narcoleptic response and reduced food intake, food intake at 30 min post-injection was enhanced by lower doses (25 and 50 ng) of CLON. Central administration of FA (25, 50 and 100 microg) increased food intake in a dose-dependent fashion. It is suggested that feeding behavior is stimulated by low levels of CLON and decreased by further production of norepinephrine (NE), and FA may play the disturbance of sleeping and then enhance food intake.

The present study was done to determine whether i.c.v, injection of morphine, or kyotorphin (KTP), an endogenous [Met5]-enkephalin-releasing dipeptide in mammals, increases feeding behavior in the neonatal chick. Food intake was significantly suppressed by intracerebroventricular (i.c.v.) administration of morphine with a narcoleptic response. However, i.c.v. administration of KTP at the levels of 2.5-50μg failed to alter food intake of chicks compared with the saline control over 2hr. It is suggested that KTP may not affect endogenous opioids release in the brain of neonatal chicks.

Methionine synthase catalyzes the transfer of a methyl group from methylcobalamin enzyme to homocysteine, generating methionine and cob(I)alamin enzyme, and then from methyltetrahydrofolate to cob(I)alamin enzyme, generating tetrahydrofolate and regenerating the methylcobalamin enzyme. The reactions catalyzed by methionine synthase require deprotonation of the substrate, homocysteine, and protonation of the product tetrahydrofolate, with no net change in proton stoichiometry for a complete turnover cycle. In addition, formation of the intermediate cob(I)alamin enzyme requires a change in the cobalt ligand geometry from 6-coordinate to 4-coordinate, and this rearrangement may require the transient protonation of protein residues to stabilize the cob(I)alamin enzyme. In the E. coli enzyme, the lower face of the methylcobalamin cofactor is coordinated by histidine 759, which is hydrogen bonded to aspartate 757 and then to serine 810, forming a "ligand triad". It has previously been shown that reduction of cob(II)alamin enzyme to cob(I)alamin is associated with the uptake of a proton from solution, and it has been postulated that this proton resides within the His759-Asp757 pair. Cob(I)alamin can also be generated by demethylation of methylcobalamin enzyme by homocysteine; it was not known whether this mode of cob(I)alamin formation was associated with proton uptake. In this paper, we use equilibrium titrations and kinetic analyses in the presence of the pH indicator dye phenol red, along with studies of the pH dependence of oxidation/reduction equilibria, to identify and characterize mechanistic steps associated with proton uptake and release in both the turnover and reactivation of the enzyme. We confirm that cob(I)alamin formation by reduction of cob(II)alamin enzyme is associated with proton uptake and show that mutation of Asp757 to Glu abolishes the pH dependence of this reduction. Demethylation of methylcobalamin enzyme also leads to cob(I)alamin formation and is also shown to be associated with proton uptake. By observing pre-steady-state reactions with homocysteine and methyltetrahydrofolate in the presence of phenol red, we show that this proton uptake occurs at a rate that is equal to the rate of formation of the cob(I)alamin enzyme. In addition, we show that binding of homocysteine to the enzyme results in the rapid release of a proton, presumably the homocysteine thiol proton. In contrast, binding methyltetrahydrofolate to the enzyme does not result in proton uptake, suggesting that the proton destined for the product tetrahydrofolate is already present on the free methylcobalamin enzyme.

In order to investigate whether food intake suppression elicited by inhibition of nitric oxide (NO) synthase (NOS) is affected by dietary levels of L-arginine (Arg), chicks (one week old) were prefect either an Arg-deficient (AD), Arg-moderate deficient (AM), Arg-standard (AS) or Arg-excess (AE) diet for 3 days. Birds were then intraperitoneally administered NG-nitro-L-arginine methyl ester HCl (L-NAME), a NOS inhibitor, or saline and given the same diet used during the prefeeding stage. Food intake was reduced by L-NAME over 2 h after feeding, compared to the saline control group, and the relative suppressive effect of L-NAME increased as dietary Arg levels decreased.

We have reported that both central and peripheral administrations of an inhibitor of nitric oxide (NO) synthase (NOS) decrease food intake in the chicken. This fact leads to a hypothesis that NO stimulates food intake in the chicken. The present study was done to clarify the involvement of peripheral NO in food consumption. L-arginine (Arg), a NOS substrate, was orally or intraperitoneally administered to chicks in fasting or refeeding condition. Food intake was suppressed or not altered by Arg administration. Though an NO donor, sodium nitroprusside (SNP), and a NOS cofactor, tetrahydrobiopterin (H4B), were also intraperitoneally administered to chicks, any significant changes were observed.These results suggested that peripheral NO above physiological levels was not an important factor in the regulation of food intake in the chicken.

Two new polyhydroxylated macrolides, seimatopolides A (1) and B (2), were isolated from an EtOAc extract of Seimatosporium discosioides culture medium. The structures of the new compounds were established on the basis of spectroscopic analysis, including 1D and 2D NMR, and their absolute configurations were determined using the modified Mosher's method. Seimatopolides A (1) and B (2) activated peroxisome proliferator-activated receptor (PPAR)-γ with EC(50) values of 1.15 and 11.05 μM, respectively. The expression of PPAR-γ target genes in HepG2 hepatocytes was significantly altered; in particular, expression of the gluconeogenic genes glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was reduced upon stimulation with 1, supporting the proposal that compound 1 is both a PPAR-γ agonist and a possible therapeutic candidate for treatment of diabetes.

A new synthetic route to highly substituted cyclobutenones is reported. This involves the 1,6-addition of both heteroatom- and carbon-based nucleophiles to 4,4-dimethoxy-3-ethenyl-2-methyl-cyclobuten-1-one (8) to give further functionalized cyclobutenedione monoketals. These ketals function as precursors to quinones as illustrated by the synthesis of the natural benzofuranosesquiterpene 23

InSb epitaxial layers have been grown on GaAs substrates by low‐pressure metalorganic chemical vapor deposition. A 3.15‐μm‐thick film yielded an x‐ray full width at half maximum of 171 arcsec. A Hall mobility of 76 200 cm2/V s at 240 K and a full width at half maximum of 174 arcsec have been measured for a 4.85‐μm‐thick epilayer. Measured Hall data have shown anomalous behavior. A decrease in Hall mobility with decreasing temperature has been observed and room‐temperature Hall mobility has increased with thickness. In order to explain the anomalous Hall data, and the thickness dependence of the measured parameters, the Hall coefficient and Hall mobility have been simulated using a three‐layer model including a surface layer, a bulklike layer, and an interface layer with a high density of defects. Theoretical analysis has shown that anomalous behavior can be attributed to donorlike defects caused by the large lattice mismatch and to a surface layer which dominates the transport in the material at low temperatures.

A new synthetic route to highly substituted cyclobutenones is reported. This involves the 1,6-addition of both heteroatom- and carbon-based nucleophiles to 4,4-dimethoxy-3-ethenyl-2-methyl-cyclobuten-1-one (8) to give further functionalized cyclobutenedione monoketals. These ketals function as precursors to quinones as illustrated by the synthesis of the natural benzofuranosesquiterpene 23

A new flavonoid, 7-demethylageconyflavone A (1), and five known compounds, tricin (2), ageconyflavone A (3), corylin (4), nectandrin B (5), and 4-ketopinoresinol (6) were isolated from the aerial parts of Eragrostis ferruginea. Their structures were determined using spectroscopic techniques, including 1D- and 2D-NMR. All compounds were tested for the neuroprotective effects against amyloid beta peptide (Abeta) using PC12 cells, a major cause of the pathology of Alzheimer's disease. Tricin (2) was found to have a neuroprotective effect with an ED(50) value of 20.3 microM against Abeta-induced toxicity in PC12 cells. Ageconyflavone A (3), nectandrin B (5) and 4-ketopinoresinol (6) demonstrated moderate neuroprotective effects with ED(50) values of 58.7, 44.1, and 54.8 microM, respectively.

Scoparone is known to have a wide range of pharmacological properties in vitro. However, the roles of scoparone in immediate-type allergic reactions have not yet been investigated. In this study, we demonstrated that scoparone attenuated IgE-mediated allergic response in mast cells. Oral administration of scoparone inhibited passive cutaneous anaphylaxis in rats. Presence of scoparone dose-dependently decreased histamine release from rat peritoneal mast cells (RPMC) stimulated by anti-dinitrophenyl IgE. Moreover, scoparone reduced the expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in RPMC. Pretreatment with scoparone inhibited the calcium uptake and p38 mitogen-activated protein kinase (MAPK) activity. Furthermore, scoparone blocked translocation of nuclear factor-kappa B (NF-kappaB) p65 subunit by suppressing IkappaBalpha phosphorylation in RPMC. Reduced calcium uptake as well as the suppressed activity of p38 MAPK and NF-kappaB might be involved in the inhibitory effect of scoparone on the secretory response. Our findings suggest that scoparone may serve as an effective therapeutic agent for allergic diseases.

Immersed membrane systems, and those with in-line coagulation, have been extensively applied in drinking water systems. Sedimentation is usually replaced by membrane processes in both systems. In these systems, voluminous flocculent aggregates formed during coagulation could be potential foulants. When raw waters with high turbidity are introduced, particle loadings to membrane due to coagulation pretreatment are enormous and thus could increase fouling. In general, during the rainy season, the turbidity of the Han River water, which supplies drinking water for the City of Seoul, Korea, is more than a hundred times higher than usual. Therefore, effects of floc on membrane fouling were investigated with highly turbid waters. Two turbidity concentrations, 40 and 200 NTU, were formulated by the addition of kaolin (used as a natural particle surrogate) to the Han River raw water. The results showed that the flux decline behaviours of the highly turbid waters were different from those of natural raw water. Coagulation pretreatment was very effective at reducing membrane fouling. Flocculent aggregates showed a negative effect on the flux decline, but a positive effect on the membrane cleaning efficiency.

Melatonin is involved in a variety of biological functions including sleep and stress. Our previous study indicated that neonatal layer chicks were more susceptible to stress than broilers. However, it is not clear whether differences exist in melatonin concentrations between both types of chickens, nor is it known whether melatonin is directly involved in stress in neonatal chickens. In the present study we first compared melatonin concentrations in brain tissues (pineal gland, brain stem, telencephalon, and optic lobe) between neonatal broiler and layer chicks raised under either 12 h light:12 h dark cycle (lights on at 07:00 h) or continuous illumination. Although melatonin concentrations were much higher in broilers than layers at night under the alternative light-dark cycle, these differences disappeared under the 24 h illumination. We thus chose neonatal layers for a test system. We then investigated if intracerebroventricular (ICV) injection of melatonin modulated plasma corticosterone concentrations under continuous illumination. Neonatal layer chicks housed in groups were ICV injected (1) with melatonin (0, 0.116 and 1.16 microg) or with nothing as an intact control followed by isolation in an open-field environment for 10 min; and (2) were given one of the followings treatments: nothing (intact control), control (0 microg), corticotropin-releasing factor (CRF) (0.01 microg), melatonin (1.16 microg), or CRF (0.01 microg) + melatonin (1.16 microg). Ten minutes thereafter blood was collected via heart puncture to determine plasma corticosterone content. Isolation resulted in a significant increase in corticosterone concentration, and both doses of ICV melatonin completely suppressed this increase (P

The present study compared the plasma corticosterone concentrations between meat- and layer-type neonatal chicks (Gallus gallus) (1) exposed to isolation-induced stress or (2) injected intracerebroventricularly (ICV) with corticotropin-releasing factor (CRF). Both types of neonatal chicks housed in groups were individually introduced to an open field arena and locomotion and distress-induced vocalizations were monitored for 10 min. The responses of the two strains were remarkably different, with meat-type chicks being less active than layer-type chicks. Distress-induced vocalizations were drastically decreased over time in meat-type chicks while they remained high in layer-type chicks throughout the test. Plasma corticosterone concentrations measured at the end of the test were significantly higher in layer-type chicks than in meat-type ones. Plasma corticosterone concentrations measured 10 min after the ICV injection of CRF were significantly higher in layer- than meat-type chicks. These results indicate that meat-type chicks have either a greater capability to acclimatize to novel environments, or a blunted HPA axis compared with layer-type chicks.

The effect of sodium nitroprusside (SNP), a spontaneous NO releaser, on the forward passage of the crop contents of chicks receiving a diet containing medium chain triacylglycerol (MCT) was studied, because dietary MCT or inhibition of NO production delayed the crop emptying of chicks. MCT diets containing graded levels (0, 0.01, 0.1 and 1%) of SNP were given to chicks by gavage. Crop emptying rate was significantly delayed as dietary SNP increased, which suggested that the effect of dietary MCT on the crop emptying might not be associated with NOS inhibition.

The authors report the relationship between the water tree retardation phenomena and the mechanical properties in ethylene vinyl acetate (EVA) blended XLPE (cross-linked polyethylene). They also studied the electrical properties, such as the dissipation factor and the AC breakdown strength. It has been found that, by blending with EVA, growth of water trees in XLPE is retarded considerably and the toughness corresponding to the stress-crack resistance of materials increases with the VA content of blended samples. The results obtained indicate that the mechanical properties of the polymer have a strong influence on the water tree growth and that the material properties of XLPE can be improved substantially by EVA blending. >

Optical properties of InTlSb, a new long wavelength infrared material, are investigated. InTlSb/InSb epilayers grown by low‐pressure metal‐organic chemical vapor deposition on semi‐insulating GaAs substrates were characterized using Auger electron spectroscopy and Fourier transform infrared spectroscopy. Auger electron spectra confirm the presence of thallium. Transmission measurements at 77 K indicate an absorption shift from 5.5 μm for InSb up to 8 μm for InTlSb that is confirmed by photoconductivity measurements.

The erythrocytic growth stage of Plasmodium falciparum involves hemoglobin proteolysis as the primary nutrient source with the concomitant release of free heme. The liberated heme is processed by the parasite into hemozoin, a polymeric porphyrin dimer. Histidine-rich protein binds heme and mediates the formation of hemozoin, which is inhibited by the antimalarial drug chloroquine. Interference with heme binding was determined using a microtiterplate assay. Combinatorial libraries were screened and tested against parasite growth, revealing a good correlation between heme binding interference and the inhibition of parasite growth. Several of these compounds retain their potency against a chloroquine-resistant strain of Plasmodium falciparum . The most potent compounds have IC 50 values less than or equal to 50 nM against chloroquine-resistant and chloroquine-sensitive parasites.

We have measured the temperature and magnetic field dependence of the Hall mobility and transverse magnetoresistance in n‐type InSb films epitaxially grown on GaAs substrates by metalorganic chemical vapor deposition. The films show a giant magnetoresistance: e.g., at 240 K the resistivity increases over 20 times at a magnetic field of 5 T; the low field coefficient of resistivity at 77 K is as high as 47.5 μΩ cm/G. The Hall mobility decreases with magnetic field and saturates at higher fields. By taking the interface carrier transport into account, the observed field dependence of the Hall mobility and magnetoresistance may be understood based on a two‐layer model.

We report the growth of In1−xTlxSb, a new III‐V alloy for long‐wavelength infrared detector applications, by low‐pressure metalorganic chemical vapor deposition. In1−xTlxSb with good surface morphology was obtained on both GaAs and InSb substrates at a growth temperature of 455 °C. X‐ray diffraction measurements showed resolved peaks of In1−xTlxSb and InSb films. Infrared absorption spectrum of In1−xTlxSb showed a shift toward lower energies compared to InSb spectrum. Hall mobility data on In1−xTlxSb/InSb/GaAs structure showed enhanced mobility at low temperatures compared to InSb/GaAs structure.

Introduction: Insulin receptor substrate 1 (IRS1) is one of the major mediators of IGF signals . Recently, we have reported that L6 myoblasts stably expressing IRS1 (L6-IRS1) were not able to differentiate into myotubes . We have also shown that constitutive Foxo1 nuclear exclusion is one of the reasons why this stable line could not differentiate . The present study was undertaken to elucidate alternative molecular mechanisms underlying the inhibition of myogenesis by constitutive IRS1 expression . Method and results: At first, cell numbers were counted during proliferation in L6-GFP control cells or L6-IRS1 cells . Before confluence, we did not detect any differences between these two cell lines . However, even after reaching confluence L6-GFP control cells could continue to proliferate and cell number increased, whereas L6-IRS1 cells did not proliferate further and cell number decreased instead . In addition, after induction of differentiation, cell density gradually increased in control cells, whereas cell density decreased in L6-IRS1 cells . In order to test the migrating activity, L6-GFP cells or L6-IRS1 cells were overlaid on L6-mock cell monolayer . L6-GFP cells migrated into the confluent cell monolayer, but L6-IRS1 cells did not . Next, the mixture of L6-GFP cells and L6-IRS1 cells at a ratio of 1:9 were cultured for 8 days . Two days later, only 20% of cells were control cells, but control cells occupied more than 70% of cell monolayer 8 days later . In addition, immunofluorescent analyses revealed that L6-IRS1 cells surrounded by control cells showed condensed nuclei and cleaved Caspase3 expression, indicating that L6-IRS1 cells underwent apoptosis . These data indicated that constitutive expression of IRS-1 causes cell competition . Conclusion: Taken together we hypothesized that during differentiation, cells compete with each other and that cells highly expressing IRS-1 undergo apoptosis . IRS-1 constitutive expression causes this cellular competition, leading to defective in myogenic differentiation .

One possible mechanism by which food consumption signals feeding centers is through the resulting changes in amino acid profiles in the brain. In this study we examined the effect of voluntary consumption of a 50% protein diet or a 0% protein (carbohydrate) diet on extracellular amino acid profiles in the hypothalamic paraventricular nucleus (PVN) of freely moving rats from 1800 to 2100 h. Dialysates were continuously collected via microdialysis probes inserted in the PVN at 1500 h. Extracellular concentrations of isoleucine, leucine, methionine, tyrosine and valine were elevated within the first or second 20 min following the start of the 50% protein diet (P

The effect of dietary medium chain triglyceride (MCT) on shortterm food intake was compared with the effect of long chain triglyceride (LCT) in rats. Corn oil and glyceryl tricaprylate were used as LCT and MCT sources, respectively. Rats were given diets containing 200 g MCT/kg diet (MCT diet), 100 g MCT + 100 g LCT/kg diet (ML diet), or 200 g LCT/kg diet (LCT diet) in Experiment 1. Cumulative food intake was determined every h for the first 12 h, then at 2-h intervals thereafter during the subsequent 12 h. As early as 1 h after feeding, cumulative food intake significantly decreased in MCT-fed animals in a dose-dependent fashion. In Experiment 2, rats were given a choice between MCT and LCT diets for 1 h to confirm whether or not the palatability of diets was influenced by dietary fat sources. There was no difference in food intake between the two diets. In Experiment 3, the responsibility of endogenous cholecytokinin (CCK) for the difference in food intake between the two diets was investigated for 6 h by using a CCK-A receptor antagonist, Devazepide (DVZ, 1 mg/kg b. wt.). Food intake in the MCT diet and also in the LCT diet was improved by DVZ. It is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceride sources, although the responsibility of endogenous CCK is very small.