Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight‐week‐old dogs

The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8‐week‐old Beagle dogs. Thirty‐two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28‐day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14‐day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham‐dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day ‐14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment‐related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.     

Three AFLP markers tightly linked to the genic male sterility <Emphasis Type="Italic">ms</Emphasis><Subscript><Emphasis Type="Italic">3</Emphasis></Subscript> gene in chili pepper (<Emphasis Type="Italic">Capsicum annuum</Emphasis> L.) and conversion to a CAPS marker

Genic male sterility (GMS) has long been used as a tool for hybrid seed production in chili pepper (Capsicum annuum L.). We developed DNA markers linked to the GMS ms ₃ gene in a segregating population using bulked segregant analysis (BSA) and amplified fragment length polymorphism (AFLP) techniques. The segregating population was subjected to BSA-AFLP with 512 primer combinations. Three AFLP markers (Eagg/Mccc₂₇₆, Eagc/Mctt₁₇₈, and Ecag/Mtgc₂₀₄) were identified as tightly linked to the ms ₃ locus. Among them, we converted the AFLP marker Ecag/Mtgc₂₀₄ to the cleavage amplified polymorphic sequence (CAPS) marker, named GMS3-CAPS, based on sequencing analysis of internal and flanking regions for the markers between male-fertile and sterile plants. This marker will be useful for pepper breeding using the GMS system.     

Allosteric supramolecular triple-layer catalysts

Allosteric regulation of organometallic catalysts could allow for greater control over reactions. We report an allosteric supramolecular structure in which a monometallic catalytic site has been buried in the middle layer of a triple-layer complex. Small molecules and elemental anions can open and close this complex and reversibly expose and conceal the catalytic center. The ring-opening polymerization of ε-caprolactone can be turned on by the in situ opening of the triple-layer complex and then completely turned off by reforming it through the abstraction of Cl(-), the allosteric effector agent, without appreciable loss of catalytic activity. This process can regulate the molecular weights of the resulting polymers.     

64-Channel multi-detector row CT angiographic evaluation of the micropigs for potential living donor lung transplantation

Micropigs are the most likely source animals for xenotransplantation. However, an appropriate method for evaluating the lung of micropigs had not been established. Therefore, this study was performed to evaluate the feasibility of 64-channel multi-detector row computed tomography (MDCT) to measure the diameter of the pulmonary arteries and the lung volume in micropigs. The mean diameters of the trachea, and left and right bronchi were 1.6 ± 0.17, 1.18 ± 0.14, and 1.1 ± 0.11 cm, respectively. The mean diameters of the main, right, and left pulmonary arteries were 1.38 ± 0.09, 1.07 ± 0.26, and 0.98 ± 0.13 cm and the diameters of right, left, and common inferior pulmonary veins were 0.97 ± 0.20, 0.76 ± 0.20, and 1.99 ± 0.26 cm, respectively. The mean lung volume was 820.3 ± 77.11 mL. The data presented in this study suggest that the MDCT may be a noninvasive, rapid, and accurate investigational method for pulmonary anatomy in living lung donors.     

Effect of silicon on growth and salinity stress of soybean plant grown under hydroponic system

Silicon (Si) is abundant in the soil, yet its role in plant biology has been poorly understood. The role of Si in soybean growth and its effectiveness in salt stress alleviation was investigated. Sodium metasilicate (Na₂SiO₃) was given as Si source to hydroponically grown soybean (Glycine max (L.) Merr.). The plant growth attributes, i.e. plant height, plant fresh and dry biomass, chlorophyll contents and endogenous gibberellins (GAs) level improved with 2.5 mM Si, while endogenous abscisic acid (ABA) and free proline contents were not affected as compared to control. Sodium chloride (NaCl) significantly decreased growth attributes and endogenous gibberellins levels but markedly enhanced ABA and proline contents of soybean leaves. An addition of Si to salt stressed plants substantially alleviated the adverse effects of NaCl on growth, as it enhanced endogenous gibberellins, while reduced the levels of ABA and proline. GAs analysis of soybean leaves also showed that both early C13 hydroxylation and non C13 hydroxylation pathways of gibberellin biosynthesis were operating in soybean. The major GA biosynthesis pathway was identified as non C13 hydroxylation, which led to the formation of bioactive GA₄. Current study suggests that Si application alleviates the detrimental effect of salinity stress on growth and development of soybean.     

Effect of hydrogen peroxide exposures on mucous cells and lysozymes of gill tissues of olive flounder Paralichthys olivaeceus

We investigated the effects of hydrogen peroxide on mucous cells and lysozymes in gill tissue of olive flounder. Morphological analysis revealed significant changes in the number of mucous cells after exposure to 300 and 500 mg L ^{? 1} hydrogen peroxide; however, there was no detectable difference in the 100 mg L ^{? 1} group. Lysozyme activities declined gradually in the gill mucus, but in contrast activities in serum increased significantly following the completion of treatment. The hepatic c‐ and g‐type lysozyme levels showed significant responses, indicating that the liver is a major lysozyme producer in response to stress condition; however, in the head kidney, there were no significant changes in the g‐type lysozyme level in all the groups, while the only detectable difference with the c‐type gene in the 300 mg L ^{? 1}. While the treatments showed no significant changes compared with the control for either branchial lysozyme, there were significant differences in c‐type lysozyme between the 3rd treatment and 5 day. Taken together, our data indicate that hydrogen peroxide treatment may lead to modulation of the innate immune response of olive flounder; therefore, the application of hydrogen peroxide in a field system will require more attention to dose and timing effects.     

Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood pressure elevation in spontaneously hypertensive rats by affecting the Akt-dependent phosphorylation of endothelial nitric oxide synthase

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a fundamental regulator of systemic blood pressure. Ginsenosides from Panax ginseng have been investigated in vitro for the molecular and biochemical mechanisms by which they stimulate NO release in vascular endothelial cells; however, little research has been done to confirm the physiological relevance of these in vitro studies. To address this research gap, the effects of a P. ginseng extract rich in ginsenosides from protopanaxatriol on spontaneously hypertensive rats (SHRs) was examined. Ginseng extract administration stimulated nongenomic Akt-mediated eNOS activation, enhanced NO production, improved vessel wall thickening, and alleviated hypertension in SHRs, confirming the physiological relevance of previous in vitro studies with ginsenosides.     

Bowman-Birk and Kunitz Protease Inhibitors among Antinutrients and Bioactives Modified by Germination and Hydrolysis in Brazilian Soybean Cultivar BRS 133

Soybean contains constituents that have antinutritional and bioactive properties. Enzymatic hydrolysis and germination can enhance the biological activity of these compounds in soybean. The objective of this study was to investigate the effect of germination, Alcalase (protease) hydrolysis, and their combination on the concentrations of antinutritional and bioactive compounds in Brazilian soybean cultivar BRS 133. A combination of germination and Alcalase hydrolysis resulted in the degradation of Bowman-Birk inhibitor (BBI), Kunitz trypsin inhibitor (KTI), and lunasin by 96.9, 97.8, and 38.4%. Lectin was not affected by any of the processing treatments when compared to nongerminated and nonhydrolyzed soy protein extract. Total isoflavones (ISF) and total saponins (SAP) increased by 16.2 and 28.7%, respectively, after 18 h of germination, while Alcalase hydrolysis led to the reduction of these compounds. A significant correlation was found between concentrations of BBI and KTI, BBI and lunasin, BBI and ISF, KTI and lunasin, KTI and ISF, KTI and SAP, lunasin and ISF, and ISF and SAP. Germination and Alcalase hydrolysis interacted in reducing BBI, ISF, and SAP. This study presents a process of preparing soy flour ingredients with lower concentrations of antinutritional factors and with biologically active constituents, important for the promotion of health associated with soybean consumption. In conclusion, 18 h of germination and 3 h of Alcalase hydrolysis is recommended for elimination of protease inhibitors, while bioactives are maintained by at least 50% of their original concentrations.     

Different response of silicate fertilizer having electron acceptors on methane emission in rice paddy soil under green manuring

Cultivation of green manure plants during the fallow season in rice paddy soil has been strongly recommended to improve soil properties. However, green manuring may impact greenhouse gas emission, methane (hereafter, CH₄) in particular, under the flooded rice cultivation and thus, application of chemical amendments being electron acceptors can be an effective mitigation strategy to reduce CH₄ emissions in irrigated rice (Oryza sativa L.) field amended with green manure. To investigate the effect of iron (Fe) slag silicate fertilizer (hereafter, silicate fertilizer), which was effective in reducing CH₄ emission and increasing rice productivity, in green manure-amended paddy soil, the aboveground biomass of Chinese milk vetch (hereafter, vetch) was added at rates of 0, 10, 20, and 40 Mg (fresh weight) ha⁻¹ before the application of silicate fertilizer, which was added at rates of 0 and 2.3 Mg ha⁻¹. Silicate fertilization reduced the seasonal CH₄ flux by ca. 14.5% and increased rice yield by ca. 15.7% in the control (no vetch application) treatment. However, CH₄ production was increased by silicate fertilization in vetch-treated soil particularly at the initial rice growing stage, which was probably due to the enhanced decomposition of added organic matters by the silicate liming effect. In conclusion, silicate fertilization is not effective in reducing CH₄ production in green manure-amended rice paddy soils and its use should be properly controlled.     

Water quality and limnology of Korean reservoirs

Reservoirs are the predominant type of lentic ecosystem in Korea, and they account for a considerable proportion (~59%) of the agricultural water uses. There are 18,797 reservoirs in Korea; most (~90%) are small (storage capacity <1,000,000 m³), and most provide irrigation water for paddy farming. Characteristics of Korean agricultural reservoirs are high watershed-reservoir area ratios, shallow depth, unstable hydrodynamics, and eutrophic conditions. Many agricultural reservoirs are relatively old; 54% of all reservoirs were constructed more than 50 years ago. As a result, they have a considerable amount of organic matter accumulation on the sediment, which may contribute to the internal loading of nutrients. Deterioration of water quality and ecosystem health, resulting from cultural eutrophication and harmful algal blooms, are common problems in most Korean agricultural reservoirs. Environmental considerations about reservoirs, especially their ecological functions, have largely been ignored in past management plans. Limnology, the multidisciplinary study of lakes and reservoirs, can provide conceptual models of reservoirs and fundamental information needed to determine causes and potential solutions for environmental stresses. Problems prevailing in Korean reservoirs, such as cultural eutrophication and harmful algal blooms, are complicated ecosystem-level phenomena with many factors interacting with each other. Thus, limnological understanding is a prerequisite to identifying sound solutions and to making wise judgments about reservoir management and restoration. Cooperation with other related disciplines is necessary to establish the proper management plans and applications. Also, international cooperation is suggested to solve environmental problems in agricultural reservoirs, particularly among the countries with similar agricultural practices, climate, geology, and water uses. Electronic Publication