Apricot carotenoids possess potent anti-amyloidogenic activity in vitro

Alzheimer's disease (AD) is the most common form of dementia and is characterized by the progressive accumulation of amyloid β protein (Aβ) in areas of the brain. There has been an increased interest in screening for food-grade anti-amyloidogenic compounds in foodstuffs. The purpose of this study was to screen and identify bioactive compounds with anti-amyloidogenicity in apricot fruits using synthetic Aβ(1-42). The anti-amyloidogenicity was investigated using thioflavin T fluorescence assay, electron microscopy, and dot blotting analysis. The carotenoid fraction from apricot showed strong inhibitory effects against oligomer and fibril formation of Aβ and fibril-destabilizing effects. Among the peaks in the HPLC chromatogram, lutein showed the strongest inhibitory effect on Aβ fibril formation. The inhibitory effect was dependent on the number and portion of hydroxyl groups on both sides of carotenoids. These findings suggest that lutein in fruits may be useful as a preventive agent for amyloid-associated diseases.     

The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

Xylazine, the classical α₂‐adrenoceptor (α₂‐AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for α₂‐ARs. Previous pharmacological studies suggested that the α_2A‐AR subtype plays a role in mediating the clinical effects of xylazine; however, these studies were hampered by the poor subtype‐selectivity of the antagonists used and a lack of knowledge of their bioavailability in vivo. Here, we attempted to elucidate the role of the α_2A‐AR subtype in mediating the clinical effects of xylazine by comparing the analgesic and sedative effects of this drug in wild‐type mice with those in α_2A‐AR functional knockout mice using the hot‐plate and open field tests, respectively. Hippocampal noradrenaline turnover in both mice was also measured to evaluate the contribution of α_2A‐AR subtype to the inhibitory effect of xylazine on presynaptic noradrenaline release. In wild‐type mice, xylazine (10 or 30 mg/kg) increased the hot‐plate latency. Furthermore, xylazine (3 or 10 mg/kg) inhibited the open field locomotor activity and decreased hippocampal noradrenaline turnover. By contrast, all of these effects were abolished in α_2A‐AR functional knockout mice. These results indicate that the α_2A‐AR subtype is mainly responsible for the clinical effects of xylazine.     

恒温高温调节对赤点石斑鱼幼鱼的生长、性腺发育以及gnrh、fshβ和lhβ基因表达的影响

为了解恒定高温对赤点石斑鱼(Epinephelus akaara)生长和繁殖的影响, 以孵化后120~420 日龄的幼鱼为研究对象, 对性腺发育以及与繁殖相关的基因gnrh、fshβ和lhβ表达进行了研究。对照组为自然水温(13.2~27.1 ℃)饲养, 实验组为26 ℃恒温饲养。每隔30 d或40 d采样1次, 比较两组中鱼的体长、体重、性腺指数(GSI)、性腺发育情况以及gnrh、fshβ和lhβ基因表达的差异。结果表明, 从240日龄开始, 实验组鱼的体长和体重均显著高于对照组(P<0.05)。实验结束时, 实验组体长约为对照组的1.3倍, 体重约为对照组的2倍。对照组GSI一直维持在0.25%以下的低值, 实验组GSI在330日龄前处于0.4%以下, 但在360日龄时出现GSI 1%以上的个体。在360、390和420日龄的个体中, 实验组GSI显著高于对照组(P<0.05)。实验结束时, 对照组中未检测到具有卵黄形成期卵母细胞的个体, 但实验组在330、360和390日龄出现了具有卵黄成熟期卵母细胞的个体。对照组和实验组间幼鱼脑中gnrh基因表达在各年龄段均无显著性差异(P>0.05), 但脑垂体中fshβ表达在360、390和420日龄, lhβ在390和420日龄时, 实验组均显著高于对照组(P<0.05)。研究表明, 26 ℃恒温调节不仅能促进赤点石斑鱼幼鱼体长、体重和GSI的增加, 同时也能显著提高脑垂体中fshβ和lhβ基因含量, 从而加速性腺发育成熟。     

RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation

Facultative heterochromatin that changes during cellular differentiation coordinates regulated gene expression, but its assembly is poorly understood. Here, we describe facultative heterochromatin islands in fission yeast and show that their formation at meiotic genes requires factors that eliminate meiotic messenger RNAs (mRNAs) during vegetative growth. Blocking production of meiotic mRNA or loss of RNA elimination factors, including Mmi1 and Red1 proteins, abolishes heterochromatin islands. RNA elimination machinery is enriched at meiotic loci and interacts with Clr4/SUV39h, a methyltransferase involved in heterochromatin assembly. Heterochromatin islands disassemble in response to nutritional signals that induce sexual differentiation. This process involves the antisilencing factor Epe1, the loss of which causes dramatic increase in heterochromatic loci. Our analyses uncover unexpected regulatory roles for mRNA-processing factors that assemble dynamic heterochromatin to modulate gene expression.     

Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia

Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats. Follicular cell adenomas were found in 5 out of 9 rats with thyroid dysplasia and in 7 out of 105 rats without thyroid dysplasia. The incidence of adenoma was significantly increased in rats with thyroid dysplasia (55.6%) compared with that in rats without thyroid dysplasia (6.7%). Adenomas in rats with thyroid dysplasia were observed as single or multiple nodules, well demarcated and composed of variously sized vacuolated cells or unvacuolated cells. These histopathological features and staining profiles of luminal colloid for PAS and thyroglobulin, together with PCNA-positive cells, were fundamentally similar to those of rats without thyroid dysplasia. On the other hand, the luminal colloid in adenomas of rats with thyroid dysplasia had a tendency to be poorly stained for T(4) compared with that of rats without thyroid dysplasia. From these findings, it appears that dysplastic thyroids of rats showing normal growth are more sensitive to carcinogens than normal thyroids. In addition, the morphological features of carcinogen-induced thyroid proliferative lesions in GALAS rats with thyroid dysplasia were fundamentally similar to those of rats without thyroid dysplasia, except for the vacuoles and T(4) staining profile.     

Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives

Chemoreceptor cells aggregating in clusters in the chicken thoracic aorta contain 5-hydroxytryptamine (5-HT) and have voltage-dependent ion channels and nicotinic acetylcholine receptors, which are characteristics typically associated with neurons. The aim of the present study was to investigate the effects of 5-HT uptake inhibitors, fluvoxamine, fluoxetine and clomipramine (CLM), and amphetamine derivatives, p-chloroamphetamine (PCA) and methamphetamine (MET), on endogenous 5-HT outflow from the isolated chick thoracic aorta in vitro. 5-HT was measured by using a HPLC system with electrochemical detection. The amphetamine derivatives and 5-HT uptake inhibitors caused concentration-dependent increases in endogenous 5-HT outflow. PCA was about ten times more effective in eliciting 5-HT outflow than MET. The 5-HT uptake inhibitors examined had similar potency for 5-HT outflow. PCA and CLM increased 5-HT outflow in a temperature-dependent manner. The outflow of 5-HT induced by PCA or 5-HT uptake inhibitors was independent of extracellular Ca²⁺ concentration. The 5-HT outflow induced by CLM, but not that by PCA, was dependent on the extracellular NaCl concentration. These results suggest that the 5-HT uptake system of 5-HT-containing chemoreceptor cells in the chicken thoracic aorta has characteristics similar to those of 5-HT-containing neurons in the mammalian central nervous system (CNS).     

Toxicological pathology in the rat placenta

The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.     

Molecular epidemiology of VapA-positive Rhodococcus equi in thoroughbred horses in Kagoshima,Japan

The prevalence of virulent R. equi having 15- to 17-kDa antigens (VapA) in fecal isolates from 13 thoroughbred foals and their dams on 5 farms in Kagoshima, Japan, and the plasmid profiles of VapA-positive isolates by restriction fragment digestion patterns were investigated to compare the genotypic variation among virulence plasmids of R. equi isolates from Japan. In total, 218 (24.6%) of 886 isolates from the feces of the 13 foals and 13 (12.5%) of 104 isolates from the feces of their dams demonstrated VapA-positive R. equi. Plasmid DNA preparations of 231 virulent isolates from foals and dams were analyzed by restriction enzyme digestion with endonucleases EcoRI, EcoT22I and HindIII and were divided into 3 types: 172 isolates contained a 90-kb type I plasmid, 57 contained a 90-kb type III plasmid and 2 contained a 90-kb type IV plasmid. This study demonstrates a geographic character in the distribution of virulence plasmids found in VapA-positive isolates from thoroughbred foals in Kagoshima.     

Origin of host-specificity resistance genes of common wheat against non-adapted pathotypes of Pyricularia oryzae inferred from D-genome diversity in synthetic hexaploid wheat lines

Journal of General Plant Pathology - Wheat resistance genes Rwt3 and Rwt4 constitute a host-specificity barrier against non-wheat pathotypes of the blast fungus, Pyricularia oryzae. To understand...