Behavioral analysis of the effects of long-term treatment with L-ornithine in mice

L-ornithine has recently received considerable attention as an anxiolytic-like or antifatigue agent in both human and animal studies. However, most previous results were obtained from a single administration of L-ornithine. Accordingly, this study was designed to clarify the effects of long-term L-ornithine treatment on psychological stress and locomotor activity in mice using a variety of behavioral pharmacology methods. In a stress-induced hyperthermia test, 10 days of L-ornithine treatment induced hyperthermia elevation. Pentobarbital-induced sleep time was shortened by the treatment. However, no significant effects were detected in the elevated plus-maze, running wheel, or forced swim tests. These results suggest that long-term treatment with L-ornithine elevates stress sensitivity and arousal level in mice

α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression

α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis

BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes

The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes

Background: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. Purpose: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. Methods: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). Results: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. Conclusions: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research

Biotin levels in blood and follicular fluid

It has been shown that biotin, a water-soluble vitamin (B7), plays roles in reproductive functions, such as oocyte maturation and embryo development, in experimental animals. On the other hand, little is known about the clinical effects of biotin on human reproduction. In this study, serum and follicular fluid biotin levels were measured in patients who underwent in vitro fertilization / intracytoplasmic sperm injection (IVF / ICSI), and their associations with reproductive outcomes were evaluated. As a result, biotin was detected in follicular fluid, as well as serum, and the biotin levels of follicular fluid were found to be positively correlated with those of serum. The biotin levels of serum were higher than those of follicular fluid, suggesting that biotin may be taken up into the follicular fluid from the blood. Although serum and follicular fluid biotin levels tended to be higher in pregnant patients than in non-pregnant patients, these data did not show the significant statistical difference. These findings indicate that biotin does not contribute to the maintenance of oocyte quality, and hence, it does not increase fertilization and pregnancy rates

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan

IntroductionFatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs.Materials and methodsThis trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires).ResultsThe frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed.ConclusionIn this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations

Life Cycle Replacement by Gene Introduction under an Allee Effect in Periodical Cicadas

Periodical cicadas (Magicicada spp.) in the USA are divided into three species groups (-decim, -cassini, -decula) of similar but distinct morphology and behavior. Each group contains at least one species with a 17-year life cycle and one with a 13-year cycle; each species is most closely related to one with the other cycle. One explanation for the apparent polyphyly of 13- and 17-year life cycles is that populations switch between the two cycles. Using a numerical model, we test the general feasibility of life cycle switching by the introduction of alleles for one cycle into populations of the other cycle. Our results suggest that fitness reductions at low population densities of mating individuals (the Allee effect) could play a role in life cycle switching. In our model, if the 13-year cycle is genetically dominant, a 17-year cycle population will switch to a 13-year cycle given the introduction of a few 13-year cycle alleles under a moderate Allee effect. We also show that under a weak Allee effect, different year-classes (“broods”) with 17-year life cycles can be generated. Remarkably, the outcomes of our models depend only on the dominance relationships of the cycle alleles, irrespective of any fitness advantages