神経誘導因子Netrin-1は軟骨形成や骨形成においてBMPまたはNogginにより調節される

This is the first report describing neurogenic factor of Netrin-1 related to chondrogenesis or osteogenesis in a human cells. Netrin is a morphogenetic factor that induces a growth cone of an axial filament of the nervous system. However, the roles of Netrin in chondrogenesis or osteogenesis are not yet understood. We analyzed the relationship between Netrin and bone morphogenetic protein-2 (BMP-2) in chondrogenesis or osteogenesis, using a human chondrocyte-like cell line (USAC), which also retains multi-potency to differentiate into osteoblasts and adipocytes. Netrin-1 mRNA was decreased in USAC cells, though the expression was increased during osteogenic differentiation at the stage when osteocalcin mRNA were increased by BMP-2. Furthermore, inhibition of Netrin-1 gene increased Cbfa1 mRNA expression, and decreased Sox9 mRNA expression. We also found that Netrin-1was strongly expressed in immature chondrocytes of cartilage-like tissues that were formed in an exo vivo experiment with diffusion chambers. The se findings indicate that Netrin-1 and BMP-2 regulates in the stage dependent process of mesenchymal cell differentiation to chondrocytes or osteoblasts.骨芽細胞または脂肪細胞への分化多能を保持するヒト軟骨細胞様細胞系(USAC)を用い、軟骨形成または骨形成におけるNetrinと骨形成蛋白質-2(BMP-2)との関係を調べた。Netrin-1 mRNAはUSAC細胞中では減少するが、オステオカルシンmRNA濃度がBMPによって上昇する際の骨芽細胞分化時にNetrin-1 mRNAの発現が増加した。Netrin-1遺伝子を阻害すると、Cbfal mRNA発現は増加しSox9 mRNA発現は減少した。またNetrin-1は軟骨様組織の未成熟軟骨細胞において強く発現した。Netrin-1とBMP-2が、間葉細胞の軟骨細胞または骨芽細胞へ分化プロセスを制御すると考えた

A Cardiac Rhabdomyoma in a Guinea Pig

A guinea pig (9-week-old) that had been placed in a control group for a pharmacological test was found to have a single nodule on the surface of the right ventricular wall. In a transverse section of the heart after fixation, a whitish mass was found that extended from the subendocardium to the subepicardium of the right ventricular wall. Histopathological examination revealed a spongy network consisting of vacuolated spaces in the myocardium of the right ventricle extending to the myocardium and subepicardium of the right atrium. The vacuolated space was PAS-positive. Immunohistochemical examinations revealed that the lesions contained striated fibers that were positive for anti-desmin and anti-myoglobin. Electron micrographs revealed the lesions resulting in affected striated muscle fibers and accumulations of many glycogen granules. Based on the findings, the lesions were diagnosed as a cardiac rhabdomyoma. This is the first report of application of immunohistochemical examinations to diagnosis of cardiac rhabdomyoma in the guinea pig

Nutrient intake if matsumoto dental university students -analysis using BDHQ-

A brief diet history questionnaire was issued to first–year Japanese students (１8–29 years old) at the School of Dentistry of Matsumoto Dental University to determine their nutrient and food intakes for future nutrition education programs. The subjects of this study were １96 people (１38 males, 58 females). １) The contribution of protein, particularly of plant origin, to energy intake was significantly higher in female than in male students. 2) Compared with men, women had significantly higher intakes (weight per １,000 kcal) of minerals (sodium, potassium, calcium, magnesium, phosphorus, iron, and copper), fat–soluble vitamins (β–carotene equivalents and vitamin E [ α–tocopherol]), water–soluble vitamins (B １ , B 2 , B 6 , folic acid, pantothenic acid, and C), cholesterol, and fiber. 3) In terms of food–group intake (weight per １,000 kcal), a significantly higher intake in men than in women was only observed for grains. Consistent with the energy and nutrient intakes, dietary intakes of legumes, dark–colored vegetables, other (light–colored) vegetables, fruits, and sweets/snacks were significantly higher in women. In this survey, differences in nutrient and food intakes were noted in male and female students. In general, it was shown that female students eat a more varied and nutrient–richer diet

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson’s disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding

Improvement of Propylene Epoxidation Caused by Silver Plasmon Excitation by UV-LED Irradiation on a Sodium-Modified Silver Catalyst Supported on Strontium Carbonate

The effect that UV-LED irradiation exerted on a sodium-modified silver catalyst supported on strontium carbonate (Ag-Na/SrCO3) was examined during an epoxidation of propylene to propylene oxide. Based on our previous study, we used Ag(56)-Na(1)/SrCO3 in this study. The numbers in parentheses refer to the weight percentage of silver and sodium. Although this catalyst system did not contain typical photocatalysts such as titanium oxide or tungsten oxide, UV-LED irradiation of Ag(56)-Na(1)/SrCO3 resulted in an evident improvement in the selectivity and yield of propylene oxide. Such an advantageous effect of UV-LED irradiation could not be discussed based on the bandgap used in photocatalysts and, therefore, we proposed a mechanism based on the plasmon excitation of silver, which could be accomplished using the irradiation wavelength of UV-LED to produce electrons. Since the lifespan of these electrons is expected to be short, it is difficult to place them into direct contact with the gas phase of oxygen. Once the generated electrons move to SrCO3, however, the lifespan is improved, which could allow suitable contact with oxygen in the gas phase to form active oxygen. If the oxygen is active for epoxidation as hydrogen peroxide, this could explain the improvement in activity from UV-LED irradiation

Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription

A method for the isolation of genomic fragments of RNA virus based on cDNA representational difference analysis (cDNA RDA) was developed. cDNA RDA has been applied for the subtraction of poly(A)(+) RNAs but not for poly(A)(−) RNAs, such as RNA virus genomes, owing to the vast quantity of ribosomal RNAs. We constructed primers for inefficient reverse transcription of ribosomal sequences based on the distribution analysis of hexanucleotide patterns in ribosomal RNA. The analysis revealed that distributions of hexanucleotide patterns in ribosomal RNA and virus genome were different. We constructed 96 hexanucleotides (non-ribosomal hexanucleotides) and used them as mixed primers for reverse transcription of cDNA RDA. A synchronous analysis of hexanucleotide patterns in known viral sequences showed that all the known genomic-size viral sequences include non-ribosomal hexanucleotides. In a model experiment, when non-ribosomal hexanucleotides were used as primers, in vitro transcribed plasmid RNA was efficiently reverse transcribed when compared with ribosomal RNA of rat cells. Using non-ribosomal primers, the cDNA fragments of severe acute respiratory syndrome coronavirus and bovine parainfluenza virus 3 were efficiently amplified by subtracting the cDNA amplicons derived from uninfected cells from those that were derived from virus-infected cells. The results suggest that cDNA RDA with non-ribosomal primers can be used for species-independent detection of viruses, including new viruses

Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)­(2,4′-bipyridin-3-yl)­methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies

Full-Length Transcriptome Analysis of Human Retina-Derived Cell Lines ARPE-19 and Y79 Using the Vector-Capping Method

PURPOSE. To collect an entire set of full-length cDNA clones derived from human retina-derived cell lines and to identify full-length transcripts for retinal preferentially expressed genes. METHODS. The full-length cDNA libraries were constructed from a retinoblastoma cell line, Y79, and a retinal pigment epithelium cell line, ARPE-19, using the vector-capping method, which generates a genuine full-length cDNA. By single-pass sequencing of the 5Ј-end of cDNA clones and subsequent mapping to the human genome, the authors determined their transcriptional start sites and annotated the cDNA clones. RESULTS. Of the 23,616 clones isolated from Y79-derived cDNA libraries, 19,229 full-length cDNA clones were identified and classified into 4808 genes, including genes of Ͼ10 kbp. Of the 7067 genes obtained from the Y79 and ARPE-19 libraries, the authors selected 72 genes that were preferentially expressed in the eye, of which 131 clones corresponding to 57 genes were fully sequenced. As a result, we discovered many variants that were produced by different transcriptional start sites, alternative splicing, and alternative polyadenylation. CONCLUSIONS. The bias-free, full-length cDNA libraries constructed using the vector-capping method were shown to be useful for collecting an entire set of full-length cDNA clones for these retinal cell lines. Full-length transcriptome analysis of these cDNA libraries revealed that there were, unexpectedly, many transcript variants for each gene, indicating that obtaining the full-length cDNA for each variant is indispensable for analyzing its function. The full-length cDNA clones (approximately 80,000 clones each for ARPE-19 and Y79) will be useful as a resource for investigating the human retina. (Invest Ophthalmol Vis Sci. 2011;52:6662-6670