Establishment of an experimental ferret ocular hypertension model for the analysis of central visual pathway damage

Glaucoma optic neuropathy (GON) is a condition where pathogenic intraocular pressure (IOP) results in axonal damage following retinal ganglion cell (RGC) death, and further results in secondary damage of the lateral geniculate nucleus (LGN). Therapeutic targets for glaucoma thus focus on both the LGN and RGC. However, the temporal and spatial patterns of degeneration and the mechanism of LGN damage have not been fully elucidated. Suitable and convenient ocular hypertension (OH) animal models with binocular vision comparable to that of monkeys are strongly needed. The ferret is relatively small mammal with binocular vision like humans - here we report on its suitability for investigating LGN. We developed a new method to elevate IOP by injection of cultured conjunctival cells into the anterior chamber to obstruct aqueous outflow. Histologically, cultured conjunctival cells successfully proliferated to occlude the angle, and IOP was elevated for 13 weeks after injection. Macroscopically, the size of the eye gradually expanded. Subsequent enlargement of optic nerve head cupping and atrophic damage of LGN projected from the OH eye were clearly observed by anterograde staining with cholera toxin B. We believe the ferret may be a promising OH model to investigate secondary degeneration of central nervous system including LGN

Identification of glycosylation genes and glycosylated amino acids of flagellin in Pseudomonas syringae pv. tabaci

A glycosylation island is a genetic region required for glycosylation. The glycosylation island of flagellin in Pseudomonas syringae pv. tabaci 6605 consists of three orfs: orf1, orf2 and orf3. Orf1 and orf2 encode putative glycosyltransferases, and their deletion mutants, Delta orf1 and Delta orf2, exhibit deficient flagellin glycosylation or produce partially glycosylated flagellin respectively. Digestion of glycosylated flagellin from wild-type bacteria and non-glycosylated flagellin from Delta orf1 mutant using aspartic N-peptidase and subsequent HPLC analysis revealed candidate glycosylated amino acids. By generation of site-directed Ser/Ala-substituted mutants, all glycosylated amino acid residues were identified at positions 143, 164, 176, 183, 193 and 201. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) analysis revealed that each glycan was about 540 Da. While all glycosylation-defective mutants retained swimming ability, swarming ability was reduced in the Delta orf1, Delta orf2 and Ser/Ala-substituted mutants. All glycosylation mutants were also found to be impaired in the ability to adhere to a polystyrene surface and in the ability to cause disease in tobacco. Based on the predicted tertiary structure of flagellin, S176 and S183 are expected to be located on most external surface of the flagellum. Thus the effect of Ala-substitution of these serines is stronger than that of other serines. These results suggest that glycosylation of flagellin in P. syringae pv. tabaci 6605 is required for bacterial virulence. It is also possible that glycosylation of flagellin may mask elicitor function of flagellin molecule

Cognitive behavior therapy for autistic adolescents, awareness and care for my autistic traits program: a multicenter randomized controlled trial

BACKGROUND: Autistic people demonstrate focused interests, sensitivity to sensory stimulation, and, compared with the general population, differences in social communication and interaction. We examined whether a combination of the Awareness and Care for My Autistic Traits (ACAT) program and treatment-as-usual is more effective than only treatment-as-usual in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among autistic adolescents and their parents/guardians. METHODS: Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and treatment-as-usual or only treatment-as-usual. The combined group received six weekly 100-minute ACAT sessions, while the treatment-as-usual group received no additional intervention. The primary outcome was the change in understanding of autistic attributes (Autism Knowledge Quiz-Child), administered from pre- to post-intervention. The secondary outcomes included the change in Autism Knowledge Quiz-Parent, reduced treatment stigma, and improved mental health and social adaptation among autistic adolescents and their parents/guardians. A primary outcome measure scale was scored by assessors who were blind to the group assignment. RESULTS: The combined group (both autistic adolescents and their parents/guardians) showed an increase in Autism Knowledge Quiz scores compared to those in the treatment-as-usual group. Autistic adolescents in the combined group also demonstrated a decrease in treatment-related stigma and an improvement in general mental health compared to those in the treatment-as-usual group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, general mental health, adaptive skills, or attitudes toward their children. CONCLUSIONS: The ACAT program could be an effective treatment modality to increase the understanding of autistic attributes among both autistic adolescents and their parents/guardians. The ACAT program positively affects self-understanding, reduces treatment stigma, and stabilizes behavioral issues for autistic adolescents as a part of mental health measures, but it does not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial. TRIAL REGISTRATION: The study was registered in UMIN (UMIN000029851, 06/01/2018)

Development of a Multifunctional Lightweight Membrane with a High Specific Power Generation Capacity

As a lighter power generation system, Japan Aerospace Exploration Agency (JAXA) and Sakase Adtech Corp. are developing a demonstrator component named “Harvesting Energy with Lightweight Integrated Origami Structure” (HELIOS), which is a deployable lightweight membrane structure. HELIOS has solar arrays on its surface and demonstrates the technology which enables higher specific power generation capacity compared to the conventional solar array panels. The membrane also has communication antennas, showing the potency of lightweight membrane’s multifunctionality such as large data transmitting by 5G antennas and high-resolution observation by interferometer antennas. This paper presents the component’s concept and design, and the expected achievements

Low compression ratio diesel engines fueled with biodiesel by using spark-induced compression ignition

The objective of this study is to demonstrate a novel combustion system in which auto-ignition is induced by spark discharge into a pre-mixture formed during a long ignition delay time at a direct injection(DI) diesel engine with a low compression ratio. An experiment is conducted to investigate the potential of spark discharge on the auto-ignition process by changing the spark timing, injection timing, equivalence ratio, and fuel amount. The fuel used is lauric methyl ester, which is a fatty acid methyl ester that has relatively higher volatility and higher ignition quality than petro diesel fuel. The results obtained by single cylinder common-rail DI diesel engine show that with a volumetric efficiency of 34%, spark-induced compression ignition (SICI) combustion is observed. In this study, the auto-ignition timing is advanced by spark discharge and is controlled by the spark timing within 5 deg. CA. We also observed SICI combustion flame by constant volume combustion vessel using direct flame high-speed photography and OH radical chemiluminescence spectroscopy by means of the combination of an optical band-pass filter, an image intensifier and CCD camera. As a result, it was found that SICI occurs not by flame propagation due to spark ignition but by auto-ignition of pre-mixture formed by spray. It was also clear that the auto-ignition is induced by transportation of OH radical at spark plug with spray flow

前立腺癌のLH-RHアゴニストによる治療における, ホスフェストロール及びクロルマジノンによるフレアー現象の抑制効果について

未治療前立腺癌患者を無作為に3群に分けた.ホスフェストロール300mg/day(N=17), クロルマジノン100mg/day(N=16), 無治療(N=16)をLH-RHアゴニスト初回投与の2週間前より開始した.LH, テストステロン, PSA値を定期的に測定した.ホスフェストロール, クロルマジノンの前投与によりPSAは早期に低下した.テストステロンの平均値はホスフェストロール, クロルマジノンの前投与群で, アゴニスト投与後も治療前の値を越えることはなく, PSA平均値も前投与群ではアゴニスト投与後も有意の上昇を認めなかった.一方, 前投与を行わなかった群では初回のアゴニスト投与により一過性にテストステロン及びPSA平均値は治療前値よりも上昇した.以上の結果よりホスフェストロール300mg/day, クロルマジノン100mg/dayの2週間前投与は, 初回LH-RHアゴニスト投与後のフレアー現象に対し極めて有用であるTo determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer

Novel oral SPT inhibitor CH5169356 inhibits hepatic stellate cell activation and ameliorates hepatic fibrosis in mouse models of non‐alcoholic steatohepatitis (NASH)

Abstract Ceramide is a central molecule of sphingolipid metabolism and is involved in the development of non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). It has already been reported that the inhibition of serine palmitoyltransferase (SPT), the rate‐limiting enzyme in the sphingolipid biosynthetic pathway, has an inhibitory effect on hepatic lipidosis, but its effect on severe hepatic fibrosis is not clear. In this study, we examined whether a SPT inhibitor could suppress the activation of hepatic stellate cells (HSC) and ameliorate the progression of NASH. Effects on sphingolipid metabolism and HSC activation marker genes by NA808, a SPT inhibitor, were evaluated in an immortalized HSC cell line (E14C12). NA808 decreased sphingolipid synthesis and the expression of α‐smooth muscle actin (α‐SMA) and collagen 1A1 mRNA in HSC. We identified a novel oral SPT inhibitor, CH5169356, which is a prodrug of NA808. CH5169356 was administered in the Ath+HF model, a NASH mouse model with liver fibrosis induced by atherogenic and high‐fat content diets. CH5169356 showed a significant decrease in the expression of α‐SMA and collagen 1A1 mRNA in the liver and an inhibition of liver fibrosis progression. CH5169356 was also evaluated in a Stelic animal model (STAM), a NASH mouse model induced through a different mechanism than that of the Ath+HF model, and showed a significant anti‐fibrotic effect. In conclusion, CH5169356 could inhibit the progression of hepatic fibrosis in the pathogenesis of NASH by suppressing HSC activation, suggesting that CH5169356 would be a potential oral NASH therapeutic agent