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The circadian clock controls daily rhythms of various physiological processes, and impairment of its function causes many diseases including sleep disorders. Chemical compounds that regulate clock function are expected to be applied for treatment of circadian clock-related diseases. We previously identified small-molecule compounds KL001, KL101 and TH301 that lengthen the period of cellular circadian clock by directly targeting clock proteins cryptochromes (CRYs) in mammals. KL001 targets both CRY1 and CRY2 isoforms, while KL101 and TH301 are isoform-selective compounds and require CRY C-terminal region for their effects. For further application of these compounds, the effects on locomotor activity rhythms at the organismal level need to be investigated. Here we used zebrafish larvae as an in vivo model system and found that KL001 lengthened the period of locomotor activity rhythms in a dose-dependent manner. In contrast, KL101 and TH301 showed no effect on the period. The amino acid sequences of CRY C-terminal regions are diverged in zebrafish and mammals, supporting the importance of this region for the effects of KL101 and TH301. This study demonstrated efficacy of CRY modulation for controlling circadian behavioural rhythms in organisms and suggested species-dependent differences in the effects of isoform-selective CRY-modulating compounds., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

In this study, we report on phase retrieval by the maximum likelihood method with conjugate gradient method (CG-MAL) using through-focus images in Lorentz transmission electron microscopy (LTEM). The method was evaluated using 32 simulated and experimentally obtained through-focus images of magnetic bubbles; these images were collected under a defocus range from approximately -3 mm to 3 mm. Consequently, we obtained the magnetic domain structures of the magnetic bubbles in both the simulation and the LTEM experiment. Furthermore, the CG-MAL method showed better convergence behavior than other iterative phase retrieval methods. Therefore, the method can also be widely and effectively applied to the observation of magnetic domain structures other than magnetic bubbles when highly defocused through-focus images are used.

TSH secreted from the pars distalis (PD) of the pituitary gland stimulates the thyroid gland. In contrast, TSH secreted from the pars tuberalis (PT) of the pituitary gland regulates seasonal reproduction. The ontogeny of thyrotrophs and the regulatory mechanisms of TSH are apparently different between the PD and the PT. Interestingly, fish do not have an anatomically distinct PT, and the saccus vasculosus (SV) of fish is suggested to act as a seasonal sensor. Thus, it is possible that the SV is analogous to the PT. Here we examined the ontogeny of the pituitary gland and SV using rainbow trout. A histological analysis demonstrated the development of the pituitary anlage followed by that of the SV. Lhx3 and Pit-1, which are required for the development of PD thyrotrophs, clearly labeled the pituitary anlage. The common glycoprotein α-subunit (CGA) and TSH β-subunit (TSHB) genes were also detected in the pituitary anlage. In contrast, none of these genes were detected in the SV anlage. We then performed a microarray analysis and identified parvalbumin (Pvalb) as a marker for SV development. Because Pvalb expression was not detected in the pituitary anlage, no relationship was observed between the development of the SV and the pituitary gland. In contrast to embryos, Lhx3, Pit-1, CGA, and TSHB were all expressed in the adult SV. These results suggest that the morphological differentiation of SV occurs during the embryonic stage but that the functional differentiation into a seasonal sensor occurs in a later developmental stage.

In temperate zones, animals restrict breeding to specific seasons to maximize the survival of their offspring. Birds have evolved highly sophisticated mechanisms of seasonal regulation, and their testicular mass can change 100-fold within a few weeks. Recent studies on Japanese quail revealed that seasonal gonadal development is regulated by central thyroid hormone activation within the hypothalamus, depending on the photoperiodic changes. By contrast, the mechanisms underlying seasonal testicular regression remain unclear. Here we show the effects of short day and low temperature on testicular regression in quail. Low temperature stimulus accelerated short day-induced testicular regression by shutting down the hypothalamus-pituitary-gonadal axis and inducing meiotic arrest and germ cell apoptosis. Induction of T3 coincided with the climax of testicular regression. Temporal gene expression analysis over the course of apoptosis revealed the suppression of LH response genes and activation of T3 response genes involved in amphibian metamorphosis within the testis. Daily ip administration of T3 mimicked the effects of low temperature stimulus on germ cell apoptosis and testicular mass. Although type 2 deiodinase, a thyroid hormone-activating enzyme, in the brown adipose tissue generates circulating T3 under low-temperature conditions in mammals, there is no distinct brown adipose tissue in birds. In birds, type 2 deiodinase is induced by low temperature exclusively in the liver, which appears to be caused by increased food consumption. We conclude that birds use low temperature-induced circulating T3 not only for adaptive thermoregulation but also to trigger apoptosis to accelerate seasonal testicular regression.

Energy distributions of secondary charged particles were calculated in tissue substitutes irradiated by neutrons from 0.14 to 65 MeV, using the Particle and Heavy Ion Transport code System. The calculations were compared with experimental data measured by tissue equivalent proportional counters (TEPC). It is found that the calculated distributions of the lineal energy, y, generally agree well with the measured ones for neutrons from several 100 keV to 15 MeV. In the case of 40 and 65 MeV neutron irradiations, wall effects of TEPC should be considered and the fluence of alphas is underestimated by the calculations. Integrated dose contributions of the secondary charged particles are generally in good agreement with those of the measured ones.

A quasi-monoenergetic neutron field using the (7)Li(p,n)(7)Be reaction has been developed at the ring cyclotron facility at the Research Center for Nuclear Physics (RCNP), Osaka University. Neutrons were generated from a 10-mm-thick Li target injected by 250, 350 and 392 MeV protons and neutrons produced at 0 degrees were extracted into the time-of-flight (TOF) room of 100-m length through the concrete collimator of 10 x 12 cm aperture and 150 cm thickness. The neutron energy spectra were measured by a 12.7-cm diam x 12.7-cm long NE213 organic liquid scintillator using the TOF method. The peak neutron fluence was 1.94 x 10(10), 1.07 x 10(10) and 1.50 x 10(10) n sr(-1) per muC of 250, 350 and 392 MeV protons, respectively. The neutron spectra generated from various thick (stopping length) targets of carbon, aluminium, iron and lead, bombarded by 250 and 350 MeV protons, were also measured with the TOF method. Although these measurements were performed to obtain thick target neutron yields, they are also used as a continuous energy neutron field. These neutron fields are very useful for characterising neutron detectors, measuring neutron cross sections, testing irradiation effects for various materials and performing neutron shielding experiments.

The High-Intensity Proton Accelerator Project, named J-PARC, is in progress, with the aim of enabling studies on the latest basic science and the advancement of nuclear technology. In the project, a high-energy proton accelerator complex with the world's highest instantaneous intensity is under construction. In order to establish a reasonable shielding design, both simplified and detailed design methods were used in the shielding design of J-PARC. This paper reviews the present status of the radiation safety design study for J-PARC.

A phase II clinical trial has started in the South West region of Japan to investigate the efficacy and safety of weekly paclitaxel chemotherapy for the treatment of patients with ascites-forming advanced gastric cancer. A novel trial design was created to assess more effectively prospective changes in symptomatology. The study design focuses on the typical features seen in patients with ascites-forming advanced gastric cancer, including girth of the abdomen and impaired performance status, which is evaluated in the endpoint of 'Clinical Benefit Response - Gastric Cancer'. The more traditional endpoints, objective tumor response and survival, are also included. As nearly 40% of patients with this disease are excluded from traditional phase II trials owing to the absence of 'measurable' disease, this study should more precisely illustrate the disease entity affecting patients with advanced gastric cancer.

Background: Pylorus-preserving gastrectomy (PPG) has the advantages of preventing dumping syndrome and duodenogastric reflux. However, time was required to reduce symptoms of gastric fullness or to improve food intake after surgery. The aim of this study was to investigate whether the length of the retained antral segment influenced the postoperative symptoms in patients who underwent PPG., Methods: Thirty patients with early gastric cancer who underwent PPG were divided into two groups according to the length of the retained antrum. In group 1 (n = 20) the transection was 1.5 cm and in group 2 (n = 10) it was 2.5 cm proximal to the oral edge of the pyloric ring. The subjects were interviewed and examined periodically to assess symptoms, food intake, body-weight and serum nutritional variables. Endoscopy and a radioisotope gastric emptying test were performed 1 year after the operation., Results: In group 1 gastric fullness after meals was common, resulting in poor food intake and poor recovery of body-weight. A high incidence of food residue in the remnant stomach was found in group 1. With regard to gastric emptying, seven of 20 patients in group 1 and one of ten in group 2 had a delayed emptying curve 1 year after operation., Conclusion: Group 2 was superior to group 1 in terms of postprandial symptoms, food intake, recovery of body-weight and gastric emptying. The length of the retained antrum may play an important role in the motility of the pyloric ring following PPG.

This paper investigates the characteristic response of plastic track detectors to high-energy neutrons. Three types of plastic nuclear track detector (PNTD), Baryotrak made of pure CR-39, TD-1 made of CR-39 containing an antioxidant and TNF-1 made of a copolymer of CR-39/N-isopropylacrylamide, were exposed in quasi-monoenergetic neutron fields generated by p-Li reactions. The total efficiencies for TD-1 and TNF-1 were more than double and triple that of Baryotrak respectively. In addition, the species of particles were classitied into three groups, i.e. proton relatives, alpha particles and heavy ions, by analysing the etch-pit growth curve obtained by step-by-step etching. In a 65 MeV neutron field about half of the tracks recorded in pure CR-39 were due to heavy ions, whereas the TNF-1 detector could effectively register the protons, accounting for 70% of the tracks. The results could be explained by the difference in the sensitivity to high-energy protons.

The lineal-energy spectra for monoenergetic and quasi-monoenergetic neutrons of 8 keV to 65 MeV were obtained using a tissue-equivalent proportional counter (TEPC). The frequency-mean lineal energy, the dose-average lineal energy and mean quality factor were estimated from the measured data. The neutron absorbed doses obtained with this TEPC were compared with the kerma coefticient for A-150 plastic defined by ICRP 26 and the mean quality factors were compared with the data of ICRP 74. respectively. These comparisons indicated good agreement between them.

The main purpose of the study was to evaluate quality of life (QOL) among cancer patients using the WHOQOL-100 instrument and to see if any significant differences were seen in cancer stages, treatment status and prognosis. This study consisted of two parts; qualitative and quantitative. For the qualitative study, two focus groups were conducted by medical professionals to establish the applicability of the WHOQOL instrument in evaluating the QOL of cancer patients, but most participants were negative about using a generic instrument such as WHOQOL. For the quantitative study, 197 cancer patients (average age 55.86) from eight medical centers using the WHOQOL instrument, in addition to each patient's information sheet filled in by their own physicians, were analyzed. The average overall QOL score was 3.39. There was high reliability (Cronbach's alpha = 0.9685) and a high correlation between the psychological and the environmental domains (r = 0.7021), the physical domain and the level of independence (r = 0.6031) and social relations and the environment (r = 0.6856) and between health conditions perceived by patients and QOL scores. In addition, differences by gender, treatments and cancer sites were also found to be significantly different at the 5% significance level. The results indicated that the WHOQOL core instrument was sensitive enough to evaluate the QOL of cancer patients.

To improve the stability of IgY antibody in oral administration, encapsulation of IgY in a W/O/W emulsion was attempted. A stable W/O/W emulsion containing 1% IgY was prepared by using polyglyceryl condensed ricinolate (PGCR) and dextran-casein conjugate as the primary and secondary emulsifier, respectively. However, the activity of IgY antibody was reduced to less than 20% by encapsulation, suggesting that denaturation/inactivation of IgY had occurred at the oil/water interface. Adsorption of IgY to the inner water droplet surface was observed by electron microscopy. Rabbit IgG, alpha-amylase, and lysozyme also lost their activity after being encapsulated, although the rate of inactivation was lower than that of IgY. Molecular characterization of these proteins suggested that the rate of inactivation after encapsulation is likely to be dependent on the surface hydrophobicity and molecular stability of each protein.

This article examines epidemiological studies of schizophrenia in Japan. It is divided into three major sections: (1) methodological problems associated with epidemiological studies; (2) an overview of the history of epidemiology in Japan; and (3) an epidemiological study on incidence rates in Nagasaki, which was conducted as part of the World Health Organization Collaborative Study on Determinants of Outcome of Severe Mental Disorders. In general, although some differences in schizophrenic subtypes have been found, prevalence and incidence rates of schizophrenia in Japan are not significantly different from those reported in other countries.

The diagnostic and therapeutic options in early gastric cancer are reviewed. In Japan, the rate of detection of early gastric cancers has increased so that minute gastric cancers can now be identified as a result of advances in diagnostic methods. The results of histopathological staging of a large number of resected specimens have led to three surgical options based on size and depth of the primary lesion, namely classical R2 resection, radical resection with limited lymphadenectomy and endoscopic surgery.

Survival rates after curative gastrectomy for advanced gastric cancer among 238 patients in whom the cancer was invading the serosa were compared with 283 patients without serosal invasion. Generalized Wilcoxon estimates for 5-year survival rate were 47.1 per cent for patients exhibiting serosal invasion and 75.9 per cent for patients without serosal invasion. The frequency of lymph node metastasis increased proportionately with the extent of serosal invasion: 18.4 per cent in cases of S0; 53.8 per cent in cases of S1; 80.0 per cent in cases of S2; and 91.4 per cent in cases of S3. The higher the aggregate total of S (serosal invasion) and n (lymph node metastasis) factors, the lower the 5-year survival rate. In addition, patients with serosal invasion had a propensity for peritoneal dissemination of cancer cells; the percentage of cases with intraperitoneal free cancer cells increased with the extent of serosal invasion. It is worth noting that when cancer infiltration proceeded to the deeper layers and was accompanied by nodal metastasis, cancerous invasion of the perinodal fatty tissue was frequently evident. Therefore, unfavourable prognosis after curative resection in gastric cancer patients with serosal invasion may be largely dependent on whether or not the cancer has invaded the peritoneal cavity and the perinodal fatty tissue.