The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK-JNK Signaling Pathway in Axon Regeneration.

The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury. The scaffold protein SHC-1 interacts with both DDR-2 and SVH-2. Furthermore, we demonstrate that overexpression of svh-2 and shc-1 suppresses the delay in axon regeneration observed in ddr-2 mutants, suggesting that DDR-2 functions upstream of SVH-2 and SHC-1. These results suggest that DDR-2 modulates the SVH-2-JNK pathway via SHC-1. We thus identify two different RTK signaling networks that play coordinated roles in the regulation of axonal regeneration.

Japanese sake yeast supplementation improves the quality of sleep: a double-blind randomised controlled clinical trial.

Activation of adenosine A2a receptors in cerebral neurons induces sleep in various mammals. It was previously found that Japanese sake yeast enriched in adenosine analogues activates A2a receptors in vitro and induces sleep in mice. Here it is reported that sake yeast activated A2a receptors in a cultured human cell line and improved human sleep quality in a clinical trial. Sake yeast activated A2a receptors in HEK cells in a dose-dependent manner with an EC50 of 40 µg mL(-1), and the activation was attenuated almost completely by the A2a receptor antagonist ZM241385 with an IC50 of 73 nm. In a double-blind placebo-controlled crossover clinical study, 68 healthy participants ingested tablets containing either 500 mg of sake yeast powder or a placebo (cellulose) 1 h before sleep for 4 days. Electroencephalograms were recorded during sleep at home with a portable device for 4 week days. Electroencephalogram analyses revealed that sake yeast supplementation significantly (P = 0.03) increased delta power during the first cycle of slow-wave sleep by 110%, without changing other sleep parameters. Sake yeast supplementation also significantly increased growth hormone secretion in the urine on awakening by 137% from 3.17 ± 0.41 (placebo) to 4.33 ± 0.62 (sake yeast) pg mg(-1) creatinine (P = 0.03). Subjective sleepiness (P = 0.02) and fatigue (P = 0.06) in the morning were improved by sake yeast. Given these benefits and the absence of adverse effects during the study period, it was concluded that sake yeast supplementation is an effective and safe way to support daily high-quality, deep sleep.

Association between blood pressure and circadian timing of physical activity of Japanese workers.

High blood pressure (BP) is reported to be accounted for more than 10 million deaths, and the high prevalence of hypertension is a global issue. Exercise is known to reduce BP and the optimal exercise prescription has been discussed. Furthermore, since the circadian clock plays an important role in BP regulation and its related physiological functions, the time-of-day difference in the effect of exercise on BP is suggested. However, when people should regularly exercise for the prevention of hypertension remains unclear. In this cross-sectional research, we analyzed the association of habitual exercise and BP depending on their performed timing, time length, and frequency for three levels of intensity from an analysis of questionnaire answered by Japanese male workers (N = 2,343, mean age ± SE = 49.2 ± 0.2 years old, date: June 2021). From the subjects who responded, subjects with irregularly high or low BP, no regular physical activity or under the treatment of hypertension were excluded from the analysis. From the comparison of SBP and DBP between those who performed physical activity at each time period, vigorous or moderate physical activity in the evening (18:00-21:00) showed significantly lower average BP. On the other hand, those who walked in early morning (03:00-06:00) showed higher DBP. These time-specific differences were confirmed from multiple regression analysis, eliminating the confounding factors such as age and BMI. When participants were divided into groups according to their BP, compared to normal BP groups, higher BP groups exercised less in the evening. Our findings suggest that when to exercise is important, and that exercising in the evening (18:00-21:00) may be better to achieve the hypotensive effect of exercise.

Effects of Differences of Breakfast Styles, Such as Japanese and Western Breakfasts, on Eating Habits.

A balanced diet and protein source intake are reportedly good for health. However, many people skip breakfast or have a light breakfast. Thus, this study aimed to examine the influence of breakfast styles on eating habits among Japanese workers, including traditional Japanese-style breakfast (JB), a pattern in which Japanese foods are eaten; Japanese-Western-style breakfast (J-W B), a pattern in which Japanese and Western foods are eaten alternately; Western-style breakfast (WB), a pattern in which Western foods are eaten; and cereal-style breakfast (CB), a pattern in which cereal is eaten. We hypothesized that breakfast style may be related to good eating habits. Data from 4274 respondents (67.97% male, 33.03% female, age 48.12 ± 0.19 years), excluding night shift workers and breakfast absentees out of a total of 5535 respondents, were analyzed. The results suggest that Japanese food is linked to the intake of protein sources such as fish, eggs, and soy. Furthermore, it was suggested that Japanese food breakfast is effective for good eating habits, such as not eating irregular amounts of food, not eating snacks, not drinking sweet juices, and having a balanced diet.

Association between Breakfast Meal Categories and Timing of Physical Activity of Japanese Workers.

BACKGROUND: Breakfast is the most important meal of the day and has been associated with longevity. Regular breakfast consumers often have a healthy lifestyle, including a healthy diet and regular physical activity. METHODS: We examined the association between breakfast type, chronotype (morningness-eveningness), and physical activity in 3395 Japanese workers using a cross-sectional web survey. RESULTS: Participants who ate Japanese breakfasts showed an early chronotype, while those who ate breakfast cereal exhibited a later chronotype. Physical activity was positively associated with adopting a Japanese breakfast style. Japanese breakfast eaters performed physical activities from 6:00-9:00 compared with other breakfast eaters. CONCLUSION: Our findings suggest that eating a Japanese breakfast is associated with an earlier chronotype (morningness) and higher physical activity.

Association between Irregular Meal Timing and the Mental Health of Japanese Workers.

Breakfast skipping and nighttime snacking have been identified as risk factors for obesity, diabetes, and cardiovascular diseases. However, the effects of irregularity of meal timing on health and daily quality of life are still unclear. In this study, a web-based self-administered questionnaire survey was conducted involving 4490 workers (73.3% males; average age = 47.4 ± 0.1 years) in Japan to investigate the association between meal habits, health, and social relationships. This study identified that irregular meal timing was correlated with higher neuroticism (one of the Big Five personality traits), lower physical activity levels, and higher productivity loss. Irregular meal timing was also associated with a higher incidence of sleep problems and lower subjective health conditions. Among health outcomes, a high correlation of irregular meal timing with mental health factors was observed. This study showed that irregularity of meal timing can be explained by unbalanced diets, frequent breakfast skipping, increased snacking frequency, and insufficient latency from the last meal to sleep onset. Finally, logistic regression analysis was conducted, and a significant contribution of meal timing irregularity to subjective mental health was found under adjustment for other confounding factors. These results suggest that irregular meal timing is a good marker of subjective mental health issues.

Activin ligands are required for the re-activation of Smad2 signalling after neurulation and vascular development in Xenopus tropicalis.

The importance of Transforming Growth Factor ß (TGFß) signalling during early development has been well established. In particular, Nodal ligands have been shown to play essential roles for the specification and the patterning of the mesendoderm, axes formation and organogenesis. Activin ligands, like Nodal, signal by inducing the phosphorylation of the intracellular signal transducers Smad2 and Smad3. However, the roles of Activins during embryonic development are much less understood. Here, we report that during Xenopus tropicalis development two waves of Smad2 phoshorylation can be observed, first during gastrulation and then a second one after neurulation. Using a knock-down approach, we show that the second wave of Smad2 phosphorylation depends on activinßa (actßa) and activinßb (actßb) expression. Knocking down the expression of actßa, or treating the embryos with a chemical inhibitor inhibiting TGFß receptor I (TGFßRI) activity after neurulation result in a decrease of the expression of endothelial cell markers and a lack of blood flow in Xenopus tadpoles. Taken together these data suggest that Activin ligands play an important role during vascular development in Xenopus tropicalis embryos.

Generation of reactive oxygen species by interaction between antioxidants used as food additive and metal ions.

Food additives, such as preservatives, sweeteners, coloring agents, and flavoring agents, are widely used in food manufacturing. However, their combined effects on the human body are not known. The purpose of this study was to examine whether combinations of antioxidants and metal ions generate reactive oxygen species (ROS) under in vitro conditions using electron spin resonance (ESR). Among the metal ions examined, only iron and copper generated ROS in the presence of antioxidants. Moreover, certain phenolic antioxidants having pro-oxidant activity induced DNA oxidation and degradation via the generation of high levels of ROS in the presence of copper ion, resulting in complete degradation of DNA in vitro.