Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

Synthesis and Preliminary Evaluation of 11C-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M₁–M₅) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M₁/M₄-preferring agonist, in patients of schizophrenia and Alzheimer's disease, M₁- or M₄-selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of ¹¹C-labeled positron emission tomography (PET) ligands based on a validated M₄R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [¹¹C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay-corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol⁻¹). In vitro autoradiography studies indicated that these three ligands possess moderate-to-high in vitro specific binding to M₄R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

A Hydrogen Management Method in Residential Distributed Generation Systems with Photovoltaic Cells and Hydrogen‐Storage Type Fuel Cells

Recently, renewable energy has been attracting attention as a result of global warming and the depletion of fossil fuels. Photovoltaic (PV) systems have spread rapidly around the world because they generate electric power quietly and can be installed in many places. The output power generated in a PV system fluctuates with changes in solar irradiance and panel temperature. The reverse flow of surplus power in output spikes may have a negative effect on electric power quality, such as on the frequency and voltage in a power system. A residential distributed generation (DG) system composed of a fuel cell (FC) unit, an electrolyzer (EL) unit, and a PV system has been proposed in order to resolve these problems. In order to operate this system without interruption, the hydrogen storage volume must be managed. This paper proposes a novel hydrogen management method for a residential DG system with PV cells and hydrogen‐storage type FCs. The hydrogen storage volume is maintained at the preset frequency by operating the FC unit and the EL unit. Models of the PV, FC, and EL were constructed for a simulation. In the simulation, we showed that the proposed management method is viable for a residential DG system with PV cells and hydrogen‐storage FCs.     

A Study on the Distances of Small Mobile Robot Moves towards Infants

In recent years, it is remarkable that various robots are being developed, and the development of robot technology is beginning to be taken into an actual living space. There are still many questions that we will have to answer for the harmonization of living together with a robot. This study is focused on ＂the study of how to plan and design a living space in harmonizing with robots＂, and focused on the effects of infants （subjects） along with the distance between robots and themselves. The study is to seek for the minimum distance for the subjects who felt that ＂I do not want a robot to be any closer being approached to me＂. This experiment was conducted among 30 infants at the kindergarten, utilizing a small experimental robot. A small robot whose dimension is 120 mm （W） ×130 mm （D） × 70 mm （H）, approaching infants as is to see if it would make any differences to the infant＇s reactions.     

Dietary exposure to acrylamide in a group of Japanese adults based on 24-hour duplicate diet samples

Acrylamide is a probable human carcinogen and known human neurotoxin that can be generated in food through heating. Using a mathematical modelling approach, our previous study estimated long-term average dietary exposure to acrylamide in the Japanese people; however, the validity of these estimates remained unknown. Here, we aimed to obtain a more accurate estimate of acrylamide exposure that would reflect the usual practice of heat processing and consumption of foods in the population. We collected duplicate diet samples and dietary records during 24 h from a group of Japanese adults. A total of 110 duplicate diet samples were analysed for acrylamide by LC-MS/MS. Data from individual dietary records were used to examine the association between dietary acrylamide exposure and consumption of selected food groups (e.g., coffee, tea, confectioneries, and vegetables prepared at high temperature [deep-frying, stir-frying, sautéing, and baking]). Of the 110 homogenised diet samples, 108 contained detectable levels of acrylamide. Dietary exposure to acrylamide ranged from 8 to 1582 ng/kg body weight (bw)/day, with the mean value of 215 ng/kg-bw/day and median value of 143 ng/kg-bw/day. This mean value was higher than the value we previously estimated for Japanese adults using a mathematical approach. Multiple linear regression analysis showed log dietary acrylamide exposure was significantly associated with consumption of coffee and vegetables prepared at high temperature during 24-hr of sampling (adj. R² = 0.250, p < 0.001). We revealed significant difference in dietary acrylamide exposure between participants who had coffee and vegetables prepared at high temperature (median, 169 ng/kg-bw/day; range, 35–1224 ng/kg-bw/day, n = 42) and those who had none of them (median, 75 ng/kg-bw/day; range, 8–311 ng/kg-bw/day, n = 15) (Steel-Dwass test, p < 0.05).     

Development of rapid hygrothermal pasteurization using saturated water vapor

We developed a novel rapid hygrothermal pasteurization (RHP) method using saturated water vapor with a dew point of 100 °C. In the present study, the effects of RHP on microbiological quality and quality attributes such as color changes, firmness and ascorbic acid content on many fresh-cut fruits and vegetables (cabbage, cucumber, carrot, cherry tomato, bell pepper, strawberry, pineapple and melon) were investigated. The RHP was performed within a second by free-falling samples through a cylindrical processing chamber filled with steam. The RHP resulted in a 0.7–2.0 log order reduction in the numbers of naturally inoculated mesophilic bacteria. Furthermore, the RHP induced no significant changes in color and firmness of samples, except on the leafy vegetable, cabbage. Ascorbic acid was also retained approximately 80% and above. These results indicate that the RHP is a clean and effective method for decontaminating mesophilic bacteria on fresh fruits and vegetables with minimal changes in quality.Industrial relevanceIn fresh-cut industry, an effective and risk-free decontamination technology is required for use in place of a conventional method, washing by chlorine that can produce carcinogenic chlorinated by-products. In this study, the rapid hygrothermal pasteurization (RHP) method using saturated water vapor was invented and their ability for applying minimal processing was evaluated. The results showed that RHP, without using chemicals, can reduce microorganism load and preserve quality attributes in many kinds of fresh-cut fruits and vegetables. Therefore, RHP could be used as a novel method, which can be generally applicable to fresh-cut fruits and vegetables in the food industry.     

Effect of inorganic salts,amino acids and proteins on the degradation of pure magnesium in vitro

The possibility of magnesium and its alloys in medical applications is actively investigated in these days for the realization of biodegradable metallic devices. However, the degradation behavior and mechanisms of magnesium and its alloys in physiological environment such as inside the human body have not been elucidated. In this study, we performed 14-d long immersion tests of pure magnesium (3N) in 4 kinds of physiological solutions simulating the body fluids to examine the effects of the chemical components of the body fluids on the degradation of magnesium. The degradation rate of pure magnesium was strongly influenced by the kinds of the solution used. The highest degradation rate was obtained in NaCl, followed by E-MEM, Earle's solution, and E-MEM+FBS. The average degradation rate in NaCl for 8–14 d is about 100 times larger than that in E-MEM+FBS, which is the closest solution to human blood plasma. These results show that protein adsorption and insoluble salt formation retarded magnesium degradation, whereas organic compounds such as amino acids encourage the dissolution of magnesium. Buffering the solution also influenced the degradation rate; buffering NaCl with HEPES increased the degradation rate but buffering with NaHCO₃ decreased it. Based on these results, the use of appropriate solution such as E-MEM+FBS is important for in vitro evaluation of the magnesium degradation rate under the physiological environment simulating inside the human body.     

Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients

Vascular calcification is associated with a poor prognosis in dialysis patients. It can be assessed with computed tomography but simple inoffice techniques may provide useful information. We compared the results obtained with a simple noninvasive technique with those obtained using multidetector computed tomography for aortic arch calcification volume (AoACV) in chronic hemodialysis (HD) patients. The enrolled study subjects were 63 (32 men and 31 women) maintenance HD patients. Calcification of the aortic arch was semiquantitatively estimated with a AoAC score (AoACS) on plain chest radiology. The AoACV was increased, with a mean value of 6.6 ranging from 0% to 36.5%. The coefficient of intraobserver variation was less than 2.5%. Aortic arch calcification score was highly correlated with AoACV (r=0.635, P<0.001). Multiple regression analysis showed age (F value=12.62, P<0.001) and pulse pressure (F value=4.54, P=0.037) to be significant independent determinants of AoACS. In conclusion, a simple measurement of AoACS may be useful for inoffice imaging to choose a therapeutic regimen in HD patients.