Augmented very low frequency component of heart rate variability during obstructive sleep apnea

After documenting the presence of obstructive sleep apnea syndrome (OSAS) through polysomnographic monitoring, we performed simultaneous ambulatory recordings of electrocardiogram, oronasal airflow, and pulse oximetry on 12 OSAS patients with normal autonomic nervous function for a period of 24 hours. The power spectrum of heart rate variability was investigated before and during treatments using dental appliances. Freuquency domain analysis showed that the very low frequency component of heart rate (0.008-0.04 Hz) was increased in OSAS patients and that a very low frequency peak appeared during episodes of obstructive sleep apnea. The increase in very low frequency identification was synchronized with episodes of absence of air exchange or hypoxemia (decreased arterial oxygen saturation) that occurred repeatedly at a cycle length of 25-120 seconds in our subjects. Frequency domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed that only the very low frequency was significantly decreased during prosthetic mandibular advancement treatment, whereas the other frequencies, i.e. high, low, and ultralow frequency component values, showed no significant changes. Time domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed no significant changes in any of these parameters. Frequency domain analysis of heart rate variability during nocturnal sleep, especially investigation of very low frequency and very low frequency peak, can be a noninvasive low-cost approach to diagnose and even better monitor subjects undergoing treatment at home, particularly considering that R-R intervals can be extracted from pulse oximetry and that analysis software programs are already commercially available.     

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.     

Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties

Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms. A broad-spectrum PLC inhibitor suppressed the viability of GSCs, but not their stemness. Nevertheless, the knockdown of PLCε suppressed the survival of GSCs and induced cell death. The stem cell capacity of residual viable cells was also suppressed. Moreover, the survival of mice that were transplanted with PLCε knockdown-GSCs was longer than the control group. PLCε maintained the stemness of GSCs via the activation of JNK. The present study demonstrated for the first time that PLCε plays a critical role in maintaining the survival, stemness, and tumor initiation capacity of GSCs. Our study suggested that PLCε is a promising anti-GSC therapeutic target.     

Inhibitory Effects of Saururus chinensis Extract on Receptor for Advanced Glycation End-Products-Dependent Inflammation and Diabetes-Induced Dysregulation of Vasodilation

Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) are implicated in inflammatory reactions and vascular complications in diabetes. Signaling pathways downstream of RAGE are involved in NF-κB activation. In this study, we examined whether ethanol extracts of Saururus chinensis (Lour.) Baill. (SE) could affect RAGE signaling and vascular relaxation in streptozotocin (STZ)-induced diabetic rats. Treatment with SE inhibited AGEs-modified bovine serum albumin (AGEs-BSA)-elicited activation of NF-κB and could compete with AGEs-BSA binding to RAGE in a dose-dependent manner. Tumor necrosis factor-α (TNF-α) secretion induced by lipopolysaccharide (LPS)—a RAGE ligand—was also reduced by SE treatment in wild-type Ager^+/+ mice as well as in cultured peritoneal macrophages from Ager^+/+ mice but not in Ager^−/− mice. SE administration significantly ameliorated diabetes-related dysregulation of acetylcholine-mediated vascular relaxation in STZ-induced diabetic rats. These results suggest that SE would inhibit RAGE signaling and would be useful for the improvement of vascular endothelial dysfunction in diabetes.     

Synthesis of L-[5-11C]Leucine and L-α-[5-11C]Methylleucine via Pd0-mediated 11C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging

The efficient synthesis of L-[5-¹¹C]leucine and L-α-[5-¹¹C]methylleucine has been investigated using a continuous two-step sequence of rapid reactions consisting of Pd⁰-mediated ¹¹C-methylation and microfluidic hydrogenation. The synthesis of L-[5-¹¹C]leucine and L-α-[5-¹¹C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15–38 % based on [¹¹C]CH₃I, radiochemical purity of 95–99 %, and chemical purity of 95–99 %. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L-[5-¹¹C]leucine or L-α-[5-¹¹C]methyl leucine in A431 tumor-bearing mice was performed. As a result, L-α-[5-¹¹C]methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L-α-[5-¹¹C]methylleucine in tumor tissue was high [12±3% injected dose/g tissue (%ID/g)].     

Combination of AFM with an objective-type total internal reflection fluorescence microscope (TIRFM) for nanomanipulation of single cells

A new instrument was constructed by combining an objective-type total internal reflection fluorescence microscope with an atomic force microscope (AFM). Our purpose of constructing such an instrument is to detect and confirm the result of cellular level manipulations made with the AFM part through the detection system of the highly sensitive fluorescence microscope part. In this combination, manipulations are now possible from the nanometer to the micrometer scales and the fluorescence detection system is sensitive enough even for localizing single molecules. In this paper, we applied the system as a precise intracellular injector (nanoplanter). Fluorescent beads were first chemically immobilized onto a ZnO whisker that was glued to an AFM tip and were injected into a living BALB/3T3 cell together with the whisker. It was demonstrated that the system could clearly show the result of injection, that is, the presence of a small number of fluorescent beads in the cell.     

Encapsulation of hemoglobin in mesoporous silica (FSM)-enhanced thermal stability and resistance to denaturants

Hemoblogin (Hb), which is a typical oligomeric protein, was introduced into the pores of mesoporous silica (FSM: folded-sheet mesoporous material) that had a diameter of 7.5 nm. Soret CD spectra of Hb-FSM-7.5 conjugates showed a peak that was identical to that of free Hb. This suggests that Hb retained its highly ordered structure in the mesoporous silica. In addition, the UV-visible absorption spectrum showed that Hb had an increased resistance to heat denaturation in the silica. Even after heat treatment at 85 degrees C, Hb-FSM-7.5 retained its ligand-binding activity. The stability of Hb-FSM-7.5 was examined further by measuring its peroxidase-like activity. Encapsulation of Hb resulted in the retention of activity in the presence of high NaCl or Gdn-HCl levels. This suggests that encapsulation prevented dissociation and denaturing. Thus, it seems that the mesopores created a favorable environment for the oligomeric protein to perform its function, even under harsh conditions.     

Constructive understanding and reproduction of functions of gluteus medius by using a musculoskeletal walking robot

Several factors affect the performance of humanoid walking. One factor is the complex nature of lower limbs, especially the muscles around the pelvis that contribute significantly to the stability and adaptivity of humanoid locomotion. The significance of this muscle group assures a impact on the facility of walking robots once the nature of its contribution is understood, and it can be replicated on robots. To propose a mechanical structure that facilitates walking in robots, we realized a muscle by modeling its pelvis region like that of a humanoid and developing a musculoskeletal humanoid robot. Especially, we focused on the gluteus medius, which is important for the general stability against frontal movements of the hip. Furthermore, it passively changes its influence on such motions; this is helpful during the different phases of locomotion. These changes depend on the alignment of the pelvis and femur. We confirmed the viability of the robotic gluteus medius, which was simplified to a model of two partial muscles by accomplishing the walking using this robot. This accomplishment verifies our hypothesis that using this model, the supporting functionality for the locomotion of the muscle can be reproduced and enhances the biological plausibility.     

Simultaneous measurement of lens accommodation and convergence in natural and artificial 3D vision

Recent advances in 3D technology have been accompanied by increasing complaints of visual fatigue. The usual explanation for such fatigue is that accommodation and convergence are mismatched during stereoscopic vision. The aim of this study was to measure fixation distances between lens accommodation and convergence in young subjects while they viewed real objects and 3D video clips. Measurements were made using an original instrument. The 3D video clips were presented to subjects using a liquid crystal shutter glass system. The results showed that when viewing real objects, the diopter values of subjects' accommodation and convergence were similar and changed periodically. This measurement method was thus considered to be appropriate for the measurement of stereoscopic vision. We also investigated lens accommodation and convergence when subjects viewed 3D video clips. Both accommodation and convergence were found to move along with the virtual position of 3D video clips. Therefore, there was little discrepancy between accommodation and convergence during the viewing of 3D images.