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Sake is a Japanese alcoholic beverage produced by fermenting steamed rice and koji (a culture of Aspergillus oryzae on steamed rice) with sake yeast, a strain of Saccharomyces cerevisiae. Sake yeast strains are important for maintaining product quality and process efficiency. In this study, a S. cerevisiae strain from Muramatsu Park, Gosen City, Niigata Prefecture was isolated using a loop-mediated isothermal amplification (LAMP) assay. The yeast strain was cultured using the mass spore-cell/cell-cell mating method with a sake yeast haploid. The resultant hybrid yeast strain, HG-3-F2, exhibited superior efficiency in alcoholic fermentation compared with the HG-3 strain. Our findings support the applicability of these original and mating strains in sake brewing., (2024, by The Mycological Society of Japan.)

Objective: To evaluate the effect of body posture on occlusal contact., Methods: A total of 30 healthy subjects were evaluated. T-Scan™ III was used to analyze the center of occlusal force (COF) and occlusal force distribution while subjects remained supine (SP), upright sitting with the head fixed (UP-HFI), upright sitting with the head free (UP-HFR), and natural standing (NS)., Results: The total trajectory length of COF was significantly longer in NS than in SP, UP-HFI, and UP-HFR. The COF area was significantly larger in UP-HFR than in SP and UP-HFI and also significantly larger in NS than in SP, UP-HFI, and UP-HFR. The anteroposterior occlusal force distribution (AOD) in NS shifted significantly forward, compared to SP, UP-HFI, and UP-HFR. AOD in UP-HFI and UP-HFR shifted significantly forward, compared to the SP position., Conclusion: Changes in body posture affect the stability and anteroposterior balance of occlusal contacts.

Meteorite studies suggest that each solar system object has a unique oxygen isotopic composition. Chondrites, the most primitive of meteorites, have been believed to be derived from asteroids, but oxygen isotopic compositions of asteroids themselves have not been established. We measured, using secondary ion mass spectrometry, oxygen isotopic compositions of rock particles from asteroid 25143 Itokawa returned by the Hayabusa spacecraft. Compositions of the particles are depleted in (16)O relative to terrestrial materials and indicate that Itokawa, an S-type asteroid, is one of the sources of the LL or L group of equilibrated ordinary chondrites. This is a direct oxygen-isotope link between chondrites and their parent asteroid.

Unlabelled: Recently, we reported that beta-carotene, vitamin D(2), and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti-HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved in their anti-HCV activities. However, the molecular mechanism by which oxidative stress induces anti-HCV status remains unknown. Oxidative stress is also known to activate extracellular signal-regulated kinase (ERK). Therefore, we hypothesized that oxidative stress induces anti-HCV status via the mitogen activated protein kinase (MAPK)/ERK kinase (MEK)-ERK1/2 signaling pathway. In this study, we found that the MEK1/2-specific inhibitor U0126 abolished the anti-HCV activities of the three nutrients in a dose-dependent manner. Moreover, U0126 significantly attenuated the anti-HCV activities of polyunsaturated fatty acids, interferon-gamma, and cyclosporine A, but not statins. We further demonstrated that, with the exception of the statins, all of these anti-HCV nutrients and reagents actually induced activation of the MEK-ERK1/2 signaling pathway, which was inhibited or reduced by treatment not only with U0126 but also with vitamin E. We also demonstrated that phosphorylation of ERK1/2 by cyclosporine A was attenuated with N-acetylcysteine treatment and led to the negation of inhibition of HCV RNA replication. We propose that a cellular process that follows ERK1/2 phosphorylation and is specific to oxidative stimulation might lead to down-regulation of HCV RNA replication., Conclusion: Our results demonstrate the involvement of the MEK-ERK1/2 signaling pathway in the anti-HCV status induced by oxidative stress in a broad range of anti-HCV reagents. This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication.

Cyclosporine A (CsA) is a well-characterized anti-HCV reagent. Recently it was reported that the genotype 2a JFH-1 strain was more resistant than genotype 1 HCV strains to CsA in a cell culture system. However, the JFH-1 responsible region for the resistance to CsA remains unclear. It was also demonstrated that in genotype 1b HCVs, NS5B interacts with cyclophilin (CyP). To clarify whether or not NS5B of JFH-1 is significant for CsA resistance, we developed a chimeric replicon with NS5B of JFH-1 in the genotype 1b backbone. The chimeric replicon was more resistant to CsA than the parental genotype 1b replicon. Furthermore, reduction of CyPA had a greater effect on HCV RNA replication and sensitivity to CsA than reduction of CyPB. Here, we demonstrated that NS5B of JFH-1 contributed to this strain's CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV's sensitivity to CsA.

We recently developed a genome-length hepatitis C virus (HCV) RNA replication system (OR6) with luciferase as a reporter. The OR6 assay system has enabled prompt and precise quantification of HCV RNA replication. Pegylated interferon (IFN) and ribavirin combination therapy is the world standard for chronic hepatitis C, but its effectiveness is limited to about 55% of patients. Newer therapeutic approaches are needed. In the present study, we used the OR6 assay system to evaluate the anti-HCV activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, called statins, and their effects in combination with IFN-alpha. Five types of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) were examined for their anti-HCV activities. Fluvastatin exhibited the strongest anti-HCV activity (IC50: 0.9 micromol/L), whereas atorvastatin and simvastatin showed moderate inhibitory effects. However, lovastatin, reported recently as an inhibitor of HCV replication, was shown to exhibit the weakest anti-HCV activity. The anti-HCV activities of statins were reversed by the addition of mevalonate or geranylgeraniol. Surprisingly, however, pravastatin exhibited no anti-HCV activity, although it worked as an inhibitor for HMG-CoA reductase. The combination of IFN and the statins (except for pravastatin) exhibited strong inhibitory effects on HCV RNA replication. In combination with IFN, fluvastatin also exhibited a synergistic inhibitory effect. In conclusion, statins, especially fluvastatin, could be potentially useful as new anti-HCV reagents in combination with IFN.

Background/aims: We previously established hepatitis C virus (HCV) replicon-harboring cell lines possessing two interferon (IFN)-resistant phenotypes: a partially resistant phenotype (alphaR series) and a severely resistant phenotype (betaR series). We recently found that the severe IFN resistance of the betaR-series cells is caused by the functional disruption of type I IFN receptors. Here, we aimed to clarify the mechanism(s) underlying the partial IFN resistance of the alphaR-series cells., Methods: alphaR-series cells were pre-treated with 5-azacytidine to evaluate the effects of DNA demethylation on IFN resistance. cDNA microarray analysis was carried out in order to compare 1alphaR cells, which belong to the alphaR series, treated with both 5-azacytidine and IFN-alpha with cells treated with 5-azacytidine or IFN-alpha alone., Results: We found that the IFN-resistant phenotype of alphaR-series cells was impaired by treatment with 5-azacytidine. cDNA microarray analysis identified seven IFN-stimulated genes, which were up-regulated by 5-azacytidine treatment. We demonstrated here that the ectopic expression of each of these seven genes in 1alphaR cells frequently weakened the IFN resistance of these cells., Conclusions: The present results suggest that the epigenetic silencing of IFN-stimulated genes is implicated in the acquisition of a partially IFN-resistant phenotype of HCV replicon-harboring cells.

Nowadays, a rotary blood pump can be used as not only for a bridge to transplantation (BTT) but also for a bridge to recovery (BTR) and a destination therapy (DT). In such cases, evaluation of the recovery level of the native heart provides useful information to improve the clinical strategy and decide adequate timing for removing of the RBP. In contrast, the indices for cardiac function have been studied. However, most of them do not consider the assistance with the RBP. In this study, we aimed at evaluating whether Emax, which is an index for cardiac function based on the pressure-volume relationships, is still valid during assistance with the RBP from an animal experiment. In the acute animal experiment with an adult goat, we measured pressure-volume (P-V) loops while cardiac function was normal, augmented or diminished. The experimental results revealed that there were typical differences in the shapes of P-V loops when the cardiac function was altered, and Emax can still be used as an index for the cardiac function even if the assistance with the RBP is ongoing.

To evaluate the biological effects of visual stimulation on multiple subjects watching a same image, a more compact and low-cost device measuring both ECG and photo-plethysmogram was developed. On the basis of these physiological parameters, the maximum cross-correlation coefficient, ρmax, from pulse wave transmission time to heart rate could be calculated. This index reflects the activity of the autonomic nervous system and is considered as a good index for evaluating the effect of visual stimulation on humans. The result of simultaneous experiment with 6 subjects watching a video image taken by an intentionally swaying handy camera has shown that ρmaxof almost all subjects decreased in the latter part of the video image and that ρmaxof the subjects who felt motion sickness strongly decreased after watching the video image at a time.

Rotary blood pumps are expected to be used as an implantable ventricular assist device (VAD). In the VAD system, flow rate is important for monitoring of the state of a recipient and for automatic control to maintain appropriate blood perfusion. To obtain flow rate of the pump without any sensors, we proposed a method of estimating flow rate with supplied power and rotational speed using a time series model. To evaluate the accuracy of the proposed estimation method from the aspect of long-term use, we implanted NEDO PI Gyro pumps in a calf and performed a chronic animal experiment. Flow rate, supplied power and rotational speed were measured until post operation day (POD) 63, and the estimated flow rate was compared with the measured one. We confirmed that waveforms of the measured flow rate was sufficiently similar to the measured one, and correlation between them was higher than 0.9 in all the datasets. On the other hand, the root mean square error increased after 15 days. This error was probably due to the change in physiological condition, the operating point of the pump, or mild intima formation.

It is desirable for the dynamic behavior of the drive rate of the artificial heart to be as similar as possible to that of the recipient's heart rate (HR) before implantation. This requires a model which can simulate the behavior of HR on the basis of only the information measured with the limited number of approvable implanted sensors. This article provides a linear time series model for explaining the behavior of HR only with aortic pressure and right atrial pressure. This could be obtained from open-loop analysis using a total artificial heart, which was introduced for measuring HR in vivo and for eliminating its effect on blood pressure. The model was identified in a goat equipped with a special biventricular assist device called the effectively total artificial heart (ETAH). The ETAH was introduced to make an open loop and awake situation in the animal with almost intact autonomic nerves, which could enhance the accuracy and reliability of the identification of the model. The adequacy of the proposed model was ascertained in several data sets measured in two goats, which were different from the data set used for identification. Most of the mean estimation errors were less than 3 beats/min and auto-correlation analysis showed approvable statistical appropriateness. However, it was clarified through comparison with the 1/R control method that the proposed model has a few problems still to be solved before its future implementation as an automatic controller of the TAH.

Mayer wave (0.1Hz fluctuation) included in heart rate variability and blood pressure variability appears apparently in the resting state. On the other hand, it can be predicted that a strong emotional reaction may affect the relationship between these variabilities. This prediction suggests that the human emotional reaction can be quantified by the maximum correlation coefficient rho/sub max/ between heart rate and blood pressure whose frequency components are limited to the Mayer wave-band. However, the conventional method of obtaining rho/sub max/ needs a bulky and expensive device for measuring continuous blood pressure. In this study, a smaller and cheaper device for measuring pulse wave transmission time (PTT) has been developed. This work has shown that the PTT can give rho/sub max/ instead of blood pressure and that rho/sub max/ obtained by the PTT may significantly reflect the emotional reaction on the basis of an experiment using nine healthy subjects with nine self-produced devices in which pictures were presented to the subjects to induce their emotional reactions.

Several years ago, a famous accident occurred in Japan. Hundreds of children, who were watching a cartoon on television, suddenly complained of spasms and vertigo, and were taken to hospital. In this study, the autonomic nervous system was evaluated during audiovisual stimulation with three dimensional Virtual Reality (VR) imaging. In our previous studies, we designed the diagnosis machine for an autonomic function using multi-parameters, including electrocardiography, arterial blood pressure, respiration and stroke volume as detected by ultrasonic cardiography. Healthy adult volunteers were used in this experiment with their satisfactory informed consent. The three-dimensional content for VR included dinosaur images in a pre-historic scene. The content was projected on a wide screen and volunteers watched an audiovisual screen for about 20 minutes and the 3-D and 2-D images were compared. There was no significant arrhythmia during experiments in both images. No significant alteration was observed in the quantified hemodynamic data during the experiment. Spectral analysis was performed to evaluate the heart rate variability (HRV) during the experiment. LF, HF and LF/HF of HRV were calculated. However, there were no significant changes during the experiment. Significant change was observed in the fractal dimension of the stroke volume during 2-D and 3-D image VR immersion. Our results suggest that a significant response was observed in the autonomic function according to the 2-D or 3-D images. Our study, which aims at safe audiovisual stimulating equipment, must be developed.