Mutations in the genes responsible for the synthesis of furan fatty acids resolve the light-induced off-odor in soybean oil.

Soybean oil is the second most produced edible vegetable oil and is used for many edible and industrial materials. Unfortunately, it has the disadvantage of 'reversion flavor' under photooxidative conditions, which produces an off-odor and decreases the quality of edible oil. Reversion flavor and off-odor are caused by minor fatty acids in the triacylglycerol of soybean oil known as furan fatty acids, which produce 3-methyl-2,4-nonanedione (3-MND) upon photooxidation. As a solution to this problem, a reduction in furan fatty acids leads to a decrease in 3-MND, resulting in a reduction in the off-odor induced by light exposure. However, there are no reports on the genes related to the biosynthesis of furan fatty acids in soybean oil. In this study, four mutant lines showing low or no furan fatty acid levels in soybean seeds were isolated from a soybean mutant library. Positional cloning experiments and homology search analysis identified two genes responsible for furan fatty acid biosynthesis in soybean: Glyma.20G201400 and Glyma.04G054100. Ectopic expression of both genes produced furan fatty acids in transgenic soybean hairy roots. The structure of these genes is different from that of the furan fatty acid biosynthetic genes in photosynthetic bacteria. Homologs of these two group of genes are widely conserved in the plant kingdom. The purified oil from the furan fatty acid mutant lines had lower amounts of 3-MND and reduced off-odor after light exposure, compared with oil from the wild-type.

Metallothionein synthesis increased by Ninjin-yoei-to, a Kampo medicine protects neuronal death and memory loss after exposure to amyloid ß1-42.

BACKGROUND: It is possible that increased synthesis of metallothioneins (MTs), Zn2+-binding proteins is linked with the protective effect of Ninjin-yoei-to (NYT) on Zn2+ toxicity ferried by amyloid ß1-42 (Aß1-42). METHODS: Judging from the biological half-life (18-20 h) of MTs, the effective period of newly synthesized MT on capturing Zn2+ is estimated to be approximately 2 days. In the present paper, a diet containing 3% NYT was administered to mice for 2 days and then Aß1-42 was injected into the lateral ventricle of mice. RESULTS: MT level in the dentate granule cell layer was elevated 2 days after administration of NYT diet, while the administration reduced intracellular Zn2+ level increased 1 h after Aß1-42 injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aß1-42 injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aß1-42 into the dentate granule cell layer of rats. CONCLUSION: The present study indicates that pre-administration of NYT diet for 2 days increases synthesis of MTs, which reduces intracellular Zn2+ toxicity ferried by extracellular Aß1-42, resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aß1-42.

Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized, Double-Blinded, Placebo-Controlled Study.

Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), ß-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.

Fluid Movement in the Apical Area Beyond the Ledge During Er:YAG Laser-Activated Irrigation: A Particle Image Velocimetry Analysis.

Objective: This study aimed to examine the irrigant flow generated by laser-activated irrigation (LAI), in comparison with ultrasonic-activated irrigation (UAI) and syringe irrigation (SI), in the area beyond the ledge using particle image velocimetry (PIV). Background data: There was no reported study about cleaning efficacy of LAI beyond the ledge. Materials and methods: Forty-nine J-shaped root canal models (40° curvature) were instrumented to no. 35/0.06, and a ledge, 2.5 mm deep, was created with no. 60/0.08 instrument at 5 mm from the apical foramen in each canal. The samples were irrigated with LAI [30 mJ/5 pulse per second (pps), 30 mJ/10 pps, 30 mJ/20 pps, 50 mJ/10 pps, 70 mJ/10 pps], UAI, and SI with a tip/needle insertion depth of 5 mm from the apical foramen (n = 7). PIV was performed with glass beads and a high-speed camera. Velocities were compared in the coronal and apical areas to the ledge, respectively. Results: In the apical area, all LAI groups and UAI produced a higher velocity than that of SI, and LAI at 30 mJ/20 pps and 70 mJ/10 pps showed significantly higher velocity than that of UAI (p < 0.05). In the coronal area, LAI at 30 mJ/20 pps generated a significantly higher velocity than that of UAI and SI (p < 0.05). Velocity was significantly slower in the apical area than in the coronal area in UAI and SI (p < 0.05), but was similar between both areas in LAI except at 30 mJ/20 pps. Conclusions: Among tested laser settings, higher velocity was significantly achieved by LAI at 30 mJ/20 pps and 70 mJ/10 pps compared with UAI in the canal area beyond the ledge. SI generated lower fluid movement than LAI and UAI in both canal regions.

Effect of Pulse Energy, Pulse Frequency, and Tip Diameter on Intracanal Vaporized Bubble Kinetics and Apical Pressure During Laser-Activated Irrigation Using Er:YAG Laser.

Objective: Er:YAG laser-activated irrigation (LAI) is an effective method of root canal cleaning, but irrigant extrusion from the apical foramen has been a concern. We aimed to analyze the effects of pulse energy, pulse frequency, and laser tip diameter on intracanal vapor bubble kinetics and periapical pressure generation during LAI with Er:YAG laser. Background: Irrigant vapor bubble kinetics are one of indices of root canal cleaning efficacy. However, few studies have compared laser pulse conditions to vapor bubble kinetics, in relation to periapical pressure. Methods: A plastic root canal model (apical diameter 0.50 mm, 6% taper, 20 mm long) was filled with distilled water, and LAI with Er:YAG laser (Erwin AdvErl Unit; 30, 50, or 70 mJ; 10, or 20 pulses per second; laser tip R200T or R600T) was performed with the end of the tip fixed at 15 mm from the root apex. The number, maximum diameter, and velocity of vapor bubbles were analyzed by high-speed video imaging. Pressure generated outside the apical foramen was measured with a pressure sensor. Results: Vapor bubble count and maximum diameter increased significantly with pulse energy, pulse frequency, and tip diameter. Vapor bubble velocity increased significantly with pulse frequency, but not with pulse energy or tip diameter. Periapical pressure increased significantly with pulse energy, pulse frequency, and tip diameter. Conclusions: The pulse frequency was the single factor that significantly affected all the examined parameters (the number, diameter, and velocity) of vapor bubble kinetics together with the periapical pressure.

Real-time PCR Detection Methods for Food Allergens (Wheat, Buckwheat, and Peanuts) Using Reference Plasmids.

Specific and sensitive real-time qualitative polymerase chain reaction (PCR) methods for the detection of food allergens including wheat, buckwheat, and peanuts were developed that could cancel between instrument effects and avoid risks of false-positives and false-negatives. In these real-time PCR analysis, the cutoff for determination of positive samples was set in every PCR run by using reference plasmids containing known copies of the target sequences. The copy numbers of the plasmids were used to detect the allergenic ingredients corresponding to 10 ppm (w/w) protein in highly processed foods (cooked for more than 30 min at 122 °C). Reference plasmid analysis for each real-time PCR run helped to minimize variability between runs and instruments (7900HT Real-Time PCR systems and Light Cycler Nano). It also helped to avoid false positives due to trace levels of contaminants from the laboratory environment or agricultural products. The specificity of the real-time PCR method was verified using 79 commonly used food materials and some of their relatives. The method was sensitive enough to detect those allergenic ingredients corresponding to 10 ppm (w/w) in seven types of incurred samples. The current official Japanese method was not able to detect the allergens in some of the incurred samples. The developed method can avoid false negatives due to lack of sensitivity and is useful to confirm positive ELISA screening tests.

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics.

Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins in Escherichia coli and mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substrate L-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.

Effect of Laser Energy and Tip Insertion Depth on the Pressure Generated Outside the Apical Foramen During Er:YAG Laser-Activated Root Canal Irrigation.

OBJECTIVE: The risk of extrusion of irritative irrigants into the extraradicular tissue should be minimized during root canal irrigation. This study aimed to examine the pressure generated outside the apex during Er:YAG laser-activated irrigation (LAI) in comparison with passive ultrasonic irrigation (PUI) and conventional syringe irrigation (SI). BACKGROUND DATA: LAI is reported to be efficient for root canal debridement, whereas the apical pressure generated during LAI has not been investigated in detail. METHODS: Plastic root canal models (apical diameter = 0.40 mm, taper = 6%, and length = 20 mm) were irrigated with water using either LAI with an Er:YAG laser (Erwin AdvEr; 30, 50, or 70 mJ, 10 pps), PUI, or SI. The tip insertion depth was set at 2, 5, or 10 mm from the apex. The pressure generated outside the apical foramen was measured with a pressure sensor connected to the apex of the model. RESULTS: When the tip was positioned at 2 mm and the power setting was changed, the mean maximum pressure values were LAI (30 mJ) = PUI < LAI (70 mJ) < SI (p < 0.05). When LAI was performed at 70 mJ and the tip was positioned at 5 or 10 mm, the pressure values were PUI < LAI = SI (p < 0.05). CONCLUSIONS: LAI generated similar or lower pressure outside the apical foramen compared with SI, irrespective of the laser energy and tip insertion depth examined. However, LAI generated higher pressure compared with PUI.

Nephrotoxicity of cisplatin combination chemotherapy in thoracic malignancy patients with CKD risk factors.

BACKGROUND: Nephrotoxicity is the major side effect that limits the dose of cisplatin that can be safely administered, and it is a clinical problem in cancer patients who received cisplatin combination chemotherapy. Recent evidence has demonstrated that patients with chronic kidney disease (CKD) have an increased risk of developing acute kidney injury (AKI). The present study was conducted to evaluate the prevalence of CKD risk factors in patients who received cisplatin and to assess the correlation between CKD risk factors and cisplatin-induced AKI. METHODS: We retrospectively analyzed 84 patients treated with cisplatin combination chemotherapy for thoracic malignancies. AKI was defined as a decrease in the estimated glomerular filtration rate (eGFR) > 25% from base line, an increase in the serum creatinine (sCre) level of > 0.3 mg/dl or ≥ 1.5 times the baseline level. RESULTS: Eighty of the 84 patients (95.2%) had at least one risk factor for CKD. All enrolled patients received cisplatin with hydration, magnesium supplementation and mannitol. Cisplatin-induced AKI was observed in 18 patients (21.4%). Univariate analysis revealed that cardiac disease and use of non-steroidal anti-inflammatory drugs (NSAIDs) were associated with cisplatin-induced nephrotoxicity (odds ratios [OR] 6 and 3.56, 95% confidence intervals [CI] 1.21-29.87 and 1.11-11.39, p = 0.04 and p = 0.04, respectively). Multivariate analysis revealed that cisplatin nephrotoxicity occurred significantly more often in patients with both risk factors (OR 13.64, 95% CI 1.11-326.83, p = 0.04). Patients with more risk factors for CKD tended to have a greater risk of developing cisplatin-induced AKI. CONCLUSIONS: We should consider avoiding administration of cisplatin to patients with CKD risk factors, particularly cardiac disease and NSAID use.

Direct output of electrical signals from LSPR sensors on the basis of plasmon-induced charge separation.

Potentiometric and conductometric sensors based on localized surface plasmon resonance were developed. The sensors can be applied to coloured and turbid samples because light need not pass through the sample solution.

Identification and structure of a novel archaeal HypB for [NiFe] hydrogenase maturation.

HypB (metal-binding GTPase) and HypA (nickel metallochaperone) are required for nickel insertion into [NiFe] hydrogenase. However, the HypB homolog proteins are not found in some archaeal species including Thermococcales. In this article, we identify a novel archaeal Mrp/MinD family ATPase-type HypB from Thermococcus kodakarensis (Tk-mmHypB) and determine its crystal structure. The mmhypB gene is conserved among species lacking the hypB gene and is located adjacent to the hypA gene on their genome. Deletion of the mmhypB gene leads to a significant reduction in hydrogen-dependent growth of T. kodakarensis, which is restored by nickel supplementation. The monomer structure of Tk-mmHypB is similar to those of the Mrp/MinD family ATPases. The ADP molecules are tightly bound to the protein. Isothermal titration calorimetry shows that Tk-mmHypB binds ATP with a K(d) value of 84 nM. ADP binds more tightly than does ATP, with a K(d) value of 15 nM. The closed Tk-mmHypB dimer in the crystallographic asymmetric unit is consistent with the ATP-hydrolysis-deficient dimer of the Mrp/MinD family Soj/MinD proteins. Structural comparisons with these proteins suggest the ATP-binding dependent conformational change and rearrangement of the Tk-mmHypB dimer. These observations imply that the nickel insertion process during the [NiFe] hydrogenase maturation is performed by HypA, mmHypB, and a nucleotide exchange factor in these archaea.

Effects of dentin surface modifications treated with Er:YAG and Nd:YAG laser irradiation on fibroblast cell adhesion.

OBJECTIVE: The purpose of this in vitro study was to evaluate the effect of surface modifications induced by erbium (Er):YAG and neodymium (Nd):YAG laser irradiation on cell adhesion by comparing it to that of conventional methods for surface preparation after root-end resection. BACKGROUND DATA: Many studies have been seeking a favorable method to produce a resected root end with optimal conditions for cell response. However, little improvement has been achieved. This study evaluated the biocompatibilities of resected root surfaces after Er:YAG or Nd:YAG laser irradiation on initial cell adhesion. MATERIALS AND METHODS: Dentin disks were divided into three groups. Group A was left untreated, Group B was treated with Er:YAG laser irradiation (60 mJ/pulse, 10 pps, 60 sec), and Group C with Nd:YAG laser irradiation (60 mJ/pulse, 10 pps, 60 sec). After laser irradiation, the dentin disks were incubated with NIH/3T3 fibroblasts cultured in Dulbecco's modified Eagle's medium. A morphological analysis of the dentin surface and cell adhesion was observed under a scanning electron microscope. Surface roughness was measured using a confocal laser scanning microscope. The statistical analysis was undertaken using ANOVA at a level of significance of 5% (p<0.05). RESULTS: Morphological analysis and roughness measurement showed that dentin surfaces treated with Er:YAG laser irradiation were rougher than those in Groups A and C. Group B (Er:YAG) exhibited the greatest number of attached cells among all groups after 12 and 24 h. CONCLUSIONS: Morphological alteration induced by Er:YAG laser irradiation showed a favorable effect on the attachment of fibroblasts to dentin surfaces.

Dentin strain induced by laser irradiation.

The purpose of this study was to investigate the strain and temperature change in dentin induced by laser irradiation of human root canals with or without water cooling. Twenty-eight palatal roots of extracted human maxillary first molars were used. The strain in dentin was measured using strain gauges fixed on the apical third of the buccal root surface. The temperature change of the root dentin was monitored using thermocouples embedded into dentin near the apex. The root canal was irradiated with Er:YAG or Nd:YAG laser at an output of 1 W (100 mJ, 10 pps) for 5 s. The tip of the irradiation fibre was located 2.0 mm from the root apex. With water cooling, the mean maximum strain induced by Er:YAG laser was significantly lower than that by Nd:YAG laser (P < 0.05). However, without water cooling, no significant difference between the two lasers (P > 0.05) was found. The results suggest that the strain induced by Er:YAG laser irradiation in dentin with water cooling may be minimal, but there still might be a risk of root micro-fracture if cooling is not sufficient.

Brain activation associated with changes in heart rate, heart rate variability, and plasma catecholamines during rectal distention.

OBJECTIVE: To test the hypothesis that gut stimulation provokes autonomic arousal via activation of regional cerebral cortices. How the human brain processes interoceptive signals and forms initial autonomic arousal is one of the key questions to be answered in research on emotion. METHODS: Twelve healthy males participated in this study. A barostat bag was inserted in the rectum and intermittently inflated with 0, 20, or 40 mm Hg at random for 80 seconds. H(2)(15)O positron emission tomography (PET) of the brain, electrocardiography, and blood sampling for catecholamines were performed. Changes in regional cerebral blood flow were interpreted using statistical parametric mapping. RESULTS: Rectal distention with 40 mm Hg induced a significant increase in heart rate, low frequency (LF)/high frequency (HF) ratio of heart rate variability, and plasma adrenaline. Activated brain areas that were associated with increased heart rate during rectal distention were the right insula, right operculum, right dorsolateral prefrontal cortex, putamen, thalamus, periaqueductal gray, and cerebellum (p < .001, uncorrected), whereas those that were associated with an increased LF/HF ratio were the bilateral insula, putamen, thalamus, midbrain, pons, and cerebellum (p < .001, uncorrected). Activated brain areas that were associated with increased plasma adrenaline were the right insula, right orbitofrontal cortex, right parahippocampal gyrus, putamen, thalamus, periaqueductal gray, pons, and cerebellum (p < .001, uncorrected). CONCLUSION: Our results suggest that the right insula and the related body mapping regions may form the functional module of sympathetic arousal in response to gut stimulation.

Antinociceptive effect of methyleugenol on formalin-induced hyperalgesia in mice.

The effects of methyleugenol, an essential oil isolated from Asiasari radix, on antinociception were examined using the formalin test in mice. Oral administration of 10 mg/kg methyleugenol significantly decreased the duration of licking and biting behavior in the second phase without affecting that of the first phase, as did diclofenac, a non-steroidal anti-inflammatory drug. Methyleugenol also inhibited pain-related behaviors induced by intrathecal injection of N-methyl-d-aspartic acid (NMDA), while diclofenac did not affect these behaviors. These effects of methyleugenol were suppressed by bicuculline, a gamma-aminobutyric acid(A) (GABA(A)) antagonist. Muscimol, a GABA(A) agonist, displays the same action as methyleugenol with respect to the formalin test and NMDA-induced behaviors. Methyleugenol did not affect cyclooxygenase-1 and -2 activities. These results suggest that the antinociceptive effect of methyleugenol on the second phase of formalin-induced pain may be due to the inhibition of NMDA receptor-mediated hyperalgesia via GABA(A) receptors.

A randomized controlled trial of postoperative adjuvant immunochemotherapy for colorectal cancer with oral medicines.

Postoperative adjuvant chemotherapy reportedly improves advanced colorectal cancer patients' survival, however, it is necessary to assess what regimens are useful. Doxifluridine (5'-DFUR) is an intermediate of capecitabine approved in Europe and USA to treat metastatic colorectal cancer. 5'-DFUR is metabolized to 5-fluorouracil (5-FU) by thymidine phosphorylase existing in tumor at high concentrations, suggesting high 5-FU levels in tumor tissues and lesser complications. Present study compared usefulness of 5'-DFUR to that of oral 5-FU. Patients were enrolled at 38 centers from April 1993 to September 1996. They had diagnosed colorectal cancer of TNM stages II and III, and underwent macroscopic curative resection. Patients were prestratified into colon or rectum cancer and allocated into either 5'-DFUR (5'-DFUR 460 mg/m(2)/day + PSK 3 g/day) or 5-FU (5-FU 115 mg/m(2)/day + PSK 3 g/day) group by dynamic randomization (stratification factors such as depth of tumor, degree of lymph node metastasis, and location of tumor). Drugs were orally administered daily from postoperative week 2 to 54, with 6 mg/m(2) mitomycin C at operation and following days. Subjects for analysis were 277 in 5'-DFUR and 281 in 5-FU groups. Median follow-up was 6.5 years. Although no differences in overall survival curves were detected, multivariate analysis showed that 5'-DFUR + PSK regimen was a significantly better prognostic factor in patients with Dukes B or C (risk ratio, 1.451; p=0.048); with tumor depth of pT3 or pT4 (risk ratio, 1.568; p=0.020). For patients with advanced colorectal cancer, 5'-DFUR + PSK therapy may possibly be more useful than 5-FU + PSK, but further study is required.