Sensitivity to tumor development by TALEN-mediated Trp53 mutant genes in the susceptible FVB/N mice and the resistance C57BL/6 mice.

BACKGROUND: This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53em2Hwl/Korl and C57BL/6-Trp53em1Hwl/Korl knockout (KO) mice over 16 weeks. RESULTS: Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53em2Hwl/Korl KO mice, but were not detected in C57BL/6-Trp53em1Hwl/Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53em2Hwl/Korl KO mice. CONCLUSIONS: Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice over 16 weeks.

A Data-Based Framework for Identifying a Source Location of a Contaminant Spill in a River System with Random Measurement Errors.

This study addresses the problem of identifying the source location of a contaminant spill in a river system when a sensor network returns observations containing random measurement errors. To solve this problem, we suggest a new framework comprising three main steps: (i) spill detection, (ii) data preprocessing, and (iii) source identification. Specifically, we applied a statistical process control chart to detect a contaminant spill with measurement errors while keeping the false alarm rate at less than or equal to a user-specified value. After detecting a spill, we generated a nonlinear regression model to estimate a breakthrough curve of the observations and derive a characteristic vector of the estimated curve. Using the characteristic vector as an input, a random forest model was constructed with the sensor raising the first alarm. The model provides output values between 0 and 1 to represent the possibility of each candidate location being the true spill source. These possibility values allow users to identify strong candidate locations for the spill. The accuracy of our framework was tested on part of the Altamaha River system in Georgia, USA.

Synergic Laxative Effects of an Herbal Mixture of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia in Loperamide-Induced Constipation of Sprague Dawley Rats.

Constipation is an acute or chronic illness attributed to various causes, ranging from lifestyle habits to side effects of a disease. To improve the laxative effects of some traditional medicines, herbal mixtures of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia (LGC) were evaluated for their mechanism of action and therapeutic effects in loperamide (Lop)-induced constipated Sprague Dawley rats by examining alterations in excretion parameters, histological structure, mucin secretion, and related protein levels. Food intake and water consumption were constant for all animals. We observed that the Lop+LGC-treated group had significantly greater excretion of stool and urine than was observed in the Lop+Vehicle-treated group. Administration of LGC in the constipation model restored the intestinal transit ratio to normal levels, and increased the number of goblet cells, mucosal layer, and muscle thickness. Mucin secretion was greater in the Lop+LGC-treated group than in the Lop+Vehicle-treated group, and the expression of MUC2 and AQP8 genes were also increased. In addition, reverse transcription polymerase chain reaction and Western blot revealed an increase in the muscarinic acetylcholine receptors (mAChRs) in the Lop+LGC-treated group compared to the Lop+Vehicle-treated group. Furthermore, compared with the Lop+Vehicle-treated group, treatment with LGC reduced the phosphorylation of PKC and PI3K, and expression of Gα protein, but increased levels of IP3. Our results suggest that the traditional herbal mixture of LGC induces a potent laxative effect in Lop-induced constipation through mucosal tissue changes and mucin production. We also demonstrated that the laxative effect of LGC is closely related to the expression of mAChR and its downstream signals, suggesting the possibility of developing a constipation-laxative agent using LGC.

Butanol extracts of Asparagus cochinchinensis fermented with Weissella cibaria inhibit iNOS-mediated COX-2 induction pathway and inflammatory cytokines in LPS-stimulated RAW264.7 macrophage cells.

Roots of Asparagus cochinchinesis have been widely used to treat fever, cough, kidney disease, breast cancer, inflammatory and brain disease, although the effects of their fermented products have not been assessed until now. To investigate the anti-inflammatory effects on macrophages of a butanol extract from A. cochinchinensis roots fermented with Weissella cibaria (BAW), alterations in the inducible nitric oxide synthase (iNOS)-mediated cyclooxygenase-2 (COX-2) induction pathway and inflammatory cytokine expression were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following pretreatment with BAW. Briefly, W. cibaria was selected from two bacterial strains for the fermentation of A. cochinchinensis roots based on its hyaluronidase inhibition and NO suppression rates. Following fermentation with W. cibaria, the level of various key components including total phenols and protodioscin were significantly enhanced in BAW. In addition, BAW exhibited high free radical scavenging activity (IC50=31.62 µg/ml) and induced a decrease of intracellular ROS production in RAW264.7 cells following DCFH-DA staining. Significant suppressions in the expression level of important members of the iNOS-mediated COX-2 induction pathway and the phosphorylation of mitogen-activated protein kinase members were detected. The expressions of pro-inflammatory and anti-inflammatory cytokines were recovered in BAW pretreated RAW264.7 cells. Overall, these results suggest that BAW may suppress inflammatory responses through differential regulation of the iNOS-mediated COX-2 induction pathway and inflammatory cytokine expressions in LPS-activated RAW264.7 cells.

Effect of exercise performance by elderly women on balance ability and muscle function.

[Purpose] The aim of this study was to investigate the effect of an exercise intervention on the balance ability and muscle function of elderly women. [Subjects] The subjects were randomly divided into a control group (n=10) and an exercise group (n=10). [Methods] The subjects participated in an elastic band exercise program lasting for 8 weeks, exercising for 40 minutes, four days a week with resting terms of 60 sec. Subjects used a band corresponding to 60% of the strength of the color band with which repetitive exercise was possible up to twelve times. The subjects performed elastic band exercises, with variations to the number of band exercises according to the improvement of their physical fitness levels. When fifteen repetitive elastic band exercises could be performed with no damage of the body, we changed the band for one which was one level up from the former one and subjects used the same band for the upper body and lower body. [Results] Leg muscular strength measured as sit-stand repetitions in 30 s significantly increased in the exercise group after the intervention compared to before the intervention. Leg muscular endurance measured as the number of knee ups in 2 minutes significantly increased in the exercise group after the intervention compared to before the intervention. Balance measured by one-leg standing time with the eyes open significantly improved in the exercise group after the intervention compared to before the intervention. [Conclusion] Balance ability and muscle function significantly improved in the exercise group and showing that the intervention is effective at improving balance, muscle strength, and muscle endurance of elderly women.

Reactive strategies for containing developing outbreaks of pandemic influenza.

BACKGROUND: In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza. METHODS: We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city. RESULTS: Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US$81 million for such a city. Attack rates and economic costs can be reduced to 5.4% and US$37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy. CONCLUSIONS: Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza.