Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1) Gene in Primary Breast Cancer

Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1) gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC) with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP) in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004). Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007). Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.     

Impact of Registered Dietitian Expertise in Health Guidance for Weight Loss

Background & Objectives

Expertise of registered dietitians (RDs) is important for health guidance but has been poorly evaluated. We evaluated the kind of RD expertise that would improve their skills.

Design, Setting, Participants, Measurements

This study was a post-hoc analysis of our randomized controlled trial, which compared the weight change between participants using the web-based self-disclosure health support and those using the email health support. Healthy men and women aged 35–64 years with a body mass index (BMI) of > = 24.5 kg/m² were recruited for this study. We evaluated the relationship of RD expertise indicators including the duration of working as an RD, the experience of health counseling, and membership in the Japan Dietetic Association (JDA) with the weight loss of study participants. The primary endpoint was the change in body weight. Comparison of changes in body weight by the RD expertise indicators was evaluated using analysis of covariance.

Results

A total of 175 participants were eligible for analyses. Changes in body weight were significantly greater when they were supported by the RDs in the routine counseling group than when supported by the RDs in the non-routine counseling group (-1.8 kg versus -0.4 kg, fully adjusted P = 0.0089). Duration of working as an RD and JDA membership did not significantly affect changes in body weight.

Conclusions

Among some indices of RD experience, the experience of providing routine experience of health counseling was associated with weight loss.     

Practical one-step glucuronidation via biotransformation

We herein report a practical one-step glucuronidation method by biotransformation using Streptomyces sp. SANK 60895. This novel direct method of biotransformation has been shown to be more practical and scalable for glucuronidation than previously reported chemical and enzymatic procedures given its simplicity, high β-selectivity, cost-effectiveness, and reproducibility. We applied the present method to the synthesis of acyl glucuronide and hydroxy-β-glucuronide of mycophenolic acid and compound 4, respectively. This method was also shown to be applicable to the N-glucuronidation of various compounds.     

Environmental analysis of packaging‐derived changes in food production and consumer behavior

This study analyzed the environmental impacts of packaging‐derived changes in food production and consumer behavior to assist packaging designers in making environmentally conscious decisions. Packaging can be functionalized to prevent food loss and waste (FLW), for example, extending the expiration date and apportioning the package size, but it can generate additional environmental impacts from changes in food and packaging production. Previous studies assessed additional impacts from packaging production; however, the effects of packaging functionalization are yet to be connected with food production and consumer behavior. To examine the effect of functionalization on these aspects, we analyzed packaging‐derived changes in food production for milk and cabbage products. The case study compared products with functionalized packaging that permits a longer expiration date or a smaller portion size to their base‐case products. Our results showed that the packaging‐derived changes increased the global warming potential (GWP) of food production more than other processes did. Thus, changes in food production weakened the effectiveness of the packaging functionalization to decrease the GWP. Moreover, the analysis of consumer behavior scenarios showed that consumers’ perception of the expiration date decisively influences the effectiveness of packaging functionalization. When consumers discarded food after the expiration date, provided they consumed in small quantities, the packaging functionalization reduced FLW. From the scenario analysis, we identified appropriate combinations of packaging functionalization and consumer behaviors to effectively decrease total GWP. With our expanded analysis, packaging designers can understand the effectiveness of their decisions on the product life cycle in reducing FLW and environmental impacts.     

Forest characteristics and population structure of Glyptostrobus pensilis,a globally endangered relict species of southeastern China

The Chinese water pine Glyptostrobus pensilis is the sole surviving species of the genus Glyptostrobus. It is endemic to southern China, central Vietnam, and eastern Laos, and today it is nearly extinct in the wild. Forest community characteristics and population structure of G. pensilis in China have remained un-known up to now. We investigated six swamp forest stands and analyzed their forest community characteristics (i.e. vertical stratification, species composition, and diversity) and population structure, including the frequency distribution of DBH (diameter at breast height) and age-classes as found in Fujian Province, southeastern China. The vertical stratifications of all the forest stands were rather simple. The remaining wild specimens ranged from roughly 15 to some 357 years for an average of ca. 85 years, with only a few individuals less than 20 years old. Compared with the stands and populations of G. pensilis in Vietnam, the taxonomic compositions of the stands in the two regions were different, except for the dominant species-G. pensilis. The Shannon-Wiener index showed the overstory of each stand had much lower diversity (0.26 on average) in Fujian Province than that (1.97 on average) in Vietnam, whereas the diversity indices were about the same (around 2.41) for the understories in the two regions. Furthermore, we discovered 18 G. pensilis seedlings at the study sites in Fujian Province. This discovery demonstrates that G. pensilis regeneration is extremely poor and its populations are declining, although these populations are rela-tively healthier than those in Vietnam.     

Leucyl/phenylalanyl(L/F)-tRNA-protein transferase-mediated aminoacyl transfer of a nonnatural amino acid to the N-terminus of peptides and proteins and subsequent functionalization by bioorthogonal reactions

We report here a new strategy for derivatizing peptides and proteins at the N-terminus. To achieve this, a nonnatural amino acid was charged onto a tRNA and then enzymatically transferred to a lysine (Lys) unit at the N-terminus of a peptide or a protein by using L/F-tRNA-protein transferase. By using the chemoenzymatic technique, beta-(2-quinolyl)-L-alanine, p-azido-L-phenylalanine, and p-acetyl-L-phenylalanine were introduced to the N-terminus. The latter two nonnatural amino acids possess bioorthogonal functional groups to which artificial tags can be introduced. Actually, a biotin tag was coupled to the bioorthogonal ketone group of acetylphenylalanine at the N-terminus of a peptide. N-terminal-specific biotinylation and fluorescence derivatization of the bioorthogonal azido-containing protein or peptide was also carried out based on a [3 + 2] cycloaddition. The enzymatic transfer of a nonnatural amino acid to the N-terminus of target peptides or proteins was also successfully achieved in the presence of other peptides or crude protein mixtures.     

Disulfide bond mediates aggregation, toxicity, and ubiquitylation of familial amyotrophic lateral sclerosis-linked mutant SOD1

Mutations in the Cu/Zn-superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS) through the gain of a toxic function; however, the nature of this toxic function remains largely unknown. Ubiquitylated aggregates of mutant SOD1 proteins in affected brain lesions are pathological hallmarks of the disease and are suggested to be involved in several proposed mechanisms of motor neuron death. Recent studies suggest that mutant SOD1 readily forms an incorrect disulfide bond upon mild oxidative stress in vitro, and the insoluble SOD1 aggregates in spinal cord of ALS model mice contain multimers cross-linked via intermolecular disulfide bonds. Here we show that a non-physiological intermolecular disulfide bond between cysteines at positions 6 and 111 of mutant SOD1 is important for high molecular weight aggregate formation, ubiquitylation, and neurotoxicity, all of which were dramatically reduced when the pertinent cysteines were replaced in mutant SOD1 expressed in Neuro-2a cells. Dorfin is a ubiquityl ligase that specifically binds familial ALS-linked mutant SOD1 and ubiquitylates it, thereby promoting its degradation. We found that Dorfin ubiquitylated mutant SOD1 by recognizing the Cys(6)- and Cys(111)-disulfide cross-linked form and targeted it for proteasomal degradation.     

Physiological effects of Shinrin-yoku (taking in the atmosphere of the forest)--using salivary cortisol and cerebral activity as indicators

The purpose of this study is to examine the physiological effects of Shinrin-yoku (taking in the atmosphere of the forest). The subjects were 12 male students (22.8+/-1.4 yr). On the first day of the experiments, one group of 6 subjects was sent to a forest area, and the other group of 6 subjects was sent to a city area. On the second day, each group was sent to the opposite area for a cross check. In the forenoon, the subjects were asked to walk around their given area for 20 minutes. In the afternoon, they were asked to sit on chairs and watch the landscapes of their given area for 20 minutes. Cerebral activity in the prefrontal area and salivary cortisol were measured as physiological indices in the morning at the place of accommodation, before and after walking in the forest or city areas during the forenoon, and before and after watching the landscapes in the afternoon in the forest and city areas, and in the evening at the place of accommodation. The results indicated that cerebral activity in the prefrontal area of the forest area group was significantly lower than that of the group in the city area after walking; the concentration of salivary cortisol in the forest area group was significantly lower than that of the group in the city area before and after watching each landscape. The results of the physiological measurements show that Shinrin-yoku can effectively relax both people's body and spirit.