Solution structures of a DNA dodecamer duplex with and without a cisplatin 1,2-d(GG) intrastrand cross-link: comparison with the same DNA duplex containing an oxaliplatin 1,2-d(GG) intrastrand cross-link

Proteins that discriminate between cisplatin-DNA adducts and oxaliplatin-DNA adducts are thought to be responsible for the differences in tumor range, toxicity, and mutagenicity of these two important chemotherapeutic agents. However, the structural basis for differential protein recognition of these adducts has not been determined and could be important for the design of more effective platinum anticancer agents. We have determined high-resolution NMR structures for cisplatin-GG and undamaged DNA dodecamers in the AGGC sequence context and have compared these structures with the oxaliplatin-GG structure in the same sequence context determined previously in our laboratory. This structural study allows the first direct comparison of cisplatin-GG DNA and oxaliplatin-GG DNA solution structures referenced to undamaged DNA in the same sequence context. Non-hydrogen atom rmsds of 0.81 and 1.21 were determined for the 15 lowest-energy structures for cisplatin-GG DNA and undamaged DNA, respectively, indicating good structural convergence. The theoretical NOESY spectra obtained by back-calculation from the final average structures showed excellent agreement with the experimental data, indicating that the final structures are consistent with the NMR data. Several significant conformational differences were observed between the cisplatin-GG adduct and the oxaliplatin-GG adduct, including buckle at the 5' G6.C19 base pair, opening at the 3' G7.C18 base pair, twist at the A5G6.T20C19 base pair step, slide, twist, and roll at the G6G7.C19C18 base pair step, slide at the G7C8.C18G17 base pair step, G6G7 dihedral angle, and overall bend angle. We hypothesize that these conformational differences may be related to the ability of various DNA repair proteins, DNA binding proteins, and DNA polymerases to discriminate between cisplatin-GG and oxaliplatin-GG adducts.     

Roles of MMP/TIMP in regulating matrix swelling and cell migration during chick corneal development

Tissue remodeling is central to embryonic development. Here, we used immunohistochemistry, Western blotting, and RT-PCR analysis to investigate the roles of matrix metalloproteinases (MMPs) and the related "a disintegrin and metalloproteinase" (ADAM) family proteinases in chick corneal development. While MMP-13 was expressed in developing chick corneas from embryonic day (ED) 5 to ED 10, its inhibitor, tissue inhibitors of metalloproteinase-1 (TIMP-1), was expressed from ED 18 to 2 days post-hatching (P2). Early MMP-13 activity may be associated with degradation of type IX collagen from the primary stroma, which loosens the collagen fibrils and facilitates neural crest (NC) cell migration. The membrane-bound and secreted forms of ADAM10 were both detected throughout corneal development, and active ADAM10 formed a cleavage complex with CD44v6, a CD44 splice variant that is a major cell surface adhesion molecule for hyaluronic acid (HA) and has been implicated in cell migration. Both CD44v6 and its ectodomain cleavage products were detected from ED 5 to ED 14, and a broad-spectrum MMP inhibitor blocked ectodomain cleavage in cultured stromal cells. These findings suggest that ADAM10 mediates CD44v6 cleavage in the developing cornea, facilitating NC cell-derived mesenchymal cell migration. Finally, we identified high levels of active membrane-type 3-MMP (MT3-MMP) in developing corneas at ED 7, ED 14, and ED 18. MT3-MMP takes part in MMP-2 activation and possibly also CD44v6 shedding, suggesting that this pathway may be involved in cell migration. These findings collectively show for the first time that multiple MMPs, ADAMs, and TIMPs appear to functionally interact during corneal development.     

A novel adenoviral vector-mediated mouse model of Charcot-Marie-Tooth type 2D (CMT2D)

Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. Here, we report a novel GARS-associated mouse neuropathy model using an adenoviral vector system that contains a neuronal-specific promoter. In this model, we found that wild-type GARS is distributed to peripheral axons, dorsal root ganglion (DRG) cell bodies, central axon terminals, and motor neuron cell bodies. In contrast, GARS containing a G240R mutation was localized in DRG and motor neuron cell bodies, but not axonal regions, in vivo. Thus, our data suggest that the disease-causing G240R mutation may result in a distribution defect of GARS in peripheral nerves in vivo. Furthermore, a distributional defect may be associated with axonal degradation in GARS-associated neuropathies.     

Improving the performance of data center with real-time service image placement in mobile cloud environment

Mobile Cloud Computing (MCC) is broadening the ubiquitous market for mobile devices. Because of the hardware limitation of mobile devices, the heavy computing tasks should be processed by service images (SIs) on the cloud. Due to the scalability and mobility of users and services, dynamic resource demands and time-varying network condition, SIs must be re-located to adapt the new circumstances. In this paper, we formulate the SI placement as an optimization problem which minimizes the communication cost subject to resource demand constraints. We then propose a real-time SI placement scheme which includes two sequent stages of clustering/filtering and condensed placement to solve the formulated problem. The former omits the infeasible slots prior to placement in order to improve computational complexity. The latter focuses on the SI placement through a novel condensed solution. The numerical results show that our solution converges to the global optimum with a negligible gap while performing much faster execution time compared with the exhaustive search method. This improvement leverages the real-time services especially in MCC environment.     

Ethanol production from galactose by a newly isolated Saccharomyces cerevisiae KL17

A wild-type yeast strain with a good galactose-utilization efficiency was newly isolated from the soil, and identified and named Saccharomyces cerevisiae KL17 by 18s RNA sequencing. Its performance of producing ethanol from galactose was investigated in flask cultures with media containing various combination and concentrations of galactose and glucose. When the initial galactose concentration was 20 g/L, it showed 2.2 g/L/h of substrate consumption rate and 0.63 g/L/h of ethanol productivity. Although they were about 70 % of those with glucose, such performance of S. cerevisiae KL17 with galactose was considered to be quite high compared with other strains reported to date. Its additional merit was that its galactose metabolism was not repressed by the existence of glucose. Its capability of ethanol production under a high ethanol concentration was demonstrated by fed-batch fermentation in a bioreactor. A high ethanol productivity of 3.03 g/L/h was obtained with an ethanol concentration and yield of 95 and 0.39 g/L, respectively, when the cells were pre-cultured on glucose. When the cells were pre-cultured on galactose instead of glucose, fermentation time could be reduced significantly, resulting in an improved ethanol productivity of 3.46 g/L/h. The inhibitory effects of two major impurities in a crude galactose solution obtained from acid hydrolysis of galactan were assessed. Only 5-Hydroxymethylfurfural (5-HMF) significantly inhibited ethanol fermentation, while levulinic acid (LA) was benign in the range up to 10 g/L.     

Gender Differences and Socioeconomic Status in Relation to Overweight among Older Korean People

Background

The ever-increasing older population and its association with serious overweight problems have garnered much attention. The correlation between being overweight and socioeconomic status factors could be helpful for understanding the inequalities among the overweight population. We examined the correlation between being overweight and some key variables, such as demographics, socioeconomic status, general health status, and health behavior in a large sample of older individuals, by each gender.

Methods

We used data from the 2008 Korean Longitudinal Study of Aging and it included 8,157 participants who were 45 years or older. To understand the relationship between the overweight participants in accordance to demographic and socioeconomic characteristics, health status, and health behaviors, a weighted chi-square test and logistic regression analysis were conducted by separating variables related to overweight, according to the genders.

Results

The number of people in the normal group was 6,347 (77.8%), while the people who were considered overweight were 1,810 (22.2%). Women (n = 4,583) constituted 52.7% of the subject, 24.9% of whom were classified as overweight. Meanwhile, 20.6% of the 47.3% (n = 3,574) of the sample who were men were classified as overweight. Participants between the ages of 45 and 64 with chronic diseases were more likely to be overweight. Men in the 4th quartile of household income were more likely to be overweight than those who were in the 1st quartile, in contrast, while unemployed women with lower education levels and urban residents were at greater risk for being overweight.

Conclusions

Among the men, health status and health behavior appeared to show a correlation with being overweight; however, among women, socioeconomic status factors were strongly related to being overweight. These findings appear to support the association of gender-specifics with the prevalence of being overweight.     

CD163 Expression Was Associated with Angiogenesis and Shortened Survival in Patients with Uniformly Treated Classical Hodgkin Lymphoma

Background

Recent studies have reported the prognostic value of tissue-associated magrophages (TAMs) in classical Hodgkin lymphoma (cHL). In addition, TAMs are implicated in the tumor angiogenesis. In this study, we examined the prognostic relevance of TAMs in relation to vascular endothelial growth factor (VEGF) expression and angiogenesis in uniformly treated cases of cHL.

Methods

Diagnostic tissue from 116 patients with ABVD-treated cHL was evaluated retrospectively by immunohistochemical analysis for CD68, CD163 and VEGF expression and for CD31 expression as a measure of microvessel density (MVD).

Results

High CD163 expression (≥35% of cellularity) correlated with VEGF expression (Pearson’s Chi-square test, P = 0.008) and MVD (Spearman correlation coefficient 0.310, P<0.001). High CD163 expression was associated with inferior event-free survival (EFS, P = 0.005) and overall survival (OS, P<0.001) in univariate analysis. In multivariate analysis, high CD163 expression was strongly associated with inferior EFS (P = 0.043) and OS (P = 0.008). Patients with high MVD had a lower OS than those with low MVD, but the difference was not significant (P = 0.071, respectively). While high expression of CD68 was also associated with inferior EFS (P = 0.007), it showed no correlation with VEGF or MVD.

Conclusions

Our data confirms that CD163 expression provides independent prognostic information in cHL. The correlation of CD163 with VEGF expression and MVD suggests the role of CD163-positive cells in tumor angiogenesis of cHL.     

Circulating Irisin Levels Are Not Affected by Coffee Intake: A Randomized Controlled Trial

Irisin, secreted by skeletal muscle and possibly fat, is hypothesized to play an important role in modulating energy expenditure, obesity and metabolism. Coffee consumption also increases energy expenditure and leads to positive metabolic effects, but whether these effects are mediated by irisin remains unknown. The objective of this study was to determine the association between baseline irisin levels and the metabolic profile in humans and to investigate whether consumption of caffeinated coffee alters irisin levels. To this end, a secondary analysis was performed investigating irisin levels at baseline and after eight weeks in 32 healthy, overweight coffee drinkers who were randomized to consumption of 5 cups per day of instant caffeinated coffee, decaffeinated coffee, or water. Spearman correlation and analysis of covariance analyses were performed to identify possible associations. Irisin levels were positively correlated with waist circumference (r = 0.41, p = 0.02), fat mass (r = 0.44, p = 0.01) and CRP (r = 0.47, p = 0.007). Though there was a trend towards increased levels of irisin over time in the caffeinated coffee group (+1.8%) when compared to the placebo group (−4%) this did not reach statistical significance (p = 0.75 for the trend). This first randomized trial failed to reveal any effects of coffee consumption on irisin levels, but a larger trial, appropriately sized on the basis of data provided by this study, is needed to conclusively investigate such a relationship.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00305097","term_id":"NCT00305097"}}NCT00305097     

Effect of intake of gardenia fruits and combined exercise of middle-aged obese women on hormones regulating energy metabolism

[Purpose]

This study is aimed at analyzing how exercise and gardenia affect hormones that regulate energy metabolism by having middle aged, obese women exercise and take gardenia simultaneously.

[Methods]

This study assigned a total of 35 middle-aged obese women with body fat percentage of more than 35 percent into 9 people of the complex treatment group of intake of gardenia and exercise, 9 people of the exercise group, 9 people of the gardenia group and 8 people of the control group in order to find out the effect of the intake of gardenia fruits and Combined exercise of 8 weeks on the body composition, hormones regulating energy metabolism. This study arranged .08 g per weight of 1 kg of the gardenia fruits to be taken twice a day for 8 weeks after breakfast and dinner through the numerical method of roasting the gardenia fruits on fire. And the exercise program was set to be five times a week for 8 weeks, whereas the aerobic exercise of 60 to 70 minutes was 50 to 60 percent for HRmax; thus, the resistance exercise was set to be 1-RM 50 percent. As for the data analysis, the two-way repeated measures ANOVA was utilized for the analysis of interactive effect between groups and times.

[Results]

Thus, the obtained conclusion is as follows: The %fat and WHR has decreased further in the gardenia+exercise group and the exercise group as compared with the control group. And the visceral fat area has decreased further in the gardenia and exercise group and the gardenia group as compared with the control group (p<.05). In addition, the gardenia+exercise group and the exercise group were found to have a significant improvement effect in all the items of body composition, and the gardenia group has reduced the fat percentage and BMI after the treatment (p<.05). Leptin has decreased further in the gardenia+exercise group and the exercise group as compared with the control group, and the insulin resistance and GLP-1 have decreased in all the treatment groups (p<.05).

[Conclusion]

As a result of this study, all the treatment groups were found to have an improvement effect of research variables in general; therefore, the single treatment and complex treatment for the middle-aged obese women were found to have a positive impact on body composition, adjusting factors for energy metabolism. Also, the complex treatment was found to be more positive in terms of change amount. In particular, in the case of visceral fat area that is the major risk factor for metabolic disease of middle-aged obese women, it was found to have decreased further in the complex treatment group than the gardenia group; therefore, the complex treatment was found to be more advantageous.