FXR signaling in metabolic disease

AbstractFarnesoid X receptor (FXR), a member of the nuclear receptor superfamily, has been shown to be important in controlling numerous metabolic pathways; these include roles in maintaining bile acid, lipid and glucose homeostasis, in preventing intestinal bacterial infection and gallstone formation and in modulating liver regeneration and tumorigenesis. The accumulating data suggest that FXR may be a pharmaceutical target for the treatment of certain metabolic diseases

Designing a mobile augmented memory system for people with traumatic brain injuries

Augmented memory systems help people remember events in their lives. Individuals with Traumatic Brain Injury (TBI) often have memory impairments. We conducted a user study to learn about strategies individuals with TBI use to remember events in their lives. We explored what characteristics individuals with TBI expect of an augmented memory system. We then investigated these aspects in an initial mobile app design, and propose here a concept for a rehearsal application that addresses the issues found in our studies

Erosion patterns in a sediment layer

We report here on a laboratory-scale experiment which reproduces a rich variety of natural patterns with few control parameters. In particular, we focus on intriguing rhomboid structures often found on sandy shores and flats. We show that the standard views based on water surface waves come short to explain the phenomenon and we evidence a new mechanism based on a mud avalanche instability.Comment: 4 pages, 4 figures, to appear as Phys. Rev. E rapid com

DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML

<b>Background</b>. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are neoplastic disorders of hematopoietic stem cells. DNA methyltransferase inhibitors (DNMTi), 5-azacytidine (AzaC) and 5-aza-2’-deoxycytidine (Decitabine), benefit some MDS/AML patients. However, the role of DNMTi-induced DNA hypomethylation in regulation of gene expression in AML is unclear.<p></p> <b>Results. </b> We compared the effects of AzaC on DNA methylation and gene expression using whole-genome single-nucleotide bisulfite-sequencing (WGBS) and RNA-sequencing in OCI-AML3 (AML3) cells. For data analysis, we used an approach recently developed for discovery of differential patterns of DNA methylation associated with changes in gene expression, that is tailored to single-nucleotide bisulfite-sequencing data (Washington University Interpolated Methylation Signatures (WIMSi)). By this approach, a subset of genes upregulated by AzaC was found to be characterized by AzaC-induced signature methylation loss flanking the transcription start site. These genes are enriched for genes increased in methylation and decreased in expression in AML3 cells compared to normal hematopoietic stem and progenitor cells. Moreover, these genes are preferentially upregulated by Decitabine in human primary AML blasts, and control cell proliferation, death and development. <p></p> <b>Conclusions.</b> Our WGBS and WIMSi data analysis approach has identified a set of genes whose is methylation and silencing in AML is reversed by DNMTi. These genes are good candidates for direct regulation by DNMTi, and their reactivation by DNMTi may contribute to therapeutic activity. This study also demonstrates the ability of WIMSi to reveal relationships between DNA methylation and gene expression, based on single-nucleotide bisulfite-sequencing and RNA-seq data.<p></p&gt

Willingness to communicate among Korean learners of English

Many Koreans not only feel strongly motivated to study English but they also enthusiastically pursue learning the language, and yet when real contact situations arise in which English could be used, many Koreans remain unwilling to do so. Better understanding this phenomenon could benefit not only Koreans but also other groups of people who see great value in learning a language but undercut their own efforts by avoiding opportunities to use it. Through a series of interviews leading to a large quantitative study, this research investigates some underlying factors which influence Korean learners' decision over whether to use English in a particular situation. The main findings suggest that the quality and quantity of previous contact with the non-Korean world, for example through travel and friendship, along with the presence and relative status of other Koreans at the communication event, significantly influence language use. These results generally support the theories of the Contact Hypothesis (CH) and Willingness to Communicate (WTC). These disparate theories, together in the Korean context, suggest a need for greater focus on L2 friendship and L 1 status issues in language learning

The utility of single nucleotide polymorphisms in inferences of population history

Single nucleotide polymorphisms (SNPs) represent the most widespread type of sequence variation in genomes, yet they have only emerged recently as valuable genetic markers for revealing the evolutionary history of populations. Their occurrence throughout the genome also makes them ideal for analyses of speciation and historical demography, especially in light of recent theory suggesting that many unlinked nuclear loci are needed to estimate population genetic parameters with statistical confidence. In spite of having lower variation compared with microsatellites, SNPs should make the comparison of genomic diversities and histories of different species (the core goal of comparative biogeography) more straightforward than has been possible with microsatellites. The most pervasive, but correctable, complication to SNP analysis is a bias towards analyzing only the most variable loci, an artifact that is usually introduced by the limited number of individuals used to screen initially for polymorphisms. Although the use of SNPs as markers in population studies is still new, innovative methods for SNP identification, automated screening, haplotype inference and statistical analysis might quickly make SNPs the marker of choice

Willingness to communicate among Korean learners of English

Many Koreans not only feel strongly motivated to study English but they also enthusiastically pursue learning the language, and yet when real contact situations arise in which English could be used, many Koreans remain unwilling to do so. Better understanding this phenomenon could benefit not only Koreans but also other groups of people who see great value in learning a language but undercut their own efforts by avoiding opportunities to use it. Through a series of interviews leading to a large quantitative study, this research investigates some underlying factors which influence Korean learners' decision over whether to use English in a particular situation. The main findings suggest that the quality and quantity of previous contact with the non-Korean world, for example through travel and friendship, along with the presence and relative status of other Koreans at the communication event, significantly influence language use. These results generally support the theories of the Contact Hypothesis (CH) and Willingness to Communicate (WTC). These disparate theories, together in the Korean context, suggest a need for greater focus on L2 friendship and L 1 status issues in language learning

Photocatalytic degradation of eleven microcystin analogues and nodularin by TiO2 coated glass microspheres

Microcystins and nodularin are toxic cyanobacterial secondary metabolites produced by cyanobacteria that pose a threat to human health in drinking water. Conventional water treatment methods often fail to remove these toxins. Advanced oxidation processes such as TiO2 photocatalysis have been shown to effectively degrade these compounds. A particular issue that has limited the widespread application of TiO2 photocatalysis for water treatment has been the separation of the nanoparticulate powder from the treated water. A novel catalyst format, TiO2 coated hollow glass spheres (Photospheres™), is far more easily separated from treated water due to its buoyancy. This paper reports the photocatalytic degradation of eleven microcystin variants and nodularin in water using Photospheres™. It was found that the Photospheres™ successfully decomposed all compounds in 5min or less. This was found to be comparable to the rate of degradation observed using a Degussa P25 material, which has been previously reported to be the most efficient TiO2 for photocatalytic degradation of microcystins in water. Furthermore, it was observed that the degree of initial catalyst adsorption of the cyanotoxins depended on the amino acid in the variable positions of the microcystin molecule. The fastest degradation (2min) was observed for the hydrophobic variants (microcystin-LY, -LW, -LF). Suitability of UV-LEDs as an alternative low energy light source was also evaluated

Clinical and medication profiles stratified by household income in patients referred for diabetes care

BACKGROUND: Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles. METHODS: This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses. RESULTS: Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005). CONCLUSION: Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings