Large-Scale Discovery of Promoter Motifs in Drosophila melanogaster

A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs) that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes

A Better Index of Body Adiposity

Obesity is a growing problem in the United States and throughout the world. It is a risk factor for many chronic diseases. The BMI has been used to assess body fat for almost 200 years. BMI is known to be of limited accuracy, and is different for males and females with similar %body adiposity. Here, we define an alternative parameter, the body adiposity index (BAI = ((hip circumference)/((height)1.5)–18)). The BAI can be used to reflect %body fat for adult men and women of differing ethnicities without numerical correction. We used a population study, the “BetaGene” study, to develop the new index of body adiposity. %Body fat, as measured by the dual-energy X-ray absorptiometry (DXA), was used as a “gold standard” for validation. Hip circumference (R = 0.602) and height (R = −0.524) are strongly correlated with %body fat and therefore chosen as principal anthropometric measures on which we base BAI. The BAI measure was validated in the “Triglyceride and Cardiovascular Risk in African-Americans (TARA)” study of African Americans. Correlation between DXA-derived %adiposity and the BAI was R = 0.85 for TARA with a concordance of C_b = 0.95. BAI can be measured without weighing, which may render it useful in settings where measuring accurate body weight is problematic. In summary, we have defined a new parameter, the BAI, which can be calculated from hip circumference and height only. It can be used in the clinical setting even in remote locations with very limited access to reliable scales. The BAI estimates %adiposity directly

Effects of interactions on the relaxation processes in magnetic nanostructures

Controlling the relaxation of magnetization in magnetic nanostructures is key to optimizing magnetic storage device performance. This relaxation is governed by both intrinsic and extrinsic relaxation mechanisms and with the latter strongly dependent on the interactions between the nanostructures. In the present work we investigate laser induced magnetization dynamics in a broadband optical resonance type experiment revealing the role of interactions between nanostructures on the relaxation processes of granular magnetic structures. The results are corroborated by constructing a temperature dependent numerical micromagnetic model of magnetization dynamics based on the Landau-Lifshitz-Bloch equation. The model predicts a strong dependence of damping on the key material properties of coupled granular nanostructures in good agreement with the experimental data. We show that the intergranular, magnetostatic and exchange interactions provide a large extrinsic contribution to the damping. Finally we show that the mechanism can be attributed to an increase in spin-wave degeneracy with the ferromagnetic resonance mode as revealed by semianalytical spin-wave calculations

Polybrominated Diphenyl Ethers (PBDEs) and Bioaccumulative Hydroxylated PBDE Metabolites in Young Humans from Managua, Nicaragua

OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum

A simple intravenous glucose tolerance test for assessment of insulin sensitivity

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.</p> <p>Methods</p> <p>In 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the M_bw(glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (<it>V</it>_d) and the clearance (<it>CL</it>) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUC_ins). Uptake of glucose during the clamp was corrected for body weight (M_bw).</p> <p>Results</p> <p>There was a 7-fold variation in M_bw. Algorithms based on the slope of the glucose-elimination curve (<it>CL/V</it>_d) in combination with AUC_insobtained during the IVGTT showed statistically significant correlations with M_bw, the linearity being r²= 0.63-0.83. The best algorithms were associated with a 25-75^thprediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.</p> <p>Conclusion</p> <p>Simple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.</p

Exploring the planetary boundary for chemical pollution

Rockström et al. (2009a, 2009b) have warned that humanity must reduce anthropogenic impacts defined by nine planetary boundaries if “unacceptable global change” is to be avoided. Chemical pollution was identified as one of those boundaries for which continued impacts could erode the resilience of ecosystems and humanity. The central concept of the planetary boundary (or boundaries) for chemical pollution (PBCP or PBCPs) is that the Earth has a finite assimilative capacity for chemical pollution, which includes persistent, as well as readily degradable chemicals released at local to regional scales, which in aggregate threaten ecosystem and human viability. The PBCP allows humanity to explicitly address the increasingly global aspects of chemical pollution throughout a chemical's life cycle and the need for a global response of internationally coordinated control measures. We submit that sufficient evidence shows stresses on ecosystem and human health at local to global scales, suggesting that conditions are transgressing the safe operating space delimited by a PBCP. As such, current local to global pollution control measures are insufficient. However, while the PBCP is an important conceptual step forward, at this point single or multiple PBCPs are challenging to operationalize due to the extremely large number of commercial chemicals or mixtures of chemicals that cause myriad adverse effects to innumerable species and ecosystems, and the complex linkages between emissions, environmental concentrations, exposures and adverse effects. As well, the normative nature of a PBCP presents challenges of negotiating pollution limits amongst societal groups with differing viewpoints. Thus, a combination of approaches is recommended as follows: develop indicators of chemical pollution, for both control and response variables, that will aid in quantifying a PBCP(s) and gauging progress towards reducing chemical pollution; develop new technologies and technical and social approaches to mitigate global chemical pollution that emphasize a preventative approach; coordinate pollution control and sustainability efforts; and facilitate implementation of multiple (and potentially decentralized) control efforts involving scientists, civil society, government, non-governmental organizations and international bodies

Search for Point Sources of Ultra-High Energy Cosmic Rays Above 40 EeV Using a Maximum Likelihood Ratio Test

We present the results of a search for cosmic ray point sources at energies above 40 EeV in the combined data sets recorded by the AGASA and HiRes stereo experiments. The analysis is based on a maximum likelihood ratio test using the probability density function for each event rather than requiring an a priori choice of a fixed angular bin size. No statistically significant clustering of events consistent with a point source is found.Comment: 7 pages, 7 figures. Accepted for publication in The Astrophysical Journa

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure