Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex

We report the single-crystal X-ray structure for the complex of the bisacridine bis-(9-aminooctyl(2-(dimethylaminoethyl)acridine-4-carboxamide)) with the oligonucleotide d(CGTACG)2 to a resolution of 2.4 Å. Solution studies with closed circular DNA show this compound to be a bisintercalating threading agent, but so far we have no crystallographic or NMR structural data conforming to the model of contiguous intercalation within the same duplex. Here, with the hexameric duplex d(CGTACG), the DNA is observed to undergo a terminal cytosine base exchange to yield an unusual guanine quadruplex intercalation site through which the bisacridine threads its octamethylene linker to fuse two DNA duplexes. The 4-carboxamide side-chains form anchoring hydrogen-bonding interactions with guanine O6 atoms on each side of the quadruplex. This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions.

Determination by MAD-DM of the structure of the DNA duplex d[ACGTACG(5-BrU)]2 at 1.46 Å and 100 K

A four-wavelength MAD experiment on a new brominated octanucleotide is reported here. d[ACGTACG(5-BrU)], C77H81BrN30O32P7, (DNA) = 2235, tetragonal, P43212 (No. 96), a = 43.597, c = 26.268 Å, V = 49927.5 Å3, Z = 8, T = 100 K, R = 10.91% for 4312 reflections between 15.0 and 1.46 Å resolution. The self-complementary brominated octanucleotide d[ACGTACG(5-BrU)]2 has been crystallized and data measured to 1.45 Å at both 293 K and a second crystal flash frozen at 100 K. The latter data collection was carried out to the same resolution at the four wavelengths 0.9344, 0.9216, 0.9208 and 0.9003 Å, around the Br K edge at 0.92 Å and the structure determined from a map derived from a MAD data analysis using pseudo-MIR methodology, as implemented in the program MLPHARE. This is one of the first successful MAD phasing experiments carried out at Sincrotrone Elettra in Trieste, Italy. The structure was refined using the data measured at 0.9003 Å, anisotropic temperature factors and the restrained least-squares refinement implemented in the program SHELX96, and the helical parameters are compared with those previously determined for the isomorphous d(ACGTACGT)2 analogue. The asymmetric unit consists of a single strand of octamer with 96 water molecules. No countercations were located. The A-DNA helix geometry obtained has been analysed using the CURVES program.

Sleepwalking from New York to Miami

In the winter of 2007, Doug Aitken’s moving image installation, sleepwalkers, was projected onto the exterior walls of the Museum of Modern Art in New York. The project was a collaboration between Aitken, the museum and Creative Time, a New York-based organisation that commissions public art projects. A site-specific version of the installation has been commissioned by the Miami Art Museum for the opening of its new facility, designed by Swiss architects Herzog and de Meuron, in 2013: “sleepwalkers (Miami) will expand the work’s landscape and characters in a manner that reflects the diverse social fabric of Miami.” This essay examines sleepwalkers as an example of the emerging form of film as public art. There are three strands to my argument: first, an examination of the role of film in the redefinition of public art, shifting away from spatial practices concerned with fixed and permanent notions of space, community and art and towards transient and experimental spatial and artistic practices; second,a discussion of the relationship between projection and the built environment and the ways that the qualities of luminescence, transparency, movement and connectivity are transferred from projected images to the surfaces on which they are projected and the spaces around them; and third, an examination of the ways that sleepwalkers uses only certain aspects of narrativity, those concerned with movement and change, and avoids hermeneutic absorption in order to keep the spectators moving (transposing the idea of sleepwalking from characters to spectators). Transience and transparency are key ideas in the conceptualisation of the work, and these are deployed with significant differences in relation to the distinctive characteristics of each city and each museum.

The data-mining of studies database 'HHdbIV'

This article clarifies what was done with the sub-7-man positions in data-mining Harold van der Heijden's 'HHdbIV' database of chess studies prior to its publication. It emphasises that only positions in the main lines of studies were examined and that the information about uniqueness of move was not incorporated in HHdbIV. There is some reflection on the separate technical and artistic dimensions of study evaluation.

The role of UK retailing in urban regeneration

This research examines the role of retailing in urban regeneration nationally and locally in the UK. The research uses data at a national level and local shopping centre case studies to examine the employment and property impacts of retailing. Focusing on schemes built during the first part of the 1990s it shows that retail can bring employment and economic benefits to town centres, but that the impact on the inner city should not be overlooked. Valuable lessons can be learned from the experience of centres built during this period of recession, and new challenges such as eCommerce now face these centres and others being developed today. The research examines the multiplier effect of retail regeneration schemes nationally using National Accounts data, and the local property and employment impacts of shopping centre schemes in the case study towns of Aberdeen, Bristol, Norwich, Bromley, Worcester and Leicester. The report includes valuable statistical sources, a full literature and policy review and will be of interest to those involved in property investment, regeneration and planning. The research was funded by the Office of Science & Technology and the Harold Samuel Educational Trust.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

The response of the sea ice edge to atmospheric and oceanic jet formation

The sea ice edge presents a region of many feedback processes between the atmosphere, ocean, and sea ice (Maslowski et al.). Here the authors focus on the impact of on-ice atmospheric and oceanic flows at the sea ice edge. Mesoscale jet formation due to the Coriolis effect is well understood over sharp changes in surface roughness such as coastlines (Hunt et al.). This sharp change in surface roughness is experienced by the atmosphere and ocean encountering a compacted sea ice edge. This paper presents a study of a dynamic sea ice edge responding to prescribed atmospheric and oceanic jet formation. An idealized analytical model of sea ice drift is developed and compared to a sea ice climate model [the Los Alamos Sea Ice Model (CICE)] run on an idealized domain. The response of the CICE model to jet formation is tested at various resolutions. It is found that the formation of atmospheric jets at the sea ice edge increases the wind speed parallel to the sea ice edge and results in the formation of a sea ice drift jet in agreement with an observed sea ice drift jet (Johannessen et al.). The increase in ice drift speed is dependent upon the angle between the ice edge and wind and results in up to a 40% increase in ice transport along the sea ice edge. The possibility of oceanic jet formation and the resultant effect upon the sea ice edge is less conclusive. Observations and climate model data of the polar oceans have been analyzed to show areas of likely atmospheric jet formation, with the Fram Strait being of particular interest.

Die Schwalbe Chess Study #16206

This study contains a maxDTM KRRPKQ position, the deepest known underpromotion and an echo of the famous Saavedra theme. The original problem and solution can be found in the attached files here.

Half-remembered quotations from mostly forgotten speeches: the limits of Labour’s European policy discourse

This article uses discourse analysis to study the continuities in British foreign policy thinking within the Labour party from the 1960s to the present day. Using representative extracts from speeches by Hugh Gaitskell, Harold Wilson, Tony Blair and Gordon Brown, it identifies the ideational consis- tencies in the leaders’ attitudes to: Empire; federalism in the EEC/EU; and laying down conditions that have to be met before any constructive engagement with ‘Europe’ can be countenanced. We argue that these consistencies, spanning a 50-year period, exemplify a certain stagnation both within Labour’s European discourses and within British foreign policy thinking more widely. We develop the idea that Labour party thinking has been crucially framed by both small ‘c’ conser- vative and upper-case Conservative ideology, popularised by Winston Churchill in his ‘three circles’ model of British foreign policy.

Delivery of crop pollination services is an insufficient argument for wild pollinator conservation

There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

BACKGROUND AND OBJECTIVE: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). DESIGN AND METHODS: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. RESULTS: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). CONCLUSION: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

Non-bee insects are important contributors to global crop pollination

Wild and managed bees are well documented as effective pollinators of global crops of economic importance. However, the contributions by pollinators other than bees have been little explored despite their potential to contribute to crop production and stability in the face of environmental change. Non-bee pollinators include flies, beetles, moths, butterflies, wasps, ants, birds, and bats, among others. Here we focus on non-bee insects and synthesize 39 field studies from five continents that directly measured the crop pollination services provided by non-bees, honey bees, and other bees to compare the relative contributions of these taxa. Non-bees performed 25–50% of the total number of flower visits. Although non-bees were less effective pollinators than bees per flower visit, they made more visits; thus these two factors compensated for each other, resulting in pollination services rendered by non-bees that were similar to those provided by bees. In the subset of studies that measured fruit set, fruit set increased with non-bee insect visits independently of bee visitation rates, indicating that non-bee insects provide a unique benefit that is not provided by bees. We also show that non-bee insects are not as reliant as bees on the presence of remnant natural or seminatural habitat in the surrounding landscape. These results strongly suggest that non-bee insect pollinators play a significant role in global crop production and respond differently than bees to landscape structure, probably making their crop pollination services more robust to changes in land use. Non-bee insects provide a valuable service and provide potential insurance against bee population declines.