“Deoxyribo Nanonucleic Acid” Antiparallel, Parallel, and Unparalleled

AbstractThe crystal structure of a single-stranded DNA oligonucleotide has revealed formation of a unique three-dimensional array by continuous antiparallel and parallel pairing between monomers [1]. The array is based on tertiary interactions and represents a second-generation nanotechnological system

Syntheses of 4′-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4′-thiocytosine

A facile synthetic route for the 4′-thioribonucleoside building block 4′SN (N = U, C, A and G) with the ribose O4′ replaced by sulfur is presented. Conversion of l-lyxose to 1,5-di-O-acetyl-2,3-di-O-benzoyl-4-thio-d-ribofuranose was achieved via an efficient four-step synthesis with high yield. Conversion of the thiosugar into the four ribonucleoside phosphoramidite building blocks was accomplished with additional four steps in each case. Incorporation of 4′-thiocytidines into oligoribonucleotides improved the thermal stability of the corresponding duplexes by ∼1°C per modification, irrespective of whether the strand contained a single modification or a consecutive stretch of 4′SC residues. The gain in thermodynamic stability is comparable to that observed with oligoribonucleotides containing 2′-O-methylated residues. To establish potential conformational changes in RNA as a result of the 4′-thio modification and to better understand the origins of the observed stability changes, the crystal structure of the oligonucleotide 5′-r(CC4′SCCGGGG) was determined and analyzed using the previously solved structure of the native RNA octamer as a reference. The two 4′-thioriboses adopt conformations that are very similar to the C3′-endo pucker observed for the corresponding sugars in the native duplex. Subtle changes in the local geometry of the modified duplex are mostly due to the larger radius of sulfur compared to oxygen or appear to be lattice-induced. The significantly increased RNA affinity of 4′-thio-modified RNA relative to RNA, and the relatively minor conformational changes caused by the modification render this nucleic acid analog an interesting candidate for in vitro and in vivo applications, including use in RNA interference (RNAi), antisense, ribozyme, decoy and aptamer technologie

Syntheses of 4′-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4′-thiocytosine

A facile synthetic route for the 4′-thioribonucleoside building block (4′S)N (N = U, C, A and G) with the ribose O4′ replaced by sulfur is presented. Conversion of l-lyxose to 1,5-di-O-acetyl-2,3-di-O-benzoyl-4-thio-d-ribofuranose was achieved via an efficient four-step synthesis with high yield. Conversion of the thiosugar into the four ribonucleoside phosphoramidite building blocks was accomplished with additional four steps in each case. Incorporation of 4′-thiocytidines into oligoribonucleotides improved the thermal stability of the corresponding duplexes by ∼1°C per modification, irrespective of whether the strand contained a single modification or a consecutive stretch of (4′S)C residues. The gain in thermodynamic stability is comparable to that observed with oligoribonucleotides containing 2′-O-methylated residues. To establish potential conformational changes in RNA as a result of the 4′-thio modification and to better understand the origins of the observed stability changes, the crystal structure of the oligonucleotide 5′-r(CC(4′S)CCGGGG) was determined and analyzed using the previously solved structure of the native RNA octamer as a reference. The two 4′-thioriboses adopt conformations that are very similar to the C3′-endo pucker observed for the corresponding sugars in the native duplex. Subtle changes in the local geometry of the modified duplex are mostly due to the larger radius of sulfur compared to oxygen or appear to be lattice-induced. The significantly increased RNA affinity of 4′-thio-modified RNA relative to RNA, and the relatively minor conformational changes caused by the modification render this nucleic acid analog an interesting candidate for in vitro and in vivo applications, including use in RNA interference (RNAi), antisense, ribozyme, decoy and aptamer technologies

Disease burden of rotavirus gastroenteritis in children up to 5years of age in two Swiss cantons: paediatrician- and hospital-based surveillance

Rotavirus gastroenteritis (RV GE) is a leading cause of diarrhoea in young children. The purpose of this epidemiological surveillance was to measure the disease burden of RV GE among children <5years of age in two regions of Switzerland, Geneva and Lucerne. One hospital and four paediatricians participated per region. The surveillance lasted from December 2006 to June 2007. The population denominator for calculation of the RV GE incidence rate was the average of the overall study population <5years of age under surveillance during the surveillance period. At the study sites, 513 children with GE were presented. Stool sample was collected and examined in 341 cases, of which 130 were RV positive (38.1%). Informed consent to participate in the study was obtained for 113 RV positive subjects. The overall RV GE incidence rate was 0.97% in Lucerne [lower incidence interval (LCI), 0.71%; upper incidence interval (UCI), 1.2%] compared with 0.65 and in Geneva (LCI, 0.50%; UCI, 0.81%). Disease severity assessments using the Vescari score showed that the RV GE episodes were more severe in Lucerne than in Geneva (14.05 ± 3.05 vs 12.85 ± 2.87), which was confirmed by a higher hospitalisation rate in Lucerne at the study visit (82.9% vs 23.6%). More children had fever in Geneva than in Lucerne (42.9% vs 26.8%), and more children were hospitalised during the follow-up period in Geneva than in Lucerne (14.5% vs 2.5%). Genotyping of RV positive stool samples revealed that both G1 and P8 were the most prevalent types in both regions. There was a statistically significant difference in the distribution frequency of G1 between the two regions (p = 0.039). Assessment of health economic data confirmed the economic burden of RV GE episodes. In conclusion, RV GE episodes are a health burden as well as an economic burden also for the children in a developed country such as Switzerlan

Tourist’s understanding of sustainable tourism An analysis in eight countries

The goal of this study is to learn moreabout tourists’ understanding of sustainable tourism.The empirical survey with over 6,000 respondents ineight countries identifies the most relevant aspects ofsustainable tourism from a tourists’ perspective.Overall the perception is balanced over the differentdimensions. Furthermore, five different typesregarding tourists’ understanding of sustainabletourism are identified in a cluster analysis and apotential market size of sustainable tourism of 22%of all tourists can be identified

Crystal structures of an A-form duplex with single-adenosine bulges and a conformational basis for site-specific RNA self-cleavage

AbstractBackground: Bulged nucleotides are common secondary structural motifs in RNA molecules and are often involved in RNA-RNA and RNA-protein interactions. RNA is selectively cleaved at bulge sites (when compared to other sites within stems) in the presence of divalent metal cations. The effects of bulge nucleotides on duplex stability and topology have been extensively investigated, but no detailed X-ray structures of bulge-containing RNA fragments have been available.Results: We have crystallized a self-complementary RNA-DNA chimeric 11-nucleotide sequence containing single-adenosine bulges under two different conditions, giving two distinct crystal forms. In both lattices the adenosines are looped out, leaving the stacking interactions in the duplex virtually unaffected. The bulges cause the duplex to kink in both cases. In one of the structures, the conformation of the bulged nucleotide places its modeled 2′-oxygen in line with the adjacent phosphate on the 3′ side, where it is poised for nucleophilic attack.Conclusions: Single adenosine bulges cause a marked opening of the normally narrow RNA major groove in both crystal structures, rendering the bases more accessible to interacting molecules compared with an intact stem. The geometries around the looped-out adenosines are different in the two crystal forms, indicating that bulges can confer considerable local plasticity on the usually rigid RNA double helix. The results provide a conformational basis for the preferential, metal-assisted self-cleavage of RNA at bulged sites

Mineral Magnetic Characterization of High‐Latitude Sediments From Lake Levinson‐Lessing, Siberia

Levinson-Lessing Lake in northern Central Siberia is a sedimentary archive characterized by continuous, widely constant sedimentation at high rates (0.7 m ka−1 for >32 ka). This study provides the first evidence of the suitability of the lake′s sediments for paleomagnetic analyses using the 46-m-long core Co1401. Although the lowermost 8 m are disturbed, the upper 38 m of Co1401 provide the preconditions for an exceptional, high-resolution paleomagnetic record located within the tangent cylinder of the inner core. High-resolution analyses of magnetic susceptibility, anhysteretic remanent magnetization, isothermal remanent magnetization, and hysteresis parameters show largely uniform mineral magnetic properties. First-order reversal curves indicate magnetite particles in pseudo-single domain state are the main remanence carrier, supplemented by single-domain particles, originating likely from magnetotactic bacteria. Above 6.7 m, the bulk magnetic mineralogy is slightly harder than below and initial greigite formation occurs. However, the main remanence carriers are still of detrital origin

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2′-O-[2-(methoxy)ethyl]-2-thiothymidines

Substitution of oxygen atoms by sulfur at various locations in the nucleic acid framework has led to analogs such as the DNA phosphorothioates and 4′-thio RNA. The phosphorothioates are excellent mimics of DNA, exhibit increased resistance to nuclease degradation compared with the natural counterpart, and have been widely used as first-generation antisense nucleic acid analogs for applications in vitro and in vivo. The 4′-thio RNA analog exhibits significantly enhanced RNA affinity compared with RNA, and shows potential for incorporation into siRNAs. 2-Thiouridine (s(2)U) and 5-methyl-2-thiouridine (m(5)s(2)U) are natural nucleotide analogs. s(2)U in tRNA confers greater specificity of codon–anticodon interactions by discriminating more strongly between A and G compared with U. 2-Thio modification preorganizes the ribose and 2′-deoxyribose sugars for a C3′-endo conformation, and stabilizes heteroduplexes composed of modified DNA and complementary RNA. Combination of the 2-thio and sugar 2′-O-modifications has been demonstrated to boost both thermodynamic stability and nuclease resistance. Using the 2′-O-[2-(methoxy)ethyl]-2-thiothymidine (m(5)s(2)Umoe) analog, we have investigated the consequences of the replacement of the 2-oxygen by sulfur for base-pair geometry and duplex conformation. The crystal structure of the A-form DNA duplex with sequence GCGTAT*ACGC (T* = m(5)s(2)Umoe) was determined at high resolution and compared with the structure of the corresponding duplex with T* = m(5)Umoe. Notable changes as a result of the incorporation of sulfur concern the base-pair parameter ‘opening’, an improvement of stacking in the vicinity of modified nucleotides as measured by base overlap, and a van der Waals interaction between sulfur atoms from adjacent m(5)s(2)Umoe residues in the minor groove. The structural data indicate only minor adjustments in the water structure as a result of the presence of sulfur. The observed small structural perturbations combined with the favorable consequences for pairing stability and nuclease resistance (when combined with 2′-O-modification) render 2-thiouracil-modified RNA a promising candidate for applications in RNAi

Complex patterns of schist tor exposure and surface uplift, Otago (New Zealand)

Landscapes are subjected to surface denudation during their complex and non-linear evolution. In order to quantify the in situ surface lowering and, thus, denudation or soil erosion rates, new, multi-millennia archives are needed and must be rigorously tested. Large residual rocks, tors, are the basis for the Tor Exhumation Approach. Here we present novel results on meta-sedimentary (schist) rock tors using this approach, which previously has only been applied in granitic terrains. The exhumation patterns of eight schist tors in three landscape locations (valley, ridge, distal) of Otago, New Zealand, were studied using cosmogenic dating. The in situ 10Be ages have high variability along individual vertical tor profiles. Average surface age is 122 ± 12 ka and ranges from 836 ± 89 ka to 19 ± 2 ka. The majority of investigated tors have surfaced during the MIS 5 which was one of the wettest and warmest climate periods. The resulting surface denudation trend of the three locations differs. The valley commenced denudation no earlier than ~200 ka with rates of ~0.22 [m kyr−1] to ~0.02 [m kyr−1]. In contrast, exposure started at the ridge position around 230 ka at ~0.03 [m kyr−1]. An age inversion found in the valley is considered to be the result of mushroom-like exposure by undercutting and repeated rock breakoffs. The distal site tor has been exhumed continuously for ~120 ka at a rate of ~0.2 to ~0.05 [m kyr−1]. We identified a mix of surface emergence patterns of the tors such as continuous-, mushroom-, tafoni- and structural-like. The comparison to modern erosion rates indicates that surface erosion has increased up to a factor of ten during the last few decades. To determine the actual surface uplift, we linked the tor derived surface denudation rates with rock uplift data. The data indicates that the surface uplift rates started to decrease during the Middle Pleistocene (0.04–0.09 [m kyr−1]), remained relatively low during the Late Pleistocene (~0.01 [m kyr−1]) and started to increase again during the Holocene (c. 0.21–0.64 [m kyr−1]). In summary, the emergence pattern of local tors enabled reconstruction of the evolution of Pleistocene-Holocene surfaces in East Otago

Screen space animation of fire

International audienceWe present a simple and physically inspired method to animate realistically looking fire directly in 2D instead of along a 3D simulation. This naturally reduces the complexity of the animation from O(n3) to O(n2). The fire is represented as a 2D scalar density field located on a plane facing the camera, and is advected under a 2.5D velocity field. In our method, the apparent motion of the fire on the viewing axis is mimicked by introducing vibrations in the velocity field. We model these rapid vibrations as pressure waves found in compressible fluids and therefore consider the full Navier-Stokes equations. The equations can be solved in a single pass and our method entirely runs on the GPU. A natural extension is to make use of this method directly in screen space: instead of filtering down the fire's simulation grid in world space, we rasterize the fire's source, and perform the simulation on a coarser grid directly in screen space. The results are constantly renewed 3D-looking fires computed solely in 2D