Influence of a fluorobenzene nucleobase analogue on the conformational flexibility of RNA studied by molecular dynamics simulations

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair

Synthesis of 1,4-Disubstituted Mono and Bis-triazolocarbo-acyclonucleoside Analogues of 9-(4-Hydroxybutyl)guanine by Cu(I)-Catalyzed Click Azide-Alkyne Cycloaddition

A series of novel mono-1,2,3-triazole and bis-1,2,3-triazole acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine was prepared via copper(I)-catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurine, N-1-propargylpyrimidines/as-triazine with the azido-pseudo-sugar 4-azidobutylacetate under solvent-free microwave conditions, followed by treatment with K2CO3/MeOH, or NH3/MeOH. All compounds studied in this work were screened for their antiviral activities [against human rhinovirus (HRV) and hepatitis C virus (HCV)] and antibacterial activities against a series of Gram positive and negative bacteria

Meeting review : ESF workshop on "Impact of nucleic acid chemistry on gene function analysis: antisense, aptamers, ribozymes and RNAi"

The shortage of functional information compared to the abundance of sequence information characterizes today’s situation in functional genomics. For many years the knock-down of a gene’s product has been the most powerful way of analysing its function. In addition to the complete knock-out by homologous recombination, several different techniques have been developed to temporarily knock down gene expression through methods based on specific sequence recognition, such as knockdown by antisense oligonucleotides, ribozymes, aptamers or RNAi. The ESF workshop on ‘Impact of Nucleic Acid Chemistry on Gene Function Analysis’ brought together researchers who use techniques that are different but highly related. It offered an opportunity for an in-depth discussion of recent progress and common problems. Antisense oligonucleotides aptamers and ribozymes are techniques that have been used successfully for many years to validate targets. However, recent developments, such as increased tightness of binding (e.g. locked nucleic acids) or the combination of different methods (e.g. using aptamers to design ribozymes), have continued to improve the existing techniques. RNA interference (RNAi) is a defence mechanism of the cell against viruses. Since the exact mechanism of action within the cell is still unclear, RNAi was a particularly exciting topic at the workshop and was addressed in the largest number of presentations. Predictability of positional effects (accessibility of RNA) is a problem shared by all techniques using sequence-specific recognition and was the subject of quite controversial debates. The meeting comprised over 50 people from 14 countries (13 European countries and the USA)

Disappearance of the Abrikosov vortex above the deconfining phase transition in SU(2) lattice gauge theory

We calculate the solenoidal magnetic monopole current and electric flux distributions at finite temperature in the presence of a static quark antiquark pair. The simulation was performed using SU(2) lattice gauge theory in the maximal Abelian gauge. We find that the monopole current and electric flux distributions are quite different below and above the finite temperature deconfining phase transition point and agree with predictions of the Ginzburg-Landau effective theory.Comment: 12 pages, Revtex Latex, 6 figures - ps files will be sent upon reques

Polarized Fusion. Can Polarization Help to Increase the Energy Output of Fusion Reactors?

Since more than 60 years scientists are working on the idea to produce energy from nuclear fusion of light particles like the Hydrogen isotopes. In the meantime, the energy output of e.g. tokamak reactors was increased by five orders and modern experiments like JET are approaching the border for energy production. The international ITER collaboration is preparing the first fusion reactor that will produce about ten times more energy, compared to the energy that is needed to run the experiment. Today, the laser-induced inertial fusion reached the same level and experiments at the National Ignition Facility (NIF) in California, USA, demonstrate a ratio between produced and induced energy about one at the end of 2013.1 In parallel, it is discussed since 1970 to use nuclear polarized fuel to increase the total cross sections of the different fusion reactions.2 The energy gain of fusion reactors does not depend linearly on the total cross section. Depending on the different concepts for nuclear fusion, magnetic confinement or inertial fusion, the energy gain This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 3.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited. 1660112-1 Int. J. Mod. Phys. Conf. Ser. 2016.40. Downloaded from www.worldscientific.com by UNIVERSITY OF FERRARA on 04/19/16. For personal use only. R. Engels & G. Ciullo is improved above average. M. Temporal et al. have shown, e.g., that the energy gain of laser-induced inertial fusion might be increased by a factor four, or that the necessary laser power can be reduced by 20 %, if the nuclear fuel was polarized before.3 The downsized laser power will reduce the costs of the corresponding project by a reasonable amount. In addition, the differential cross sections can be modified so that it will be possible to focus the ejectiles, e.g. the neutrons, on special wall areas. In a tokamak this can be used to concentrate the neutron flux to special outer parts of the blanket, where the cooling can be improved and the neutrons be used for Tritium production via the exothermic reaction 6Li+n → 4He+t.4 At the same time, less cooling is needed for the inner parts of the blanket that allows to bring the magnetic field coils closer to the fusion plasma. The increased magnetic field in the plasma will increase the energy gain additionally. Another option of polarized fuel is a new kind of plasma diagnostic inside a tokamak. In combination with modern Nuclear Magnetic Resonance technologies (NMR) anisotropies in the plasma can be measured to learn more about the different plasma mode

Polarized Fusion. Can Polarization Help to Increase the Energy Output of Fusion Reactors

For more than 50 years it has been discussed to increase the gain of nuclear fusion reactors with the use of polarized fuel. For example, the total cross secti ons of the most interesting fusion reactions d+ t ! 4 He+n or 3 He+d ! 4 He+p are increased by 50% if the spins of both incoming particles are aligned. This effect will increase the energy output of a fusion reactor more than linearly, e.g. by a factor 4. However, before polarized fuel can be used for energy production in the different types of reactors, a number of questions must be answered. In this contribution we give an overview on our various activities in this field of res earch

Dual Ginzburg-Landau Theory for Nonperturbative QCD

Nonperturbative QCD is studied with the dual Ginzburg-Landau theory, where color confinement is realized through the dual Higgs mechanism by QCD-monopole condensation. We obtain a general analytic formula for the string tension. A compact formula is derived for the screened inter-quark potential in the presence of light dynamical quarks. The QCD phase transition at finite temperature is studied using the effective potential formalism. The string tension and the QCD-monopole mass are largely reduced near the critical temperature, $T_c$. The surface tension is estimated from the effective potential at $T_c$. We propose also a new scenario of the quark-gluon-plasma creation through the color-electric flux-tube annihilation. Finally, we discuss a close relation between instantons and QCD-monopoles.Comment: Talk presented by H. Suganuma at the Int. Conf. ``CONFINEMENT95'', March 22-24, 1995, Osaka, Japan, 12 pages, uses PHYZZ