RNA secondary structure design

We consider the inverse-folding problem for RNA secondary structures: for a given (pseudo-knot-free) secondary structure find a sequence that has that structure as its ground state. If such a sequence exists, the structure is called designable. We implemented a branch-and-bound algorithm that is able to do an exhaustive search within the sequence space, i.e., gives an exact answer whether such a sequence exists. The bound required by the branch-and-bound algorithm are calculated by a dynamic programming algorithm. We consider different alphabet sizes and an ensemble of random structures, which we want to design. We find that for two letters almost none of these structures are designable. The designability improves for the three-letter case, but still a significant fraction of structures is undesignable. This changes when we look at the natural four-letter case with two pairs of complementary bases: undesignable structures are the exception, although they still exist. Finally, we also study the relation between designability and the algorithmic complexity of the branch-and-bound algorithm. Within the ensemble of structures, a high average degree of undesignability is correlated to a long time to prove that a given structure is (un-)designable. In the four-letter case, where the designability is high everywhere, the algorithmic complexity is highest in the region of naturally occurring RNA.Comment: 11 pages, 10 figure

No Evidence of Persisting Unrepaired Nuclear DNA Single Strand Breaks in Distinct Types of Cells in the Brain, Kidney, and Liver of Adult Mice after Continuous Eight-Week 50 Hz Magnetic Field Exposure with Flux Density of 0.1 mT or 1.0 mT

BACKGROUND: It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. METHODS: In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. RESULTS: Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. CONCLUSION: No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT

Chloride concentration discriminates between foot-and-mouth disease virus IRES-dependent translation and classical scanning translation: New aspects of the picornavirus shutoff mechanism

Some picornaviruses might use the general increase of ionic strength in the host cell that occurs successively after infection to induce shutoff of host protein synthesis and to stimulate viral protein synthesis. In order to investigate this discrimination mode on a molecular level, in vitro experiments under different salt conditions comparing the Foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES)-dependent translation with the translation via the classical scanning mechanism were performed. For classical mRNA optimum concentrations of all investigated salts ranged between 70 and 100 mmol/l. However, for FMDV IRES-dependent translation the optima depended strongly on the anion used. While acetates caused only a weak stimulation of translation efficiency with maxima ranging between 150 and 180 mmol/l, chlorides lead to a strong stimulation with maxima ranging between 120 and 150 mmol/l. Competition experiments revealed that the concentration of chlorides had a greater influence on the discrimination between cellular and viral RNA translation than the total ionic strength. Taken together, the data support a model in which a specific increase in the chloride concentration rather than a general increase in the ionic strength is responsible for the shutoff effect induced by some picornaviruses

Chloride concentration discriminates between foot-and-mouth disease virus IRES-dependent translation and classical scanning translation: New aspects of the picornavirus shutoff mechanism

Some picornaviruses might use the general increase of ionic strength in the host cell that occurs successively after infection to induce shutoff of host protein synthesis and to stimulate viral protein synthesis. In order to investigate this discrimination mode on a molecular level, in vitro experiments under different salt conditions comparing the Foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES)-dependent translation with the translation via the classical scanning mechanism were performed. For classical mRNA optimum concentrations of all investigated salts ranged between 70 and 100 mmol/l. However, for FMDV IRES-dependent translation the optima depended strongly on the anion used. While acetates caused only a weak stimulation of translation efficiency with maxima ranging between 150 and 180 mmol/l, chlorides lead to a strong stimulation with maxima ranging between 120 and 150 mmol/l. Competition experiments revealed that the concentration of chlorides had a greater influence on the discrimination between cellular and viral RNA translation than the total ionic strength. Taken together, the data support a model in which a specific increase in the chloride concentration rather than a general increase in the ionic strength is responsible for the shutoff effect induced by some picornaviruses