Jihong Ren | PubMed Health

PubMed2005

HotKnots: heuristic prediction of RNA secondary structures including pseudoknots.

We present HotKnots, a new heuristic algorithm for the prediction of RNA secondary structures including pseudoknots. Based on the simple idea of iteratively forming stable stems, our algorithm explores many alternative secondary structures, using a free energy minimization algorithm for pseudoknot free secondary structures to identify promising candidate stems. In an empirical evaluation of the algorithm with 43 sequences taken from the Pseudobase database and from the literature on pseudoknotted structures, we found that overall, in terms of the sensitivity and specificity of predictions, HotKnots outperforms the well-known Pseudoknots algorithm of Rivas and Eddy and the NUPACK algorithm of Dirks and Pierce, both based on dynamic programming approaches for limited classes of pseudoknotted structures. It also outperforms the heuristic Iterated Loop Matching algorithm of Ruan and colleagues, and in many cases gives better results than the genetic algorithm from the STAR package of van Batenburg and colleagues and the recent pknotsRG-mfe algorithm of Reeder and Giegerich. The HotKnots algorithm has been implemented in C/C++ and is available from http://www.cs.ubc.ca/labs/beta/Software/HotKnots.

Algorithms↗

PubMed2003

Decoding of synaptic voltage waveforms by specific classes of recombinant high-threshold Ca(2+) channels.

Studies suggest that the preferential role of L-type voltage-sensitive Ca(2+) channels (VSCCs) in coupling strong synaptic stimulation to transcription is due to their selective activation of local chemical events. However, it is possible that selective activation of the L-type channel by specific voltage waveforms also makes a contribution. To address this issue we have examined the response of specific Ca(2+) channel types to simulated complex voltage waveforms resembling those encountered during synaptic plasticity (gamma and theta firing frequency). L-, P/Q- and N-type VSCCs (alpha1C, alpha1A, alpha1B/beta1B/alpha2delta, respectively) were all similarly activated by brief action potential (AP) waveforms or sustained step depolarization. When complex waveforms containing large excitatory postsynaptic potentials (EPSPs), APs and spike accommodation were applied under voltage clamp we found that the integrated L-type VSCC current was approximately three times larger than that produced by the P/Q- or N-type Ca(2+) channels (gamma frequency 1 s stimulation). For P/Q- or N-type channels the complex waveforms led to a smaller current than that expected from the response to a simple 1 s step depolarization to 0 or +20 mV. EPSPs present in the waveforms favoured the inactivation of P/Q- and N-type channels. In contrast, activation of the L-type channel was dependent on both EPSP- and AP-mediated depolarization. Expression of P/Q-type channels with reduced voltage-dependent inactivation (alpha1A/beta2A/alpha2delta) or the use of hyperpolarized intervals between AP stimuli greatly increased their response to complex voltage stimuli. We propose that in response to complex synaptic voltage waveforms P/Q- and N-type channels can undergo selective voltage-dependent inactivation leading to a Ca(2+) current mediated predominantly by L-type channels.

Action Potentials↗