DNA splicing: computing by observing

Motivated by several techniques for observing molecular processes in real-time we introduce a computing device that stresses the role of the observer in biological computations and that is based on the observed behavior of a splicing system. The basic idea is to introduce a marked DNA strand into a test tube with other DNA strands and restriction enzymes. Under the action of these enzymes the DNA starts to splice. An external observer monitors and registers the evolution of the marked DNA strand. The input marked DNA strand is then accepted if its observed evolution follows a certain expected pattern. We prove that using simple observers (finite automata), applied on finite splicing systems (finite set of rules and finite set of axioms), the class of recursively enumerable languages can be recognized. © Springer Science+Business Media B.V. 2007

Real-Time Imaging and Quantification of Amyloid-β Peptide Aggregates by Novel Quantum-Dot Nanoprobes

Background: Protein aggregation plays a major role in the pathogenesis of neurodegenerative disorders, such as Alzheimer’s disease. However, direct real-time imaging of protein aggregation, including oligomerization and fibrillization, has never been achieved. Here we demonstrate the preparation of fluorescent semiconductor nanocrystal (quantum dot; QD)-labeled amyloid-b peptide (QDAb) and its advanced applications. Methodology/Principal Findings: The QDAb construct retained Ab oligomer-forming ability, and the sizes of these oligomers could be estimated from the relative fluorescence intensities of the imaged spots. Both QDAb coaggregation with intact Ab42 and insertion into fibrils were detected by fluorescence microscopy. The coaggregation process was observed by real-time 3D imaging using slit-scanning confocal microscopy, which showed a typical sigmoid curve with 1.5 h in the lag-time and 12 h until saturation. Inhibition of coaggregation using an anti-Ab antibody can be observed as 3D images on a microscopic scale. Microglia ingested monomeric QDAb more significantly than oligomeric QDAb, and the ingested QDAb was mainly accumulated in the lysosome. Conclusions/Significance: These data demonstrate that QDAb is a novel nanoprobe for studying Ab oligomerization an