An information-bearing seed for nucleating algorithmic self-assembly

Self-assembly creates natural mineral, chemical, and biological structures of great complexity. Often, the same starting materials have the potential to form an infinite variety of distinct structures; information in a seed molecule can determine which form is grown as well as where and when. These phenomena can be exploited to program the growth of complex supramolecular structures, as demonstrated by the algorithmic self-assembly of DNA tiles. However, the lack of effective seeds has limited the reliability and yield of algorithmic crystals. Here, we present a programmable DNA origami seed that can display up to 32 distinct binding sites and demonstrate the use of seeds to nucleate three types of algorithmic crystals. In the simplest case, the starting materials are a set of tiles that can form crystalline ribbons of any width; the seed directs assembly of a chosen width with >90% yield. Increased structural diversity is obtained by using tiles that copy a binary string from layer to layer; the seed specifies the initial string and triggers growth under near-optimal conditions where the bit copying error rate is 17 kb of sequence information. In sum, this work demonstrates how DNA origami seeds enable the easy, high-yield, low-error-rate growth of algorithmic crystals as a route toward programmable bottom-up fabrication

Templated Synthesis of Nylon Nucleic Acids and Characterization by Nuclease Digestion

Nylon nucleic acids containing oligouridine nucleotides with pendent polyamide linkers and flanked by unmodified heteronucleotide sequences were prepared by DNA templated synthesis. Templation was more efficient than the single-stranded synthesis; coupling step yields were as high as 99.2%, with up to 7 amide linkages formed in the synthesis of a molecule containing 8 modified nucleotides. Controlled digestion by calf spleen phosphodiesterase enabled the mapping of modified nucleotides in the sequences. a combination of complete degradation of nylon nucleic acids by snake venom phosphodiesterase and dephosphorylation of the resulting nucleotide fragments by bacterial alkaline phosphatase, followed by LCMS analysis, clarified the linear structure of the oligo-amide linkages. the templated synthesis strategy afforded nylon nucleic acids in the target structure and was compatible with the presence heteronucleotides. the complete digestion procedure produced a new species of DNA analogues, nylon ribonucleosides, which display nucleosides attached via a 2\u27-alkylthio linkage to each diamine and dicarboxylate repeat unit of the original nylon nucleic acids. the binding affinity of a nylon ribonucleoside octamer to the complementary DNA was evaluated by thermal denaturing experiments. the octamer was found to form stable duplexes with an inverse dependence on salt concentration, in contrast to the salt-dependent DNA contro

Exciton Delocalization in a DNA-Templated Organic Semiconductor Dimer Assembly

A chiral dimer of an organic semiconductor was assembled from octaniline (octamer of polyaniline) conjugated to DNA. Facile reconfiguration between the monomer and dimer of octaniline–DNA was achieved. The geometry of the dimer and the exciton coupling between octaniline molecules in the assembly was studied both experimentally and theoretically. The octaniline dimer was readily switched between different electronic states by protonic doping and exhibited a Davydov splitting comparable to those previously reported for DNA–dye systems employing dyes with strong transition dipoles. This approach provides a possible platform for studying the fundamental properties of organic semiconductors with DNA-templated assemblies, which serve as candidates for artificial light-harvesting systems and excitonic devices

Site-Specific Inter-Strand Cross-Links of DNA Duplexes

We report the development of technology that allows inter-strand coupling across various positions within one turn of DNA. Four 2\u27-modified nucleotides were synthesized as protected phosphoramidites and incorporated into DNA oligonucleotides. The modified nucleotides contain either 5-atom or 16-atom linker components, with either amine or carboxylic acid functional groups at their termini, forming 10 or 32 atom (11 or 33 bond) linkages. Chemical coupling of the amine and carboxylate groups in designed strands resulted in the formation of an amide bond. Coupling efficiency as a function of trajectory distance between the individual linker components was examined. For those nucleotides capable of forming inter-strand cross-links (ICLs), coupling yields were found to depend on temperature, distance, and linker length, enabling several approaches that can control regioselective linkage. In the most favorable cases, the coupling yields are quantitative. Spectroscopic measurements of strands that were chemically cross-linked indicate that the global structure of the DNA duplex does not appear to be distorted from the B form after coupling. Thermal denaturing profiles of those strands were shifted to somewhat higher temperatures than those of their respective control duplexes. Thus, the robust amide ICLs formed by this approach are site-specific, do not destabilize the rest of the duplex, and only minimally perturb the secondary structure

Algorithmic Self-Assembly of DNA Sierpinski Triangles

Algorithms and information, fundamental to technological and biological organization, are also an essential aspect of many elementary physical phenomena, such as molecular self-assembly. Here we report the molecular realization, using two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update rule computes the binary function XOR and thus fabricates a fractal pattern—a Sierpinski triangle—as it grows. To achieve this, abstract tiles were translated into DNA tiles based on double-crossover motifs. Serving as input for the computation, long single-stranded DNA molecules were used to nucleate growth of tiles into algorithmic crystals. For both of two independent molecular realizations, atomic force microscopy revealed recognizable Sierpinski triangles containing 100–200 correct tiles. Error rates during assembly appear to range from 1% to 10%. Although imperfect, the growth of Sierpinski triangles demonstrates all the necessary mechanisms for the molecular implementation of arbitrary cellular automata. This shows that engineered DNA self-assembly can be treated as a Turing-universal biomolecular system, capable of implementing any desired algorithm for computation or construction tasks

SuperB: a linear high-luminosity B Factory

This paper is based on the outcome of the activity that has taken place during the recent workshop on "SuperB in Italy" held in Frascati on November 11-12, 2005. The workshop was opened by a theoretical introduction of Marco Ciuchini and was structured in two working groups. One focused on the machine and the other on the detector and experimental issues. The present status on CP is mainly based on the results achieved by BaBar and Belle. Estabilishment of the indirect CP violation in B sector in 2001 and of the direct CP violation in 2004 thanks to the success of PEP-II and KEKB e+e- asymmetric B Factories operating at the center of mass energy corresponding to the mass of the Y(4s). With the two B Factories taking data, the Unitarity Triangle is now beginning to be overconstrained by improving the measurements of the sides and now also of the angles alpha, and gamma. We are also in presence of the very intriguing results about the measurements of sin(2 beta) in the time dependent analysis of decay channels via penguin loops, where b --> s sbar s and b --> s dbar d. Tau physics, in particular LFV search, as well as charm and ISR physics are important parts of the scientific program of a SuperB Factory. The physics case together with possible scenarios for the high luminosity SuperB Factory based on the concepts of the Linear Collider and the related experimental issues are discussed.Comment: 22 pages, 22 figures, INFN Roadmap Repor

Structural and cellular features in metaphyseal and diaphyseal periosteum of osteoporotic rats

Despite the important physiological role of periosteum in the pathogenesis and treatment of osteoporosis, little is known about the structural and cellular characteristics of periosteum in osteoporosis. To study the structural and cellular differences in both diaphyseal and metaphyseal periosteum of osteoporotic rats, samples from the right femur of osteoporotic and normal female Lewis rats were collected and tissue sections were stained with hematoxylin and eosin, antibodies or staining kit against tartrate resistant acid phosphatase (TRAP), alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), von Willebrand (vWF), tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP). The results showed that the osteoporotic rats had much thicker and more cellular cambial layer of metaphyseal periosteum compared with other periosteal areas and normal rats (P < 0.001). The number of TRAP+ osteoclasts in bone resorption pits, VEGF+ cells and the degree of vascularization were found to be greater in the cambial layer of metaphyseal periosteum of osteoporotic rats (P < 0.05), while no significant difference was detected in the number of ALP+ cells between the two groups. Sympathetic nerve fibers identified by TH staining were predominantly located in the cambial layer of metaphyseal periosteum of osteoporotic rats. No obvious difference in the expression of CGRP between the two groups was found. In conclusion, periosteum may play an important role in the cortical bone resorption in osteoporotic rats and this pathological process may be regulated by the sympathetic nervous system

Socioeconomic position across the lifecourse & allostatic load: data from the West of Scotland Twenty-07 cohort study

Background: We examined how socioeconomic position (SEP) across the lifecourse (three critical periods, social mobility and accumulated over time) is associated with allostatic load (a measure of cumulative physiological burden). Methods. Data are from the West of Scotland Twenty-07 Study, with respondents aged 35 (n = 740), 55 (n = 817) and 75 (n = 483). SEP measures representing childhood, the transition to adulthood and adulthood SEP were used. Allostatic load was produced by summing nine binary biomarker scores (1 = in the highest-risk quartile). Linear regressions were used for each of the lifecourse models; with model fits compared using partial F-tests. Results: For those aged 35 and 55, higher SEP was associated with lower allostatic load (no association in the 75-year-olds). The accumulation model (more time spent with higher SEP) had the best model fit in those aged 35 (b = -0.50, 95%CI = -0.68, -0.32, P = 0.002) and 55 (b = -0.31, 95%CI = -0.49, -0.12, P < 0.001). However, the relative contributions of each life-stage differed, with adulthood SEP less strongly associated with allostatic load. Conclusions: Long-term, accumulated higher SEP has been shown to be associated with lower allostatic load (less physiological burden). However, the transition to adulthood may represent a particularly sensitive period for SEP to impact on allostatic load. © 2014 Robertson et al.; licensee BioMed Central Ltd