We examined associations of biochemical markers of bone turnover with rapid bone loss, as measured by changes in bone mineral density (BMD). To improve the precision of bone loss estimates, calcaneal BMD was measured up to eight times over a long interval (13 years) among postmenopausal women (mean age ‫؍‬ 62 years at baseline). Women with fractures during the previous year, and users of corticosteroids, active vitamin D, bisphosphonates or calcitonin were excluded to avoid potential transient effects on marker levels. Among the remaining 354 women, markers were measured for 100 women with the fastest BMD loss (rapid loss group; mean ‫؍‬ 2.2%/year) and 100 with the slowest loss (mean ‫؍‬ 0.4%/year). Two markers of bone formation, serum bone alkaline phosphatase (Alkphase-B; BAP) and osteocalcin (NovoCalcin; OC), and two markers of bone resorption, urinary creatininecorrected free deoxypyridinoline (Pyrilinks-D; DPD) and free pyridinolines (Pyrilinks; PYD), were measured. In separate logistic regression models, each of the markers was strongly associated with rapid loss: the odds of rapid loss increased by 1.8 to 2.0 times for each 1.0 standard deviation (SD) increase of the marker. For BAP levels 2 SD above the mean, the probability of rapid bone loss was 80%; in contrast, the probability was only 20% at 2 SD below the mean. The other markers yielded similar results. We conclude that these markers are associated with rapid bone loss; this relationship appears to be continuous, with progressively greater risk of rapid bone loss with increasing levels of biomarkers. Prospective studies that include the entire distribution of bone loss rates are warranted to confirm these findings. (J Bone Miner Res 1998;13:297-302)

DNA origami templated self-assembly has shown its potential in creating rationally designed nanophotonic devices in a parallel and repeatable manner. In this investigation, we employ a multiscaffold DNA origami approach to fabricate linear waveguides of 10 nm diameter gold nanoparticles. This approach provides independent control over nanoparticle separation and spatial arrangement. The waveguides were characterized using atomic force microscopy and far-field polarization spectroscopy. This work provides a path toward large-scale plasmonic circuitry.

Nanoarchitectural control of matter is crucial for next-generation technologies. DNA origami templates are harnessed to accurately position single molecules; however, direct single molecule evidence is lacking regarding how well DNA origami can control the orientation of such molecules in three-dimensional space, as well as the factors affecting control. Here, we present two strategies for controlling the polar (θ) and in-plane azimuthal (ϕ) angular orientations of cyanine Cy5 single molecules tethered on rationally-designed DNA origami templates that are physically adsorbed (physisorbed) on glass substrates. By using dipolar imaging to evaluate Cy5′s orientation and super-resolution microscopy, the absolute spatial orientation of Cy5 is calculated relative to the DNA template. The sequence-dependent partial intercalation of Cy5 is discovered and supported theoretically using density functional theory and molecular dynamics simulations, and it is harnessed as our first strategy to achieve θ control for a full revolution with dispersion as small as ±4.5°. In our second strategy, ϕ control is achieved by mechanically stretching the Cy5 from its two tethers, being the dispersion ±10.3° for full stretching. These results can in principle be applied to any single molecule, expanding in this way the capabilities of DNA as a functional templating material for single-molecule orientation control. The experimental and modeling insights provided herein will help engineer similar self-assembling molecular systems based on polymers, such as RNA and proteins.

Molecular excitons play a foundational role in chromophore aggregates found in light-harvesting systems and offer potential applications in engineered excitonic systems. Controlled aggregation of chromophores to promote exciton delocalization has been achieved by covalently tethering chromophores to deoxyribonucleic acid (DNA) scaffolds. Although many studies have documented changes in the optical properties of chromophores upon aggregation using DNA scaffolds, more limited work has investigated how structural modifications of DNA via bridged nucleotides and chromophore covalent attachment impact scaffold stability as well as the configuration and optical behavior of attached aggregates. Here we investigated the impact of two types of bridged nucleotides, LNA and BNA, as a structural modification of duplex DNA-templated cyanine (Cy5) aggregates. The bridged nucleotides were incorporated in the domain of one to four Cy5 chromophores attached between adjacent bases of a DNA duplex. We found that bridged nucleotides increase the stability of DNA scaffolds carrying Cy5 aggregates in comparison with natural nucleotides in analogous constructs. Exciton coupling strength and delocalization in Cy5 aggregates were evaluated via steady-state absorption, circular dichroism, and theoretical modeling. Replacing natural nucleotides with bridged nucleotides resulted in a noticeable increase in the coupling strength (≥10 meV) between chromophores and increased H-like stacking behavior (i.e., more face-to-face stacking). Our results suggest that bridged nucleotides may be useful for increasing scaffold stability and coupling between DNA templated chromophores.