Activity modulation and allosteric control of a scaffolded DNAzyme using a dynamic DNA nanostructure.

Recognition of the fundamental importance of allosteric regulation in biology dates back to not long after its discovery in the 1960s. Our ability to rationally engineer this potentially useful property into normally non-allosteric catalysts, however, remains limited. In response we report a DNA nanotechnology-enabled approach for introducing allostery into catalytic nucleic acids. Specifically, we have grafted one or two copies of a peroxidase-like DNAzyme, hemin-bound G-quadruplex (hemin-G), onto a DNA tetrahedral nanostructure in such a manner as to cause them to interact, modulating their catalytic activity. We achieve allosteric regulation of these catalysts by incorporating dynamically responsive oligonucleotides that respond to specific "effector" molecules (complementary oligonucleotides or small molecules), altering the spacing between the catalytic sites and thus regulating their activity. This designable approach thus enables subtle allosteric modulation in DNAzymes that is potentially of use for nanomedicine and nanomachines

Network properties of written human language

We investigate the nature of written human language within the framework of complex network theory. In particular, we analyse the topology of Orwell's \textit{1984} focusing on the local properties of the network, such as the properties of the nearest neighbors and the clustering coefficient. We find a composite power law behavior for both the average nearest neighbor's degree and average clustering coefficient as a function of the vertex degree. This implies the existence of different functional classes of vertices. Furthermore we find that the second order vertex correlations are an essential component of the network architecture. To model our empirical results we extend a previously introduced model for language due to Dorogovtsev and Mendes. We propose an accelerated growing network model that contains three growth mechanisms: linear preferential attachment, local preferential attachment and the random growth of a pre-determined small finite subset of initial vertices. We find that with these elementary stochastic rules we are able to produce a network showing syntactic-like structures

A review of ecogeochemistry approaches to estimating movements of marine animals

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2013. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 58 (2013): 697-714, doi:10.4319/lo.2013.58.2.0697.Ecogeochemistry—the application of geochemical techniques to fundamental questions in population and community ecology—has been used in animal migration studies in terrestrial environments for several decades; however, the approach has received far less attention in marine systems. This review includes comprehensive meta-analyses of organic zooplankton δ13C and δ15N values at the base of the food web, dissolved inorganic carbon δ13C values, and seawater δ18O values to create, for the first time, robust isoscapes for the Atlantic Ocean. These isoscapes present far greater geographic variability in multiple geochemical tracers than was previously thought, thus forming the foundation for reconstructions of habitat use and migration patterns of marine organisms. We review several additional tracers, including trace-element-to-calcium ratios and heavy element stable isotopes, to examine anadromous migrations. We highlight the value of the ecogeochemistry approach by examining case studies on three components of connectivity: dispersal and natal homing, functional connectivity, and migratory connectivity. We also discuss recent advances in compound-specific stable carbon and nitrogen isotope analyses for tracking animal movement. A better understanding of isotopic routing and fractionation factors, particularly of individual compound classes, is necessary to realize the full potential of ecogeochemistry.We were supported by funding from the National Science Foundation (Division of Ocean Sciences–0825148 to S.R.T.), Award USA 00002 and KSA 00011 from the King Abdullah University of Science and Technology (to S.R.T.), and a National Science Foundation Graduate Research Fellowship (to L.H.)

Flow over mountains: Coriolis force, transient troughs and three dimensionality

Some issues, concerning uniform, stratified flow over a three-dimensional mountain, that have not been fully explored are studied using primitive-equation models.This research was in part supported by the National Science Foundation, Division of Atmospheric Science, under Grant ATM9106495

Willmore minimizers with prescribed isoperimetric ratio

Motivated by a simple model for elastic cell membranes, we minimize the Willmore functional among two-dimensional spheres embedded in R^3 with prescribed isoperimetric ratio

Duplication-divergence model of protein interaction network

We show that the protein-protein interaction networks can be surprisingly well described by a very simple evolution model of duplication and divergence. The model exhibits a remarkably rich behavior depending on a single parameter, the probability to retain a duplicated link during divergence. When this parameter is large, the network growth is not self-averaging and an average vertex degree increases algebraically. The lack of self-averaging results in a great diversity of networks grown out of the same initial condition. For small values of the link retention probability, the growth is self-averaging, the average degree increases very slowly or tends to a constant, and a degree distribution has a power-law tail.Comment: 8 pages, 13 figure

Intraocular pressure in inbred mouse strains

PURPOSE: To develop a protocol to measure the intraocular pressure (IOP) of living mice and to determine the IOP of genetically different mouse strains. METHODS: Eyes of anesthetized animals were cannulated with a very fine fluid-filled glass microneedle. The microneedle was connected to a pressure transducer, and the pressure signal was analyzed with a computer system. Intraocular pressures of male C3H/He iota, C57BL/ 6 iota, A/iota, and BALB/c iota mice were determined. RESULTS: Differences in IOP were detected between genetically distinct mouse strains maintained in virtually identical environments. C3H/He iota was the strain with the highest average IOP (13.7 +/- 0.8 mm Hg). This strain average was 1.4 mm Hg higher than that for C57BL/6 iota (12.3 +/- 0.5 mm Hg; P = 0.14), 4.3 mm Hg higher than that for A/iota (9.4 +/- 0.5 mm Hg; P < 0.001), and 6 mm Hg higher than that for BALB/c iota (7.7 +/- 0.5 mm Hg; P < 0.001). CONCLUSIONS: The authors have developed an accurate and reliable procedure for measuring intraocular pressure in living mice. This procedure can detect IOP differences between groups of mice that differ by genotype

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications