EARLY FLOWERING4 recruitment of EARLY FLOWERING3 in the nucleus sustains the Arabidopsis circadian clock

The plant circadian clock is proposed to be a network of several interconnected feedback loops, and loss of any component leads to changes in oscillator speed. We previously reported that Arabidopsis thaliana EARLY FLOWERING4 (ELF4) is required to sustain this oscillator and that the elf4 mutant is arrhythmic. This phenotype is shared with both elf3 and lux. Here, we show that overexpression of either ELF3 or LUX ARRHYTHMO (LUX) complements the elf4 mutant phenotype. Furthermore, ELF4 causes ELF3 to form foci in the nucleus. We used expression data to direct a mathematical position of ELF3 in the clock network. This revealed direct effects on the morning clock gene PRR9, and we determined association of ELF3 to a conserved region of the PRR9 promoter. A cis-element in this region was suggestive of ELF3 recruitment by the transcription factor LUX, consistent with both ELF3 and LUX acting genetically downstream of ELF4. Taken together, using integrated approaches, we identified ELF4/ELF3 together with LUX to be pivotal for sustenance of plant circadian rhythms. © 2012 American Society of Plant Biologists.

Robust estimation of local genetic ancestry in admixed populations using a nonparametric Bayesian approach.

We present a new haplotype-based approach for inferring local genetic ancestry of individuals in an admixed population. Most existing approaches for local ancestry estimation ignore the latent genetic relatedness between ancestral populations and treat them as independent. In this article, we exploit such information by building an inheritance model that describes both the ancestral populations and the admixed population jointly in a unified framework. Based on an assumption that the common hypothetical founder haplotypes give rise to both the ancestral and the admixed population haplotypes, we employ an infinite hidden Markov model to characterize each ancestral population and further extend it to generate the admixed population. Through an effective utilization of the population structural information under a principled nonparametric Bayesian framework, the resulting model is significantly less sensitive to the choice and the amount of training data for ancestral populations than state-of-the-art algorithms. We also improve the robustness under deviation from common modeling assumptions by incorporating population-specific scale parameters that allow variable recombination rates in different populations. Our method is applicable to an admixed population from an arbitrary number of ancestral populations and also performs competitively in terms of spurious ancestry proportions under a general multiway admixture assumption. We validate the proposed method by simulation under various admixing scenarios and present empirical analysis results from a worldwide-distributed dataset from the Human Genome Diversity Project.

Composite hydrogels for nucleus pulposus tissue engineering

Tissue engineering offers a paradigm shift in the treatment of back pain. Engineered intervertebral discs could replace degenerated tissue and overcome the limitations of current treatments, which substantially alter the biomechanical properties of the spine. The centre of the disc, the nucleus pulposus, is an amorphous gel with a large bound water content and it can resist substantial compressive loads. Due to similarities in their compositions, hydrogels have frequently been considered as substitutes for the nucleus pulposus. However, there has been limited work characterising the time-dependent mechanical behaviour of hydrogel scaffolds for nucleus pulposus tissue engineering. Poroelastic behaviour, which plays a key role in nutrient transport, is of particular importance. Here, we investigate the time-dependent mechanical properties of gelatin and agar hydrogels and of gelatin-agar composites. The time-dependent properties of these hydrogels are explored using viscoelastic and poroelastic frameworks. Several gel formulations demonstrate comparable equilibrium elastic behaviour to the nucleus pulposus under unconfined compression, but permeability values that are much greater than those of the native tissue. A range of time-dependent responses are observed in the composite gels examined, presenting the opportunity for targeted design of custom hydrogels with combinations of mechanical properties optimized for tissue engineering applications. © 2011 Elsevier Ltd.

Local stability results for the collective behaviors of infinite populations of pulse-coupled oscillators

In this paper, we investigate the behavior of pulse-coupled integrate-and-fire oscillators. Because the stability analysis of finite populations is intricate, we investigate stability results in the approximation of infinite populations. In addition to recovering known stability results of finite populations, we also obtain new stability results for infinite populations. In particular, under a weak coupling assumption, we solve for the continuum model a conjecture still prevailing in the finite dimensional case. © 2011 IEEE.

Electrospun fiber - Hydrogel composites for nucleus pulposus tissue engineering

New materials are needed to replace degenerated intervertebral disc tissue and to provide longer-term solutions for chronic back-pain. Replacement tissue potentially could be engineered by seeding cells into a scaffold that mimics the architecture of natural tissue. Many natural tissues, including the nucleus pulposus (the central region of the intervertebral disc) consist of collagen nanofibers embedded in a gel-like matrix. Recently it was shown that electrospun micro- or nano-fiber structures of considerable thickness can be produced by collecting fibers in an ethanol bath. Here, randomly aligned polycaprolactone electrospun fiber structures up to 50 mm thick are backfilled with alginate hydrogels to form novel composite materials that mimic the fiber-reinforced structure of the nucleus pulposus. The composites are characterized using both indentation and tensile testing. The composites are mechanically robust, exhibiting substantial strain-to-failure. The method presented here provides a way to create large biomimetic scaffolds that more closely mimic the composite structure of natural tissue. © 2012 Materials Research Society.