Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties.

IntroductionMultipotent progenitor populations exist within the tendon proper and peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.MethodsIsolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types.ResultsThe cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors.ConclusionsData demonstrate that, relative to peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies

Elliptical slice sampling

Many probabilistic models introduce strong dependencies between variables using a latent multivariate Gaussian distribution or a Gaussian process. We present a new Markov chain Monte Carlo algorithm for performing inference in models with multivariate Gaussian priors. Its key properties are: 1) it has simple, generic code applicable to many models, 2) it has no free parameters, 3) it works well for a variety of Gaussian process based models. These properties make our method ideal for use while model building, removing the need to spend time deriving and tuning updates for more complex algorithms.Comment: 8 pages, 6 figures, appearing in AISTATS 2010 (JMLR: W&CP volume 6). Differences from first submission: some minor edits in response to feedback

Functions on the model orbit in E8

First published in Representation Theory in Vol.2,1998. Published by the American Mathematical Society.We decompose the ring of regular functions on the unique coadjoint orbit for complex E8 of dimension 128, finding that every irreducible representation appears exactly once. This confirms a conjecture of McGovern. We also study the unique real form of this orbit

IMPLICATIONS OF GLOBAL CLIMATE CHANGE FOR WESTERN AGRICULTURE

Global climate change from increases in atmospheric carbon dioxide and other trace gases is an issue of international concern. Adverse climate conditions are expected to reduce crop yields and alter the demand for and supply of water. These potential adjustments imply economic costs to agriculture and its constituents. This paper explores possible economic implications for U.S. agriculture, with particular reference to the West. Results from a series of spatial equilibrium model analyses suggest that climate change is not a food security issue for the United States. However, regional adjustments in agricultural production and associated resource use are expected. This implies additional pressure in rural communities. Environmental quality reductions are also likely.Environmental Economics and Policy,

Monovalent and divalent cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic ganglia

Acetylcholine-evoked currents mediated by activation of nicotinic receptors in rat parasympathetic neurons were examined using whole-cell voltage clamp. The relative permeability of the neuronal nicotinic acetylcholine (nACh) receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements. The channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Cs+ \u3e K+ \u3e Rb+ \u3e Na+ \u3e Li+, and permeability ratios relative to Na+ (P(x)/P(Na)) ranging from 1.27 to 0.75. The selectivity of the alkaline earths was also weak, with the sequence of Mg2+ \u3e Sr2+ \u3e Ba2+ \u3e Ca2+, and relative permeabilities of 1.10 to 0.65. The relative Ca2+ permeability (P(Ca)/P(Na)) of the neuronal nACh receptor channel is ~ fivefold higher than that of the motor endplate channel (Adams, D. J., T. M. Dwyer, and B. Hille. 1980. Journal of General Physiology. 75:493-510). The transition metal cation, Mn2+ was permeant (P(x)/P(Na) = 0.67), whereas Ni2+, Zn2+, and Cd2+ blocked ACh-evoked currents with half-maximal inhibition (IC50) occurring at ~500 μM, 5 μM and 1 mM, respectively. In contrast to the muscle endplate AChR channel, that at least 56 organic cations which are permeable to (Dwyer et al. 1980), the majority of organic cations tested were found to completely inhibit ACh-evoked currents in rat parasympathetic neurons. Concentration-response curves for guanidinium, ethylammonium, diethanolammonium and arginine inhibition of ACh-evoked currents yielded IC50s of ~2.5-6.0 mM. The organic cations, hydrazinium, methylammonium, ethanolammonium and Tris, were measurably permeant, and permeability ratios varied inversely with the molecular size of the cation. Modeling suggests that the pore has a minimum diameter of 7.6 Å. Thus, there are substantial differences in ion permeation and block between the nACh receptor channels of mammalian parasympathetic neurons and amphibian skeletal muscle which represent functional consequences of differences in the primary structure of the subunits of the ACh receptor channel

The azimuth structure of nuclear collisions -- I

We describe azimuth structure commonly associated with elliptic and directed flow in the context of 2D angular autocorrelations for the purpose of precise separation of so-called nonflow (mainly minijets) from flow. We extend the Fourier-transform description of azimuth structure to include power spectra and autocorrelations related by the Wiener-Khintchine theorem. We analyze several examples of conventional flow analysis in that context and question the relevance of reaction plane estimation to flow analysis. We introduce the 2D angular autocorrelation with examples from data analysis and describe a simulation exercise which demonstrates precise separation of flow and nonflow using the 2D autocorrelation method. We show that an alternative correlation measure based on Pearson's normalized covariance provides a more intuitive measure of azimuth structure.Comment: 27 pages, 12 figure