Characterization and immunomodulatory effects of canine adipose tissue- and bone marrow-derived mesenchymal stromal cells

Background Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies. Hypothesis and Objectives We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC (derived from the same dogs) will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1) proliferation rate, 2) cell surface marker expression, 3) DNA methylation levels, 4) potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5) immunomodulatory potency in vitro. Results 1) AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days) for passage (P) 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21). 2) Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3) Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4) Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3)-based induction medium. 5) Immunomodulatory capacity was equal regardless of cell source when tested in mitogen-stimulated lymphocyte reactions. Priming of MSC with pro-inflammatory factors interferon-gamma and/or tumour necrosis factor did not increase the lymphocyte suppressive properties of the MSC compared to untreated MSC. Conclusions/Significance No significant differences were found between AT- and BM-MSC with regard to their immunophenotype, progenitor, and non-progenitor functions. Both MSC populations showed strong adipogenic and osteogenic potential and poor chondrogenic potential. Both significantly suppressed stimulated peripheral blood mononuclear cells. The most significant differences found were the higher isolation success and proliferation rate of AT-MSC, which could be realized as notable benefits of their use over BM-MSC

Recent progress on the chiral unitary approach to meson meson and meson baryon interactions

We report on recent progress on the chiral unitary approach, analogous to the effective range expansion in Quantum Mechanics, which is shown to have a much larger convergence radius than ordinary chiral perturbation theory, allowing one to reproduce data for meson meson interaction up to 1.2 GeV. Applications to physical processes so far unsuited for a standard chiral perturbative approach are presented. Results for the extension of these ideas to the meson baryon sector are discussed, together with applications to kaons in a nuclear medium and $K^-$ atoms.Comment: Contribution to the KEK Tanashi Symposium on Physics of Hadrons and Nuclei, Tokyo, December 1998, 10 pages, 3 postscript figures. To be published as a special issue of Nuclear Physics

Spectra and waiting-time densities in firing resonant and nonresonant neurons

The response of a neural cell to an external stimulus can follow one of the two patterns: Nonresonant neurons monotonously relax to the resting state after excitation while resonant ones show subthreshold oscillations. We investigate how do these subthreshold properties of neurons affect their suprathreshold response. Vice versa we ask: Can we distinguish between both types of neuronal dynamics using suprathreshold spike trains? The dynamics of neurons is given by stochastic FitzHugh-Nagumo and Morris-Lecar models with either having a focus or a node as the stable fixpoint. We determine numerically the spectral power density as well as the interspike interval density in response to a random (noise-like) signals. We show that the information about the type of dynamics obtained from power spectra is of limited validity. In contrast, the interspike interval density gives a very sensitive instrument for the diagnostics of whether the dynamics has resonant or nonresonant properties. For the latter value we formulate a fit formula and use it to reconstruct theoretically the spectral power density, which coincides with the numerically obtained spectra. We underline that the renewal theory is applicable to analysis of suprathreshold responses even of resonant neurons.Comment: 7 pages, 8 figure

Constraining interactions mediated by axion-like particles with ultracold neutrons

We report a new limit on a possible short range spin-dependent interaction from the precise measurement of the ratio of Larmor precession frequencies of stored ultracold neutrons and $^{199}$Hg atoms confined in the same volume. The measurement was performed in a $\sim$1$\mu$ T vertical magnetic holding field with the apparatus searching for a permanent electric dipole moment of the neutron at the Paul Scherrer Institute. A possible coupling between freely precessing polarized neutron spins and unpolarized nucleons of the wall material can be investigated by searching for a tiny change of the precession frequencies of neutron and mercury spins. Such a frequency change can be interpreted as a consequence of a short range spin-dependent interaction that could possibly be mediated by axions or axion-like particles. The interaction strength is proportional to the CP violating product of scalar and pseudoscalar coupling constants $g_Sg_P$. Our result confirms limits from complementary experiments with spin-polarized nuclei in a model-independent way. Limits from other neutron experiments are improved by up to two orders of magnitude in the interaction range of $10^{-6}<\lambda<10^{-4}$ m

Indirect Dark Matter Detection from Dwarf Satellites: Joint Expectations from Astrophysics and Supersymmetry

We present a general methodology for determining the gamma-ray flux from annihilation of dark matter particles in Milky Way satellite galaxies, focusing on two promising satellites as examples: Segue 1 and Draco. We use the SuperBayeS code to explore the best-fitting regions of the Constrained Minimal Supersymmetric Standard Model (CMSSM) parameter space, and an independent MCMC analysis of the dark matter halo properties of the satellites using published radial velocities. We present a formalism for determining the boost from halo substructure in these galaxies and show that its value depends strongly on the extrapolation of the concentration-mass (c(M)) relation for CDM subhalos down to the minimum possible mass. We show that the preferred region for this minimum halo mass within the CMSSM with neutralino dark matter is ~10^-9-10^-6 solar masses. For the boost model where the observed power-law c(M) relation is extrapolated down to the minimum halo mass we find average boosts of about 20, while the Bullock et al (2001) c(M) model results in boosts of order unity. We estimate that for the power-law c(M) boost model and photon energies greater than a GeV, the Fermi space-telescope has about 20% chance of detecting a dark matter annihilation signal from Draco with signal-to-noise greater than 3 after about 5 years of observation

A versatile method for simulating pp -> ppe+e- and dp -> pne+e-p_spec reactions

We have developed a versatile software package for the simulation of di-electron production in $pp$ and $dp$ collisions at SIS energies. Particular attention has been paid to incorporate different descriptions of the Dalitz decay $\Delta \to N e^+e^-$ via a common interface. In addition, suitable parameterizations for the virtual bremsstrahlung process $NN \to NN e^+e^-$ based on one-boson exchange models have been implemented. Such simulation tools with high flexibility of the framework are important for the interpretation of the di-electron data taken with the HADES spectrometer and the design of forthcoming experiments

Wetting films on chemically heterogeneous substrates

Based on a microscopic density functional theory we investigate the morphology of thin liquidlike wetting films adsorbed on substrates endowed with well-defined chemical heterogeneities. As paradigmatic cases we focus on a single chemical step and on a single stripe. In view of applications in microfluidics the accuracy of guiding liquids by chemical microchannels is discussed. Finally we give a general prescription of how to investigate theoretically the wetting properties of substrates with arbitrary chemical structures.Comment: 56 pages, RevTeX, 20 Figure