Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation

SummaryObjectiveThe effects of inflammation on bone development from mesenchymal stem cells (MSC) are unclear due to the difficulty in isolating MSC. The aim of this study was to develop a MSC isolation method and to determine the in vitro effects of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) on their osteogenic differentiation.MethodsMurine MSC were isolated from the limbs of C57/Bl6 mice through collagenase digestion of bone and enriched as the Stem cell antigen (Sca-1)+ CD31− CD45− population, using lineage immunodepletion, followed by fluorescence-activated cell sorting (FACS). They were differentiated along the osteoblast linage in the presence or absence of IL-1β and TNFα. Mineralization was measured as was the expression of a number of osteogenic genes by quantitative polymerase chain reaction (PCR).ResultsWe show that osteogenic differentiation from the MSC population is suppressed by IL-1β and TNFα. In addition to suppression of bone mineralization, both cytokines inhibited the differentiation-associated increases in alkaline phosphatase (ALP) activity and the gene expression for ALP, α1(I) procollagen, runt-related transcription factor 2 (Runx2) and osterix. However, only TNFα inhibited osteonectin and osteopontin mRNA expression and only IL-1β reduced cell proliferation.ConclusionsThe convenient isolation technique enables the easy generation of sufficient MSC to permit the molecular analysis of their differentiation. We were thus able to show that the proinflammatory cytokines, IL-1β and TNFα, can compromise bone development from this primary MSC population, although with some significant differences. The potential involvement of specific inflammatory mediators needs to be taken into account if optimal bone repair and presumably that of other tissues are to be achieved with MSC

The Aharonov-Bohm Effect in the Fractional Quantum Hall Regime

We have investigated experimentally resonant tunnelling through single-particle states formed around an antidot by a magnetic field, in the fractional quantum Hall regime. For 1/3 filling factor around the antidot, Aharonov-Bohm oscillations are observed with the same magnetic field period as in the integer quantum Hall regime. All our measurements are consistent with quasiparticles of fractional charge e*. However, the results are also consistent with particles of any charge (>= e*) as the system must rearrange every time the flux enclosed increases by h/e.Comment: Postscript, 4 pages, gzipped (350 kB

Correlations, compressibility, and capacitance in double-quantum-well systems in the quantum Hall regime

In the quantum Hall regime, electronic correlations in double-layer two-dimensional electron systems are strong because the kinetic energy is quenched by Landau quantization. In this article we point out that these correlations are reflected in the way the partitioning of charge between the two-layers responds to a bias potential. We report on illustrative calculations based on an unrestricted Hartree-Fock approximation which allows for spontaneous inter-layer phase coherence. The possibility of studying inter-layer correlations by capacitive coupling to separately contacted two-dimensional layers is discussed in detail.Comment: RevTex style, 21 pages, 6 postscript figures in a separate file; Phys. Rev. B (in press

The effect of temperature on adhesion forces between surfaces and model foods containing whey protein and sugar

The formation of fouling deposit from foods and food components is a severe problem in food processing and leads to frequent cleaning. The design of surfaces that resist fouling may decrease the need for cleaning and thus increase efficiency. Atomic force microscopy has been used to measure adhesion forces between stainless steel (SS) and fluoro-coated glass (FCG) microparticles and the model food deposits (i) whey protein (WPC), (ii) sweetened condensed milk, and (iii) caramel. Measurements were performed over a range of processing temperatures between 30 and 90 oC and at contact times up to 60 s. There is a significant increase in adhesion force of both types of microparticle to WPC at 90 oC for all contact times. For confectionary deposits adhesion to SS was similar. Adhesion of confectionary deposits to FCG at 30 oC revealed a decrease in adhesion compared to SS; at higher temperatures the adhesion forces were similar

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and eventual paralysis. Until recently, ALS was classified primarily within the neuromuscular domain, although new imaging and neuropathological data have indicated the involvement of the non-motor neuraxis in disease pathology. In most patients, the mechanisms underlying the development of ALS are poorly understood, although a subset of patients have familial disease and harbour mutations in genes that have various roles in neuronal function. Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria

PET imaging of T cells derived from umbilical cord blood

Progress in understanding tumor-specific immune responses, genetic engineering and ex vivo manufacturing, have led to improvements in the safety and feasibility of adoptive transfer of genetically modified T cells. However, rational design, application and evaluation of T-cell therapy requires monitoring methods that can detect, locate and serially quantify these cell-mediated immune responses. Currently, such monitoring methods are chiefly limited to invasive techniques to investigate recovered cell populations for in vitro measurements including histology, flow cytometry, Q-PCR or the detection of cytokines. These assays provide episodic glimpses of the bio distribution of T cells and are limited by the number and sites of sampling. In contrast, imaging provides a methodology for quantitative, non-invasive, longitudinal and spatial in vivo information about the dynamic processes of infused T cells

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter