Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) controls adipogenesis in obesity in mice and in humans

Aims/hypothesis: Extracellular matrix reorganisation is a crucial step of adipocyte differentiation and is controlled by the matrix metalloproteinase-tissue inhibitor of matrix metalloproteinase (TIMP) enzyme system. We therefore sought to define the role of TIMP1 in adipogenesis and to elucidate whether upregulation of TIMP1 in obesity has direct effects on adipocyte formation. Methods: TIMP1 protein levels and mRNA were measured in lean and obese mice with a focus on levels in adipose tissue. We also analysed the effect of recombinant murine TIMP1 on adipogenesis, adipocyte size and metabolic control in vitro and in vivo. Results: TIMP1 levels were increased in the serum and adipose tissue of obese mouse models. Recombinant murine TIMP1 inhibited adipocyte differentiation in 3T3-L1 as well as in subcutaneous primary pre-adipocytes. Conversely, neutralising TIMP1 with a specific antibody enhanced adipocyte differentiation. In vivo, injection of recombinant TIMP1 in mice challenged with a high-fat diet led to enlarged adipocytes. TIMP1-treated mice developed an impaired metabolic profile with increased circulating NEFA levels, hepatic triacylglycerol accumulation and accelerated insulin resistance. Altered glucose clearance in TIMP1-injected mice was due to changes in adipose tissue glucose uptake, whereas muscle glucose clearance remained unaffected. Conclusions/interpretation: TIMP1 is a negative regulator of adipogenesis. In vivo, TIMP1 leads to enlarged adipocytes in the state of overnutrition. This might contribute to the detrimental metabolic consequences seen in TIMP1-injected mice, such as systemic fatty acid overload, hepatic lipid accumulation and insulin resistanc

Semiclassical model for calculating fully differential ionization cross sections of the H2_2 molecule

Fully differential cross sections are calculated for the ionization of H$_2$ by fast charged projectiles using a semiclassical model developed previously for the ionization of atoms. The method is tested in case of 4 keV electron and 6 MeV proton projectiles. The obtained results show good agreement with the available experimental data. Interference effects due to the two-center character of the target are also observed and analyzed.Comment: 11 pages, 4 figure

Phase Separation in Electronic Models for Manganites

The Kondo lattice Hamiltonian with ferromagnetic Hund's coupling as a model for manganites is investigated. The classical limit for the spin of the (localized) $t_{2g}$ electrons is analyzed on lattices of dimension 1,2,3 and $\infty$ using several numerical methods. The phase diagram at low temperature is presented. A regime is identified where phase separation occurs between hole undoped antiferromagnetic and hole-rich ferromagnetic regions. Experimental consequences of this novel regime are discussed. Regions of incommensurate spin correlations have also been found. Estimations of the critical temperature in 3D are compatible with experiments.Comment: Accepted in Phys. Rev. Letter

High precision measurement of the associated strangeness production in proton proton interactions

A new high precision measurement of the reaction pp -> pK+Lambda at a beam momentum of 2.95 GeV/c with more than 200,000 analyzed events allows a detailed analysis of differential observables and their inter-dependencies. Correlations of the angular distributions with momenta are examined. The invariant mass distributions are compared for different regions in the Dalitz plots. The cusp structure at the N Sigma threshold is described with the Flatt\'e formalism and its variation in the Dalitz plot is analyzed.Comment: accepted for publication in Eur. Phys. J.

First Model-Independent Measurement of the Spin Triplet pΛp\Lambda Scattering Length from Final State Interaction in the p⃗p→pK+Λ\vec{p}p \rightarrow pK^{+}\Lambda Reaction

The $\vec{p}p \rightarrow pK^{+}\Lambda$ reaction has been measured with the COSY-TOF detector at a beam momentum of $2.7\,\mathrm{GeV}/c$. The polarized proton beam enables the measurement of the beam analyzing power by the asymmetry of the produced kaon ($A_N^{K}$). This observable allows the $p\Lambda$ spin triplet scattering length to be extracted for the first time model independently from the final-state interaction in the reaction. The obtained value is $a_{t} = (-2.55 ^{+0.72}_{-1.39} {}_{\textrm{stat.}} \pm 0.6_{\textrm{syst.}} \pm 0.3_{\textrm{theo.}})\mathrm{fm}$. This value is compatible with theoretical predictions and results from model-dependent analyses.Comment: Revised version as accepted for publication in PR

Observation of two time scales in the ferromagnetic manganite La(1-x)Ca(x)MnO(3), x = 0.3

We report new zero-field muon spin relaxation and neutron spin echo measurements in ferromagnetic (FM) (La,Ca)MnO3 which taken together suggest two spatially separated regions in close proximity possessing very different Mn-ion spin dynamics. One region corresponds to an extended cluster which displays 'critical slowing down' near Tc and an increasing volume fraction below Tc. The second region possesses more slowly fluctuating spins and a decreasing volume fraction below Tc. These data are discussed in terms of the growth of small polarons into overlapping regions of correlated spins below Tc, resulting in a microscopically inhomogeneous FM transition.Comment: 10 pages, 3 figure

Monte Carlo Simulations for the Magnetic Phase Diagram of the Double Exchange Hamiltonian

We have used Monte Carlo simulation techniques to obtain the magnetic phase diagram of the double exchange Hamiltonian. We have found that the Berry's phase of the hopping amplitude has a negligible effect in the value of the magnetic critical temperature. To avoid finite size problems in our simulations we have also developed an approximated expression for the double exchange energy. This allows us to obtain the critical temperature for the ferromagnetic to paramagnetic transition more accurately. In our calculations we do not observe any strange behavior in the kinetic energy, chemical potential or electron density of states near the magnetic critical temperature. Therefore, we conclude that other effects, not included in the double exchange Hamiltonian, are needed to understand the metal-insulator transition which occurs in the manganites.Comment: 6 pages Revtex, 8 PS figure

Coupling to optical phonons in the one-dimensional t-J model: Effects on superconducting fluctuations and phase separation

The one-dimensional (1D) $t$-$J$ Holstein model is studied by exact diagonalization of finite rings using a variational approximation for the phonon states. Due to renormalization effects induced by the phonons, for intermediate electron-phonon coupling, the phase separation (PS) boundary, and with it the region of dominating superconducting fluctuations is shifted substantially to smaller values of $J/t$ as compared to the pure $t$-$J$ model. Superconducting correlations are weakened through charge density wave interactions mediated by the phonons. Possible consequences for the high $T_c$ oxides are discussed.Comment: 4 pages, Latex2

Mass-Transport Models with Multiple-Chipping Processes

We study mass-transport models with multiple-chipping processes. The rates of these processes are dependent on the chip size and mass of the fragmenting site. In this context, we consider k-chip moves (where k = 1, 2, 3, ....); and combinations of 1-chip, 2-chip and 3-chip moves. The corresponding mean-field (MF) equations are solved to obtain the steady-state probability distributions, P (m) vs. m. We also undertake Monte Carlo (MC) simulations of these models. The MC results are in excellent agreement with the corresponding MF results, demonstrating that MF theory is exact for these models.Comment: 18 pages, 4 figures, To appear in European Physical Journal

Phase Separation Induced by Orbital Degrees of Freedom in Models for Manganites with Jahn-Teller Phonons

The two-orbital Kondo model with classical Jahn-Teller phonons is studied using Monte Carlo techniques. The observed phase diagram is rich, and includes a novel regime of phase separation induced by the orbital degrees of freedom. Experimental consequences of our results are discussed. In addition, the optical conductivity $\sigma(\omega)$ of the model is presented. It is shown to have several similarities with experimental measurements for manganites.Comment: Accepted for publication in Phys. Rev. Letters, revised version of the paper, 5 pages, Revtex, with 4 figures embedde