Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis.

OBJECTIVE: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. METHODS: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. RESULTS: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1ß and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. CONCLUSION: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

GC-MS method for metabolic profiling of mouse femoral head articular cartilage reveals distinct effects of tissue culture and development.

OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum (FBS). We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between five and 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted six out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development.

Electrical transport properties of CuS single crystals.

Electrical resistivity, transverse magnetoresistance and thermoelectric power measurements were performed on CuS high quality single crystals in the range 1.2-300 K and under fields of up to 16 T. The zero field resistivity data are well described below 55 K by a quasi-2D model, consistent with a carrier confinement at lower temperatures, before the transition to the superconducting state. The transverse magnetoresistance develops mainly below 30 K and attains values as large as 470% for a 16 T field at 5 K, this behaviour being ascribed to a band effect mechanism, with a possible magnetic field induced DOS change at the Fermi level. The transverse magnetoresistance shows no signs of saturation, following a power law with field Δρ/ρ(0) ∝ H(1.4), suggesting the existence of open orbits for carriers at the Fermi surface. The thermoelectric power shows an unusual temperature dependence, probably as a result of the complex band structure of CuS.

Single-crystal study on the heavy-fermion antiferromagnet UZn12.

Millimetre size UZn(12) single crystals were grown by the high temperature solution growth method using zinc as the solvent. Single-crystal x-ray diffraction data confirm that this compound crystallizes in the hexagonal high temperature form of SmZn(12) (S.G. P6/mmm) and points to a U(1.01(1))Zn(11.7(1)) stoichiometry for the crystals, with ∼ 4% of the U atoms being located at the 2c site due to the partial substitution of 4h Zn pairs. UZn(12) orders antiferromagnetically at T(N) = 5.0(2) K, and the magnetization and resistivity measurements suggest that the magnetic moments are confined within the a-b plane. The Sommerfeld coefficient, derived from the paramagnetic region by the standard method, is γ(p)≈200 mJ (mol K(2))( - 1), which definitely classifies UZn(12) as a moderate heavy-fermion system. The heavy-fermion character of UZn(12) is also manifested in the overall shape of temperature-dependent electrical resistivity that is dominated by a single-ion Kondo effect at high temperatures and coherent Kondo scattering at low temperatures. The paramagnetic magnetoresistivity isotherms can be fairly well superimposed onto each other using Schlottmann's scaling for the single-ion Kondo model, as expected for a Kondo system.

Gold complexes with dithiothiophene ligands: a metal based on a neutral molecule.

The gold complexes n-Bu4N[Au(alpha-tpdt)2] (5), n-Bu4N[Au(dtpdt)2] (4) and n-Bu4N[Au(tpdt)2] (6) based on new dithiothiophene ligands (alpha-tpdt= 2,3-thiophenedithiolate, dtpdt=2,3-dihydro-5,6-thiophenedithiolate and tpdt = 3,4-thiophenedithiolate) have been prepared and characterised. These gold(III) complexes are diamagnetic, but they can be oxidised with iodine to the paramagnetic compounds [Au(alpha-tpdt)2] (8), [Au(dtpdt)2] (7) and n-Bu4N[[Au(tpdt)2]n-2] (9), which were isolated as fine powders and which exhibit paramagnetic susceptibilities that are almost temperature independent with room temperature values of 2.5 x 10(-4), 2.0 x 10(-4) and 5 x 10(-4) emu x mol(-1), respectively. Interestingly, the neutral complex [Au(alpha-tpdt)2] (8) as a polycrystalline sample displays the properties of a metallic system with a room temperature electrical conductivity of 6 S x cm(-1) and a thermoelectric power of 5.5 microVK(-1); this is the first time that this metallic property has been observed in a molecular system based on a neutral species.