Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair

Overview of the Iseult 11.7 T MRI Cryoplant Operation

International audienceThe Iseult whole-body MRI delivered its first images in October 2021. The masterpiece of this MRI is an actively shielded NbTi magnet providing a homogeneous magnetic field of 11.7 T within a 90 cm warm bore. A dedicated cryoplant was constructed to cool the magnet at 1.8 K using a superfluid helium bath and it is in nominal operation since March 2019. This paper will present the cryoplant design, as well as the connection of the cryogenic ancillary equipment with the magnet. Estimated thermal losses will be compared with experimental data collected since the beginning of the cooling phase. Then, we will describe the system maintenance and the periodic controls of the various pressurized components performed keeping the continuous nominal operation of the MRI. Finally, we will present the first lessons learned on this unique cryogenic system operation and possible options to improve its reliability

Test Results of the MQYYM: A 90 Mm NbTi Quadrupole Magnet Option for HL-LHC

International audienceFor the HL-LHC project, a 90 mm NbTi cos(2θ) double aperture quadrupole magnet with an operating gradient of 120 T/m at 1.9 K has been designed as an option to replace the 70 mm aperture LHC quadrupole MQY. CEA in collaboration with CERN designed and manufactured a single aperture short model magnet with a magnetic length of 1.215 m at 1.9 K called MQYYM. The MQYYM cold test occurred at CEA at 4.2 K in a vertical cryogenic station. During the power test, the operating gradient at 1.9 K has been reached after two training quenches. All along the test, magnetic and mechanical measurements were done using respectively a rotating probe and strain gauges. This paper describes the performance of the MQYYM at 4.2 K and gives an analysis of the data acquired during the test, including training behavior, quench detection, protection and field quality measurements

Test Results of the MQYYM: A 90 Mm NbTi Quadrupole Magnet Option for HL-LHC

For the HL-LHC project, a 90 mm NbTi cos(2θ) double aperture quadrupole magnet with an operating gradient of 120 T/m at 1.9 K has been designed as an option to replace the 70 mm aperture LHC quadrupole MQY. CEA in collaboration with CERN designed and manufactured a single aperture short model magnet with a magnetic length of 1.215 m at 1.9 K called MQYYM. The MQYYM cold test occurred at CEA at 4.2 K in a vertical cryogenic station. During the power test, the operating gradient at 1.9 K has been reached after two training quenches. All along the test, magnetic and mechanical measurements were done using respectively a rotating probe and strain gauges. This paper describes the performance of the MQYYM at 4.2 K and gives an analysis of the data acquired during the test, including training behavior, quench detection, protection and field quality measurements

Development, Integration, and Test of the MACQU Demo Coil Toward MADMAX Quench Analysis

The MADMAX project aims at detecting axion dark matter in the mass range of 100 μeV. To facilitate axion to photon conversion with detectable rate a superconducting dipole magnet with a large bore is needed. The MADMAX dipole magnet has to generate ~9 T in a 1.35 m aperture over ~1.3 m in length. A key challenge for a magnet made of a cable in-conduit conductor (CICC), operating at 1.8 K with an indirect bath cooling is the quench detection. In order to validate feasibility, a mock-up coil with a quench behavior scalable to MADMAX was designed and produced. This mock-up was used to benchmark numerical simulations of the quench in the THEA code. The paper gives an overview of the technicaldetails of the MACQU test coil. The conductor, the magnet, the busbar and the supporting and cryogenic systems were designed at CEA. The cable was manufactured in China at the Chang Tong INC from WST Nb-Ti strands, the insertion and compaction was achieved in the ASIPP institute with a copper profile from Aurubis. The winding of the coil and the busbar pre-forming were performed at Bilfinger Noell as well as the assembly of the supporting structure and the thermal shield. The magnet was integrated in the JT60 test station at CEA Saclay and extensively tested

Differential Effects of pH on the Pore-Forming Properties of Bacillus thuringiensis Insecticidal Crystal Toxins

The effect of pH on the pore-forming ability of two Bacillus thuringiensis toxins, Cry1Ac and Cry1C, was examined with midgut brush border membrane vesicles isolated from the tobacco hornworm, Manduca sexta, and a light-scattering assay. In the presence of Cry1Ac, membrane permeability remained high over the entire pH range tested (6.5 to 10.5) for KCl and tetramethylammonium chloride, but was much lower at pH 6.5 than at higher pHs for potassium gluconate, sucrose, and raffinose. On the other hand, the Cry1C-induced permeability to all substrates tested was much higher at pH 6.5, 7.5, and 8.5 than at pH 9.5 and 10.5. These results indicate that the pores formed by Cry1Ac are significantly smaller at pH 6.5 than under alkaline conditions, whereas the pore-forming ability of Cry1C decreases sharply above pH 8.5. The reduced activity of Cry1C at high pH correlates well with the fact that its toxicity for M. sexta is considerably weaker than that of Cry1Aa, Cry1Ab, and Cry1Ac. However, Cry1E, despite having a toxicity comparable to that of Cry1C, formed channels as efficiently as the Cry1A toxins at pH 10.5. These results strongly suggest that although pH can influence toxin activity, additional factors also modulate toxin potency in the insect midgut