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

Effects of the d-donor level of vanadium on the properties of Zn_(1-x)V_(x)O films

We report the effect of d-levels of vanadium atoms on the electronic band structure of ZnO. Polycrystalline layers of Zn_(1-x)V_(x)O with 0 ≤ x ≤ 0.08 were synthesized using magnetron sputtering technique. Electrical measurements show that electron concentration increases with vanadium up to x = 0.04 and then decreases and films become insulating for x > 0.06. Optical characterization reveals that the absorption edge shifts to higher energy, while the photoluminescence (PL) peak shows a shift to lower energy with increasing vanadium content. This unusual optical behavior can be explained by an anticrossing interaction between the vanadium d-levels and the conduction band (CB) of ZnO. The interaction results in an upward shift of unoccupied CB (E+) and the downward shift of the fully occupied E- band derived from the vanadium d-levels. The composition dependence of optical absorption edge (E+) and PL peak (E-) can be fitted using the Band Anticrossing model with the vanadium d-level located at 0.13 eV below CB of ZnO and a coupling constant of 0.65 eV

Goal-setting, feedback, and assessment practices reported by australian clinical supervisors

Objective: The objective of the current study was to compare current supervisory practices in Australia against those derived from pedagogic principles and/or practice guidelines recommended by experts in the field. Three core supervisor competencies, namely goal-setting, providing formative feedback, and conducting summative assessments, were chosen for scrutiny. Methods: One hundred thirteen accredited psychology supervisors in Australia completed an online questionnaire that had supervisors report details about their goal-setting, feedback, and summative assessment practices in supervision. Results: Several aspects pertaining to summative assessment require improvement. Specifically, the limited use of observational techniques was inconsistent with principles of competency-based pedagogies and with recommendations by experts. A significant percentage of supervisors believed that summative ratings of trainee competence conducted by themselves (58%) and by their peers (66%) were compromised by leniency effects. Further, half the supervisors surveyed reported that summative assessments were made difficult by little or no guidance from training institutions about the benchmarks trainees were expected to meet at the end of placements. Conclusions: Supervisory practices concerning goal-setting were generally consistent with best-practice guidelines derived from the literature. However, improvements are warranted in key supervisory practices, including more frequent use of observational techniques to inform formative feedback, more effective strategies to counter leniency in summative assessment, and better communication between training institutions and supervisors

Statistical coevolution analysis and molecular dynamics: Identification of amino acid pairs essential for catalysis

Molecular dynamics (MD) simulations of HhaI DNA methyltransferase and statistical coupling analysis (SCA) data on the DNA cytosine methyltransferase family were combined to identify residues that are coupled by coevolution and motion. The highest ranking correlated pairs from the data matrix product (SCA·MD) are colocalized and form stabilizing interactions; the anticorrelated pairs are separated on average by 30 Å and form a clear focal point centered near the active site. We suggest that these distal anti-correlated pairs are involved in mediating active-site compressions that may be important for catalysis. Mutants that disrupt the implicated interactions support the validity of our combined SCA·MD approach

FULLSPECTRUM, a New PV Wave of more Efficient Use of the Solar Spectrum.

Abstract not availableJRC.H-Institute for environment and sustainability (Ispra