[1] Cenozoic gneiss domes-exposing middle-lower crustal rocks-cover~30% of the surface exposure of the Pamir, western India-Asia collision zone; they allow an unparalleled view into the deep crust of the Asian plate. We use titanite, monazite, and zircon U/Th-Pb, mica Ar/ 39 Ar, zircon and apatite fission track, and zircon (U-Th)/He ages to constrain the exhumation history of the~350 × 90 km Shakhdara-Alichur dome, southwestern Pamir. Doming started at 21-20 Ma along the Gunt top-to-N normal-shear zone of the northern Shakhdara dome. The bulk of the exhumation occurred by~NNW-ward extrusion of the footwall of the crustal-scale South Pamir normal-shear zone along the southern Shakhdara dome boundary. Footwall extrusion was active from~18-15 Ma to~2 Ma at~10 mm/yr slip and with vertical exhumation rates of 1-3 mm/yr; it resulted in up to 90 km~N-S extension, coeval with~N-S convergence between India and Asia. Erosion rates were 0.3-0.5 mm/yr within the domes and 0.1-0.3 mm/yr in the horst separating the Shakhdara and Alichur domes and in the southeastern Pamir plateau; rates were highest along the dome axis in the southern part of the Shakhdara dome. Incision along the major drainages was up to 1.0 mm/yr. Thermal modeling suggests geothermal gradients as high as 60°C/km along the trace of the South Pamir shear zone and their strong N-S variation across the dome; the gradients relaxed to ≤40-45°C/km since the end of doming.

The osteogenic differentiation of mesenchymal stem cells is now a standard procedure in modern bone tissue engineering. As this is a promising field for future clinical applications, many cell culture media exist to promote osteogenic differentiation. Prior to differentiation, cells must be expanded to obtain sufficient numbers for experiments. Little evidence is available regarding the optimal media combination for expansion and differentiation to maximize the osteogenic response. Therefore, human BM-MSCs (n = 6) were expanded in parallel in DMEM (Dulbecco’s Modified Eagle Medium) LG (Low Glucose) and α-MEM (Minimum Essential Media alpha-modification), followed by simultaneous monolayer differentiation toward the osteogenic lineage in: 1. DMEM LG (Low Glucose), 2. DMEM HG (High Glucose), 3. α-MEM, 4. “Bernese medium”, and 5. “Verfaillie medium,” with a corresponding negative control (total 20 groups). As a marker for osteogenic differentiation, hydroxyapatite was accessed using radioactive 99mTc-HDP labeling and quantitative alizarin red staining. The results indicate that all media except “Bernese medium” are suitable for osteogenic differentiation, while there was evidence that DMEM LG is partly superior when used for expansion and differentiation of BM-hMSCs. Using “Verfaillie medium” after DMEM LG expansion led to the highest grade of osteogenic differentiation. Nevertheless, the difference was not significant. Therefore, we recommend using DMEM LG for robust osteogenic differentiation, as it is highly suitable for that purpose, economical compared to other media, and requires little preparation time.

Treatment of infected nonunions and severe bone infections is a huge challenge in modern orthopedics. Their treatment routinely includes the use of anti-infective agents. Although frequently used, little is known about their impact on the osteogenesis of mesenchymal stem cells. In a high- and low-dose set-up, this study evaluates the effects of the antibiotics Gentamicin and Vancomycin as well as the antifungal agent Voriconazole on the ability of mesenchymal stem cells to differentiate into osteoblast-like cells and synthesize hydroxyapatite in a monolayer cell culture. The osteogenic activity was assessed by measuring calcium and phosphate concentrations as well as alkaline phosphatase activity and osteocalcin concentration in the cell culture medium supernatant. The amount of hydroxyapatite was measured directly by radioactive 99mTechnetium-HDP labeling. Regarding the osteogenic markers, it could be concluded that the osteogenesis was successful within the groups treated with osteogenic cell culture media. The results revealed that all anti-infective agents have a cytotoxic effect on mesenchymal stem cells, especially in higher concentrations, whereas the measured absolute amount of hydroxyapatite was independent of the anti-infective agent used. Normed to the number of cells it can therefore be concluded that the above-mentioned anti-infective agents actually have a positive effect on osteogenesis while high-dose Gentamycin, in particular, is apparently capable of boosting the deposition of minerals.