Context. Wolf-Rayet (WR) stars have a severe impact on their environments owing to their strong ionizing radiation fields and powerful stellar winds. Since these winds are considered to be driven by radiation pressure, it is theoretically expected that the degree of the wind mass-loss depends on the initial metallicity of WR stars. Aims. Following our comprehensive studies of WR stars in the Milky Way, M 31, and the LMC, we derive stellar parameters and massloss rates for all seven putatively single WN stars known in the SMC. Based on these data, we discuss the impact of a low-metallicity environment on the mass loss and evolution of WR stars. Methods. The quantitative analysis of the WN stars is performed with the Potsdam Wolf-Rayet (PoWR) model atmosphere code. The physical properties of our program stars are obtained from fitting synthetic spectra to multi-band observations. Results. In all SMC WN stars, a considerable surface hydrogen abundance is detectable. The majority of these objects have stellar temperatures exceeding 75 kK, while their luminosities range from 10 5.5 to 10 6.1 L . The WN stars in the SMC exhibit on average lower mass-loss rates and weaker winds than their counterparts in the Milky Way, M 31, and the LMC. Conclusions. By comparing the mass-loss rates derived for WN stars in different Local Group galaxies, we conclude that a clear dependence of the wind mass-loss on the initial metallicity is evident, supporting the current paradigm that WR winds are driven by radiation. A metallicity effect on the evolution of massive stars is obvious from the HRD positions of the SMC WN stars at high temperatures and high luminosities. Standard evolution tracks are not able to reproduce these parameters and the observed surface hydrogen abundances. Homogeneous evolution might provide a better explanation for their evolutionary past.

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration.

Purpose: Meningiomas are frequent intracranial or spinal neoplasms, which recur frequently and can show aggressive clinical behaviour. We elucidated the impact of the integrin inhibitor cilengitide on migration, proliferation, and radiosensitization of meningioma cells.Experimental Design: We analyzed integrin expression in tissue microarrays of human meningiomas and the antimeningioma properties of cilengitide in cell cultures, subcutaneous and intracranial nude mouse models by measuring tumor volumes and survival times.Results: avb5 was the predominantly expressed integrin heterodimer in meningiomas, whereas avb3 was mainly detected in tumor blood vessels. Application of up to 100 mg/mL cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. Effects on cell survival could be enhanced by irradiation. One mg/mL cilengitide was sufficient to significantly inhibit meningioma cell migration and invasion in vitro. A daily dosage of 75 mg/kg did neither affect tumor volumes nor overall survival (P ¼ 0.813, log-rank test), but suppressed brain invasion in a significant fraction of treated animals. A combination of 75 mg/kg cilengitide daily and irradiation (2 Â 5 Gy) led to a 67% reduction of MRI-estimated tumor volumes in the intracranial model (P < 0.01), whereas the corresponding reduction reached by irradiation alone was only 55% (P < 0.05).Conclusions: These data show that a monotherapy with cilengitide is not likely to achieve major responses in rapidly growing malignant meningiomas, although brain invasion may be reduced because of the strong antimigratory properties of the drug. The combination with radiotherapy warrants further attention.