Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells

The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell–microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential.This study was supported by Fundació la Marató TV3, Project n° 111431

Timing of the Brunhes-Matuyama magnetic polarity reversal inChinese loess using 10Be

In Chinese loess, the Brunhes-Matuyama (B-M) geomagnetic reversal occurs ~25 k.y. prior to the age found in marine sediments. This offset has been attributed by some to post-depositional magnetic overprinting of loess, while others have argued it is due to errors in the loess time scale. Here we solve this long-standing debate by exploiting a new method to extract reproducible records of geomagnetic fi eld intensity from loess with 10Be&mdash;a proxy for global average geomagnetic fi eld intensity&mdash;and using it to show that a pronounced minimum in field intensity (a requirement for dipole fi eld reversal) is recorded in two separate loess records at ca. 780 &plusmn; 3 kyr B.P. This timing is synchronous with the B-M reversal timing seen in marine records, verifying the standard loess time scale as correct, but it is ~25 k.y. younger than the age (depth) of the magnetic polarity reversal recorded in these same Chinese loess sediments, demonstrating that loess magnetic overprinting has occurred.</p

EC/beta(+) decay of six medium-heavy nuclei

Previous experimental results of (EC+beta(+)) decay for the medium-heavy nuclei reported by our group since 1996, including Er-153, Yb-157, Fr-209, Ce-128, Ce-130, and Pr-128 have been briefly summarized. The observed low-lying states in their daughter nuclei have been reviewed in a systematic way and compared with different model calculations. Finally, some questions have been put forward for further study and discussion

Properties of the beta-Delayed Proton Decay of Er-147

The beta-delayed proton decay of Er-147 is studied experimentally using the Ni-58+Mo-92 reaction at a beam energy of 383 MeV. Based on a He-jet apparatus coupled with a tape transport system, the beta-delayed proton radioactivities both from the nu s(1/2) ground state and the nu h(11/2) isomer in Er-147 are identified by proton-gamma coincidence measurements. By analyzing the time distribution of the 4(+) -> 2(+) gamma transition in the grand-daughter nucleus Dy-146, a half-life of 1.6 +/- 0.2 s is determined for the nu h(11/2) isomer in Er-147. The half-life for the ground state of Er-147 is estimated to be 3.2 +/- 1.2 s