Tamoxifen, 17beta-oestradiol and the calmodulin antagonist J8 inhibit human melanoma cell invasion through fibronectin.

Invasion through stromal extracellular matrix (ECM) is part of the complex, multistep process of tumour cell invasion and metastasis. Our group has previously demonstrated that calcium and calmodulin are important in another step in the metastatic cascade - that of attachment of cells to ECM. Interestingly, the non-steroidal anti-oestrogen tamoxifen (which also has calmodulin antagonist activity), used in the treatment of breast cancer and now in metastatic cutaneous melanoma, can inhibit the attachment of normal and neoplastic cells to ECM. In this study, we investigated whether such drugs, known to inhibit cell attachment, could also subsequently reduce their invasion through a layer of human fibronectin. We examined the ability of the specific calmodulin antagonist J8, tamoxifen and its two major metabolites, N-desmethyltamoxifen (N-des) and 4-hydroxytamoxifen (4-OH), as well as the pure anti-oestrogen ICI 182,780 and 17beta-oestradiol to inhibit invasion of the human cutaneous melanoma cell line, A375-SM, uveal melanoma cells and uveal melanocytes. A375-SM cells and uveal melanoma cells showed a high level of invasion (15.2% and 33.7% respectively) compared with melanocytes (around 5%) under the experimental conditions used. Submicromolar concentrations of N-des, tamoxifen, J8 and 17beta-oestradiol significantly reduced the invasiveness of the A375-SM cell line. The uveal melanoma cells also showed similar inhibition, although at higher concentrations of these agents. 4-OH and ICI 182, 780 had little or no effect on invasion of A375-SM cells (these were not tested on uveal melanoma cells). All cells used in this study were found to be negative for type I nuclear oestrogen receptors, reinforcing the possibility that tamoxifen and 17beta-oestradiol can act via mechanisms unrelated to binding to classical oestrogen receptors to inhibit tumour cell invasion

Probing fractal magnetic domains on multiple length scales in Nd2Fe14B

Using small-angle neutron scattering, we demonstrate that the complex magnetic domain patterns at the surface of Nd2Fe14B, revealed by quantitative Kerr and Faraday microscopy, propagate into the bulk and exhibit structural features with dimensions down to 6 nm, the domain wall thickness. The observed fractal nature of the domain structures provides an explanation for the anomalous increase in the bulk magnetization of Nd2Fe14B below the spin-reorientation transition. These measurements open up a rich playground for studies of fractal structures in highly anisotropic magnetic systems.Comment: Accepted for publication in Phys. Rev. Lett. (4 pages, 4 figures

Sr2_2VO3_3FeAs: A Nanolayered Bimetallic Iron Pnictide Superconductor

One of the unifying concepts in the iron-pnictide superconductors, both for the mechanism of magnetic ordering and of unconventional order parameter character, has been the electron and hole Fermi surfaces that are approximately nested. Using the density functional methods that have predicted Fermi surfaces correctly in SrFe$_2$P$_2$, we find that the recently reported superconducting Sr$_2$VO$_3$FeAs, with $T_c$=37 K and no apparent competition between magnetism and superconductivity, possesses different Fermi surface geometry and character than previous classes of iron pnictides. The intervening layer (a V bilayer) gives rise to bands that cross the Fermi level. Coupling to the FeAs layer is small except for interaction along the zone boundary, however that coupling degrades the Fermi surface nesting. Sr$_2$VO$_3$FeAs, with its alternating layers of open shell atoms, deserves further close study that should help to understand the origin of the properties of iron pnictide compounds.Comment: 6 pages and 4 embedded figure

The conservation status of the world’s freshwater molluscs

With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time

Prominent bulk pinning effect in the MgB_2 superconductor

We report the magnetic-field dependence of the irreversible magnetization of the recently discovered binary superconductor MgB$_{2}$. For the temperature region of $T< 0.9T_c$, the contribution of the bulk pinning to the magnetization overwhelms that of the surface pinning. This was evident from the fact that the magnetization curves, $M(H)$, were well described by the critical-state model without considering the surface pinning effect. It was also found that the $M(H)$ curves at various temperatures scaled when the field and the magnetization were normalized by the characteristic scaling factors $H^\ast(T)$ and $M^\ast(T)$, respectively. This feature suggests that the pinning mechanism determining the hysteresis in $M(H)$ is unique below $T=T_c$.Comment: 4pages and 4 figures. Phys. Rev. B (accepted

Half-Metallic Ferrimagnetism in Mn_2VAl

We show that Mn_2VAl is a compound for which the generalized gradient approximation (GGA) to the exchange-correlation functional in density functional theory makes a qualitative change in predicted behavior compared to the usual local density approximation (LDA). Application of GGA leads to prediction of Mn_2VAl being a half-metallic ferrimagnet, with the minority channel being the conducting one. The electronic and magnetic structure is analyzed and contrasted with the isostructural enhanced semimetal Fe_2VAl.Comment: 5 pages, Latex, 6 postscript figures. Description and figures of the (minority) Fermi surfaces have been adde

Hexagonal and Square Flux Line Lattices in CeCoIn5

Using small-angle neutron scattering, we have imaged the magnetic flux line lattice (FLL) in the d-wave heavy-fermion superconductor CeCoIn5. At low fields we find a hexagonal FLL. Around 0.6 T this undergoes what is very likely a first-order transition to square symmetry, with the nearest neighbors oriented along the gap node directions. This orientation of the square FLL is consistent with theoretical predictions based on the d-wave order parameter symmetry.Comment: 4 pages, 3 figs (1 color

Possible new vortex matter phases in BSCCO

The vortex matter phase diagram of BSCCO crystals is analyzed by investigating vortex penetration through the surface barrier in the presence of a transport current. The strength of the effective surface barrier, its nonlinearity, and asymmetry are used to identify a possible new ordered phase above the first-order transition. This technique also allows sensitive determination of the depinning temperature. The solid phase below the first-order transition is apparently subdivided into two phases by a vertical line extending from the multicritical point.Comment: 11 pages, 3 figures, accepted for publication in PR