RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells

International audienceThe POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL

Astrophysical Neutrino Event Rates and Sensitivity for Neutrino Telescopes

Spectacular processes in astrophysical sites produce high-energy cosmic rays which are further accelerated by Fermi-shocks into a power-law spectrum. These, in passing through radiation fields and matter, produce neutrinos. Neutrino telescopes are designed with large detection volumes to observe such astrophysical sources. A large volume is necessary because the fluxes and cross-sections are small. We estimate various telescopes' sensitivities and expected event rates from astrophysical sources of high-energy neutrinos. We find that an ideal detector of km^2 incident area can be sensitive to a flux of neutrinos integrated over energy from 10^5 and 10^{7} GeV as low as 1.3 * 10^(-8) * E^(-2) (GeV/cm^2 s sr) which is three times smaller than the Waxman-Bachall conservative upper limit on potential neutrino flux. A real detector will have degraded performance. Detection from known point sources is possible but unlikely unless there is prior knowledge of the source location and neutrino arrival time.Comment: Section added +modification

Graph Theory and simple Hueckel Theory applied to benzene

We compare the results of application of graph theory and of simple Hueckel theory in its traditional form to benzene, as an instance of a conjugated molecular system. The identity of the results of solution of eigenvalues of the vertex adjacency matrix and characteristic values of the Hueckel determinant prove the isomorphism of these two formalisms. Because of the gross deficiencies of the Hueckel theory, we advocate its elimination from the teaching of chemistry in favour of graph theory that has many applications to molecular topology.Se compararon los resultados de la aplicación de la teoría de gráficos y de la teoría de Hueckel tradicional a benceno, como ejemplo de un sistema molecular conjugado. Los resultados idénticos entre los eigenvalores de la matriz de adyacencia de los vértices y los valores característicos del determinante de Hueckel verifican el isomorfismo de los dos formalismos. Se recomienda la eliminación de la teoría de Hueckel por sus deficiencias y en su lugar utilizar la teoría de gráficos que tiene muchas aplicaciones en topología molecular

An Incidence of Multi-Year Sediment Storage on Channel Snowpack in the Canadian High Arctic

During June 2005, we identified the presence of sediment buried within multi-year channel snowpack of a small river located near Cape Bounty, Melville Island, Nunavut (74°55' N, 109°35' W). Photographic evidence indicates that the sediment was deposited during the 2003 season by the initial meltwater flowing on the snowpack, which was dammed by snow upstream of a channel constriction. The resulting pond covered a minimum area of 180 m2 and contained an estimated minimum 27 Mg of sediment. Suspended sediment measurements during the 2003 season indicate that deposition on the snowpack at this location represented 49%–65% of the sediment transport prior to the ponding and emplacement of the sediment on the snow, and approximately 20% of the measured sediment flux for the entire season. Multi-year snow accumulations immediately downstream exhibited similar sediment deposition on snow, but no evidence of multi-year sediment storage was present. By contrast, a similar stream in an adjacent watershed channelized rapidly, with minimal sediment deposition on the snow, and delivered a large pulse of sediment to the downstream lake. These results provide quantitative evidence for the magnitude of sediment storage on snowpack and point to the unique role that snow plays in the fluvial geomorphology of High Arctic watersheds.En juin 2005, nous avons dénoté la présence de sédiment enterré dans une plaque de neige datant de plusieurs années d’une petite rivière située près de cap Bounty, sur l’île Melville, au Nunavut (74°55' N, 109°35' O). D’après des preuves photographiques, le sédiment a été déposé pendant la saison 2003 par l’eau de fusion initiale s’écoulant sur la plaque de neige, qui avait été endiguée par la neige en amont d’un canal confiné. L’étang qui en a découlé recouvrait une aire minimale de 180 m2 et contenait, selon les estimations, au moins 27 Mg de sédiment. Les mesures de sédiment en suspension pendant la saison 2003 indiquent que ce dépôt sur la plaque de neige à cet endroit représentait entre 49 % et 65 % du transport de sédiment avant l’accumulation d’eau et l’emplacement de sédiment sur la neige, et environ 20 % du flux de sédiment mesuré pour toute la saison. Les accumulations de neige de plusieurs années immédiatement en aval comptaient des dépôts de sédiment semblables sur la neige, quoi qu’aucun emmagasinage de sédiment sur plusieurs années n’était présent. Par contraste, un cours d’eau similaire d’un bassin hydrographique adjacent s’est canalisé rapidement, avec peu de dépôts de sédiment sur la neige, puis a laissé une grande quantité de sédiment au lac en aval. Ces résultats fournissent des preuves quantitatives quant à l’ampleur de l’emmagasinage de sédiment sur la plaque de neige et laissent envisager le rôle unique que joue la neige sur la géomorphologie fluviale des bassins hydrographiques de l’Extrême-Arctique

The Swift-UVOT ultraviolet and visible grism calibration

We present the calibration of the Swift UVOT grisms, of which there are two, providing low-resolution field spectroscopy in the ultraviolet and optical bands respectively. The UV grism covers the range 1700-5000 Angstrom with a spectral resolution of 75 at 2600 Angstrom for source magnitudes of u=10-16 mag, while the visible grism covers the range 2850-6600 Angstrom with a spectral resolution of 100 at 4000 Angstrom for source magnitudes of b=12-17 mag. This calibration extends over all detector positions, for all modes used during operations. The wavelength accuracy (1-sigma) is 9 Angstrom in the UV grism clocked mode, 17 Angstrom in the UV grism nominal mode and 22 Angstrom in the visible grism. The range below 2740 Angstrom in the UV grism and 5200 Angstrom in the visible grism never suffers from overlapping by higher spectral orders. The flux calibration of the grisms includes a correction we developed for coincidence loss in the detector. The error in the coincidence loss correction is less than 20%. The position of the spectrum on the detector only affects the effective area (sensitivity) by a few percent in the nominal modes, but varies substantially in the clocked modes. The error in the effective area is from 9% in the UV grism clocked mode to 15% in the visible grism clocked mode .Comment: 27 pages, 31 figures; MNRAS accepted 23 February 201

Thermal phase diagrams of columnar liquid crystals

In order to understand the possible sequence of transitions from the disordered columnar phase to the helical phase in hexa(hexylthio)triphenylene (HHTT), we study a three-dimensional planar model with octupolar interactions inscribed on a triangular lattice of columns. We obtain thermal phase diagrams using a mean-field approximation and Monte Carlo simulations. These two approaches give similar results, namely, in the quasi one-dimensional regime, as the temperature is lowered, the columns order with a linear polarization, whereas helical phases develop at lower temperatures. The helicity patterns of the helical phases are determined by the exact nature of the frustration in the system, itself related to the octupolar nature of the molecules.Comment: 12 pages, 9 figures, ReVTe

ΔNp63α silences a microRNA program to aberrantly initiate a wound healing program that promotes TGFβ-induced metastasis.

Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an anti-metastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFβ-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFβ effectors, SMAD4 and TβRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFβ-dependent signaling node that switches off anti-migratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel microRNA network involved in the regulation of physiological wound healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination

Neutrino Telescopes' Sensitivity to Dark Matter

The nature of the dark matter of the Universe is yet unknown and most likely is connected with new physics. The search for its composition is under way through direct and indirect detection. Fundamental physical aspects such as energy threshold, geometry and location are taken into account to investigate proposed neutrino telescopes of km^3 volume sensitivities to dark matter. These sensitivities are just sufficient to test a few WIMP scenarios. Telescopes of km^3 volume, such as IceCube, can definitely discover or exclude superheavy (M > 10^10 GeV) Strong Interacting Massive Particles (Simpzillas). Smaller neutrino telescopes such as ANTARES, AMANDA-II and NESTOR can probe a large region of the Simpzilla parameter space.Comment: 28 pages, 9 figure

Activité de traitements par ciprofloxacine et/ou amikacine, en condition planctonique et en biofilm, vis-à-vis de souches de Pseudomonas aeruginosa surexprimant un efflux.

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