GAP-independent functions of DLC1 in metastasis.

Metastases are responsible for most cancer-related deaths. One of the hallmarks of metastatic cells is increased motility and migration through extracellular matrixes. These processes rely on specific small GTPases, in particular those of the Rho family. Deleted in liver cancer-1 (DLC1) is a tumor suppressor that bears a RhoGAP activity. This protein is lost in most cancers, allowing malignant cells to proliferate and disseminate in a Rho-dependent manner. However, DLC1 is also a scaffold protein involved in alternative pathways leading to tumor and metastasis suppressor activities. Recently, substantial information has been gathered on these mechanisms and this review is aiming at describing the potential and known alternative GAP-independent mechanisms allowing DLC1 to impair migration, invasion, and metastasis formation

Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor.

TAT-RasGAP317-326, a peptide corresponding to the 317-326 sequence of p120 RasGAP coupled with a cell-permeable TAT-derived peptide, sensitizes the death response of various tumor cells to several anticancer treatments. We now report that this peptide is also able to increase cell adherence, prevent cell migration and inhibit matrix invasion. This is accompanied by a marked modification of the actin cytoskeleton and focal adhesion redistribution. Interestingly, integrins and the small Rho GTP-binding protein, which are well-characterized proteins modulating actin fibers, adhesion and migration, do not appear to be required for the pro-adhesive properties of TAT-RasGAP317-326. In contrast, deleted in liver cancer-1, a tumor suppressor protein, the expression of which is often deregulated in cancer cells, was found to be required for TAT-RasGAP317-326 to promote cell adherence and inhibit migration. These results show that TAT-RasGAP317-326, besides its ability to favor tumor cell death, hampers cell migration and invasion

Living small-sized (63-150 µm) foraminifera from mid-shelf to mid-slope environments in the Bay of Bisca

Live (rose Bengal stained) foraminiferal faunas of the 63–150 μm size fraction have been investigated in surficial sediment (0–1 cm) from mid-shelf to mid-slope environments in the Bay of Biscay. Eleven stations were sampled in April 2002 and March 2004 between 80 and 2000 m water depth (mwd). Earlier studies on the temporal variability of phytoplankton primary production suggest that our stations were sampled at the most eutrophic period of the year. In response to the decrease of exported organic matter flux to the seafloor along our bathymetric transect, foraminiferal standing stocks decrease from ~1400–2000 specimens per 50 cm3 on the continental shelf (100–140 mwd) and upper slope (550 mwd) to about 400 specimens per 50 cm3 at mid-slope stations (2000 mwd). At all stations, the faunas contain an important amount of small opportunistic species that are favored by seasonal phytodetritus input. On the continental shelf where phytoplankton bloom, events may be geographically restricted; the foraminiferal response is dependent on the distance to the surface-water primary-production cells. Textularia porrecta is very abundant at an 80-m-deep station that is close to the coast and characterized by a high sedimentation rate of fine-grained particles. Foraminiferal faunas are dominated by Nonionella iridea, Cassidulina carinata and Bolivina ex. gr. dilatata at the outer-shelf stations (110–140 mwd) that are under the direct influence of spring bloom phytodetritus input in the northern Bay of Biscay. A fauna dominated by Bolivina dilatata/spathulata and Bolivina subaenariensis is found in the southeastern Bay of Biscay at a 140-m-deep outer-shelf station located seaward of the Adour River estuary, where the sediment is probably enriched in terrestrial organic matter. Apparently, differences in foraminiferal composition between outer-shelf areas in the northern and southeastern Bay of Biscay are related to differences in organic matter quality. On the continental slope, a bathymetric zonation of taxa is observed from upper-slope sites (550–1000 mwd) rich in Epistominella exigua and Uvigerina peregrina to mid-slope stations (1600–2000 mwd), where Nuttallides pusillus and Gavelinopsis translucens dominate the small-sized living fauna. This bathymetric foraminiferal zonation probably reflects a trophic gradient between upper-slope eutrophic stations and mid-slope, more oligotrophic sites. Our zonal description of small-sized living foraminifera (63–150 μm) is new for the Bay of Biscay and may provide the basis to reconstruct former export production regimes in marginal paleo-environments from temperate latitude areas

Experimental calibration of Mn incorporation in foraminiferal calcite

International audienc

A Fully Differential Digital CMOS Pulse UWB Generator

A new fully-digital CMOS pulse generator for impulse-radio Ultra-Wide-Band (UWB) systems is presented. First, the shape of the pulse which best fits the FCC regulation in the 3.1-5 GHz sub-band of the entire 3.1-10.6 GHz UWB bandwidth is derived and approximated using rectangular digital pulses. In particular, the number and width of pulses that approximate an ideal template is found through an ad-hoc optimization methodology. Then a fully differential digital CMOS circuit that synthesizes the pulse sequence is conceived and its functionality demonstrated through post-layout simulations. The results show a very good agreement with the FCC requirements and a low power consumptio

Microstructure and oxide particle stability in a novel ODS γ-TiAl alloy processed by spark plasma sintering and laser additive manufacturing

In this work, a novel oxide dispersion strengthened titanium aluminide alloy (Ti-45Al-3Nb-<0.2Y2O3 at.%) was developed for powder-based processing technologies with a focus on spark plasma sintering and additive manufacturing. Titanium aluminides are promising structural intermetallics for weight reduction and an increased performance of high temperature components. The alloy design and selection process was supported by computational thermodynamics based on the CALPHAD approach, taking into account requirements for processing as well as long term alloy behavior under service conditions. Processing trials using spark plasma sintering, direct metal deposition and selective laser melting were conducted to study the alloy behavior, microstructure formation and introduction as well as stability of the ODS particles. Additionally, thermal annealing on the sintered and laser consolidated material was performed. Conventional dual phase α2-Ti3Al and γ-TiAl duplex and near-lamellar microstructures were obtained from the processed material. The ODS particles were homogeneously distributed in the alloy matrix after processing in the liquid state. For the direct metal deposition process, the novel alloy was compared to the established GE48-2-2 alloy (Ti-48Al-2Cr-2Nb) in terms of phases, microstructure and texture after processing. A significantly reduced texture formation was observed with the novel alloy. The hardness of the consolidated material shows superior properties for ODS-containing TiAl compared to ODS-free material. This work provides a first step towards tailored alloys for AM and the production of ODS TiAl alloys

The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner.

Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments. Recently, we discovered that this RasGAP-derived peptide possesses the ability to directly kill some cancer cells. TAT-RasGAP317-326 can cause cell death in a manner that can be either partially caspase-dependent or fully caspase-independent. Indeed, TAT-RasGAP317-326-induced toxicity was not or only partially prevented when apoptosis was inhibited. Moreover, blocking other forms of cell death, such as necroptosis, parthanatos, pyroptosis and autophagy did not hamper the killing activity of the peptide. The death induced by TAT-RasGAP317-326 can therefore proceed independently from these modes of death. Our finding has potentially interesting clinical relevance because activation of a death pathway that is distinct from apoptosis and necroptosis in tumor cells could lead to the generation of anti-cancer drugs that target pathways not yet considered for cancer treatment

Influence of model based iterative reconstruction algorithm on image quality of multiplanar reformations in reduced dose chest CT.

Model-based iterative reconstruction (MBIR) reduces image noise and improves image quality (IQ) but its influence on post-processing tools including maximal intensity projection (MIP) and minimal intensity projection (mIP) remains unknown. To evaluate the influence on IQ of MBIR on native, mIP, MIP axial and coronal reformats of reduced dose computed tomography (RD-CT) chest acquisition. Raw data of 50 patients, who underwent a standard dose CT (SD-CT) and a follow-up RD-CT with a CT dose index (CTDI) of 2-3 mGy, were reconstructed by MBIR and FBP. Native slices, 4-mm-thick MIP, and 3-mm-thick mIP axial and coronal reformats were generated. The relative IQ, subjective IQ, image noise, and number of artifacts were determined in order to compare different reconstructions of RD-CT with reference SD-CT. The lowest noise was observed with MBIR. RD-CT reconstructed by MBIR exhibited the best relative and subjective IQ on coronal view regardless of the post-processing tool. MBIR generated the lowest rate of artefacts on coronal mIP/MIP reformats and the highest one on axial reformats, mainly represented by distortions and stairsteps artifacts. The MBIR algorithm reduces image noise but generates more artifacts than FBP on axial mIP and MIP reformats of RD-CT. Conversely, it significantly improves IQ on coronal views, without increasing artifacts, regardless of the post-processing technique