B athymetry and gravity data obtained during a detailed Hydrosweep survey of the southern East Pacific Rise from 7øS to 9øS are used to investigate isostasy at the axis of a fast spreading mid-ocean ridge. In particular, we examine the manner in which the bathymetric crestal high is supported and how this support varies along the axis within the 160-km-long 7ø12'S-8ø38'S ridge segment. The crestal high stands about 400 m above the adjacent ridge flanks and has a nearly constant minimum axial depth for a distance of 140 km. The summit is broad and flat, and an axial summit caldera is present for the entire length of the ridge segment. However, the width and cross-sectional shape of the crestal high vary systematically along the axis. It is broad with gentle slopes in the center of the segment but becomes progressively narrower and steeper toward the ends of the ridge segment. The ridge crest is marked by a free-air gravity anomaly high about 15-20 km wide with an amplitude of 10-15 mGal relative to the ridge flanks. Mantle Bouguer anomalies vaxy systematically along the axis with minimum values found near the center of the segment. The axial mantle Bouguer anomalies thus do not reflect the axial depth but are correlated with changes in the cross-sectional area of the crestal bathymetric high. The effects of cooling and subsidence away from the axis were removed from the bathymetry and free-air anomalies to isolate residual topographic and gravity anomalies associated with the ridge crest. The residual crestal bathymetric high was modeled as a flexural feature resulting from the upward buoyant load of a region of low density material centered beneath the axis. The lithosphere was treated as a broken plate, either with a constant flexural rigidity or an effective elastic thickness Te which grows at a rate proportional to the square root of distance from the axis. The best fitting values of T e for the constant rigidity case are in the range of 0.3-0.6 km. For the growing plate model, Te increases at a rate of 0.2-0.3 km 1/2. The gravity constrains the mass deficiency to extend to a depth of 20-30 km for both lithospheric models. We interpret this low-density material as a region of partial melt feeding magma to the ridge axis. The best fitting density anomalies imply that a 4-9% melt fraction is present beneath the crestal high. Upwelling of melt to the axis is thus confined to a narrow zone within about 10 km of the axis. The mass deficiency and thus the upwelling partial melt are not distributed evenly along the ridge axis but rather are concentrated in the central portion of the ridge segment. It thus appears that differences between the along-axis gravity and depth patterns observed at slow spreading and at fast spreading ridges are not the result of a change from threedimensional, focused upwelling at slow spreading ridges to two-dimensional sheetlike upwelling at fast-spreading ridges. Rather, the differences in axial gravity and depth between fast and slow spreading ridges reflect differences in the efficienc...

MicroRNA (miRNA)-25 is a small non-coding RNA that has been implicated in the tumorigenesis of many cancers, but little is known on the role of miR-25 in HCC metastasis. We hereby found that miR-25 was significantly upregulated in clinical HCC tissues compared with normal liver tissues. We also revealed that miR-25 dramatically stimulates HCC cell growth and activates the epithelial-mesenchymal transition (EMT). MiR-25 is activated by the WNT/β-catenin signaling pathway, and exerts its pro-metastatic function by directly inhibiting the Rho GDP dissociation inhibitor alpha (RhoGDI1). Downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. MiR-25 levels are positively correlated with β-catenin expression, whereas negatively correlated with the level of RhoGDI1 in HCC. Our findings provide new insights into the role of miR-25 in HCC metastasis, and implicate the potential application of miR-25 in HCC therapy.

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Gravity, bathymetry, and crustal structure data from the 9° to 10°N segment of the fast spreading northern East Pacific Rise are used to investigate density variations in the mantle in order to determine the pattern of mantle upwelling and melt distribution beneath the segment. Mantle Bouguer gravity anomaly contours are nearly parallel to the ridge axis, and there is only 3–4 mGal variation in axial mantle Bouguer anomalies along the entire segment. However, inclusion of the gravity effects of variations in crustal thickness and structure results in a significant change in the pattern of gravity anomalies. The “subcrustal” gravity anomalies show a very distinct gravity low centered over the segment axial depth minimum near 9°50′N. Axial subcrustal gravity anomalies increase by ∼10 mGal between 9°50′N and 9°23′N, a gradient of 0.2 mGal/km. Since the ridge axis has a uniform cross‐sectional shape throughout the entire segment with abundant evidence of magmatic activity along its entire length, it is unlikely that there are significant variations in crustal thermal structure other than at the ridge tips. We thus attribute the subcrustal gravity anomalies to density variations within the mantle. The distinct gravity low centered over the depth minimum provides qualitative evidence that mantle upwelling is focused or enhanced at that location. The effects of lithospheric cooling and subsidence away from the axis were removed from the bathymetry and free‐air gravity anomalies to isolate residual gravity and gravity anomalies associated with the axis. The residual anomalies were modeled by considering the axial bathymetric high to be a flexural feature resulting from the upward buoyant load of a region of low‐density material beneath the axis. After accounting for the isostatic effects of variations in crustal thickness, the remaining mass deficiency necessary to support the axial high and satisfy the gravity anomalies is not evenly distributed along the axis but is 35% greater beneath the axial depth minimum at 9°50′N than between 9°17′ and 9°27′N. Mantle upwelling in this segment thus appears focused or enhanced in the area of the depth minimum.

Mammalian target of rapamycin (mTOR) is frequently upregulated in hepatocellular carcinoma (HCC). Blockage of mTOR was found to induce marked reduction in HCC growth in preclinical models. In the present study, we tested a novel mTOR inhibitor, Torin-2, for its antitumor efficacy in HCC cell lines Hep G2, SNU-182 and Hep 3B2.1-7. The HCC cell lines were cultured in vitro. These cells were treated with Torin-2. Cell apoptosis was evaluated by Annexin V staining. Cell proliferation and cell cycle progression were determined by Ki67 staining and propidium iodide staining, respectively. mTOR signaling, autophagy induction and expression of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) were assessed by western blot analysis. The UHRF1 mRNA level was determined by real-time PCR. We found that Torin-2 effectively suppressed the growth and survival of HCC cell lines, demonstrated by reduced proliferation and a high rate of apoptosis. Further study elucidated that in addition to blocking mTOR complex 1 (mTORC1)-associated cell cycle progression and induction of autophagy, Torin-2 downregulated transcription of UHRF1, an essential regulator of DNA methylation that is highly expressed in HCC cell lines. Consistently, the level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) was higher after treatment of the HCC cell lines with Torin-2. The downregulation of UHRF1 by Torin-1 was partially due to a decrease in the UHRF1 mRNA level. Torin-2 effectively inhibited HCC cell proliferation through induction of autophagy. Torin‑2-induced downregulation of UHRF1 expression may also contribute to its antitumor effect. Our research provides new clues regarding the antitumor effects of Torin-2 and sheds light on a novel therapeutic approach for HCC.