Saline aqueous fluid circulation in mantle wedge inferred from olivine wetting properties.

Recently, high electrical conductors have been detected beneath some fore-arcs and are believed to store voluminous slab-derived fluids. This implies that the for-arc mantle wedge is permeable for aqueous fluids. Here, we precisely determine the dihedral (wetting) angle in an olivine-NaCl-H2O system at fore-arc mantle conditions to assess the effect of salinity of subduction-zone fluids on the fluid connectivity. We find that NaCl significantly decreases the dihedral angle to below 60° in all investigated conditions at concentrations above 5 wt% and, importantly, even at 1 wt% at 2 GPa. Our results show that slab-released fluid forms an interconnected network at relatively shallow depths of ~80 km and can partly reach the fore-arc crust without causing wet-melting and serpentinization of the mantle. Fluid transport through this permeable window of mantle wedge accounts for the location of the high electrical conductivity anomalies detected in fore-arc regions.

Caldera-forming eruptions of mushy magma modulated by feedbacks between ascent rate, gas retention/loss and bubble/crystal framework interaction.

Caldera-forming eruptions of mushy silicic magma are among the most catastrophic natural events on Earth. In such magmas, crystals form an interlocking framework when their content reaches critical thresholds, resulting in the dramatic increase in viscous resistance to flow. Here, we propose a new mechanism for the ascent of mushy magma based on microstructural observations of crystal-rich silicic pumices and lavas from the Central Andes and decompression experiments. Microstructural data include spherical vesicles and jigsaw-puzzle association of broken crystals in pumices, whereas there is limited breakage of crystals in lavas. These observations insinuate that shearing of magma during ascent was limited. Decompression experiments reveal contrasting interaction between growing gas bubbles and the crystal framework in crystal-rich magma. Under slow decompression typical of effusive eruptions, gas extraction is promoted, whereas under rapid decompression, bubbles are retained and the crystal framework collapses. This feedback between decompression rate, retention of gas bubbles, and integrity of the crystal framework leads to strong non-linearity between magma decompression rate and eruption explosivity. We extend these findings to caldera-forming eruptions of crystal-rich magma where large overpressures are induced by caldera-collapse, resulting in magma plug-flow, rapid decompression facilitated by shear-localization at conduit margins, and explosive eruption.

Shallow magma pre-charge during repeated Plinian eruptions at Sakurajima volcano.

Vigorous explosive eruptions that produce continuous high eruption plumes (Plinian eruptions) are generally assumed to tap a magma reservoir. The 1914 Plinian eruption at the Sakurajima volcano located on the Aira caldera rim is one such case, where the main magma reservoir was assumed to be located approximately 10 km beneath the caldera. However, we report that estimated magma storage depths immediately prior to the eruption were much shallower (0.9-3.2 km) on the basis of pressure at which volatiles within the phenocryst melt inclusions and plagioclase rims were finally equilibrated. The same is observed for two historic Plinian eruptions in 1471 and 1779. This depth is even shallower than the shallowest magma reservoir estimated from the pressure source for geodetic deformation during recent Vulcanian explosions (4 km beneath the crater). We propose that the magmas were fed from a thick conduit pre-charged from deeper reservoirs. The ground subsidence observed after 1914 within the Aira caldera may have been caused by conduit recharge following the eruption. Voluminous conduit recharge could be key to forecasting the next possible large eruption at the Sakurajima volcano.

CD24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways.

The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary ovarian carcinoma tissues, which were obtained from 174 patients, and that the expression of CD24 was an independent predictor of survival in patients with ovarian cancer. The expression of CD24 has been found to be correlated with the FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the EMT phenomenon, which is involved in cell invasion, the highly proliferative phenotype, colony formation and which is associated with cisplatin resistance and the properties of CSCs, via the activation of PI3K/Akt, NF-κB and ERK in Caov-3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been shown to have a greater potential for intra-abdominal tumor cell dissemination in in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in ovarian cancer, and that CD24 amplified cell growth-related intracellular signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal pathways. We believe that CD24 is a key molecule of metastatic progression in the EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.

Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial-mesenchymal transition of the peritoneum.

OBJECTIVE: A current working model for the metastatic process of ovarian carcinoma suggests that cancer cells are shed from the ovarian tumor into the peritoneal cavity and attach to the layer of mesothelial cells that line the inner surface of the peritoneum, and several studies suggest that hepatocyte growth factor (HGF) plays an important role in the dissemination of ovarian cancer. Our objectives were to evaluate the HGF expression of ovarian cancer using clinical data and assess the effect of HGF secreted from human ovarian cancer cells to human mesothelial cells. METHODS: HGF expression was immunohistochemically evaluated in 165 epithelial ovarian cancer patients arranged as tissue microarrays. HGF expression in four ovarian cancer cell lines was evaluated by using semi-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. The effect of ovarian cancer cell derived HGF to the human mesothelial cells was assessed by using morphologic analysis, Western blotting and cell invasion assay. The effect of HGF on ovarian cancer metastasis was assessed by using in vivo experimental model. RESULTS: The clinical data showed a significantly high correlation between the HGF expression and the cancer stage. The in vivo and in vitro experimental models revealed that HGF secreted by ovarian cancer cells induces the mesothelial-to-mesenchymal transition and stimulates the invasion of mesothelial cells. Furthermore, manipulating the HGF activity affected the degree of dissemination and ascite formation. CONCLUSIONS: We demonstrated that HGF secreted by ovarian cancer cells plays an important role in cancer peritoneal implantation.

Associations between the pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in Japanese women.

AIM: To examine the associations between the pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Japanese women. METHODS: The medical records of 1883 Japanese women who delivered singleton infants from January 2010 to January 2013 at Osaka-Minami Medical Center were retrospectively reviewed. We use the BMI classification which the World Health Organization defined for Asian populations and the GWG classified based on the current 2009 Institute of Medicine (IOM) recommendations. The odds ratio (OR) of each of the groups for the different pregnancy outcomes were compared to the recommended group using a logistic regression analysis adjusted by age, gestational weeks, parity, weight gain, mode of delivery, pregnancy induced hypertension (PIH) and gestational diabetes mellitus. RESULTS: Women who were obese (BMI, ≥25 kg/m(2) ) and overweight (BMI, 23-24.9 kg/m(2) ) had a higher rate of developing PIH (adjusted OR, 6.68 and 3.21 [95% confidence interval [CI], 3.31-13.3 and 1.29-7.24]). In contrast, GWG exhibited a correlation with the weight of the infant. The inadequate GWG group had a higher rate of small-for-gestational age (SGA) infants (adjusted OR, 1.72 [95% CI, 1.22-2.46]). The rate of emergency cesarean section was not significantly different between the groups. CONCLUSION: A pre-pregnancy BMI less than 23 kg/m(2) is desirable to prevent Japanese women from developing PIH. GWG within the IOM recommendations also reduced the risk of PIH and SGA.

Malignant müllerian mixed tumor of the uterine cervix with a small cell neuroendocrine carcinoma component.

Malignant Müllerian mixed tumors (MMMTs) of the uterine cervix are extremely rare, accounting for 0.005% of all cervical malignancies. To date, only approximately 50 well-documented cases have been reported. Although several epithelial components have been described in cervical MMMTs, small cell neuroendocrine carcinoma (SCC) has not appeared in the English literature. We present a 43-year-old woman, para 2 gravida 2, who had MMMT with SCC and rhabdomyosarcoma components in the uterine cervix. She was referred to our hospital because of a cervical mass with an abnormal Pap smear result. Cervical biopsy revealed SCC. After neoadjuvant chemotherapy with balloon-occluded arterial infusion, she underwent type II radical hysterectomy with pelvic lymphadenectomy. Histological analysis revealed that the cervical tumor comprised SCC and rhabdomyosarcoma components. Genotype analysis indicated human papillomavirus type 18. She underwent concurrent chemoradiation therapy. The patient had been free of the disease and showed no evidence of recurrence 38 months after operation.

Clathrin anchors deubiquitinating enzymes, AMSH and AMSH-like protein, on early endosomes.

Endosomal sorting of ubiquitinated membrane proteins for trafficking to lysosomes is executed by a complex of two ubiquitin-binding proteins, Hrs and STAM, that localizes on a microdomain of early endosomes with a flat clathrin coat. AMSH is a deubiquitinating enzyme that interacts with STAM and is implicated in the down-regulation of epidermal growth factor receptor. AMSH has a close homolog, AMSH-like protein (AMSH-LP). Here we show that AMSH-LP is also a deubiquitinating enzyme that acts on early endosomes. We further show that AMSH and AMSH-LP bind to the terminal domain of clathrin heavy chain via a novel clathrin-binding site conserved between these proteins. Exogenously expressed AMSH and AMSH-LP co-localized with clathrin on early endosomes. However, deletion of the clathrin-binding site from the proteins, as well as RNA interference-mediated depletion of clathrin heavy chain, resulted in a failure of AMSH and AMSH-LP to localize on endosomes. In contrast, a mutant of AMSH that lacks the ability to bind STAM localized normally on endosomes. We suggest that AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat.

A behavior therapy program combined with liquid nutrition designed for anorexia nervosa.

We have introduced behavior therapy as standard in-patient treatment for anorexia nervosa and have modified the treatment program. At first, we used Fukamachi's activity restriction therapy (FT), followed by Token economy therapy (TET), which combined token economy with FT. Finally, we have developed Kyoto Prefectural University of Medicine Behavior Therapy (KPT). According to KPT, only liquid formula is given in the early stages of hospitalization and a target weight is not set at admission. We examined the effect of these three programs with respect to bodyweight gain. Thirty-five anorexic patients participated in these three programs in our hospital: seven completed FT, seven completed TET and 21 completed KPT. We compared the effects of these three programs on body mass index (BMI). Furthermore, the effects of these three programs on BMI were compared at admission, 1 month after admission and at discharge, 6 months after discharge. In addition, the rate of increase of BMI for the following three periods was investigated: 1 month after admission, total hospitalization (from admission to discharge) and from admission to 6 months after discharge. The result is that KPT was the most effective of the three programs with regard to both the amount and the rate of increase of BMI at all points and there is a significant difference between KPT and FT. This effectiveness may be attributable to the use of an oral liquid formula, the setting of target weight at a later stage of hospitalization and the release of activity restriction based on weight gain.