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Although slab-derived fluid significantly affects melt generation and dynamics within subduction zones, its amount and distribution are not sufficiently constrained at present. Herein, we use isotopic systematics of arc volcanic rocks, subducting materials, and intrinsic mantle components prior to metasomatism, to quantify the contribution of the slab-derived fluid that metasomatizes the overlying mantle wedge beneath the entire area of Japan arcs. Simultaneous application of several multivariate statistical analyses (clustering analysis and principal/independent component analyses) to the isotopic data set allows Japan arcs to be broadly divided into eastern and western parts at the first order. Moreover, a clear higher-order inter-arc segmentation is observed, together with some intra-arc variations that possibly correspond to the heterogeneity of incoming plates. Inter-arc segmentation is shown to be primarily controlled by the geometrical parameters of the slab and the arc (e.g., subduction of a single plate or double plates beneath either oceanic or continental crust), which results in differences between mantle wedge and slab thermal conditions. Accordingly, the Kuril and Izu arcs, which have thin arc crusts (~20 km), exhibit the lowest extent of slab-derived fluid addition (0.1 wt%) to the mantle wedge, while the NE Japan arc, with a thicker arc crust (up to 36 km), features a higher value of 0.2 wt%, although the slab thermal parameters for these three arcs are essentially the same. The Central Japan arc shows the highest extent of slab-derived fluid addition (>1.0 wt%) because of the overlapping subduction of Pacific and Philippine Sea slabs, while the SW Japan and Ryukyu arcs feature moderate values of ~0.5 wt%. Moreover, a clear exotic plume zone and spots are observed in SW Japan and the Japan Sea. In addition to the variability of slab-derived fluid composition, the intrinsic mantle composition (before slab-derived fluid–induced metasomatism) shows a clear along-arc variation that is possibly caused by a large-scale mantle flow from the continental side. Thus, slab-derived fluid addition and mantle composition variability equally contribute to inter-arc segmentation, which highlights the importance of both local and regional thermal flow structures of slab-mantle systems.

Recent statistical analyses on the isotopic compositions of oceanic, arc, and continental basalts have revealed that the Earth's mantle is broadly divided into eastern and western hemispheres. The present study aimed to characterize the isotopically defined east–west geochemical hemispheres using trace-element concentrations. Basalt data with Rb, Sr, Nd, Sm, Pb, Th, and U in addition to the isotopic ratios 87Sr/86Sr, 143Nd/144Nd, 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb were selected mostly from the GEOROC and PetDB databases. A total of 4787 samples were used to investigate the global geochemical variations. The results show that the wide trace-element variations are broadly explained by the melting of melt-metasomatized and fluid-metasomatized mantle sources. The larger amount of the fluid component derived from subducted plates in the eastern hemisphere than that in the western hemisphere is inferred from the basalts. These characteristics support the hypothesis that focused subduction towards the supercontinent created the mantle geochemical hemispheres.

The disruption of adaptive immune response has adverse effects on the establishment and maintenance of pregnancy. The adaptive immune system is regulated by several types of immune cells. However, there is limited information about cell hierarchy in the adaptive immune response to the establishment and maintenance of pregnancy in women. The assessment of the outcome of pregnancy in primary immunodeficiency diseases could help in understanding the cell hierarchy in the adaptive immune system during pregnancy. Common variable immunodeficiency (CVID) is a heterogeneous adaptive immune system disorder characterized by primary hypogammaglobulinemia. A few studies have previously reported the assessment of the T and B cell subpopulations in CVID patients. However, an assessment of the subpopulations of T and B cells and the outcome of pregnancy in women with CVID has not been reported till date. Most CVID patients show a general decrease in the expression of CD27 in B cells. The assessment of pregnancy and the subpopulations of T and B cells in CVID women with severe reduction in the naive T and switched B cells could help understand whether these cells are essential for the establishment and maintenance of pregnancy in women.

Marginal parts of a plate and subducting slab can play important roles in geodynamics. This is because in areas where a plate interacts with other plates or with the mantle thermal, geochemical, and mechanical interactions are expected. The Philippine Sea (PHS) slab that subducts beneath the Japan arcs has such an edge. To examine the relationship between arc magmatism and the slab edge in the transition zone from Northeast Japan to Central Japan, we investigated isotopic systematics of the regional volcanic rocks, incorporating data from literature and new data for five isotopic ratios of Sr, Nd, and Pb. The new data included major element compositions of 22 samples from the back-arc area, and 5 isotopic ratios for 6 samples selected from Pleistocene to early Quaternary epochs. Consequently, several findings were determined based on the spatial variation of the isotopic ratios and the estimated amount of slab-derived fluid: (1) the amount of fluid derived from the two subducting slabs (i.e., the Pacific slab and the PHS slab) decreases northward from a significantly high value (~ 5 wt% fluid added to the source mantle), away from the seismically determined edge of the PHS slab; (2) the proportion of the PHS component in the total slab-derived fluid also decays northward; and (3) the PHS component spreads to the north beyond the seismically determined edge of the PHS slab. These observations strongly suggest that the existence of an aseismic PHS slab beneath southernmost parts of Northeast Japan delivers the PHS component to the arc magmatism. As was indicated by previous geodynamical studies, subduction of the PHS and PAC slabs may generate suction force towards the corner of mantle wedge, which might account for the large amount of fluid near the seismically determined slab edge as described in (1) above.

We constructed a system for expressing the Fab of the therapeutic human monoclonal antibody adalimumab at a yield of 20 mg/L in the methylotrophic yeast Pichia pastoris. To examine the contribution of interchain disulfide bonds to conformational stability, we prepared adalimumab Fab from which the interchain disulfide bond at the C-terminal region at both the CH1 and CL domains was deleted by substitution of Cys with Ala (FabΔSS). DSC measurements showed that the Tm values of FabΔSS were approximately 5 °C lower than those of wild-type Fab, suggesting that the interchain disulfide bond contributes to conformational thermostability. Using computer simulations, we designed a novel interchain disulfide bond outside the C-terminal region to increase the stability of FabΔSS. The resulting Fab (mutSS FabΔSS) had the mutations H:V177C and L:Q160C in FabΔSS, confirming the formation of the disulfide bond between CH1 and CL. The thermostability of mutSS FabΔSS was approximately 5 °C higher than that of FabΔSS. Therefore, the introduction of the designed interchain disulfide bond enhanced the thermostability of FabΔSS and mitigated the destabilization caused by partial reduction of the interchain disulfide bond at the C-terminal region, which occurs in site-specific modification such as PEGylation.

Cholesterol and lipid homeostasis is important for male fecundity. However, the plasma total cholesterol level does not reflect sperm concentration and motility. Adipose tissue in mammals is the main tissue contributing to the dynamic equilibrium of lipid synthesis and catabolism. However, recent studies suggested that local lipolysis has an important role in male fertility. If so, which plasma lipid metabolism parameter reflects sperm concentration and motility? Leptin receptor-deficient db/db mice show hyperphagia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, morbid obesity and are reported to be infertile. Impairment of spermatogenesis and sperm motility in db/db mice was observed in our experiments. Medium-chain triglycerides (MCTs) are more quickly metabolized as fuel compared to long-chain triglycerides (LCTs). If the LCTs are replaced with MCTs in the diet, even in hyperphagia, does it affect spermatogenesis and sperm motility? In this study, we investigated the effect of a MCT replacement diet on sperm parameters using db/db mice. Six weeks of MCT replacement diet improved not only spermatogenesis but also the maturation processes in the epididymis for sperm to acquire the ability to move forward. Plasma chylomicron and large VLDL levels showed positive correlation with total and motile sperm concentrations. The MCT replacement diet could be an effective treatment for idiopathic non-obstructive oligozoospermia or asthenozoospermia men with low levels of chylomicron and large VLDL.

First-principles calculations of electron-ion dynamics based on real-time time-dependent density functional theory were performed to study the lattice dynamics in yttrium aluminum garnet (YAG) doped with cerium (Ce) following photoexcitation. The dynamics induced by the optical transitions from the valence band to the conduction band of the YAG host and from the Ce 4f to 5 d levels were examined. Significant lattice motion was observed in the latter case. This lattice motion (Franck-Condon relaxation) decreased the Ce–O bond length by 0.05 A and increased the energy of the Ce 4f level by 0.5 eV, suggesting a Stokes shift in the light emission due to the Ce 5 d→4f transition. The calculated Stokes shift is consistent with the recently reported experimental value, despite the approximations used in the present calculations. The effect of lattice temperature was also examined up to 300 K.

Background Protein antigens are degraded by endosomal protease in antigen presentation cell. T cells recognize peptides derived from antigen proteins bound to class II major histocompatibility complex molecules. We previously reported that an increase in the conformational stability of an antigen depressed its immunogenicity. However, there is little information on antigens with differences in molecular properties such as net charges and molecular weight. Methods Denaturation experiments against guanidine hydrochloride. The serum IgE levels to protein antigens at 35 days after the first immunization analyzed using ELISA. Results The Der p 2 mutations in which Ile13 is mutated to Ala (I13A) and Ala122 is mutated to Ile (A122I) were shown to have lower and higher conformational stability than the wild-type, respectively, by denaturation experiments. The amount of IgE production by the less stable I13A mutant was higher and that of the stable A122I mutant was lower than that of the wild-type. Conclusion Our results suggest that the increased conformational stability of Der p 2 depressed the IgE production in mice. General significance These findings should provide a milestone for the engineering of allergen vaccines.

Compositional variability found in modern mid-ocean ridge basalt (MORB) and ocean island basalt (OIB) reflects differentiation processes associated with material recycling in the mantle-crust system. To investigate the timing at which this recycling system was established and how it transformed into the present-day system, we present geochemical analyses of the Archean basalts from North Pole (NP) in the East Pilbara Craton, Western Australia, and the Isua supracrustal belt (ISB), southern West Greenland. These rocks represent Archean accretionary complexes with ages of ~3.5 Ga and 3.7–3.8 Ga, respectively. We analyzed the trace element contents including rare earth elements (REEs), and Sr and Nd isotopic compositions of the basalts, which may represent MORBs and OIBs, from NP and ISB. Their trace-element compositions are broadly similar, but show distinct geochemical characteristics particularly with respect to REEs that probably reflect differences in both the source mantle and degree of melting. Such differences are also evident in their initial Nd isotopic compositions, which were estimated based on equilibrium partitioning of REEs and well-defined isochron ages. In contrast, the Sr isotopic compositions of the NP and ISB basalts are highly variable and their isochron ages are inconsistent with previous studies. Furthermore, the partitioning of Rb and Sr in the NP basalts indicates disequilibrium, suggesting that the Rb-Sr system has been disturbed by post-igneous alteration and metamorphism. Based on these observations, we propose the following model to explain the temporal variations in the geochemical composition of the Archean mantle: (i) ~3800 Ma: recycling of plate material and melting occurred quite readily and, therefore, MORBs and OIBs were produced from differentiated mantle sources; (ii) 3460 Ma to ~3800 Ma: mantle-crust mixing occurred as the result of an extreme event, such as mantle overturning, reducing the compositional variation of the mantle; and (iii) after ~3460 Ma: mantle heterogeneity gradually developed in the material-recycling system, re-establishing the compositional differences between MORBs and OIBs. This model requires an extreme event to drive the homogenization during stage (ii), which may provide new insights into the evolution of the crust-mantle system.

The molecular order and orientation significantly influence the physical properties of conjugated polymers and the corresponding performance in electronic devices. The precise synthesis and characterization are the challenges to obtain high quality polymer crystalline micro/nanostructures, on the basis of which, the charge transport mechanisms can be discussed and the device performance can be improved. A micro-fibrous complex of conductive polymer and natural polysaccharide has been formed during the in situ polymerization of aniline in the aqueous solution of κ-carrageenan. With the template of the polyanion, aniline is polymerized and polyaniline (PANI) chain grows in the vicinity of sulfonic acid groups. Through the comprehensive characterizations of UV–vis spectra, wide-angle X-ray diffraction, and thermal gravimetric analysis, the assembly structure of the interpolymer complex has been illuminated, i.e., oligomers of PANI with expanded conformation are formed, the electrostatic interaction between the protonated PANI oligomers and anionic κ-carrageenan makes the chains of PANI and κ-carrageenan bound together, and a micro-fibrous complex is formed with enhanced orientation of both PANI and κ-carrageenan, leading to an enhanced conductivity of the complex. The glucose biosensor made of the complex shows high detecting sensitivity and broad linear range in the recognition of the glucose due to its high conductivity and good compatibility with the enzyme.

Many biosensors have been developed and used in recent years, and to enhance the sensitivity and stability of enzyme biosensors, immobilization of the enzymes on material surfaces is a necessary and important step. Therefore, there has been considerable interest in understanding how material interfaces affect enzyme adsorption. In this study, the influence of the crystallinity of titanium dioxide (TiO2) films on the quantity and activity of the immobilized enzyme, i.e., formaldehyde dehydrogenase (FDH), was investigated. It was found that TiO2 films with high crystallinity, which were annealed at 550 °C, showed higher enzyme immobilization and activity compared with the non-annealed TiO2 film. These results suggest that the activity of enzymes could be affected by the crystallinity of surface materials.

Protobothrops flavoviridis (habu) (Crotalinae, Viperidae) is a Japanese venomous snake, and its venom contains the enzymes with a variety of physiological activities. The phospholipases A2 (PLA2s) are the major components and exert various toxic effects. They are expressed abundantly in the venom gland. It is thought that the venom gland-specific transcription factors play a key role for activation of PLA2 genes specifically expressed in the venom gland. Thus, the full-length cDNA library for P. flavoviridis venom gland after milking of the venom was made to explore the transcription factors therein. As a result, three cDNAs encoding epithelium-specific ETS transcription factors (ESE)-1, -2, and -3 were obtained. Among them, ESE-3 was specifically expressed in the venom gland and activated the proximal promoters of venom PLA2 genes, which are possibly regarded as the representatives of the venom gland-specific protein genes in P. flavoviridis. Interestingly, the binding specificity of ESE-3 to the ETS binding motif located near TATA box is well correlated with transcriptional activities for the venom PLA2 genes. This is the first report that venom gland-specific transcription factor could actually activate the promoters of the venom protein genes.

The interaction of DNA with dipolar ruthenium(II) ammine complexes containing 4,4′-bipyridinium cations L + , [Ru(L + )(NH 3 ) 5 ] 3+ , has been investigated by spectroscopic and electrochemical methods. These ruthenium(II) complexes undergo strong stacking interactions of L + with the base-pairs of DNA duplex in addition to the electrostatic and hydrogen binding modes. The phbp + ([ 2 ] 3+ ) and pymbp + ([ 3 ] 3+ ) complexes bind to DNA more strongly than the mebp + ([ 1 ] 3+ ) complex, due to the presence of extended planar aromatic ligands. [ 3 ] 3+ which exhibited the strongest interaction with DNA can bind to supercoiled plasmid pBR322 DNA following photoinduced loss of ligands pymbp + and NH 3 . The finding led to the photocleavage of supercoiled plasmid pBR322 DNA by [ 3 ] 3+ with visible light under aerobic and unaerobic conditions. Since similar photolysis of [ 1 ] 3+ and [ 2 ] 3+ has been observed, all the dipolar ruthenium(II) ammine complexes bearing 4,4′-bipyridinium cations can function as O 2 -independent photochemotherapeutic agents.

Enzymes used in industrial applications are often immobilized onto different types of supports because they are sensitive to pH, temperature, and various other environmental conditions. However, many of the current immobilization approaches face problems such as the requirement of tedious multi-step procedures, loss of enzyme activity during immobilization, and poor reusability. In this study, we chose poly- l -lysine (Ki) as a catalyst for silica mineralization and attempted a one-step “leave to stand” synthesis method under mild conditions, so as to simultaneously maintain both high enzymatic activity and reusability. To examine the effect of Kx on the enzymatic reaction of lipase, we performed hydrolysis of 2-octylacetate without adding a silica precursor. Results indicate that Kx hardly exerts adverse influence on the enzymatic activity of lipase. The lipase encapsulated in the silica gel prepared by leave to stand (Gelstand) retained 70% of the activity compared to the free solution, which is two times higher than that obtained by mixing (Gelmix). However, the Km value was found to be similar to that of free enzymes. These results suggest that the leave to stand is a suitable procedure for immobilization, without any decrease in the mass transfer of substrate. The Gel-stand sample retained 100% activity even after the 5th cycle, and retained above 95% of its activity after 4 h of heat treatment at 65 °C. Using phenyltriethoxysilane as a silica precursor, tertiary structural stability of enzyme was obtained, and its Kcat value was improved when compared to a free solution.

Strong vascular permeability enhancing activity was found only in the venom of Gloydius tsushimaensis , in Tsushima island, Japan, when examined together with the venoms of G. blomhoffii snakes in several areas of Japan and of G. ussuriensis in South Korea. The active protein purified by using Superdex 75 and Mono Q columns showed no affinity to heparin, and migrated on SDS-PAGE with molecular weights of 26 and 13 kDa under nonreducing and reducing conditions, respectively, showing that it exists as homodimer. Its N-terminal amino acid sequence was highly homologous to those of snake venom vascular endothelial growth factors (VEGFs). The sequence of this protein, named GtVF, was inferred from the one base-substituted two cDNAs (438 bp) obtained via the 3′ RACE. The phylogenetic analysis suggested the presence of a new type of snake venom VEGFs including GtVF with no affinity to heparin in addition to the known three types of snake venom VEGFs with high affinity to heparin. Since the vascular permeability enhancement by GtVF was inhibited by the antibody against kinase insert domain-containing receptor (KDR), the vascular permeability enhancing activity of GtVF arises through KDR but without heparin binding.

Baker's yeast (BY) encapsulated in silica materials was synthesized using a yeast cell suspension and its cell-free extract during a sol–gel reaction of tetramethoxysilane with nitric acid as a catalyst. The synthesized samples were fully characterized using various methods, such as scanning electron microscopy, nitrogen adsorption–desorption, Fourier transform infrared spectroscopy, thermogravimetry, and differential thermal analysis. The BY cells were easily encapsulated inside silica-gel networks, and the ratio of the cells in the silica gel was approximately 75 wt%, which indicated that a large volume of BY was trapped with a small amount of silica. The enzyme activity (asymmetric reduction of prochiral ketones) of BY and its cell-free extract encapsulated in silica gel was investigated in detail. The activities and enantioselectivities of free and encapsulated BY were similar to those of acetophenone and its fluorine derivatives, which indicated that the conformation structure of BY enzymes inside silica-gel networks did not change. In addition, the encapsulated BY exhibited considerably better solvent (methanol) stability and recyclability compared to free BY solution. We expect that the development of BY encapsulated in sol–gel silica materials will significantly impact the industrial-scale advancement of high-efficiency and low-cost biocatalysts for the synthesis of valuable chiral alcohols.

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

A 47-year-old man with optimally controlled type-2 diabetes mellitus and chronic hepatitis B was admitted to a local hospital because of a 1-week history of cough and high-grade fever. He was diagnosed with Pneumocystis pneumonia (PCP) and Klebsiella pneumonia from a chest radiograph and sputum. Simultaneously, he was found to have HIV infection with a CD4 count of 76/μl. Despite alteration of treatment secondary to the development of allergic reaction to trimethoprim-sulfamethoxazole (TMP-SMX), the patient was able to complete a 3-week therapy for PCP after being switched to pentamidine isetionate. After the treatment of PCP, he was referred to our hospital for the initiation of anti-HIV therapy. He presented with recurrent high-grade fever of a few days' duration prior to his initial visit, which subsequently led to his admission. Chest computed tomography (CT) showed the enlargement of a previously identified infiltrate in the left upper lung field, and the sputum culture upon admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia exalbida. Due to his allergy to sulfonamide, the patient was treated with imipenem (IMP) and amikacin (AMK) given intravenously for 17 days, followed by garenoxacin (GRNX) taken orally for 6 months, without any adverse effects. The chest infiltrate resolved completely, and he remains stable without relapse 8 months after the completion of the therapy. Pulmonary nocardiosis should be considered as a differential diagnosis of recurring pneumonia in immunocompromised patients, especially in HIV-infected individuals. Oral administration of GRNX following IMP and AMK can be used as an alternative to TMP-SMX therapy in cases of pulmonary nocardiosis caused by N. exalbida.

Drug-resistant virus infection has been a major hurdle in the management of human immunodeficiency virus type 1 (HIV-1) infection. Recently, three novel antiretrovirals [raltegravir (RAL), etravirine (ETR), and darunavir (DRV)] were introduced into the market almost simultaneously, and salvage regimens containing these three antiretrovirals have been reported to exhibit strong potency against drug-resistant HIV-1 infection. However, the sustainability of such regimens remains unclear, particularly for patients infected with multidrug-resistant viruses. Here we report a case of super-multidrug-resistant HIV-1 infection which has been successfully controlled by novel combination therapy including RAL, ETR, and DRV for over 2 years, indicating that the novel combination could become an ultimate weapon against drug-resistant HIV infection and could alter the landscape of HIV salvage therapy.

The East Asian continental margin is underlain by stagnant slabs resulting from subduction of the Pacific plate from the east and the Philippine Sea plate from the south. We classify the upper mantle in this region into three major domains: (a) metasomatic–metamorphic factory (MMF), subduction zone magma factory (SZMF), and the ‘big mantle wedge’ (BMW). Whereas the convection pattern is anticlockwise in the MMF domain, it is predominantly clockwise in the SZMF and BMW, along a cross section from the south. Here we define the MMF as a small wedge corner which is driven by the subducting Pacific plate and dominated by H 2 O-rich fluids derived by dehydration reactions, and enriched in large ion lithophile elements (LILE) which cause the metasomatism. The SZMF is a zone intermediate between MMF and BMW domains and constitutes the main region of continental crust production by partial melting through wedge counter-corner flow. Large hydrous plume generated at about 200 km depth causes extensive reduction in viscosity and the smaller scale hydrous plumes between 60 km and 200 km also bring about an overall reduction in the viscosity of SZMF. More fertile and high temperature peridotites are supplied from the entrance to this domain. The domain extends obliquely to the volcanic front and then swings back to the deep mantle together with the subducting slab. The BMW occupies the major portion of upper mantle in the western Pacific and convects largely with a clockwise sense removing the eastern trench oceanward. Sporadic formation of hydrous plume at the depth of around 410 km and the curtain flow adjacent to the trench cause back arc spreading. We envisage that the heat source in BMW could be the accumulated TTG (tonalite–trondhjemite–granodiorite) crust on the bottom of the mantle transition zone. The ongoing process of transportation of granitic crust into the mantle transition zone is evident from the deep subduction of five intra-oceanic arcs on the subducting Philippine Sea plate from the south, in addition to the sediment trapped subduction by the Pacific plate and Philippine Sea plate. The dynamics of MMF, SZMF and BMW domains are controlled by the angle of subduction; a wide zone of MMF in SW Japan is caused by shallow angle subduction of the Philippine Sea plate and the markedly small MMF domain in the Mariana trench is due to the high angle subduction of Pacific plate. The domains in NE Japan and Kyushu region are intermediate between these two. During the Tertiary, a series of marginal basins were formed because of the nearly 2000 km northward shift of the subduction zone along the southern margin of Tethyan Asia, which may be related to the collision of India with Asia and the indentation. The volume of upper mantle under Asia was reduced extensively on the southern margin with a resultant oceanward trench retreat along the eastern margin of Asia, leading to the formation of a series of marginal basins. The western Pacific domain in general is characterized by double-sided subduction; from the east by the oldest Pacific plate and from the south by the oldest Indo-Australian plate. The old plates are hence hydrated extensively even in their central domains and therefore of low temperature. The cracks have allowed the transport of water into the deeper portions of the slab and these domains supply hydrous fluids even to the bottom of the upper mantle. Thus, a fluid dominated upper mantle in the western Pacific drives a number of microplates and promote the plate boundary processes.

Identifying the amount and composition of slab-derived fluid and its spatial variation is key to quantifying fluid processes in subduction zones. Based on the isotopic systematics of arc lavas, we found regional variations over the Japan arcs in terms of the amount and composition of slab-derived fluid added to the melting source region. The average amounts of slab-derived fluid differ among the arcs: 2.6 wt.% for Central Japan, 0.69 wt.% for Ryukyu, 0.17 wt.% for NE Japan, and 0.12 wt.% for both Kurile and Izu–Bonin. These differences may be attributed to the arc setting (oceanic or continental) and the geometry of the slabs. Contribution of sediment involved in the slab-derived fluid is dominant in NE Japan compared to the Izu–Bonin and Central Japan arcs. This could be attributed to mechanical features such as fractures near the subducting plate surface, in addition to the arc setting and the slab geometry. Therefore, the amount and composition of slab-derived fluid are thought to be controlled not only by the thermal conditions, but also by the tectonic and mechanical features around the subduction zone. On top of the variability of slab-derived fluid, the mantle wedge shows the regional variation in terms of proportion of the Pacific-type and Indian-type MORB-source mantle components, which also contributes to the compositional variations of arc magmas.

We investigated the clinical significance of serum and intrahepatic KL-6/MUC1 (KL-6) in patients with hepatitis C virus (HCV) antibody-positive hepatocellular carcinoma (HCC). The subjects included 76 patients diagnosed with anti-HCV positive HCC, 69 with, and 51 without, liver cirrhosis (LC). Frozen serum samples were obtained from each subject to determine the serum KL-6 levels using an enzyme-linked immunosorbent assay. Expression of KL-6 antigen in the liver was also investigated using immunoperoxidase staining. The mean serum KL-6 level in patients with HCC was [Formula: see text] U/ml (319U/ml for HCC with LC, 342.8U/ml for HCC without LC). Serum KL-6 levels in patients with HCC with LC and HCC without LC did not differ. Serum KL-6 levels were elevated with increases in the size of spaces occupied by tumors in the liver. Among patients with HCC, there was no correlation between serum KL-6 levels and alpha-fetoprotein (AFP) levels and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels. However, some patients with low levels of AFP and PIVKA-II possessed high levels of KL-6. Furthermore, serum KL-6 levels decreased after therapy for HCC nodules. Immunohistochemical staining showed KL-6 antigen was detected within the cell membrane and in the cytoplasm of cancer cells. KL-6 antigen was localized on the membrane and the endoplasmic reticulum of cancer cells in the cancerous foci by electron microscopy. Our results suggest that serum KL-6 levels represent a serological marker of HCC development, because KL-6 expression was localized to the cancer cells in HCC nodules.

Objectives: Oxidative stress in the reproductive system is thought to affect the fertilizing ability of sperm. Since 8-hydroxydeoxyguanosine (8-OHdG) and lipid peroxides are widely used as markers to quantify oxidative stress, we compared 8-OHdG and lipid peroxide concentrations in seminal plasma and spermatozoa from subfertile and fertile men. Study design: Semen obtained from 37 men of subfertile couples (21 men with normozoospermia and 16 with asthenozoospermia) and from eight fertile volunteers were examined. Seminal plasma and spermatozoa were fractionated by four-step discontinuous Percoll gradient centrifugation. 8-OHdG in seminal plasma was measured by ELISA, and lipid peroxides in seminal plasma and spermatozoa were determined using a thiobarbituric acid (TBA) assay. Results: The concentrations of 8-OHdG and lipid peroxides in the seminal plasma of the subfertile group were significantly higher than those of the fertile group. There were no significant differences in these values between patients with normozoospermia and asthenozoospermia. In all four fractions obtained by Percoll gradient fractionation, the lipid peroxide levels in spermatozoa recovered from subfertile males were significantly higher than those of fertile controls. Conclusions: Seminal plasma and spermatozoa from subfertile males showed elevated levels of oxidative stress that were detectable in ejaculated semen specimens by ELISA or TBA assay. Even the spermatozoa fraction considered to be mature and normal showed elevated oxidative stress in the subfertile group. Our results confirm the importance of oxidative stress in male reproductive function, and could be applied for the selection of patients for antioxidant therapy.

We have developed a simple method for converting the lipid envelope of an inactivated virus to a gene transfer vector. Hemagglutinating virus of Japan (HVJ; Sendai virus) envelope vector was constructed by incorporating plasmid DNA into inactivated HVJ particles. This HVJ envelope vector introduced plasmid DNA efficiently and rapidly into various cell lines, including cancer cells and several types of primary cell culture. Efficiency of gene transfer was greatly enhanced by protamine sulfate and centrifugation. Fluorescein isothiocyanate-labeled oligodeoxynucleotides (FITC-ODN) were also delivered to cells at > 95% efficiency. When HVJ envelope vector was injected into organs directly, reporter gene expression was observed in organs including liver, brain, skin, uterus, tumor masses, lung, and eye. When HVJ envelope vector containing luciferase gene was injected into mouse tail vein, luciferase gene expression was detected primarily in spleen. FITC-ODN were also delivered to spleen cells by intravenous injection of HVJ envelope. These results suggest that HVJ envelope vector will be useful for both ex vivo and in vivo gene therapy experiments.

In the human oxytocin receptor (OTR) gene, there is a CpG island from 140 bp upstream to 2338 bp downstream of the transcription start site (TSS). We investigated whether the methylation state of this region affects the transcription of the OTR gene. HepG2 derived from human hepatoblastoma, in which OTR gene transcription was suppressed, was treated with a demethylating agent, 5-azacytidine (Aza-C) for 2 days. Semiquantitative RT-PCR indicated that OTR mRNA was significantly increased by Aza-C treatment in a dose-dependent manner. We estimated the level of methylation within the CpG islands of the OTR gene in peripheral blood leukocytes, nonpregnant uterine myometrium, term uterine myometrium and liver. A 1.5-kb region located 5' upstream of the translation start site was divided into four fragments. Each was amplified by PCR after complete digestion with methylation-sensitive restriction enzyme HpaII. The amount of PCR products was largest in the liver, suggesting that this CpG island in the OTR gene is most highly methylated in liver, where the gene is always inactivated. We compared the effect of in vivo methylation of the CpG island on transcriptional activity of an OTR-reporter plasmid. The reporter gene activity of expression plasmid -2860/+1342-GL3, containing the CpG island, in HepG2 cells was suppressed to 30.6% of the control level after methylation with SssI methylase, while that of -2840/+144-GL3, without the CpG island was suppressed only to 81.4%. The deletion of the segment (MT2) where the level of methylation was most different between liver and uterus (-2860/+1342(del)MT2-GL3) rescued the suppression rate to 68.0%. These results indicate that the methylation of the CpG island in the human OTR gene promoter suppressed its transcription at least in liver and may regulate tissue specific gene expression among organs.

We have studied Y 2 PdGe 3− x Si x superconductor using magnetization and specific heat measurements. The compounds are very sensitive to changes in the honeycomb layers by Si substitution. The critical temperature shows a maximum of T c =3.55 K near x =0.3 and decreases with further increase in Si concentration. The changes in the Debye frequency and electron–phonon coupling have combined effect to control the critical temperature.