Identification of Lepidapedon oregonense as the current world's deepest trematode.

The deepest recorded depth for trematodes currently stands at approximately 6200 m. This depth record was achieved solely through sequence datasets of Lepidapedon sp. obtained from a gastropod. Given that trematodes of this genus typically use fish as definitive hosts, the origin of the trematode sequence was thought to be larval stages. However, the specific species remained unclear owing to the absence of reported adult-stage sequences. In the present study, we definitively identified the deepest trematode as Lepidapedon oregonense by comparing 28S ribosomal DNA sequences from adult worms from the macrourid fish Coelorinchus gilberti with data from the gastropod in the previous study.

Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta.

BACKGROUND AND AIMS: Advanced glycation end products (AGEs)-receptor RAGE interaction evokes oxidative stress and inflammatory reactions, thereby being involved in endothelial cell (EC) damage in diabetes. Sulforaphane is generated from glucoraphanin, a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, by myrosinase. Sulforaphane has been reported to protect against oxidative stress-mediated cell and tissue injury. However, effects of sulforaphane on AGEs-induced vascular damage remain unclear. METHODS AND RESULTS: In this study, we investigated whether and how sulforaphane could inhibit inflammation in AGEs-exposed human umbilical vein ECs (HUVECs) and AGEs-injected rat aorta. Sulforaphane treatment for 4 or 24 h dose-dependently inhibited the AGEs-induced increase in RAGE, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecular-1 (VCAM-1) gene expression in HUVECs. AGEs significantly stimulated MCP-1 production by, and THP-1 cell adhesion to, HUVECs, both of which were prevented by 1.6 µM sulforaphane. Sulforaphane significantly suppressed oxidative stress generation and NADPH oxidase activation evoked by AGEs in HUVECs. Furthermore, aortic RAGE, ICAM-1 and VCAM-1 expression in AGEs-injected rats were increased, which were suppressed by simultaneous infusion of sulforaphane. CONCLUSION: The present study demonstrated for the first time that sulforaphane could inhibit inflammation in AGEs-exposed HUVECs and AGEs-infused rat aorta partly by suppressing RAGE expression through its anti-oxidative properties. Inhibition of the AGEs-RAGE axis by sulforaphane might be a novel therapeutic target for vascular injury in diabetes.

Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis.

Advanced glycation end products (AGEs) and receptor RAGE play a role in diabetic nephropathy. We have previously shown that increased glucose uptake into proximal tubular cells via sodium-glucose cotransporter 2 (SGLT2) stimulates oxidative stress generation and RAGE expression, thereby exacerbating the AGE-induced apoptosis in this cell type. However, the protective role of SGLT2 inhibition against the AGE-RAGE-induced renal damage in diabetic animals remains unclear. In this study, we investigated the effects of empagliflozin, SGLT2 inhibitor on AGE-RAGE axis, inflammatory and fibrotic reactions, and tubular injury in the kidney of streptozotocin-induced diabetic rats.Administration of empagliflozin for 4 weeks significantly improved hyperglycemia and HbA1c, and decreased expression levels of AGEs, RAGE, 8-hydroxydeoxyguanosine (8-OHdG), and F4/80, markers of oxidative stress and macrophages, respectively, in the diabetic kidney. Although empagliflozin did not reduce albuminuria, it significantly decreased urinary excretion levels of 8-OHdG and L-fatty acid binding protein, a marker of tubular injury. Moreover, inflammatory and fibrotic gene expression such as monocyte chemoattractant protein-1, intercellular adhesion molecule-1, plasminogen activator inhibitor-1, transforming growth factor-ß, and connective tissue growth factor was enhanced in the diabetic kidney, all of which were prevented by empagliflozin. The present study suggests that empagliflozin could inhibit oxidative, inflammatory and fibrotic reactions in the kidney of diabetic rats partly via suppression of the AGE-RAGE axis. Blockade of the increased glucose uptake into renal proximal tubular cells by empagliflozin might be a novel therapeutic target for tubulointerstitial damage in diabetic nephropathy.

Temperature Dependence of Magnetically Active Charge Excitations in Magnetite across the Verwey Transition.

We study the electronic structure of bulk single crystals and epitaxial films of Fe_{3}O_{4}. Fe 2p core level spectra show clear differences between hard x-ray (HAX) and soft x-ray photoemission spectroscopy (PES). The bulk-sensitive spectra exhibit temperature (T) dependence across the Verwey transition, which is missing in the surface-sensitive spectra. By using an extended impurity Anderson full-multiplet model-and in contrast to an earlier peak assignment-we show that the two distinct Fe species (A and B site) and the charge modulation at the B site are responsible for the newly found double peaks in the main peak above T_{V} and its T-dependent evolution. The Fe 2p HAXPES spectra show a clear magnetic circular dichroism (MCD) in the metallic phase of magnetized 100-nm-thick films. The model calculations also reproduce the MCD and identify the contributions from magnetically distinct A and B sites. Valence band HAXPES shows a finite density of states at E_{F} for the polaronic half metal with a remnant order above T_{V} and a clear gap formation below T_{V}. The results indicate that the Verwey transition is driven by changes in the strongly correlated and magnetically active B-site electronic states, consistent with resistivity and optical spectra.

Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds.

Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated if JAK-3-selective inhibition alone could disrupt cytokine signalling in rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial fibroblasts isolated from patients with RA. Levels of activated JAK and signal transducer and activator of transcription (STAT) proteins were detected by immunoblot analysis. Target-gene expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3 and downstream STAT-1/-3/-5, as well as the expression levels of target proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980, suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM-stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM-stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3-selective inhibition alone is insufficient to control STAT-3-dependent signalling in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2, is needed to control the proinflammatory cascade in RA.

Coffee consumption and the risk of prostate cancer: the Ohsaki Cohort Study.

BACKGROUND: Epidemiological evidence regarding the effect of coffee on the incidence of prostate cancer is inconsistent. We aimed to investigate coffee consumption and the risk of prostate cancer risk in a general Japanese population. METHODS: We conducted a prospective cohort study in Ohsaki city, Japan, where 18 853 men aged 40-79 years participated in a baseline survey. Coffee consumption was assessed via a validated self-administered questionnaire. During 11 years of follow-up (from January 1 1995 to December 31, 2005), 318 incident cases of prostate cancer were detected. The Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). RESULTS: There was a significant inverse association between coffee consumption and the incidence risk of prostate cancer. Compared with those who did not drink coffee, the multivariate adjusted HRs were 0.81 (95% CI: 0.61-1.07), 0.73 (95% CI: 0.53-1.00), and 0.63 (095% CI: 0.39-1.00) for those who drank coffee occasionally, 1-2 cups per day, and > or =3 cups per day, respectively, with a P for trend of 0.02. CONCLUSION: This prospective finding from a Japanese population adds evidence that coffee intake is inversely associated with the incidence of prostate cancer.

Fast microtomography using bright monochromatic x-rays.

A fast microtomography system for high-resolution high-speed imaging has been developed using bright monochromatic x-rays at the BL29XU beamline of SPring-8. The shortest scan time for microtomography we attained was 0.25 s in 1.25 µm effective pixel size by combining the bright monochromatic x-rays, a fast rotating sample stage, and a high performance x-ray imaging detector. The feasibility of the tomography system was successfully demonstrated by visualization of rising bubbles in a viscous liquid, an interesting issue in multiphase flow physics. This system also provides a high spatial (a measurable feature size of 300 nm) or a very high temporal (9.8 µs) resolution in radiographs.

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.

BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS: We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Role of Ti 3d carriers in mediating the ferromagnetism of Co∶TiO2 anatase thin films.

We study the surface and bulk electronic structure of the room-temperature ferromagnet Co∶TiO(2) anatase films using soft- and hard-x-ray photoemission spectroscopy with probe sensitivities of ∼1 and ∼10 nm, respectively. We obtain direct evidence of metallic Ti(3+) states in the bulk, which get suppressed to give a surface semiconductor, thus indicating the difference in electronic structure between surface and bulk. X-ray absorption and resonant photoemission spectroscopy reveal Ti(3+) electrons at the Fermi level (E(F)) and high-spin Co(2+) electrons occurring away from E(F). The results show the importance of the charge neutrality condition: Co(2+)+V(O)(2-)+2Ti(4+)↔Co(2+)+2Ti(3+) (V(O) is oxygen vacancy), which gives rise to the elusive Ti 3d carriers mediating ferromagnetism via the Co 3d-O 2p-Ti 3d exchange interaction pathway of the occupied orbitals.

One-dimensional Wolter optics with a sub-50 nm spatial resolution.

We studied an imaging system consisting of an elliptical mirror and a hyperbolic mirror [i.e., one-dimensional (1D) Wolter optics] to realize an achromatic full-field hard x-ray microscopy with a resolution better than 50 nm. We report the performance of this 1D Wolter optical system when the mirrors were ultraprecisely figured by elastic emission machining. Experiments to form a demagnified image (demagnification factor of 385) of a 10 µm slit were conducted at an x-ray energy of 11.5 keV at BL29XUL of SPring-8. The system could form a demagnified image with a resolution better than 50 nm over a 12.1 µm field.

Evidence for a correlated insulator to antiferromagnetic metal transition in CrN.

We investigate the electronic structure of chromium nitride (CrN) across the first-order magnetostructural transition at T(N)∼286 K. Resonant photoemission spectroscopy (PES) shows a gap in the 3d partial density of states at the Fermi level and an on-site Coulomb energy U∼4.5 eV, indicating strong electron-electron correlations. Bulk-sensitive high-resolution (6 meV) laser PES reveals a clear Fermi edge indicating an antiferromagnetic metal below T(N). Hard x-ray Cr 2p core-level PES shows T-dependent changes across T(N) which originate from screening due to coherent states as substantiated by cluster model calculations using the experimentally observed U. Electrical resistivity confirms an insulator above T(N) (E(g)∼70 meV) becoming a disordered metal below T(N). Thus, CrN transforms from a correlated insulator to an antiferromagnetic metal, coupled to the magnetostructural transition.

Strong valence fluctuation in the quantum critical heavy fermion superconductor ß-YbAlB4: a hard x-ray photoemission study.

Electronic structures of the quantum critical superconductor ß-YbAlB4 and its polymorph α-YbAlB4 are investigated by using bulk-sensitive hard x-ray photoemission spectroscopy. From the Yb 3d core level spectra, the values of the Yb valence are estimated to be ∼2.73 and ∼2.75 for α- and ß-YbAlB4, respectively, thus providing clear evidence for valence fluctuations. The valence band spectra of these compounds also show Yb2+ peaks at the Fermi level. These observations establish an unambiguous case of a strong mixed valence at quantum criticality for the first time among heavy fermion systems, calling for a novel scheme for a quantum critical model beyond the conventional Doniach picture in ß-YbAlB4.

Adiposity, adult weight change and breast cancer risk in postmenopausal Japanese women: the Miyagi Cohort Study.

BACKGROUND: The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women. METHODS: A total of 10,106 postmenopausal women aged 40-64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years. RESULTS: Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05). CONCLUSION: Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk.

Anomalous state sandwiched between Fermi liquid and charge ordered Mott-insulating phases of Ti4O7.

The Magnéli phase Ti(4)O(7) exhibits two sharp jumps in resistivity with coupled structural transitions as a function of temperature at T(c1) approximately 142 K and T(c2) = 154 K. We have studied electronic structure changes across the two transitions using 7 eV laser, soft x-ray, and hard x-ray (HX) photoemission spectroscopy (PES). Ti 2p-3d resonant PES and HX PES show a clear metallic Fermi edge and mixed valency above T(c2). The low temperature phase below T(c1) shows a clear insulating gap of approximately 100 meV. The intermediate phase between T(c1) and T(c2) indicates a pseudogap coexisting with remnant coherent states. HX PES and complementary calculations have confirmed the coherent screening in the strongly correlated intermediate phase. The results suggest the existence of a highly anomalous state sandwiched between the mixed-valent Fermi liquid and charge ordered Mott-insulating phase in Ti(4)O(7).

Fermi surface-Brillouin-zone-induced pseudogap in γ-Mg17Al12 and a possible stabilization mechanism of ß-Al3Mg2.

The electronic structure of γ phase in the system Mg(17)Al(12) containing 58 atoms per unit cell with space group I43m has been calculated by using the WIEN2k-FLAPW program package. A pseudogap is found across the Fermi level. The FLAPW-Fourier spectra at the symmetry points N and Γ of the bcc Brillouin zone revealed that electronic states across the Fermi level at these symmetry points are dominated by |G|(2) = 26 and 24 states corresponding to centers of {510} + {431} and {422} zone planes, respectively. The 1253-wave nearly-free-electron (NFE) band calculations identified that a combination of the two Fermi surface-Brillouin-zone (FsBz) interactions associated with |G|(2) = 26 and 24 account well for the observed DOS pseudogap in γ-Mg(17)Al(12), most likely leading to the stabilization of this complex metallic compound. The ß-Al(3)Mg(2) containing 1178 atoms per cubic unit cell is suggested to be stabilized by satisfying the Hume-Rothery matching condition expressed in terms of e/uc, the number of electrons per unit cell, versus critical |G|(2). A critical |G|(2) is predicted to be 200 in ß-Al(3)Mg(2), which results in 84 Brillouin zone planes interacting almost simultaneously with a more or less spherical Fermi surface.

The prostate growth stimulation by progesterone is due to androgenic products and progesterone receptor-mediated mechanisms.

The antiprogestin mifepristone has been demonstrated to inhibit the growth of R3327HI rat prostatic carcinoma. A comparable antitumor effect of onapristone (ON) on rat Dunning tumors was found in our laboratories. We found the localization of progesterone (P4) receptors (PR) in prostate and prostatic tumors. These findings suggest the involvement of P4 in the mechanism of hormone-dependent growth of prostate and tumors. To study the influence of P4 on the growth of ventral (VP) and dorsolateral prostate (DLP), orchiectomized rats were treated (s.c.) daily with P4 (0.3, 1.0, 3.0 or 10.0 mg), dihydrotestosterone (DHT, 0.05 mg), estradiol (E2, 3.0 microg), ON (3.0 mg), ICI 182780 (1.0 mg) or flutamide (FL, 3.0 mg) for 12 days. One day after the last treatment, animals were sacrificed, and the organ weight of VP and DLP was determined. P4 increased the organ weight of VP and DLP in a dose-dependent manner. In contrast to DHT, which preferentially stimulated the growth of VP, P4 led rather to an increase in the weight of DLP. The effect of P4 on the DLP was enhanced by a simultaneous application of DHT or E2. The antiprogestin ON and the pure antiestrogen ICI 182780 had no appreciable effect on the P4-induced growth of VP and DLP. ON inhibited, however, the E2/P4-induced growth of DLP without affecting the growth of the VP. In contrast the antiandrogen FL suppressed the stimulatory effect of P4 on both the VP and DLP. These findings suggest that the stimulatory effect of P4 on the rat DLP may be partly due to androgenic products derived from P4 and may be also mediated by PR.

Spectroscopic evidence for competing reconstructions in polar multilayers LaAlO3/LaVO3/LaAlO3.

We have studied the valence redistribution of V in LaAlO(3)/LaVO(3)/LaAlO(3) trilayers, which are composed of only polar layers grown on SrTiO3 (001) substrates, by core-level photoemission spectroscopy. We have found that the V valence is intermediate between V3+ and V4+ for thin LaAlO3 cap layers, decreases with increasing cap-layer thickness, and finally recovers the bulk value of V3+ at approximately 10 unit-cell thickness. In order to interpret these results, we propose that the atomic reconstruction of the polar LaAlO3 surface competes with the purely electronic V valence change so that the polar catastrophe is avoided at the cost of minimum energy.

Fish consumption and the risk of colorectal cancer: the Ohsaki Cohort Study.

BACKGROUND: Evidence from laboratory and animal studies suggests that high fish consumption may reduce the risk of colorectal cancer, but the results of studies in humans have been inconsistent. The objective of this study was to prospectively examine the association between fish consumption and the risk of colorectal cancer incidence in Japan, where fish is widely consumed. METHODS: We analysed data from 39 498 men and women registered in the Ohsaki National Health Insurance Cohort Study who were 40-79 years old and free of cancer at the baseline. Fish consumption was assessed at the baseline using a self-administered food frequency questionnaire. RESULTS: During 9 years of follow-up, we identified 566 incident cases of colorectal cancer (379 men and 187 women). The hazard ratios and 95% confidence intervals (CIs) for colorectal cancer incidence in the highest quartile of fish consumption compared with the lowest quartile were 1.07 (95% CIs; 0.78-1.46, P-trend=0.43) for men, and 0.96 (95% CIs; 0.61-1.53, P-trend=0.69) for women. CONCLUSION: The results of this prospective cohort study revealed no association between fish consumption and the risk of colorectal cancer.

Recoil effect of photoelectrons in the Fermi edge of simple metals.

High energy resolution photoelectron spectroscopy of conduction electrons in the vicinity of the Fermi edge in Al and Au at excitation energies of 880 and 7940 eV was carried out using synchrotron radiation. For the excitation energy of 7940 eV, the observed Fermi energy of Al shows a remarkable shift to higher binding energy as compared with that of Au, with accompanying broadening. This is due to the recoil effect of the emitted photoelectrons. The observed spectra are well reproduced by a simple model of Bloch electrons based on the isotropic Debye model.

Revisiting the valence-band and core-level photoemission spectra of NiO.

We have reexamined the valence-band (VB) and core-level electronic structure of NiO by means of hard and soft x-ray photoemission spectroscopies. The spectral weight of the lowest energy state was found to be enhanced in the bulk sensitive Ni 2p core-level spectrum. A configuration-interaction model including a bound state screening has shown agreement with the core-level spectrum and off- and on-resonance VB spectra. These results identify the lowest energy states in the core-level and VB spectra as the Zhang-Rice (ZR) doublet bound states, consistent with the spin-fermion model and recent ab initio calculations within dynamical mean-field theory. The results indicate that the ZR character first ionization (the lowest hole-addition) states are responsible for transport properties in NiO and doped NiO.