Description: Recent theoretical simulations on the glacial isostatic adjustment (GIA) have revealed that the model differences arising from considering mantle compressibility are not necessarily negligible if compared with the observation accuracy of present-day deformation rates. In this study, a compressible model is constructed for the GIA in southeast Alaska, and the uplift rate is compared with GPS data and the incompressible case for the first time. It is shown that, for Maxwell rheology, the incompressible model potentially underestimates the mean uplift rate by approximately 27% (4 mm/yr) with respect to the compressible case and the difference is detectable given observational precision. This difference between the compressible and incompressible models is reduced to 10% by matching the flexural rigidity of both earth models. When carrying out an inversion using incompressible models, this adjustment is important to infer a physically more correct viscoelastic structure.

Description: Subduction of the oceanic plate plays an important role in the various processes in subduction zones, including arc magmatism and generation of earthquakes. Thus the nature of the incoming plate, such as its relief, thermal state, lithology, and the water content, are considered to shape these subduction zone processes. In 2014 and 2015, to reveal the nature of the incoming plate in the ocean-ward area of the 2011 M9 Tohoku earthquake, we conducted wide-angle seismic surveys in the trench-outer rise region of the Japan Trench. We designed a 600 km long seismic survey line perpendicular to the trench axis and deployed 88 OBSs at intervals of 6 km and shot a tuned airgun array of R/V Kairei. We have applied a traveltime inversion to model the P-wave velocity (Vp) structure. The resulting Vp model shows that Vp within the oceanic crust and the topmost mantle decreases in the vicinity of the trench axis probably due to the plate bending. In addition, we observed low Vp at the top of the oceanic crust in the area of petit spot volcanos. The low Vp area may be related to magma intrusions because we observed several structural interfaces in the shallow area. We found two structural features that we did not anticipate. First, crustal thickness abruptly changes at around the center of our survey line (~300-km east from the trench axis); crust thickness is 7-km in the west and 6-km in the east. Second, mantle Vp shows significant variations along the survey line, ~7.5 km/s in the bend-fault area (western area), 8.0 km/s around the center, 8.5 km/s in the eastern area. Based on the shear wave splitting observed in our data set, we infer that high mantle Vp in the eastern area is related with the changes in the orientation of the mantle anisotropy. Since we do not see any remarkable topographic features indicating the off-ridge activities, we consider that these observed structural features are related with the activities near the ancient spreading ridge when the oceanic plate formed, indicating that the oceanic plate in the NW Pacific margin, the input to the northeastern Japanese island arc, is more complicated here than we previously thought. In this presentation, we will show an overview of the Vp model along the whole profile and detailed seismic structure beneath the petit-spot area derived by the P-to-S converted waves.

Description: Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group ( n = 170), the hyperuricemia group ( n = 254) had a higher prevalence of hypertension ( P = 0.013), diabetes mellitus ( P = 0.01), dyslipidemia ( P = 0.038), atrial fibrillation ( P = 0.001), and use of diuretics ( P 〈 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P 〈 0.001) and V e /V co 2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V o 2 (14.9 vs. 17.9 ml·kg –1 ·min –1 , P 〈 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia ( P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036–3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

Description: Author(s): H. Reichlová, D. Kriegner, V. Holý, K. Olejník, V. Novák, M. Yamada, K. Miura, S. Ogawa, H. Takahashi, T. Jungwirth, and J. Wunderlich We report measurements of current-induced magnetic torques in structures containing a ∼ 1 -nm-thick layer of an antiferromagnet IrMn. We perform ac-electrical measurements in Ta/IrMn/CoFeB and Ta/IrMn structures below and above the Néel temperature of the ultrathin IrMn and compare the results with co… [Phys. Rev. B 92, 165424] Published Tue Oct 20, 2015

Description: Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 ( LOXL1 ) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (~40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1 . We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1 , a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1 . We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.

Description: Objective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Design Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. Results All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of 〉80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori -associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. Conclusions A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.

Description: Parathyroid hormone-related protein (PTHrP) has two different targeting signals: an N-terminal signal peptide for the endoplasmic reticulum (ER) targeting and an internal nuclear localization signal. The protein not only functions as a secretory protein, but is also found in the nucleus and/or nucleolus under certain conditions. PTHrP signal peptide is less hydrophobic than most signal peptides mainly due to its evolutionarily well-conserved region (QQWS). The substitution of four tandem leucine residues for this conserved region resulted in a significant inhibition of the signal peptide cleavage. At the same time, proportion of nuclear and/or nucleolar localization decreased, probably due to tethering of the protein to the ER membrane by the uncleaved mutant signal peptide. Almost complete cleavage of the signal peptide accompanied by a lack of nuclear/nucleolar localization was achieved by combining the hydrophobic h-region and an optimized sequence of the cleavage site. In addition, mutational modifications of the distribution of charged residues in and around the signal peptide affect its cleavage and/or nuclear/nucleolar localization of the protein. These results indicate that the well-conserved region in the signal peptide plays an essential role in the dual localization of PTHrP through ER targeting and/or the membrane translocation.

Description: In skeletal muscle, resting intracellular Ca 2+ concentration ([Ca 2+ ] i ) homeostasis is exquisitely regulated by Ca 2+ transport across the sarcolemmal, mitochondrial, and sarcoplasmic reticulum (SR) membranes. Of these three systems, the relative importance of the mitochondria in [Ca 2+ ] i regulation remains poorly understood in in vivo skeletal muscle. We tested the hypothesis that the capacity for Ca 2+ uptake by mitochondria is a primary factor in determining [Ca 2+ ] i regulation in muscle at rest and following contractions. Tibialis anterior muscle of anesthetized peroxisome proliferator-activated receptor- coactivator-1α (PGC-1α)-overexpressing (OE, increased mitochondria model) and wild-type (WT) littermate mice was exteriorized in vivo and loaded with the fluorescent probe fura 2-AM, and Rhod 2-AM Ca 2+ buffering and mitochondrial [Ca 2+ ] were evaluated at rest and during recovery from fatiguing tetanic contractions induced by electrical stimulation (120 s, 100 Hz). In addition, the effects of pharmacological inhibition of SR (thapsigargin) and mitochondrial [carbonyl cyanide- 4 -(trifluoromethoxy) phenylhydrazone (FCCP)] function were examined at rest. [Ca 2+ ] i in WT remained elevated for the entire postcontraction recovery period (+6 ± 1% at 450 s), but in PGC-1α OE [Ca 2+ ] i returned to resting baseline within 150 s. Thapsigargin immediately and substantially increased resting [Ca 2+ ] i in WT, whereas in PGC-1α OE this effect was delayed and markedly diminished (WT, +12 ± 3; PGC-1α OE, +1 ± 2% at 600 s after thapsigargin treatment, P 〈 0.05). FCCP abolished this improvement of [Ca 2+ ] i regulation in PGC-1α OE. Mitochondrial [Ca 2+ ] accumulation was observed in PGC-1α OE following contractions and thapsigargin treatment. In the SR, PGC-1α OE downregulated SR Ca 2+ -ATPase 1 (Ca 2+ uptake) and parvalbumin (Ca 2+ buffering) protein levels, whereas mitochondrial Ca 2+ uptake-related proteins (Mfn1, Mfn2, and mitochondrial Ca 2+ uniporter) were upregulated. These data demonstrate a heretofore unappreciated role for skeletal muscle mitochondria in [Ca 2+ ] i regulation in vivo following fatiguing tetanic contractions and at rest.

Description: A low-protein diet (LPD) protects against the progression of renal injury in patients with chronic kidney disease (CKD). However, LPD may accelerate muscle wasting in these patients. Both exercise and branched-chain amino acids (BCAA) are known to increase muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway. The aim of this study was to investigate whether endurance exercise and BCAA play a role for increasing muscle protein synthesis in LPD-fed CKD (5/6 nephrectomized) rats. Both CKD and sham rats were pair-fed on LPD or LPD fortified with a BCAA diet (BD), and approximately one-half of the animals in each group was subjected to treadmill exercise (15 m/min, 1 h/day, 5 days/wk). After 7 wk, renal function was measured, and soleus muscles were collected to evaluate muscle protein synthesis. Renal function did not differ between LPD- and BD-fed CKD rats, and the treadmill exercise did not accelerate renal damage in either group. The treadmill exercise slightly increased the phosphorylation of p70s6 kinase, a marker of mTOR activity, in the soleus muscle of LPD-fed CKD rats compared with the sham group. Furthermore, BCAA supplementation of the LPD-fed, exercise-trained CKD rats restored the phosphorylation of p70s6 kinase to the same level observed in the sham group; however, the corresponding induced increase in muscle protein synthesis and muscle mass was marginal. These results indicate that the combination of treadmill exercise and BCAA stimulates cell signaling to promote muscle protein synthesis; however, the implications of this effect for muscle growth remain to be clarified.