As neurons age, their survival depends on eliminating a growing burden of damaged, potentially toxic proteins and organelles-a capability that declines owing to aging and disease factors. Here, we ...review the two proteolytic systems principally responsible for protein quality control in neurons and their important contributions to Alzheimer disease pathogenesis. In the first section, the discovery of paired helical filament ubiquitination is described as a backdrop for discussing the importance of the ubiquitin-proteasome system in Alzheimer disease. In the second section, we review the prominent involvement of the lysosomal system beginning with pathological endosomal-lysosomal activation and signaling at the very earliest stages of Alzheimer disease followed by the progressive failure of autophagy. These abnormalities, which result in part from Alzheimer-related genes acting directly on these lysosomal pathways, contribute to the development of each of the Alzheimer neuropathological hallmarks and represent a promising therapeutic target.
From detailed angle-resolved NMR and Meissner measurements on a ferromagnetic (FM) superconductor UCoGe (T(Curie)∼2.5 K and T(SC)∼0.6 K), we show that superconductivity in UCoGe is tightly coupled ...with longitudinal FM spin fluctuations along the c axis. We found that magnetic fields along the c axis (H∥c) strongly suppress the FM fluctuations and that the superconductivity is observed in the limited magnetic-field region where the longitudinal FM spin fluctuations are active. These results, combined with model calculations, strongly suggest that the longitudinal FM spin fluctuations tuned by H∥c induce the unique spin-triplet superconductivity in UCoGe. This is the first clear example that FM fluctuations are intimately related with superconductivity.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Abstract
We have exploited the new, deep, near-infrared UltraVISTA imaging of the Cosmological Evolution Survey (COSMOS) field, in tandem with deep optical and mid-infrared imaging, to conduct a new ...search for luminous galaxies at redshifts z ≃ 7. The year-one UltraVISTA data provide contiguous Y, J, H, K
s imaging over 1.5 deg2, reaching a 5σ detection limit of Y + J ≃ 25 (AB mag, 2-arcsec-diameter aperture). The central ≃1 deg2 of this imaging coincides with the final deep optical (u*, g, r, i) data provided by the Canada-France-Hawaii Telescope (CFHT) Legacy Survey and new deep Subaru/Suprime-Cam z′-band imaging obtained specifically to enable full exploitation of UltraVISTA. It also lies within the Hubble Space Telescope (HST) I
814 band and Spitzer/Infrared Array Camera imaging obtained as part of the COSMOS survey. We have utilized this unique multiwavelength dataset to select galaxy candidates at redshifts z > 6.5 by searching first for Y + J-detected objects which are undetected in the CFHT and HST optical data. This sample was then refined using a photometric redshift fitting code, enabling the rejection of lower redshift galaxy contaminants and cool galactic M, L, T dwarf stars. The final result of this process is a small sample of (at most) 10 credible galaxy candidates at z > 6.5 (from over 200 000 galaxies detected in the year-one UltraVISTA data) which we present in this paper. The first four of these appear to be robust galaxies at z > 6.5, and fitting to their stacked spectral energy distribution yields z
phot = 6.98 ± 0.05 with a stellar mass M
* ≃ 5 × 109 M⊙ and rest-frame ultraviolet (UV) spectral slope β ≃ −2.0 ± 0.2 (where ƒ
λ ∝ λβ). The next three are also good candidates for z > 6.5 galaxies, but the possibility that they are dwarf stars cannot be completely excluded. Our final subset of three additional candidates is afflicted not only by potential dwarf star contamination, but also contains objects likely to lie at redshifts just below z = 6.5. We show that the three even-brighter z ≳ 7 galaxy candidates reported in the COSMOS field by Capak et al. are in fact all lower redshift galaxies at z ≃ 1.5-3.5. Consequently the new z ≃ 7 galaxies reported here are the first credible z ≃ 7 Lyman-break galaxies discovered in the COSMOS field and, as the most UV luminous discovered to date at these redshifts, are prime targets for deep follow-up spectroscopy. We explore their physical properties, and briefly consider the implications of their inferred number density for the form of the galaxy luminosity function at z ≃ 7.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We report a NMR and magnetometry study on the expanded intercalated fulleride Cs3C60 in both its A15 and face centered cubic structures. NMR allowed us to evidence that both exhibit a first-order ...Mott transition to a superconducting state, occurring at distinct critical pressures p{c} and temperatures T{c}. Though the ground state magnetism of the Mott phases differs, their high T paramagnetic and superconducting properties are found similar, and the phase diagrams versus unit volume per C60 are superimposed. Thus, as expected for a strongly correlated system, the interball distance is the relevant parameter driving the electronic behavior and quantum transitions of these systems.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
We present a ^{35}Cl NMR study for the spin S=1/2 perfect kagome antiferromagnet Ca-kapellasite CaCu_{3}(OH)_{6}Cl_{2}·0.6H_{2}O with a magnetic transition at T^{*}=7.2K. The static magnetic ...structure in the ground state has been determined to be a chirality-ordered Q=0 state, which is selected by a finite Dzyaloshinskii-Moriya interaction. The low-energy magnetic excitations in the ordered state are investigated by a nuclear spin-lattice relaxation rate measurement. We detect a weakly temperature-dependent contribution in the magnetic fluctuations perpendicular to the kagome plane in addition to the dispersive spin-wave contribution in the kagome plane. The low-energy magnetic excitations from the coplanar spin structure are attributed to the zero mode originating from the flat band in this kagome antiferromagnet.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
Brassinosteroids (BRs) are plant growth-promoting natural products required for plant growth and development. Physiological studies have demonstrated that exogenous BR, alone or in combination with ...auxin, enhance bending of the lamina joint of rice. However, little is known about the function of endogenous BR in rice or other grass species. We report here the phenotypical and molecular characterization of a rice dwarf mutant, d61, that is less sensitive to BR compared to the wild type. We cloned a rice gene, OsBRI1, with extensive sequence similarity to that of the Arabidopsis BRI gene, which encodes a putative BR receptor kinase. Linkage analysis showed that the OsBRI1 gene is closely linked to the d61 locus. Single nucleotide substitutions found at different sites of the d61 alleles would give rise to amino acid changes in the corresponding polypeptides. Furthermore, introduction of the entire OsBRI1 coding region, including the 5′ and 3′ flanking sequences, into d61 plants complemented the mutation to display the wild-type phenotype. Transgenic plants carrying the antisense strand of the OsBRI1 transcript showed similar or even more severe phenotypes than those of the d61 mutants. Our results show that OsBRI1 functions in various growth and developmental processes in rice, including (1) internode elongation, by inducing the formation of the intercalary meristem and the longitudinal elongation of internode cells; (2) bending of the lamina joint; and (3) skotomorphogenesis.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Background In small infants, left lateral segment grafts are sometimes too large to overcome the problems of large-for-size grafts in the abdominal compartment. To address this problem, we ...have developed a safe living donor graftectomy for neonates, a so-called “S2 monosegment graft” to minimize graft thickness. We reviewed our single-center experience to evaluate the feasibility of this technique for reducing graft size. Methods Eleven living-donor liver transplants using S2 monosegment grafts were performed between October 2008 and September 2014 at our institution. Medical records of both donors and recipients were reviewed and data collected retrospectively. Results The mean age of recipients at the time of transplantation was 125.3 days, including 3 neonates. The average S2 monosegment graft weight was 127.4 g, and the graft-to-recipient body weight ratio was successfully reduced to 3.5%. The graft livers were reduced to 4.1 cm in thickness. Two recipients with grafts larger than 5 cm could not undergo primary abdominal closure. Portal vein stenosis and biliary stenosis was observed in 1 recipient, and hepatic artery complications were seen in 2 recipients; the clinical course for all donors were uneventful. Liver regeneration was seen in every patient. The graft and patient 1-year survival rate was 100%. Conclusions Living-donor liver transplantation using S2 monosegment grafts offers a safe and useful option for treating smaller infants. Here, we introduce our method of S2 monosegment graft emphasizing the donor harvest and graft thickness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Introduction Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation ...than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. Objectives Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. Methods We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. Results The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. Conclusions Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics ...Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period.
We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012. EA was measured by means of an Et activity assay (EAA) in samples collected from a vein 1 day before LDLT, from the portal vein during the intraoperative anhepatic phase, from an artery 1 hour after reperfusion, from an artery on postoperative day (POD) 1, and from an artery or vein at PODs 7 and 14.
EAs generally remained at low levels. EA at the reperfusion period was significantly lowest. The correlation coefficient for the preoperative MELD/PELD score and the EAA was 0.837, and the corresponding P value was .009; thus, there was a significant relationship between the preoperative MELD/PELD score and the EAA. The correlation coefficients for ALT at POD 1 and EA during the anhepatic phase, at 1 hour after reperfusion, and at POD 1 were 0.64, 0.43, and 0.38, respectively, and the P values for these correlations were .08, .67, and .34. Thus, we observed that ALT and EA generally tended to be somewhat directly correlated, but no significant relationships between these 2 metrics were observed.
Endotoxin metabolism reflects the hepatic functional reserve capacity of end-stage liver disease.
•The relationships between endotoxin activity and pre-transplantation PELD/MELD score were examined.•There was a significant relationship between the preoperative PELD/MELD score and the endotoxin activity assay.•Endotoxin metabolism reflects the hepatic functional reserve of end-stage liver disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Identification of pairing mechanisms leading to the unconventional superconductivity realized in copper-oxide, heavy-fermions, and organic compounds is one of the most challenging issues in ...condensed-matter physics. Clear evidence for an electron-phonon mechanism in conventional superconductors is seen by the isotope effect on the superconducting transition temperatures TSC, since isotopic substitution varies the phonon frequency without affecting the electronic states. In unconventional superconductors, magnetic fluctuations have been proposed to mediate superconductivity, and considerable efforts have been made to unravel relationships between normal-state magnetic fluctuations and superconductivity. Here, we show that characteristic experimental results on the ferromagnetic (FM) superconductor UCoGe (TCurie ~ 2.5 K and TSC ~ 0.6 K) can be understood consistently within a scenario of the spin-triplet superconductivity induced by FM spin fluctuations. Temperature and angle dependencies of the upper critical magnetic field of the superconductivity (Hc2) are calculated on the basis of the above scenario by solving the Eliashberg equation. Calculated Hc2 well agrees with the characteristic experimental results observed in UCoGe. This is a first example that FM fluctuations are shown to be a pairing glue of superconductivity.
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