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Abstract Purpose To investigate the association between white-coat hypertension (WCH) and acute retinal vein occlusion (RVO). Methods In this retrospective case-control study, patients aged 40 years or older diagnosed with acute-phase RVO were included. Patients with other pathologies served as non-RVO controls. Blood pressure (BP) was measured in the office during their initial visit, and information about home BP and hypertension (HTN) medication was obtained through interviews. After 1:2 age and sex-matching between the RVO and non-RVO groups, the proportions of HTN cases were compared. A similar comparison was made in subgroups with or without HTN medication. Results Fifty-one patients with RVO and 102 with non-RVO were included in the analysis. For the entire cohort, the RVO group exhibited a significantly greater proportion of WCH and sustained HTN compared to the non-RVO group. In the subgroup without HTN treatment, the proportion of WCH or sustained HTN was still significantly higher in the RVO group. However, in the subgroup receiving HTN treatment, the proportion of WCH or sustained HTN was higher in the RVO group than in the non-RVO group, though not statistically significant. Conclusion This case-control study suggests that WCH may be associated with RVO, particularly in patients without HTN treatment. Given that interventions for WCH have not been standardized, a more detailed and prospective study is warranted to elucidate the risk of WCH for RVO and other retinal vascular diseases.

Abstract To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P

Background: Hypoxia plays a crucial role in regulating various cellular functions, including ion-transport mechanisms in the kidney. The sodium-chloride co-transporter (NCC) is essential for sodium reabsorption in the distal convoluted tubule (DCT). However, the effects of hypoxia on NCC expression and its regulatory pathways remain unclear. We aimed to explore the effects and potential mechanisms of hypoxia on NCC in vitro. Methods: mDCT15 cells were treated with cobalt chloride (CoCl2) at a concentration of 300 μmol/L to induce hypoxia. The cells were harvested at different time points, namely 30 min, 1 h, 6 h, and 24 h, and the expression of NCC and CaMKII-β was analyzed using Western blot. Results: A time-dependent upregulation of NCC and CaMKII-β expression in response to CoCl2-induced hypoxia. KN93 reversed the effect of CoCl2 on NCC and phosphorylated NCC expression. Conclusions: Hypoxia, mediated through cobalt chloride treatment, upregulates NCC expression via the CaMKII-β pathway in mDCT15 cells.

An antiferromagnetic metal with a two-dimensional triangular network offers a unique playground of intriguing magneto-transport properties and functionalities stemming from the interplay between conducting electrons and intricate magnetic phases. A NiAs-type CrSe is one of the candidates owing to alternate stackings of Cr and Se triangular atomic networks in its crystal structure. While the fabrication of CrSe thin films is indispensable to develop functional devices, studies on its thin-film properties have been limited to date due to the lack of metallic samples. Here, we report on the realization of metallic conductivities of CrSe thin films, which allows us to investigate their intrinsic magneto-transport properties. The metallic sample exhibits a co-occurrence of weak ferromagnetism with perpendicular magnetic anisotropy and antiferromagnetic behavior, indicating the presence of non-coplanar spin structures. In addition, control of the polarity and tilting angle of the non-coplanar spin structure is accomplished by a sign of cooling magnetic fields. The observed non-coplanar spin structure, which can be a source of emergent magnetic field acting on the conducting electrons, highlights the high potential of the triangular lattice antiferromagnet and provides a unique platform for functional thin-film devices composed of NiAs-type derivative Cr chalcogenides and pnictides.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called “decentralized science (DeSci)”. Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

We report on efficient spin current generation at room temperature in rutile-type WO2 grown on an Al2O3(0001) substrate. The optimal WO2 film has a (010)-oriented monoclinically distorted rutile structure with metallic conductivity due to 5d2 electrons, as characterized by x-ray diffraction, electronic transport, and x-ray photoelectron spectroscopy. By conducting harmonic Hall measurement in a Ni81Fe19/WO2 bilayer, we estimate two symmetries of the spin–orbit torque (SOT), i.e., dampinglike (DL) and fieldlike ones, to find that the former is larger than the latter. By comparison with the Ni81Fe19/W control sample, the observed DL SOT efficiency ξDL of WO2 (+0.174) is about two-thirds of that of W (−0.281) in magnitude, with a striking difference in their signs. The magnitude of the ξDL of WO2 exhibits a comparable value to those of widely reported Pt and Ta, and Ir oxide IrO2. The positive sign of the ξDL of WO2 can be explained by the preceding theoretical study based on the 4d oxides. These results highlight that the epitaxial WO2 offers a great opportunity of rutile oxides with spintronic functionalities, leading to future spin–orbit torque-controlled devices.

Abstract One major source of exhaustion for researchers is the redundant paperwork of three different documents—research papers, ethics review applications, and research grant applications—for the same research plan. This is a wasteful and redundant process for researchers, and it has a more direct impact on the career development of early-career researchers. Here, we propose a trinity review system based on Registered Reports that integrates scientific, ethics, and research funding reviews. In our proposed trinity review system, scientific and ethics reviews are undertaken concurrently for a research protocol before running the study. After the protocol is approved in principle through these review processes, a funding review will take place, and the researchers will begin their research. Following the experiments or surveys, the scientific review will be conducted on a completed version of the paper again, including the results and discussions (i.e., the full paper), and the full paper will be published once it has passed the second review. This paper provides the brief process of the trinity review system and discusses the need for and benefits of the proposed system. Although the trinity review system only applies to a few appropriate disciplines, it helps improve reproducibility and integrity.

Direct observation of carbon dioxide dissociation provides an origin of catalytic conversion for industrial chemical reactions. Here, the authors reveal their molecular interactions on the rhodium catalyst at near-ambient pressure by interface science techniques and computational calculations.

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

We report on spin Hall magnetoresistance (SMR) in bilayers composed of Pt and magnetic insulator MgFe _2 O _4 (MFO) with spinel structure. The Pt thickness dependence of the SMR reveals that annealing of the MFO surface before depositing the Pt layer is crucial for a large SMR with better interface quality. We also found that oxygen pressure during the MFO growth hardly affects the SMR, while it influences the magnetic property of the MFO film. Our findings provide important clues to further understanding the spin transport at interfaces containing magnetic insulators, facilitating development of low power consumption devices.

Purpose: To report the clinical findings of the patients with retinal pigment epithelium (RPE) aperture secondary to age-related macular degeneration (AMD). Methods: A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of patients with RPE aperture accompanied by AMD was performed. We investigated age, best-corrected visual acuity (BCVA), images of spectral domain optical coherence tomography, short-wave fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography, and retinal sensitivity measured with microperimetry. The change in visual acuity or the area of the aperture during the follow-up period was analyzed. Results: Five eyes of 5 patients (4 men, one woman) were included in the analysis. The mean age at presentation was 78.6 ± 9.1 years. The average length of follow-up was 23.6 ± 17.9 months. The RPE apertures appeared as round, either at the apex or at the base of PED, with no evidence of accompanying CNV but subretinal detachment (SRD) above the aperture. On FAF, the apertures appeared as sharply demarcated round areas of hypoautofluorescence. The FA revealed sharply demarcated round areas of window defects in the early and mid-phase with leakage in the late phase corresponding to SRD. The area of apertures enlarged during the follow-up period. Mean BCVA got worse from 0.20 logMAR at the initial presentation to 0.39 logMAR at the last visit. The retinal sensitivity was reduced but partly preserved above the area of aperture. Conclusions and importance: RPE aperture was found in some patients with drusenoid PED secondary to AMD. It enlarged during follow-up. Visual acuity was declined. Retinal sensitivity was decreased but partly preserved.

Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We identified that meclizine hydrochloride inhibited FGFR3 signaling in various chondrocytic cells and promoted longitudinal bone growth in mouse model of ACH. Meclizine has safely been used for more than 50 years, but it lacks the safety data for repeated administration and pharmacokinetics (PK) when administered to children. We performed a phase Ia study to evaluate the PK and safety of meclizine administered orally to ACH children. Twelve ACH children aged from 5 to younger than 11 years were recruited, and the first 6 subjects received once a day of meclizine in the fasted condition, subsequent 6 subjects received twice a day of meclizine in the fed condition. Meclizine was well tolerated in ACH children with no serious adverse events. The mean Cmax, Tmax, AUC0-24h, t1/2 during 24 hours in the fasted condition were 130 ng/mL, 1.7 hours, 761 ng·h/mL, and 8.5 hours respectively. The simulation of repeated administration of meclizine for 14 days demonstrated that plasma concentration apparently reached steady state around 10 days after the first dose both at once a day and twice a day administration. The AUC0-10h of the fasting and fed condition were 504 ng·h/mL and 813 ng·h/mL, respectively, indicating exposure of meclizine increased with the diet. Although higher drug exposure was confirmed in ACH children compared to adults, a single administration of meclizine seemed to be well tolerated.

Abstract Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db compared with control. Given downregulation of Tgfb1 expression by folic acid, antioxidant Tempol reversed DNA demethylation, with increased and decreased recruitment of DNMT1 and USF1 to the promoter, resulting in decreased Tgfb1 expression in db/db mice. Addition of H2O2 to mesangial cells induced DNA demethylation and upregulated Tgfb1 expression. Finally, Tempol attenuated mesangial fibrosis in db/db mice. We conclude that aberrant DNA methylation of Tgfb1 due to ROS overproduction play a key to mesangial fibrosis during DN progression.

Dzyaloshinskii–Moriya interaction (DMI) is one of the key factors to control the chiral spin textures in spintronic applications. Here the authors demonstrate the correlation of the DMI with the anisotropy of the orbital magnetic moment and magnetic dipole moment in Pt/Co/MgO ultrathin trilayers.

The surface chemical states of Pd(100) during CO oxidation were investigated using ambient pressure x-ray photoelectron spectroscopy and mass spectroscopy. Under the reactant ratio of CO/O2 = 0.1, i.e. an oxygen-rich reaction condition, the formation of surface oxides was observed with the onset of CO oxidation reaction at T = 525 K. As the reactant ratio (CO/O2) increased from 0.1 to 1.0, ∼ 90 % surface oxides remains on surface during the reaction. Upon the formation of surface oxides, the core level shift of oxygen gas phase peak was observed, indicating that change of surface work function. As CO oxidation takes places, i.e. making a transition from CO covered surface to the oxidic surface, the work functions of surface oxide on Pd(100) and Pt(110) display opposite behavior.

Magnetic properties in ferrimagnetic GdCo alloy films with bulk perpendicular magnetic anisotropy (PMA) are investigated as a function of annealing temperature (Tanneal) and annealing time for several capping layers. Magnetic properties in films capped by TaOx vary markedly with Tanneal; the saturation magnetization and coercivity vary progressively with increasing Tanneal up to 300°C, and above that temperature, PMA is lost abruptly. By comparing the annealing temperature dependence for Co-dominated and Gd-dominated compositions close to the magnetization compensation point, the data are readily explained by preferential oxidation of Gd during annealing. When films are capped by a Ta/Pt bilayer, the film properties are stable up Tanneal = 300 °C, indicating that oxidation at high temperatures is effectively blocked, but the abrupt loss of PMA for Tanneal > 300 °C is still observed. X-ray diffraction measurement reveals that the amorphous structure of the films remains the same after high-temperature annealing that is sufficient to remove PMA, indicating that crystallization from the amorphous phase is not responsible for the lack of PMA. Instead, our results suggest that high annealing temperatures may cause segregation of Co and Gd atoms in the films, which reduces anisotropic pair-pair correlations responsible for the observed bulk PMA in the as-grown state.

In an isostructural series of anion radical salts β′-(Me4-xEtxZ)[Pd(dmit)2]2 (Z = P, As, Sb; x = 0, 1, 2), [Pd(dmit)2]2− units form a two-dimensional Mott insulator layer with a quasi-isosceles triangular lattice. The anisotropy of the triangular lattice is characterized by a ratio of interdimer transfer integrals, t′/t. The crystal structures of EtMe3Sb, Me4Sb, Me4As, and Et2Me2As salts were determined in the range of 5–295 K by the single crystal X-ray diffraction technique. Interdimer transfer integrals, Fermi surface, and band structures at low temperatures were calculated by the tight binding method and the first-principles density-functional theory (DFT) method based on experimentally obtained crystal structures. Interdimer transfer integrals increased with lowering temperature. At 5 K, the ratio t′/t decreased by about 15% from the room temperature value in every salt. The relationship between the transfer integrals and interdimer S⋯S distances indicated that the change of the t′/t value with temperature was due to a thermal contraction, rather than the arch-shaped molecular distortion of the Pd(dmit)2 molecule associated with the cation dependence of t′/t.

Background: The COVID-19 pandemic has led to instructions and suggestions from governments and experts to maintain social (physical) distance between people to prevent aerosol transmission of the virus, which is now becoming the norm. Thus, we examined whether the pandemic extended the distance between personal belongings. Methods: We recruited 68 university students and instructed them to place their belongings on a long table following another participant (i.e., confederate). We measured the physical distance between the two belongings (i.e., the participant’s and the confederate’s). We collected data between June 10, 2022 and January 23, 2023. Pre-pandemic data was from Ariga (2016). Analysis was completed with one-tailed t-tests. Results: Compared with the pre-pandemic results, via one-tailed t-test, the distance between the two belongings during the pandemic was significantly longer. Our results supported the hypothesis that the psychological framework for processing people’s belongings has dramatically changed during this pandemic. Conclusion: This change may have been driven by social distancing practices or an increase in perceived vulnerability to disease. Our results provide new implications for future public spatial design, in other words, not only the distance between people, but also the distance between their belongings.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called “decentralized science (DeSci)”. Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called “decentralized science (DeSci)”. Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

Background: The COVID-19 pandemic has led to instructions and suggestions from governments and experts to maintain social (physical) distance between people to prevent aerosol transmission of the virus, which is now becoming the norm. Thus, we examined whether the pandemic extended the distance between personal belongings. Methods: We recruited 68 university students and instructed them to place their belongings on a long table following another participant (i.e., confederate). We measured the physical distance between the two belongings (i.e., the participant’s and the confederate’s). We collected data between June 10, 2022 and January 23, 2023. Pre-pandemic data was from Ariga (2016). Analysis was completed with one-tailed t-tests. Results: Compared with the pre-pandemic results, via one-tailed t-test, the distance between the two belongings during the pandemic was significantly longer. Our results supported the hypothesis that the psychological framework for processing people’s belongings has dramatically changed during this pandemic. Conclusion: This change may have been driven by social distancing practices or an increase in perceived vulnerability to disease. Our results provide new implications for future public spatial design, in other words, not only the distance between people, but also the distance between their belongings.

BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2- knockout mice (lcn2 KO) fed with low-Na diet (0Na). RESULTS: we show that NGAL plasma levels positively correlate with systolic blood pressure, whereas they negatively correlate with urinary Na excretion in subjects of the STANISLAS cohort. Prolonged feeding of lcn2 KO mice with a 0Na diet induced lower systolic blood pressure than that of the control group (wildtype), suggesting a role for NGAL/lcn2 in Na-balance homeostasis. Short-term or prolonged 0Na increased Na-Cl cotransporter (NCC) phosphorylation in the cortex of wildtype mice, which was prevented in lcn2 KO mice. Recombinant mouse lcn2 injections in lcn2 KO mice induced NCC phosphorylation in the kidney cortex, associated with decreased urinary Na excretion. Ex vivo experiments using kidney slices from lcn2 KO mice showed increased NCC phosphorylation by recombinant murine lcn2. In addition, recombinant murine lcn2 induced activation of CamK2ß (calcium/calmodulin-dependent protein kinase II ß subunit) phosphorylation in lcn2 KO mice and in kidney slices, providing an underlying mechanism involved in lcn2-induced NCC phosphorylation. Indeed, the inhibition of CamK2ß prevented NCC phosphorylation induced by recombinant lcn2 in kidney slices. CONCLUSIONS: we highlight a novel role of NGAL/lcn2 as a modulator of the activity of the renal sodium transporter NCC affecting salt-sensitive blood pressure. [ABSTRACT FROM AUTHOR]

Purpose To investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT). Design Retrospective consecutive observational cohort study. Methods We included highly myopic eyes (refractive error =-8.0 dioptres or axial length of =26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis. Results Twenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (p<0.0001). The average entropy at the RPE in the highly myopic eyes was significantly lower than in the control (p<0.0001). Univariate analysis followed by multivariate analysis showed that besides age, axial length or choroidal thickness, RPE entropy was independently associated with retinal sensitivity (β=4.4; 95% CI 0.5 to 8.3; p=0.03). Conclusions Decreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA. [ABSTRACT FROM AUTHOR]

Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown. In the normal kidney, Pxr was selectively expressed in the proximal tubular cells with demethylation in the promoter DNA. In db/db mice, significant increases in Pxr mRNA, further demethylation of DNA, and stimulatory histone marks in the promoter were observed. Epigenetic changes are likely to play a causative role in PXR induction, since a DNA methyltransferase inhibitor increased PXR mRNA in cultured human proximal tubular cells. Administration of a PXR agonist increased mRNA levels of solute carrier organic anion transporter family member 2B1 (Slco2b1), a xenobiotic transporter; response gene to complement 32 (Rgc32), a molecule known to exert fibrotic effects in the kidney; and phosphoenolpyruvate carboxykinase 1 (Pck1), a gluconeogenic enzyme in the kidney. The expressions of these genes were inhibited by PXR small interfering RNA in cultured proximal tubular cells. Increased mRNA levels of Slco2b1, Rgc32, and Pck1 were also observed in the kidney of db/db mice. These data indicate that PXR is upregulated in the diabetic kidney with aberrant epigenetic modifications and may modulate the course of diabetic kidney disease through the activation of these genes. [ABSTRACT FROM AUTHOR]

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na+-Cl- cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na+-Cl- cotransporter phosphorylation. Accordingly, a Na+-Cl- cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na+-Cl- cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na+-Cl- cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess. [ABSTRACT FROM AUTHOR]

Purpose: To assess the relationship between combined serum lutein and zeaxanthin (L+Z) concentration and macular pigment optical density (MPOD), and to investigate the effect of L+Z+docosahexaenoic acid (DHA) dietary supplementation on the spatial distribution of MPOD. Methods: Twenty healthy fellow eyes with unilateral wet age-related macular degeneration or chronic central serous chorioretinopathy were included. All participants received a dietary supplement for 6 months that contained 20 mg L, 1 mg Z, and 200 mg DHA. The best-corrected visual acuity and contrast sensitivity (CS) were measured at baseline and at 1, 3, and 6 months. Serum L+Z concentrations were measured at baseline and at 3 months. MPOD was calculated at each time point using fundus autofluorescent images. Results: Serum L+Z concentration was correlated with MPOD at 1°-2° eccentricity at baseline (r=0.63, P=0.003) and 3 months (r=0.53, P=0.015). Serum L+Z concentration increased by a factor of 2.3±1.0 (P<0.0001). At 6 months, MPOD was significantly higher compared to the baseline level at 0°-0.25° (P=0.034) and 0.25°-0.5° (P=0.032) eccentricity. CS improved after 3 or 6 months of L+Z+DHA supplementation (P<0.05). Conclusion: Juxtafoveal MPOD was associated with serum L+Z concentration. Foveal MPOD was increased by L+Z+DHA dietary supplementation. [ABSTRACT FROM AUTHOR]

We report the effect of the rare earth metal Gd on current-induced spin-orbit torques (SOTs) in perpendicularly magnetized Pt/Co/Gd heterostructures, characterized using harmonic measurements and spin-torque ferromagnetic resonance (ST-FMR). By varying the Gd metal layer thickness from 0 nm to 8 nm, harmonic measurements reveal a significant enhancement of the effective fields generated from the Slonczewski-like and field-like torques. ST-FMR measurements confirm an enhanced effective spin Hall angle and show a corresponding increase in the magnetic damping constant with increasing Gd thickness. These results suggest that Gd plays an active role in generating SOTs in these heterostructures. Our finding may lead to spin-orbitronics device application such as non-volatile magnetic random access memory, based on rare earth metals. [ABSTRACT FROM AUTHOR]

We investigate the in-plane field dependence of current-induced magnetic domain wall motion in asymmetric Co/Ni nanowires. The application of an in-plane field changed the direction of domain wall motion. In a systematic study, by varying the magnetic layer thickness, we show that the in-plane field induces a crossover from spin Hall torque to adiabatic spin-transfer torque for the magnetic domain wall motion. Furthermore, the dependence of the threshold current density on the in-plane longitudinal field provides a way for determining the strength of the Dzyaloshinskii-Moriya interaction. [ABSTRACT FROM AUTHOR]

We propose the fiber-based interferometric measurement of tens-of-nanometer-scale dynamic displacement that uses phase-modulated reference light with stepwise control of the operation point of modulation (OPM). It requires neither the pre-adjustment of the OPM nor feedback control for the path-length difference of the interferometer. Quantitative evaluation of the system is performed by using a phase modulator as a sample to simulate mechanical vibration. The dynamic displacement for 100-kHz vibration with an amplitude of 19 nm is measured even when the fiber interferometer is intentionally perturbed, which confirms the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

The temperature dependence of spin-orbit torques (SOTs) and spin-dependent transport parameters is measured in bilayer Ta/TbCo ferrimagnetic alloy films with bulk perpendicular magnetic anisotropy. We find that the dampinglike (DL)-SOT effective field diverges as temperature is swept through the magnetic compensation temperature (TM), where the net magnetization vanishes due to the opposing contributions from the Tb and Co sublattices. We show that DL-SOT scales with the inverse of the saturation magnetization (Ms), whereas the spin-torque efficiency is independent of the temperature-dependent Ms. Our findings provide insight into spin transport mechanisms in ferrimagnets and highlight low-Ms rare-earth/transition-metal alloys as promising candidates for SOT device applications. [ABSTRACT FROM AUTHOR]

We have investigated the temperature dependence of current-induced magnetic domain wall (DW) motion in a Co/Ni nanowire, where the spin Hall torque is responsible for the DW motion. The threshold current density (Jth) for DW motion is found to be dependent on the temperature T and the depinning magnetic field Hdep, which is different from the symmetric Co/Ni system where Jth is insensitive to T and Hdep. This result indicates that an extrinsic pinning governs the DW motion when it is driven by the spin Hall torque. Our work therefore suggests that reducing the extrinsic pinning is a key for achieving a low-power-consumption device. [ABSTRACT FROM AUTHOR]

The behavior of a three-terminal domain wall (DW) device with a perpendicularly magnetized CoFeB free layer and underlying hard magnets was investigated. In a Ta/CoFeB/MgO free layer without hard magnets, a current-induced DW motion in the direction of electron flow was observed. In a device having a hard magnet under each end of the free layer, we found that a DW nucleated by injecting current played an important role in the switching of magnetization. We concluded that the switching of magnetization in our device is due to the displacement in the direction of electron flow of the DW created by current. After deriving the principle of operation through experiments, we describe a way to reduce the current required for writing by increasing the thickness of the hard magnets. [ABSTRACT FROM AUTHOR]

We report a systematic study of the DW motion in perpendicularly magnetized Co/Ni nanowires having different thicknesses with structure inversion asymmetry. The transition from bulk to interfacial effects is confirmed as a change in the DW motion direction at a reduced layer thickness. The bias field dependence reveals that the adiabatic spin transfer torque (STT) dominates the DW motion in the thick regime, whereas the interfacial torque originating from the spin Hall effect (SHE) is responsible for the DW motion with a fixed DW chirality induced by the Dzyaloshinskii–Moriya interaction (DMI) in the thin regime. [ABSTRACT FROM AUTHOR]

Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II-induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II-induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II-induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A2 analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation. [ABSTRACT FROM AUTHOR]