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Abstract Single‐nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle‐related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p

A specific-pathogen-free (SPF) chicken colony was maintained with successive groups a month apart in age. The absence of specific pathogens, including chicken anemia virus (CAV), was confirmed through periodic serological tests for each group. However, some groups became CAV seropositive. The procedures of removing seropositive and the adjacent seronegative chickens followed with chemically disinfecting the housing did not halt CAV outbreaks. The full genome sequence of the CAV strain that appeared was closely related to low-virulence isolates in China. The outbreaks of CAV decreased with an increase in the seropositive chicken population, indicating that the progeny is protected from CAV infection by maternal anti-CAV antibodies. The persistence of CAV in erythroid and lymphoid tissues or reproductive tissues from CAV seropositive chickens was examined in chickens of various ages using polymerase chain reaction (PCR). Since a low persistence of CAV was observed in the colony, we isolated eggs from CAV seropositive hens through artificial insemination using semen collected from roosters and confirmed as CAV-free by PCR. Fertilized eggs were transferred to a new SPF facility and used for generating CAV-free progeny. To date, chickens reared in the new facility have been CAV-free for longer than two years. Redirection of eggs from seropositive hens was an effective means of eliminating CAV from chickens.

BackgroundIncreasing physical activity improves glycemic control in patients with type 2 diabetes (T2D). Mobile health (mHealth) interventions have been proven to increase exercise, but engagement often fades with time. As the use of health behavior theory in mHealth design can increase effectiveness, we developed StepAdd, an mHealth intervention based on the constructs of social cognitive theory (SCT). StepAdd improves exercise behavior self-efficacy and self-regulation through the use of goal-setting, barrier-identifying, and barrier-coping strategies, as well as automatic feedback functions. A single-arm pilot study of StepAdd among 33 patients with T2D showed a large increase in step count (mean change of 4714, SD 3638 daily steps or +86.7%), along with strong improvements in BMI (mean change of −0.3 kg/m2) and hemoglobin A1c level (mean change of −0.79 percentage points). ObjectiveIn this study, we aim to investigate the efficacy and safety of StepAdd, an mHealth exercise support system for patients with T2D, via a large, long, and controlled follow-up to the pilot study. MethodsThis is a randomized, open-label, multicenter study targeting 160 patients with T2D from 5 institutions in Japan with a 24-week intervention. The intervention group will record daily step counts, body weight, and blood pressure using the SCT-based mobile app, StepAdd, and receive feedback about these measurements. In addition, they will set weekly step count goals, identify personal barriers to walking, and define strategies to overcome these barriers. The control group will record daily step counts, body weight, and blood pressure using a non–SCT-based placebo app. Both groups will receive monthly consultations with a physician who will advise patients regarding lifestyle modifications and use of the app. The 24-week intervention period will be followed by a 12-week observational period to investigate the sustainability of the intervention’s effects. The primary outcome is between-group difference in the change in hemoglobin A1c values at 24 weeks. The secondary outcomes include other health measures, measurements of steps, measurements of other behavior changes, and assessments of app use. The trial began in January 2023 and is intended to be completed in December 2025. ResultsAs of September 5, 2023, we had recruited 44 patients. We expect the trial to be completed by October 8, 2025, with the follow-up observation period being completed by December 31, 2025. ConclusionsThis trial will provide important evidence about the efficacy of an SCT-based mHealth intervention in improving physical activities and glycemic control in patients with T2D. If this study proves the intervention to be effective and safe, it could be a key step toward the integration of mHealth as part of the standard treatment received by patients with T2D in Japan. Trial RegistrationJapan Registry of Clinical Trials (JRCT) jRCT2032220603; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2032220603 International Registered Report Identifier (IRRID)DERR1-10.2196/53514

Drag between the electron and the hole layers formed in a silicon-on-insulator MOSFET, with the estimated interlayer distance as small as 18 nm, is investigated. The drag resistance is measured at 10 K and mapped on the plane defined by the electron and hole densities. Analysis shows that the Coulomb drag predominates over the competing virtual-phonon drag. The observed drag resistance is as large as 10 ^3 -10 ^4 Ω, indicating strong Coulomb interaction between the electron and hole layers.

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle–brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were −3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and −0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = −0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

Abstract The Hokkaido Eastern Iburi Earthquake (M = 6.7) occurred on Sep. 6, 2018 in the southern part of Central Hokkaido, Japan. Since Paleogene, this region has experienced the dextral oblique transpression between the Eurasia and North American (Okhotsk) Plates and the subsequent collision between the Northeast Japan Arc and the Kuril Arc due to the oblique subduction of the Pacific Plate. This earthquake occurred beneath the foreland fold-and-thrust belt of the Hidaka Collision zone developed by the collision process, and is characterized by its deep focal depth (~ 37 km) and complicated rupture process. The reanalyses of controlled source seismic data collected in the 1998–2000 Hokkaido Transect Project revealed the detailed structure beneath the fold-and-thrust belt, and its relationship with the aftershock activity of this earthquake. Our reflection processing using the CRS/MDRS stacking method imaged for the first time the lower crust and uppermost mantle structures of the Northeast Japan Arc underthrust beneath a thick (~ 5–10 km) sedimentary package of the fold-and-thrust belt. Based on the analysis of the refraction/wide-angle reflection data, the total thickness of this Northeast Japan Arc crust is only 16–22 km. The Moho is at depths of 26–28 km in the source region of the Hokkaido Eastern Iburi Earthquake. Our hypocenter determination using a 3D structure model shows that most of the aftershocks are distributed in a depth range of 7–45 km with steep geometry facing to the east. The seismic activity is quite low within the thick sediments of the fold–thrust belt, from which we find no indication on the relationship of this event with the shallow (

Background: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments. Methods: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension. Results: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = −0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022). Conclusion: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.

Power dissipation is usually unavoidable in transistor channels due to the inelastic scattering of electrons. Here, Firdaus et al. propose a nanoscaled silicon electron-aspirator to remove this constraint, which shows enhanced current output by 3 times at 8 K without additional power supply.

The study of Maxwell's demon provides a link between information thermodynamics and modern electronics. Using integrated nanometer-scale transistors in a single electron box configuration, Chidaet al., demonstrate the extraction of electrical power by Maxwell’s demon.

In the original publication of this article (Iwasaki et al. 2019), the author name ‘Matsubara Makoto’ in author list is not correct. The correct name should be ‘Makoto Matsubara’.

Axon guidance molecules play an important role in regulating proper neuronal networking during neuronal development. They also have non-neuronal properties, which include angiogenesis, inflammation, and tumor development. Semaphorin 3F (SEMA3F), a member of the class 3 semaphorins, was initially identified as an axon guidance factor, that repels axons and collapses growth cones. However, SEMA3F has similar effects on endothelial cells (ECs) and tumor cells. In this review, we discuss the novel molecular mechanisms underlying SEMA3F activity in vascular and tumor biology. Recent evidence suggests that SEMA3F functions as a PI3K-Akt-mTOR inhibitor in mammalian cells, including T cells, ECs, and tumor cells. Therefore, SEMA3F may have broad therapeutic implications. We also discuss the key role of axon guidance molecules as regulators of the tumor microenvironment. Netrin-1, a chemoattractant factor in the neuronal system, promotes tumor progression by enhancing angiogenesis and metastasis. Moreover, our recent studies demonstrate that netrin-1/neogenin interactions augment CD4+ T cell chemokinesis and elicit pro-inflammatory responses, suggesting that netrin-1 plays a key role in modulating the function of a tumor and its surrounding cells in the tumor microenvironment. Overall, this review focuses on SEMA3F and netrin-1 signaling mechanisms to understand the diverse biological functions of axon guidance molecules.

To assess the genetic diversity of domestic Japanese quail (Coturnix japonica) populations, and their genetic relationships, we examined mitochondrial DNA (mtDNA) D-loop sequences and microsatellite markers for 19 Japanese quail populations. The populations included nine laboratory lines established in Japan (LWC, Quv, RWN, WE, AWE, AMRP, rb-TKP, NIES-L, and W), six meat-type quail lines reimported from Western countries (JD, JW, Estonia, NIES-Br, NIES-Fr, and NIES-Hn), one commercial population in Japan, and three wild quail populations collected from three Asian areas. The phylogenetic tree of mtDNA D-loop sequences revealed two distinct haplotype groups, Dloop-Group1 and Dloop-Group2. Dloop-Group1 included a dominant haplotype representing most of the quail populations, including wild quail. Dloop-Group2 was composed of minor haplotypes found in several laboratory lines, two meat-type lines, and a few individuals in commercial and wild quail populations. Taking the breeding histories of domestic populations into consideration, these results suggest that domestic quail populations may have derived from two sources, i.e., domestic populations established before and after World War II in Japan. A discriminant analysis of principal components and a Bayesian clustering analysis with microsatellite markers indicated that the domestic populations are clustered into four genetic groups. The two major groups were Microsat-Group1, which contained WE, and four WE-derived laboratory lines (LWC, Quv, RWN, and AWE), and Microsat-Group2 consisting of NIES-L, JD, JW, Estonia, NIES-Br, NIES-Fr, NIES-Hn, W, and commercial and wild populations. The remaining two lines (AMRP and rb-TKP) were each clustered into a separate clade. This hierarchical genetic difference between domestic quail populations is attributed to the genetic background derived from two different genetic sources-the pre-war and post-war populations-which is well supported by their breeding histories.

BACKGROUND: Persistent postoperative pain has a significant relationship with patient health and satisfaction.

The WW domain containing E3 ubiquitin protein ligase 1 (WWP1), an enzyme to degrade unneeded or damaged proteins, was recently identified as the responsible for chicken muscular dystrophy. Despite of intensive studies on oncogenic characters, the role of WWP1 to muscular diseases has not yet been fully understood. Since it is generally known that the switching of myosin heavy chain (MyHC) isoforms from neonatal isoform to adult one is inhibited in chicken muscular dystrophy, we transfected either of wild and mutated types of WWP1 gene into C2C12 cells to monitor the expression pattern of muscle-differentiation markers including MyHCs by real-time PCR. Excessive WWP1 expression enhanced the expression of the MyHC Ia gene but lowered the expression of the MyHC IIb gene. On the other hand, mutated WWP1 gene transfected into myoblasts was distinct from these cases in that the MyHC gene or genes expression inhibited the normal myoblast differentiation. The present data suggest that WWP1 promotes myoblast differentiation from embryonic into fast twitch phase while a mutation in WWP1 results to retain slow and fast twitch isoforms characteristic of dystrophic fast twitch muscles.

The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is classified into one of ubiquitin ligases which play an important role in ubiquitin-proteasome pathway. Previously, we identified the WWP1 gene as a candidate gene of chicken muscular dystrophy by linkage analysis and sequence comparison. However, the mechanism causing pathological changes and underlaying gene function remains elucidated. In the present study, we analyzed the WWP1 gene expression in various muscles and tissues of normal chickens, and compared with those from muscular dystrophic chickens. Two mRNA isoforms were detected in all tissues examined and revealed almost equal expression level. The WWP1 expression of dystrophic chickens was decreased in almost all skeletal muscles including unaffected muscles. These data indicate that there might not be a causal relationship between the alteration of WWP1 expression level and the severity of muscular dystrophy.

In previous studies, two types of offspring were generated from germline chimera between NH-413 strain (donor) and White Leghorn L-M strain (recipient). Phenotype and symptom of type-I offspring were quite similar to that of the NH-413 strain. In the other offspring of type-II, feather color showed mixture of white and brown and the symptom was not dominantly indicated.In the present studies, sexually matured males and females of the type-I were mated each other. Form these mating, chickens manifesting completely same phenotype to that of the donor NH-413 strain; brown feather color and symptoms of muscular dystrophy, were regenerated. Therefore, complete regeneration of the muscular dystrophy chickens could be achieved by mating males and female offspring derived from the germline chimeras. Fertility, hatchability and survival rate of these regenerated offspring were significantly improved as compared to that of the original NH-413 strain.The established strategies should be one of the useful systems to regenerate chickens with muscular dystrophy.

A novel strategy has been developed to generate muscular dystrophy chickens by means of germline chimeras. Donor embryos were obtained from the New Hampshire chicken; NH-413 strain which have genes responsible for Fukuyama type muscular dystrophy (Saito et al., 2005). Donor cells were isolated from the center of area pellucida of the blastoderms. Recipient embryos were obtained from White Leghorn chicken; Line-M. The generated chimeric chickens had the donor derived brown plumage in the down in some extent, suggesting that the cells containing muscular dystrophy were introduced into the chimeras. These chimeric chickens have been raised until sexual maturity. The chimeric chickens were back-crossed to donor strain; the NH-413 strain. The phenotype of some of the offspring was very similar to that of the donor strain. The offspring showed some characters typical to the muscular dystrophy.It was suggested that the donor derived NH-413 strain offspring was generated. The established system should be one of the powerful strategies for breeding and regeneration of the muscular dystrophy chickens.

Series-connected triple quantum dots were fabricated by a simple two-step oxidation technique using the pattern-dependent oxidation of a silicon nanowire and an additional oxidation of the nanowire through the gap of the fine gates attached to the nanowire. The characteristics of multi-dot single-electron devices are obtained. The formation of each quantum dot beneath an attached gate is confirmed by analyzing the electrical characteristics and by evaluating the gate capacitances between all pairings of gates and quantum dots. Because the gate electrode is automatically attached to each dot, the device structure benefits from scalability. This technique promises integrability of multiple quantum dots with individual control gates.

The objective of this work was to develop polymorphic microsatellite markers derived from Japanese quail embryonic and cardiac cDNA libraries and to locate these markers on Kobe-NIBS Japanese quail (KNQ) linkage map constructed mainly by AFLP markers in previous study. Of the 86 positive clones, 51 clones were unique and identified as genes or ESTs by BLAST searches, and 25 from 51 clones were possible to design the PCR primers after partial sequencing. Only six markers were polymorphic and used by linkage analysis in KNQ resource family. These markers were mapped on four linkage groups, JQG 1, JQG 9, JQG 19 and JQG 66, and then these linkage groups were assigned to chromosome of Japanese quail, CJA 2, CJA 14, CJA 17 and CJA 23, respectively. These markers derived from cDNA are useful and powerful tool, and contribute to the comparative map between Japanese quail and the other species.

A black plumage color mutant (BPC) was described in this paper. The BPC quail was a dark colored bird. The chick down feathers on the back and head were black ending with a brown tip. The face and throat were cream-yellow and the ventral surface was a mixture of gray and cream-yellow. The beak and shanks were darkly pigmented but some toes were yellow while others had spotted areas of pigmentation. When the birds reached to maturity, both males and females had pigmentation, and the feather appearance of dorsal and ventral surface were basically similar. The dorsal feather pattern was similar to that of wild-type except that the wheat-straw shafting was absent. Some of the BPC quails showed small areas of white feather at the junction of the upper and lower beaks and in the throat under the lower beak. To clarify the mode of inheritance of the BPC characters, mating experiments were performed. The segregation data for F1, F2 and backcross generations were analyzed. Genetic analysis showed that the BPC was controlled by an autosomal recessive gene. Therefore, a gene symbol “rb” was proposed.