Search

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semisupercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three nondisease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain ''beneficial'' patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations. [ABSTRACT FROM AUTHOR]

Eye contact and pointing are typical gestures in order to direct another individual's attention toward a target. We previously investigated on Japanese monkeys whether joint attention ability encouraged by eye contact and pointing was associated with the imitation of human's actions. The monkeys with the joint attention skills showed the imitation of human's actions. In the current study, we investigated on a monkey whether joint attention ability also facilitated the imitation of human body-movements. Results showed that the monkey being taught eye contact and pointing showed the imitation of human body-movements. These results suggest that the monkeys have basic potential for following another individual's motion, and that what imitation expresses depends on where the monkeys are paying attention. Thus, eye contact and pointing are suitable for directing the monkey's attention toward the human. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in psychosocial factors with positive attitudes, such as interpersonal trust, as determinants for Quality-of-life (QOL) or subjective well-being. Despite their longevity, Japanese people report a relatively poor subjective well-being, as well as lower interpersonal trust. Our aim in this study was to evaluate the possible association between interpersonal trust and QOL among Japanese people. Methodology and Principal Findings: Based on the cross-sectional data for Japanese adults (2008), we analyzed the relationship between interpersonal trust and each of four domains of the WHOQOL-BREF. Interpersonal trust was assessed using three scales for trust in people, in human fairness and in human nature. In a total of 1000 participants (mean age: 45 years; 49% women), greater trust was recognized among women (vs. men), those aged 60-69 (vs. 20-29), or the high-income group (vs. low-income). Each of three trust scales was positively correlated with all domains of QOL. Multiple line-arregression models were constructed for each of QOL and the principal component score of the trust scales, adjusted for age, gender, area size of residence, income, education, and occupation. For all QOL domains, interpersonal trust was significantly and positively associated with better QOL with p,0.001 for all four domains including physical, psychological, social, and environmental QOL. Other factors associated with QOL included gender, age class, area size of residence, and income. Education and occupation were not associated with QOL. Conclusions and Significance: Greater interpersonal trust is strongly associated with a better QOL among Japanese adults. If a causal relationship is demonstrated in a controlled interventional study, social and political measures should be advocated to increase interpersonal trust for achieving better QOL. [ABSTRACT FROM AUTHOR]

Hop stunt was a mysterious disorder that first emerged in the 1940s in commercial hops in Japan. To investigate the origin of this disorder, we infected hops with natural Hop stunt viroid (HpSVd) isolates derived from four host species (hop, grapevine, plum and citrus), which except for hop represent possible sources of the ancestral viroid. These plants were maintained for 15 years, then analyzed the HpSVd variants present. Here we show that the variant originally found in cultivated grapevines gave rise to various combinations of mutations at positions 25, 26, 54, 193, and 281. However, upon prolonged infection, these variants underwent convergent evolution resulting in a limited number of adapted mutants. Some of them showed nucleotide sequences identical to those currently responsible for hop stunt epidemics in commercial hops in Japan, China, and the United States. Therefore, these results indicate that we have successfully reproduced the original process by which a natural HpSVd variant naturally introduced into cultivated hops was able to mutate into the HpSVd variants that are currently present in commercial hops. Furthermore, and importantly, we have identified cultivated grapevines as a symptomless reservoir in which HSVd can evolve and be transmitted to hop crops to cause epidemics. [ABSTRACT FROM AUTHOR]

Characterizing relationships between individual body size and trophic niche position is essential for understanding how population and food-web dynamics are mediated by size-dependent trophic interactions. However, whether (and how) intraspecific size-trophic relationships (i.e., trophic ontogeny pattern at the population level) vary with time remains poorly understood. Using archival specimens of a freshwater predatory fish Gymnogobius isaza (Tanaka 1916) from Lake Biwa, Japan, we assembled a long-term (.40 years) time-series of the size-dependence of trophic niche position by examining nitrogen stable isotope ratios (δ15N) of the fish specimens. The size-dependence of trophic niche position was defined as the slope of the relationship between δ15N and log body size. Our analyses showed that the slope was significantly positive in about 60% of years and null in other years, changing through time. This is the first quantitative (i.e., stable isotope) evidence of long-term variability in the size-trophic relationship in a predatory fish. This finding had implications for the fish trophic dynamics, despite that about 60% of the yearly values were not statistically different from the long-term average. We proposed hypotheses for the underlying mechanism of the time-varying size-trophic relationship. [ABSTRACT FROM AUTHOR]

Background: Prenatal human immunodeficiency virus (HIV) testing is essential for the prevention of mother-to-child transmission. However, false-positive results of screening testing are a concern as they may cause unnecessary emotional stress to pregnant women waiting for confirmatory test results. In regions with an extremely low prevalence, the positive predictive values of screening are unacceptably low rate. Here, we propose a HIV screening algorithm consisting of serial two fourth-generation enzyme immunoassays to reduce the number of false-positive screening results. Methodology/Principal Findings: When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive. Confirmatory Western blots and nucleic acid amplification test also showed that one was positive and the remaining 26 were negative; the subject who was positive with the confirmatory tests was identical to the subject who was positive with the second screening test. Thus, by adding the second screening test, the false-positive rate was improved from 0.4% to 0%, and the positive predictive value from 3.7% to 100%, compared with the single screening test. Conclusion: By applying our serial screening algorithm to HIV testing in maternity hospitals, many uninfected pregnant women would not need to receive confirmatory tests and be subjected to emotional turmoil while waiting for their confirmatory test results. This algorithm would be suitable for HIV testing of pregnant women living in low prevalence regions such as Japan. [ABSTRACT FROM AUTHOR]

Background: Perceived spatial intervals between successive flashes can be distorted by varying the temporal intervals between them (the ''tau effect''). A previous study showed that a tau effect for visual flashes could be induced when they were accompanied by auditory beeps with varied temporal intervals (an audiovisual tau effect). Methodology/Principal Findings: We conducted two experiments to investigate whether the audiovisual tau effect occurs in infancy. Forty-eight infants aged 5-8 months took part in this study. In Experiment 1, infants were familiarized with audiovisual stimuli consisting of three pairs of two flashes and three beeps. The onsets of the first and third pairs of flashes were respectively matched to those of the first and third beeps. The onset of the second pair of flashes was separated from that of the second beep by 150 ms. Following the familiarization phase, infants were exposed to a test stimulus composed of two vertical arrays of three static flashes with different spatial intervals. We hypothesized that if the audiovisual tau effect occurred in infancy then infants would preferentially look at the flash array with spatial intervals that would be expected to be different from the perceived spatial intervals between flashes they were exposed to in the familiarization phase. The results of Experiment 1 supported this hypothesis. In Experiment 2, the first and third beeps were removed from the familiarization stimuli, resulting in the disappearance of the audiovisual tau effect. This indicates that the modulation of temporal intervals among flashes by beeps was essential for the audiovisual tau effect to occur (Experiment 2). Conclusions/Significance: These results suggest that the cross-modal processing that underlies the audiovisual tau effect occurs even in early infancy. In particular, the results indicate that audiovisual modulation of temporal intervals emerges by 5-8 months of age. [ABSTRACT FROM AUTHOR]

Background: Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study. Methodology/Principal Findings: Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing. Conclusions/Significance: These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers. [ABSTRACT FROM AUTHOR]

Background: In March 2009, pandemic influenza A(H1N1) (A(H1N1)pdm) emerged in Mexico and the United States. In Japan, since the first outbreak of A(H1N1)pdm in Osaka and Hyogo Prefectures occurred in the middle of May 2009, the virus had spread over 16 of 47 prefectures as of June 4, 2009. Methods/Principal Findings: We analyzed all-segment concatenated genome sequences of 75 isolates of A(H1N1)pdm viruses in Japan, and compared them with 163 full-genome sequences in the world. Two analyzing methods, distancebased and Bayesian coalescent MCMC inferences were adopted to elucidate an evolutionary relationship of the viruses in the world and Japan. Regardless of the method, the viruses in the world were classified into four distinct clusters with a few exceptions. Cluster 1 was originated earlier than cluster 2, while cluster 2 was more widely spread around the world. The other two clusters (clusters 1.2 and 1.3) were suggested to be distinct reassortants with different types of segment assortments. The viruses in Japan seemed to be a multiple origin, which were derived from approximately 28 transported cases. Twelve cases were associated with monophyletic groups consisting of Japanese viruses, which were referred to as micro-clade. While most of the micro-clades belonged to the cluster 2, the clade of the first cases of infection in Japan originated from cluster 1.2. Micro-clades of Osaka/Kobe and the Fukuoka cases, both of which were school-wide outbreaks, were eradicated. Time of most recent common ancestor (tMRCA) for each micro-clade demonstrated that some distinct viruses were transmitted in Japan between late May and early June, 2009, and appeared to spread nation-wide throughout summer. Conclusions: Our results suggest that many viruses were transmitted from abroad in late May 2009 irrespective of preventive actions against the pandemic influenza, and that the influenza A(H1N1)pdm had become a pandemic stage in June 2009 in Japan. [ABSTRACT FROM AUTHOR]

Pancreatic cancer shows very poor prognosis and is the fifth leading cause of cancer death in Japan. Previous studies indicated some genetic factors contributing to the development and progression of pancreatic cancer; however, there are limited reports for common genetic variants to be associated with this disease, especially in the Asian population. We have conducted a genome-wide association study (GWAS) using 991 invasive pancreatic ductal adenocarcinoma cases and 5,209 controls, and identified three loci showing significant association (P-value<5×10-7) with susceptibility to pancreatic cancer. The SNPs that showed significant association carried estimated odds ratios of 1.29, 1.32, and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P-value of 3.30×10-7, 3.30×10-7, and 4.41×10-7; located on chromosomes 6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located within linkage disequilibrium blocks containing genes that have been implicated some roles in the oncogenesis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Previous surveys on the relationship between physicians and pharmaceutical representatives (PRs) have been of limited quality. The purpose of our survey of practicing physicians in Japan was to assess the extent of their involvement in pharmaceutical promotional activities, physician characteristics that predict such involvement, attitudes toward relationships with PRs, correlations between the extent of involvement and attitudes, and differences in the extent of involvement according to self-reported prescribing behaviors. Methods and Findings: From January to March 2008, we conducted a national survey of 2621 practicing physicians in seven specialties: internal medicine, general surgery, orthopedic surgery, pediatrics, obstetrics-gynecology, psychiatry, and ophthalmology. The response rate was 54%. Most physicians met with PRs (98%), received drug samples (85%) and stationery (96%), and participated in industry-sponsored continuing medical education (CME) events at the workplace (80%) and outside the workplace (93%). Half accepted meals outside the workplace (49%) and financial subsidies to attend CME events (49%). Rules at the workplace banning both meetings with PRs and gifts predicted less involvement of physicians in promotional activities. Physicians valued information from PRs. They believed that they were unlikely to be influenced by promotional activities, but that their colleagues were more susceptible to such influence than themselves. They were divided about the appropriateness of low-value gifts. The extent of physician involvement in promotional activities was positively correlated with the attitudes that PRs are a valuable source of information and that gifts are appropriate. The extent of such involvement was higher among physicians who prefer to ask PRs for information when a new medication becomes available, physicians who are not satisfied with patient encounters ending only with advice, and physicians who prefer to prescribe brand-name medications. Conclusions: Involvement in pharmaceutical promotional activities is widespread among practicing physicians in Japan. The extent of such involvement varies according to certain physician characteristics. As a group, they are at risk for influence by promotional activities. [ABSTRACT FROM AUTHOR]

Background: To examine the association between individual-level social capital and physical activity. Methodology/Principal Findings: In February 2009, data were collected in a population-based cross-sectional survey in Okayama city, Japan. A cluster-sampling approach was used to randomly select 4,000 residents from 20 school districts. A total of 2260 questionnaires were returned (response rate: 57.4%). Individual-level social capital was assessed by an item inquiring about perceived trust of others in the community (cognitive dimension of social capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust (17.3%), as well as participation in voluntary groups (structural dimension of social capital), which further distinguished between bonding (8.9%) and bridging (27.1%) social capital. Using logistic regression, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with each domain of social capital. Multiple imputation method was employed for missing data. Among total participants, 68.8% were physically active and 28.9% were inactive. Higher trust was associated with a significantly lower odds of physical inactivity (OR = 0.58, 95% CI = 0.42-0.79) compared with low trust. Both bridging and bonding social capital were marginally significantly associated with lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62-1.00; bonding, OR = 0.71, 95% CI = 0.48- 1.03) compared with lack of structural social capital. Conclusions/Significance: Low individual-level social capital, especially lower trust of others in the community, was associated with physical inactivity among Japanese adults. [ABSTRACT FROM AUTHOR]

Background: A national cross-sectional survey was conducted in Japan. This is because the growing recognition of the social determinants of health has stimulated research on social capital and mental health. In recent years, systematic reviews have found that social capital may be a useful factor in the prevention of mental illness. Despite these studies, evidence on the association between social capital and mental health is limited as there have been few empirical discussions that adopt a multilevel framework to assess whether social capital at the ecological level is associated with individual mental health. The aim of this study was to use the multilevel approach to investigate the association between neighborhood social capital and mental health after taking into account potential individual confounders. Methodology/Principal Findings: We conducted a multilevel analysis on 5,956 individuals nested within 199 neighborhoods. The outcome variable of self-reported mental health was measured by the one dimension of SF-36 and was summed to calculate a score ranging from 0 to 100. This study showed that high levels of cognitive social capital, measured by trust (regression coefficient = 9.56), and high levels of structural social capital, measured by membership in sports, recreation, hobby, or cultural groups (regression coefficient = 8.72), were associated with better mental health after adjusting for age, sex, household income, and educational attainment. Furthermore, after adjusting for social capital perceptions at the individual level, we found that the association between social capital and mental health also remained. Conclusions/Significance: Our findings suggest that both cognitive and structural social capital at the ecological level may influence mental health, even after adjusting for individual potential confounders including social capital perceptions. Promoting social capital may contribute to enhancing the mental health of the Japanese. [ABSTRACT FROM AUTHOR]

Background: Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death. Methods: We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein. Results: Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs. Conclusions: Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD. [ABSTRACT FROM AUTHOR]

Background: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. Principal Findings: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24- month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated bgalactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. Significance: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors. [ABSTRACT FROM AUTHOR]

Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs) in Japanese patients with FHL. Design and Methods: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH) registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. Results: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2) and UNC13D mutation was in 10 (FHL3). In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5). Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. Conclusions: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s) responsible for FHL remain to be identified. [ABSTRACT FROM AUTHOR]

Background: DNA barcoding is expected to be an effective identification tool for organisms with heteromorphic generations such as pteridophytes, which possess a morphologically simple gametophyte generation. Although a reference data set including complete coverage of the target local flora/fauna is necessary for accurate identification, DNA barcode studies including such rich taxonomic sampling on a countrywide scale are lacking. Methodology/Principal Findings: The Japanese pteridophyte flora (733 taxa including subspecies and varieties) was used to test the utility of two plastid DNA barcode regions (rbcL and trnH-psbA) with the intention of developing an identification system for native gametophytes. DNA sequences were obtained from each of 689 (94.0%) taxa for rbcL and 617 (84.2%) taxa for trnH-psbA. Mean interspecific divergence values across all taxon pairs (K2P genetic distances) did not reveal a significant difference in rate between trnH-psbA and rbcL, but mean K2P distances of each genus showed significant heterogeneity according to systematic position. The minimum fail rate of taxon discrimination in an identification test using BLAST (12.52%) was obtained when rbcL and trnH-psbA were combined, and became lower in datasets excluding infraspecific taxa or apogamous taxa, or including sexual diploids only. Conclusions/Significance: This study demonstrates the overall effectiveness of DNA barcodes for species identification in the Japanese pteridophyte flora. Although this flora is characterized by a high occurrence of apogamous taxa that pose a serious challenge to identification using DNA barcodes, such taxa are limited to a small number of genera, and only minimally detract from the overall success rate. In the case that a query sequence is matched to a known apogamous genus, routine species identification may not be possible. Otherwise, DNA barcoding is a practical tool for identification of most Japanese pteridophytes, and is especially anticipated to be helpful for identification of non-hybridizing gametophytes. [ABSTRACT FROM AUTHOR]

When testing association between rare variants and diseases, an efficient analytical approach involves considering a set of variants in a genomic region as the unit of analysis. One factor complicating this approach is that the vast majority of rare variants in practical applications are believed to represent background neutral variation. As a result, analyzing a single set with all variants may not represent a powerful approach. Here, we propose two alternative strategies. In the first, we analyze the subsets of rare variants exhaustively. In the second, we categorize variants selectively into two subsets: one in which variants are overrepresented in cases, and the other in which variants are overrepresented in controls. When the proportion of neutral variants is moderate to large we show, by simulations, that the both proposed strategies improve the statistical power over methods analyzing a single set with total variants. When applied to a real sequencing association study, the proposed methods consistently produce smaller p-values than their competitors. When applied to another real sequencing dataset to study the difference of rare allele distributions between ethnic populations, the proposed methods detect the over-representation of variants between the CHB (Chinese Han in Beijing) and YRI (Yoruba people of Ibadan) populations with small p-values. Additional analyses suggest that there is no difference between the CHB and CHD (Chinese Han in Denver) datasets, as expected. Finally, when applied to the CHB and JPT (Japanese people in Tokyo) populations, existing methods fail to detect any difference, while it is detected by the proposed methods in several regions. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze genotype I hepatitis A virus (HAV) 5' nontranslated region (NTR) sequences from a recent outbreak in South Korea and compare them with reported sequences from Japan. We collected a total of 54 acute hepatitis A patients' sera from HAV genotype I [27 severe disease (prothrombin time INR≥1.50) and 27 mild hepatitis (prothrombin time INR <1.00)], performed nested RT-PCR of 5' NTR of HAV directly sequenced from PCR products (~300 bp), and compared them with each other. We could detect HAV 5'NTR sequences in 19 of the 54 (35.1%) cases [12 of 27 severe cases (44.4%) and 7 of 27 self-limited cases (25.9%)], all of which were subgenotype IA. Sequence analysis revealed that sequences of severe disease had 93.6%-99.0% homology and of self-limited disease 94.3%-98.6% homology, compared to subgenotype IA HAV GBM wild-type IA sequence. In this study, confirmation of the 5'NTR sequence differences between severe disease and mild disease was not carried out. Comparison with Japanese HAV A10 revealed 222C to G or T substitution in 8/12 cases of severe disease and 222C to G or T and 392G to A substitutions in 5/7 and 4/7 cases of mild disease, respectively, although the nucleotide sequences in this study showed high homology (93.6%-100%). In conclusion, HAV 5'NTR subgenotype IA from Korea had relatively high homology to Japanese sequences previously reported from Japan, and this region would be considered one of the antiviral targets. Further studies will be needed. [ABSTRACT FROM AUTHOR]

Divergent natural selection rooted in differential resource use can generate and maintain intraspecific eco-morphological divergence (i.e., resource polymorphism), ultimately leading to population splitting and speciation. Differing bottom environments create lake habitats with different benthos communities, which may cause selection in benthivorous fishes. Here, we document the nature of eco-morphological and genetic divergence among local populations of the Japanese gudgeon Sarcocheilichthys (Cyprinidae), which inhabits contrasting habitats in the littoral zones (rocky vs. pebbly habitats) in Lake Biwa, a representative ancient lake in East Asia. Eco-morphological analyses revealed that Sarcocheilichthys variegatus microoculus from rocky and pebbly zones differed in morphology and diet, and that populations from rocky environments had longer heads and deeper bodies, which are expected to be advantageous for capturing cryptic and/or attached prey in structurally complex, rocky habitats. Sarcocheilichthys biwaensis, a rock-dwelling specialist, exhibited similar morphologies to the sympatric congener, S. v. microoculus, except for body/fin coloration. Genetic analyses based on mitochondrial and nuclear microsatellite DNA data revealed no clear genetic differentiation among local populations within/between the gudgeon species. Although the morphogenetic factors that contribute to morphological divergence remain unclear, our results suggest that the gudgeon populations in Lake Biwa show a state of resource polymorphism associated with differences in the bottom environment. This is a novel example of resource polymorphism in fish within an Asian ancient lake, emphasizing the importance and generality of feeding adaptation as an evolutionary mechanism that generates morphological diversification. [ABSTRACT FROM AUTHOR]

Three Sitophilus species (S. granarius L., S. oryzae L., and S. zeamais Mots.) are closely related based on DNA analysis of their endosymbionts. All are seed parasites of cereal crops and important economic pest species in stored grain. The Sitophilus species that currently exist, including these three species, are generally believed to be endemic to Asia's forested areas, suggesting that the first infestations of stored grain must have taken place near the forested mountains of southwestern Asia. Previous archaeological data and historical records suggest that the three species may have been diffused by the spread of Neolithic agriculture, but this hypothesis has only been established for granary weevils in European and southwestern Asian archaeological records. There was little archeological evidence for grain pests in East Asia before the discovery of maize weevil impressions in Jomon pottery in 2004 using the "impression replica" method. Our research on Jomon agriculture based on seed and insect impressions in pottery continued to seek additional evidence. In 2010, we discovered older weevil impressions in Jomon pottery dating to ca. 10 500 BP. These specimens are the oldest harmful insects in the world discovered at archaeological sites. Our results provide evidence of harmful insects living in the villages from the Earliest Jomon, when no cereals were cultivated. This suggests we must reconsider previous scenarios for the evolution and propagation of grain pest weevils, especially in eastern Asia. Although details of their biology or the foods they infested remain unclear, we hope future interdisciplinary collaborations among geneticists, entomologists, and archaeologists will provide the missing details. [ABSTRACT FROM AUTHOR]

Background: The objective of the present study was to determine whether the morbidity rates of the 2009 pandemic influenza A H1N1 virus (pdmH1N1) varied by age and/or sex. Methods and Findings: Retrospective analysis of 2,024,367 cases of pdmH1N1 was performed using the national surveillance data from influenza sentinel points in Japan. The male-to-female morbidity ratios (M/F ratios) in nineteen age groups were estimated as the primary outcome. The M/F ratios for pdmH1N1 influenza were: >1 in age groups <20 years and ≥80 years (p<0.001); <1 in age groups 20-79 years (p<0.001). This data suggests that males ,20 years of age may be more likely to suffer from pdmH1N1 influenza than females in the same age categories. When the infection pattern for pdmH1N1was compared with that of seasonal influenza outbreaks between 2000 and 2008, the M/F ratio for pdmH1N1 influenza was higher in ages 3-29 years and lower in ages 40-79 years. Because the present study was based on the national surveillance, it was impossible to estimate the morbidity rate for the Japanese population. It is also likely that the data did not capture asymptomatic or mild infections. Conclusions: Although exposure to the pdmH1N1 virus is assumed to be similar in both boys and girls, M/F ratios were >1 in those younger than 20 years. The subsequent reversal of the M/F ratio in the adult generation could be due to several possibilities, including: greater immunity among adult males, more asymptomatic infections among males, less reporting of illness by males, or differences in exposure to the virus and probability of visiting a clinic. These results suggest that the infection and virulence patterns of pdmH1N1 are more complex than previously considered. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E (APOE) e4 allele has been reported to be a risk factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Previous neuropathological studies have demonstrated similar frequencies of the APOE e4 allele in AD and DLB. However, the few ante-mortem studies on APOE allele frequencies in DLB have shown lower frequencies than post-mortem studies. One reason for this may be inaccuracy of diagnosis. We examined APOE genotypes in subjects with AD, DLB, and a control group using the latest diagnostic criteria and MRI, SPECT, and MIBG myocardial scintigraphy. Methods: The subjects of this study consisted of 145 patients with probable AD, 50 subjects with probable DLB, and a control group. AD subjects were divided into two groups based on age of onset: early onset AD (EOAD) and late onset AD (LOAD). All subjects had characteristic features on MRI, SPECT, and/or myocardial scintigraphy. Results: The rate of APOE4 carrier status was 18.3% and the frequency of the e4 allele was 9.7% in controls. The rate of APOE4 carrier status and the frequency of the e4 allele were 47% and 27% for LOAD, 50% and 31% for EOAD, and 42% and 31% for DLB, respectively. Conclusion: The APOE4 genotypes in this study are consistent with previous neuropathological studies suggesting accurate diagnosis of AD and DLB. APOE4 genotypes were similar in AD and DLB, giving further evidence that the e4 allele is a risk factor for both disorders. [ABSTRACT FROM AUTHOR]

Background: Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. Methodology: A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. Results and Conclusions: Our sequence analysis has revealed that both HA-S220T and NA-N248D are major nonsynonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo. [ABSTRACT FROM AUTHOR]

Purpose: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. Methods: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups-336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chisquare test for trend. Age and gender were adjusted using logistic regression analysis. Results: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. Conclusions: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese. [ABSTRACT FROM AUTHOR]

Background: Overall pandemic A (H1N1) influenza vaccination rates remain low across all nations, including Japan. To increase the rates, it is important to understand the motives and barriers for the acceptance of the vaccine. We conducted this study to determine potential predictors of the uptake of A (H1N1) influenza vaccine in a cohort of Japanese general population. Methodology/Principal Findings: By using self-administered questionnaires, this population-based longitudinal study was conducted from October 2009 to April 2010 among 428 adults aged 18-65 years randomly selected from each household residing in four wards and one city in Tokyo. Multiple logistic regression analyses were performed. Of total, 38.1% of participants received seasonal influenza vaccine during the preceding season, 57.0% had willingness to accept A (H1N1) influenza vaccine at baseline, and 12.1% had received A (H1N1) influenza vaccine by the time of follow-up. After adjustment for potential confounding variables, people who had been vaccinated were significantly more likely to be living with an underlying disease (p = 0.001), to perceive high susceptibility to influenza (p = 0.03), to have willingness to pay even if the vaccine costs ≥ US$44 (p = 0.04), to have received seasonal influenza vaccine during the preceding season (p<0.001), and to have willingness to accept A (H1N1) influenza vaccine at baseline (p<0.001) compared to those who had not been vaccinated. Conclusions/Significance: While studies have reported high rates of willingness to receive A (H1N1) influenza vaccine, these rates may not transpire in the actual practices. The uptake of the vaccine may be determined by several potential factors such as perceived susceptibility to influenza and sensitivity to vaccination cost in general population. [ABSTRACT FROM AUTHOR]

Background: The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia. Methodology/Principal Findings: Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors. Conclusions/Significance: This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Extensive studies in different fields have been performed to reconstruct the prehistory of populations in the Japanese archipelago. Estimates the ancestral population dynamics based on Japanese molecular sequences can extend our understanding about the colonization of Japan and the ethnogenesis of modern Japanese. Methodology/Principal Findings: We applied Bayesian skyline plot (BSP) with a dataset based on 952 Japanese mitochondrial DNA (mtDNA) genomes to depict the female effective population size (Nef) through time for the total Japanese and each of the major mtDNA haplogroups in Japanese. Our results revealed a rapid Nef growth since ∼5 thousand years ago had left ∼72% Japanese mtDNA lineages with a salient signature. The BSP for the major mtDNA haplogroups indicated some different demographic history. Conclusions/Significance: The results suggested that the rapid population expansion acted as a major force in shaping current maternal pool of Japanese. It supported a model for population dynamics in Japan in which the prehistoric population growth initiated in the Middle Jomon Period experienced a smooth and swift transition from Jomon to Yayoi, and then continued through the Yayoi Period. The confounding demographic backgrounds of different mtDNA haplogroups could also have some implications for some related studies in future. [ABSTRACT FROM AUTHOR]

Background: Pacific Krill (Euphausia pacifica) are small, red crustaceans, similar to shrimp, that flourish in the North Pacific and are eaten in Japan. Methods and Findings: We investigated the effect of a water-soluble extract of Pacific Krill on adipocytes and discovered that this extract suppressed triglyceride accumulation in adipocytes. Furthermore, the water-soluble extract of Pacific Krill suppressed the expression of two master regulators of adipocyte differentiation, peroxisome proliferator-activated receptor gamma (PPAR&ggr;) and CCAAT enhancer binding protein alpha (C/EBP&agr;). C/EBPb promotes PPARc and C/EBP&agr; expression, but the water-soluble extract of Pacific Krill did not inhibit the expression of C/EBP&bgr; or C/EBP&bgr;-mediated transcriptional activation. The Pacific Krill extract was more effective than a PPAR&ggr; antagonist in suppressing PPAR&ggr; and C/EBP&agr; expression. Conclusions: These results indicated that the water-soluble extract of Pacific Krill was not simply a PPAR&ggr; antagonist, but that it prevented triglyceride accumulation in adipocytes by suppression of PPARc and C/EBP&agr; via a pathway that is independent of C/EBP&bgr;. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs of 20-25 nucleotides that play a key role in diverse biological processes. Japanese flounder undergo dramatic metamorphosis in their early development. The metamorphosis is characterized by morphological transformation from a bilaterally symmetrical to an asymmetrical body shape concomitant with extensive morphological and physiological remodeling of organs. So far, only a few miRNAs have been identified in fish and there are very few reports about the Japanese flounder miRNA. Methodology/Principal Findings: Solexa sequencing technology was used to perform high throughput sequencing of the small RNA library from the metamorphic period of Japanese flounder. Subsequently, aligning these sequencing data with metazoan known miRNAs, we characterized 140 conserved miRNAs and 57 miRNA: miRNA* pairs from the small RNA library. Among these 57 miRNA: miRNA* pairs, twenty flounder miRNA precursors were amplified from genomic DNA. We also demonstrated evolutionary conservation of Japanese flounder miRNAs and miRNA* in the animal evolution process. Using miRNA microarrays, we identified 66 differentially expressed miRNAs at two metamorphic stages (17 and 29 days post hatching) of Japanese flounder. The results show that miRNAs might play a key role in regulating gene expression during Japanese flounder metamorphosis. Conclusions/Significance: We identified a large number of miRNAs during flounder metamorphosis, some of which are differentially expressed at two different metamorphic stages. The study provides an opportunity for further understanding of miRNA function in the regulation of flounder metamorphosis and gives us clues for further studies of the mechanisms of metamorphosis in Japanese flounder. [ABSTRACT FROM AUTHOR]

Mg2+ plays important roles in numerous cellular functions. Mitochondria take part in intracellular Mg2+ regulation and the Mg2+ concentration in mitochondria affects the synthesis of ATP. However, there are few methods to observe Mg2+ in mitochondria in intact cells. Here, we have developed a novel Mg2+-selective fluorescent probe, KMG-301, that is functional in mitochondria. This probe changes its fluorescence properties solely depending on the Mg2+ concentration in mitochondria under physiologically normal conditions. Simultaneous measurements using this probe together with a probe for cytosolic Mg2+, KMG-104, enabled us to compare the dynamics of Mg2+ in the cytosol and in mitochondria. With this method, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP)-induced Mg2+ mobilization from mitochondria to the cytosol was visualized. Although a FCCP-induced decrease in the Mg2+ concentration in mitochondria and an increase in the cytosol were observed both in differentiated PC12 cells and in hippocampal neurons, the time-courses of concentration changes varied with cell type. Moreover, the relationship between mitochondrial Mg2+ and Parkinson's disease was analyzed in a cellular model of Parkinson's disease by using the 1-methyl-4-phenylpyridinium ion (MPP+). A gradual decrease in the Mg2+ concentration in mitochondria was observed in response to MPP+ in differentiated PC12 cells. These results indicate that KMG-301 is useful for investigating Mg2+ dynamics in mitochondria. All animal procedures to obtain neurons from Wistar rats were approved by the ethical committee of Keio University (permit number is 09106-(1)). [ABSTRACT FROM AUTHOR]

We have observed fallout from the recent Fukushima Dai-ichi reactor accident in samples of rainwater collected in the San Francisco Bay area. Gamma ray spectra measured from these samples show clear evidence of fission products - 131,132I, 132Te, and 134,137Cs. The activity levels we have measured for these isotopes are very low and pose no health risk to the public. [ABSTRACT FROM AUTHOR]

The recently acquired archaeological record for soybean from Japan, China and Korea is shedding light on the context in which this important economic plant became associated with people and was domesticated. This paper examines archaeological (charred) soybean seed size variation to determine what insight can be gained from a comprehensive comparison of 949 specimens from 22 sites. Seed length alone appears to represent seed size change through time, although the length6width6thickness product has the potential to provide better size change resolution. A widespread early association of small seeded soybean is as old as 9000-8600 cal BP in northern China and 7000 cal BP in Japan. Direct AMS radiocarbon dates on charred soybean seeds indicate selection resulted in large seed sizes in Japan by 5000 cal BP (Middle Jomon) and in Korea by 3000 cal BP (Early Mumun). Soybean seeds recovered in China from the Shang through Han periods are similar in length to the large Korean and Japanese specimens, but the overall size of the large Middle and Late Jomon, Early Mumun through Three Kingdom seeds is significantly larger than any of the Chinese specimens. The archaeological record appears to disconfirm the hypothesis of a single domestication of soybean and supports the view informed by recent phyologenetic research that soybean was domesticated in several locations in East Asia. [ABSTRACT FROM AUTHOR]

Immediately after the accidents in the nuclear power stations in Fukushima on March 11, the Japanese Government ordered the evacuation of the residents within a 20-km radius from the station on March 12, and asked various institutions to monitor the contamination levels of the residents. Hirosaki University, which is located 355 km north of Fukushima City, decided to send support staff to Fukushima. This report summarizes the results of the exposure of 13 individual teams from March 15 to June 20. The support teams surveyed more than 5,000 people during this period. Almost all subjects had external contamination levels of less than 13 kcpm on Geiger-Müller (GM) survey meter, which is categorized as ''no contamination level.'' The 1st team showed the highest external exposure dose, but the 4th team onward showed no significant change. Subsequently, the internal radiation exposure was measured using a whole body counter that indicated undetectable levels in all staff members. Although the measured external radiation exposure dose cannot have serious biological effects on the health of an individual, a follow-up study of the residents in Fukushima and other regions where the radioactive material has spread will be required for a long time. [ABSTRACT FROM AUTHOR]

Background: Using a knock-out mouse model, it was shown that NETO1 is a critical component of the NMDAR complex, and that loss of Neto1 leads to impaired hippocampal long term potentiation and hippocampal-dependent learning and memory. Moreover, hemizygosity of NETO1 was shown to be associated with autistic-like behavior in humans. Purpose of the Research: We examined the association between schizophrenia and the neuropilin and tolloid-like 1 gene (NETO1). First, we selected eight single nucleotide polymorphisms (SNPs) within the NETO1 locus, based on the Japanese schizophrenia genome wide association study (JGWAS) results and previously conducted association studies. These SNPs were genotyped in the replication sample comprised of 963 schizophrenic patients and 919 healthy controls. We also examined the effect of associated SNPs on scores in the Continuous Performance Test and the Wisconsin Card Sorting Test Keio version (schizophrenic patients 107, healthy controls 104). Results: There were no significant allele-wise and haplotype-wise associations in the replication analysis after Bonferroni correction. However, in meta-analysis (JGWAS and replication dataset) three association signals were observed (rs17795324: p = 0.028, rs8098760: p = 0.017, rs17086492: p = 0.003). These SNPs were followed up but we could not detect the allelespecific effect on cognitive performance measured by the Continuous performance test (CPT) and Wisconsin Card Sorting test (WCST). Major Conclusions: We did not detect evidence for the association of NETO1 with schizophrenia in the Japanese population. Common variants within the NETO1 locus may not increase the genetic risk for schizophrenia in the Japanese population. Additionally, common variants investigated in the current study did not affect cognitive performance, as measured by the CPT and WCST. [ABSTRACT FROM AUTHOR]

Periodical organisms, such as bamboos and periodical cicadas, are very famous for their synchronous reproduction. In bamboos and other periodical plants, the synchronicity of mass-flowering and withering has been often reported indicating these species are monocarpic (semelparous) species. Therefore, synchronicity and periodicity are often suspected to be fairly tightly coupled traits in these periodical plants. We investigate the periodicity and synchronicity of Strobilanthes flexicaulis, and a closely related species S. tashiroi on Okinawa Island, Japan. The genus Strobilanthes is known for several periodical species. Based on 32-year observational data, we confirmed that S. flexicaulis is 6-year periodical mass-flowering monocarpic plant. All the flowering plants had died after flowering. In contrast, we found that S. tashiroi is a polycarpic perennial with no mass-flowering from three-year individual tracking. We also surveyed six local populations of S. flexicaulis and found variation in the synchronicity from four highly synchronized populations (>98% of plants flowering in the mass year) to two less synchronized one with 11-47% of plants flowering before and after the mass year. This result might imply that synchrony may be selected for when periodicity is established in monocarpic species. We found the selective advantages for mass-flowering in pollinator activities and predator satiation. The current results suggest that the periodical S. flexicaulis might have evolved periodicity from a non-periodical close relative. The current report should become a key finding for understanding the evolution of periodical plants. [ABSTRACT FROM AUTHOR]

Intra-specific genetic diversity is important not only because it influences population persistence and evolutionary potential, but also because it contains past geological, climatic and environmental information. In this paper, we show unusually clear genetic structure of the endangered Japanese crayfish that, as a sedentary species, provides many insights into lesser-known past environments in northern Japan. Over the native range, most populations consisted of unique 16S mtDNA haplotypes, resulting in significant genetic divergence (overall F(ST) = 0.96). Owing to the simple and clear structure, a new graphic approach unraveled a detailed evolutionary history; regional crayfish populations were comprised of two distinct lineages that had experienced contrasting demographic processes (i.e. rapid expansion vs. slow stepwise range expansion) following differential drainage topologies and past climate events. Nuclear DNA sequences also showed deep separation between the lineages. Current ocean barriers to dispersal did not significantly affect the genetic structure of the freshwater crayfish, indicating the formation of relatively recent land bridges. This study provides one of the best examples of how phylogeographic analysis can unravel a detailed evolutionary history of a species and how this history contributes to the understanding of the past environment in the region. Ongoing local extinctions of the crayfish lead not only to loss of biodiversity but also to the loss of a significant information regarding past geological and climatic events.

Background: In the past decade, scientific research has developed rapidly in China, but the growth seems to vary widely between different disciplines. In this study, we aimed to compare the quantity and quality of publications in urology and nephrology journals from USA, China and Japan., Methods: Journals listed in the "Urology and Nephrology" category of Science Citation Index Expanded subject categories were included. Scientific papers in these journals written by researchers from USA, Japan and China were retrieved from the "PubMed" and "Web of Knowledge" online databases., Results: The annual number of total scientific articles increased significantly from 2001 to 2010 in China, and has ranked second in the world since 2006. In the field of urology and nephrology, the annual number increased significantly from 2001 to 2010 in USA and China; but not in Japan. The share of articles increased significantly over time in China, decreased significantly in Japan, and remained unchanged in USA. In 2010, USA contributed 32.17% of the total world output in urology and nephrology field and ranked 1(st); Japan contributed 5.19% and ranked 5(th); China contributed 3.83% and ranked 9(th). Publications from USA had the highest accumulated IFs and the highest total citations of articles (USA>Japan>China, p<0.001). No significant difference was found in average IF among the three countries. USA published the most articles in the top 10 urology and nephrology journals (USA(35165)>Japan(6704)>China(2233), p<0.001). Researchers from USA published more clinical trials and randomized controlled trials than Japan and China (USA>Japan>China, p<0.001)., Conclusion: Although China has undergone significant increase in annual number and percentage of scientific publication in urology and nephrology journals in the past decade, it still lags far behind USA and Japan in the field of urology and nephrology in terms of quantity and quality.

Background: In 2009, a pandemic (pdm) influenza A(H1N1) virus infection quickly circulated globally resulting in about 18,000 deaths around the world. In Japan, infected patients accounted for 16% of the total population. The possibility of human-to-human transmission of highly pathogenic novel influenza viruses is becoming a fear for human health and society. Methodology: To address the clinical need for rapid diagnosis, we have developed a new method, the ''RT-SmartAmp assay'', to rapidly detect the 2009 pandemic influenza A(H1N1) virus from patient swab samples. The RT-SmartAmp assay comprises both reverse transcriptase (RT) and isothermal DNA amplification reactions in one step, where RNA extraction and PCR reaction are not required. We used an exciton-controlled hybridization-sensitive fluorescent primer to specifically detect the HA segment of the 2009 pdm influenza A(H1N1) virus within 40 minutes without cross-reacting with the seasonal A(H1N1), A(H3N2), or B-type (Victoria) viruses. Results and Conclusions: We evaluated the RT-SmartAmp method in clinical research carried out in Japan during a pandemic period of October 2009 to January 2010. A total of 255 swab samples were collected from outpatients with influenza-like illness at three hospitals and eleven clinics located in the Tokyo and Chiba areas in Japan. The 2009 pdm influenza A(H1N1) virus was detected by the RT-SmartAmp assay, and the detection results were subsequently compared with data of current influenza diagnostic tests (lateral flow immuno-chromatographic tests) and viral genome sequence analysis. In conclusion, by the RT-SmartAmp assay we could detect the 2009 pdm influenza A(H1N1) virus in patients' swab samples even in early stages after the initial onset of influenza symptoms. Thus, the RT-SmartAmp assay is considered to provide a simple and practical tool to rapidly detect the 2009 pdm influenza A(H1N1) virus. [ABSTRACT FROM AUTHOR]

Background: Household transmission of influenza can affect the daily lives of patients and their families and be a trigger for community transmission, thus it is necessary to take precautions to prevent household transmission. We aimed to determine the risks of household transmission of pandemic (H1N1) 2009 influenza virus from an index patient who visited a primary clinic and was treated with antiviral drugs. Methods: We followed up all the patients who were diagnosed with influenza A by rapid diagnostic test with a questionnaire or interview from July 2009 to April 2010. Secondary cases were defined as patients visiting the clinic or other clinics and being positive for influenza A by rapid diagnostic test within 7 days of onset of an index patient. Logistic regression analysis was used to explore the association between household transmission and the studied variables. Results: We recruited 591 index patients and 1629 household contacts. The crude secondary attack rate was 7.3% [95% confidence interval (CI): 6.1-8.7]. Age of index patients (0-6 years old: odds ratio 2.56; 95% CI: 1.31-4.01; 7-12 years old: 2.44, 1.31-3.72; 30-39 years old 3.88; 2.09-5.21; 40 years old or more 2.76; 1.17-4.53) and number of household members with five or more (3.09, 2.11-4.07), medication started $48 hours from the onset of fever (2.38, 1.17-3.87) were significantly associated with household transmission. Conclusions: Household transmission was associated with index patients aged #12 years old and adults $30 years with children, with more than five persons in the household, and medication initiated $48 hours from the onset of fever among the population, in which, antiviral treatment was given to all patients. We need to warn patients at high risk of household transmission to take additional precautions. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan. [ABSTRACT FROM AUTHOR]

Background: In the current era of strong worldwide market couplings the global financial village became highly prone to systemic collapses, events that can rapidly sweep throughout the entire village. Methodology/Principal Findings: We present a new methodology to assess and quantify inter-market relations. The approach is based on the correlations between the market index, the index volatility, the market Index Cohesive Force and the meta-correlations (correlations between the intra-correlations.) We investigated the relations between six important world markets—U.S., U.K., Germany, Japan, China and India—from January 2000 until December 2010. We found that while the developed "western" markets (U.S., U.K., Germany) are highly correlated, the interdependencies between these markets and the developing "eastern" markets (India and China) are volatile and with noticeable maxima at times of global world events. The Japanese market switches "identity"—it switches between periods of high meta-correlations with the "western" markets and periods when it behaves more similarly to the "eastern" markets. Conclusions/Significance: The methodological framework presented here provides a way to quantify the evolvement of interdependencies in the global market, evaluate a world financial network and quantify changes in the world inter market relations. Such changes can be used as precursors to the agitation of the global financial village. Hence, the new approach can help to develop a sensitive "financial seismograph" to detect early signs of global financial crises so they can be treated before they develop into worldwide events. [ABSTRACT FROM AUTHOR]

Background: The largest earthquake on record in Japan (magnitude 9.0) occurred on March 11, 2011, and the subsequent tsunami devastated the Pacific coast of Northern Japan. These further triggered the Fukushima I nuclear power plant accidents. Such a hugely complex disaster inevitably has negative psychological effects on general populations as well as on the direct victims. While previous disaster studies enrolled descriptive approaches focusing on direct victims, the structure of the psychological adjustment process of people from the general population has remained uncertain. The current study attempted to establish a path model that sufficiently reflects the early psychological adaptation process of the general population to large-scale natural disasters. Methods and Findings: Participants from the primary disaster area (n = 1083) and other areas (n = 2372) voluntarily participated in an online questionnaire study. By constructing path models using a structural equation model procedure (SEM), we examined the structural relationship among psychological constructs known related to disasters. As posttraumatic stress symptoms (PTS) were significantly more present in people in the primarily affected area than in those in secondary- or non-affected areas, the path models were constructed for the primary victims. The parsimoniously depicted model with the best fit was achieved for the psychological-adjustment centered model with quality of life (QoL) as a final outcome. Conclusion: The paths to QoL via negative routes (from negative cognitive appraisal, PTS, and general stress) were dominant, suggesting the importance of clinical intervention for reducing negative cognitive appraisal, and for caring for general stress and PTS to maintain QoL at an early stage of psychological adaptation to a disaster. The model also depicted the presence of a positive route where positive cognitive appraisal facilitates post-traumatic growth (PTG) to achieve a higher QoL, suggesting the potential importance of positive psychological preventive care for unexpected natural disasters. [ABSTRACT FROM AUTHOR]

The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn-) B. pertussis was observed in Japan. The Prn- isolate was first discovered in 1997, and 33 (27%) Prn- isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn- isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1ΔSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn- isolates, notably those harboring prn1ΔSS, significantly increased since the early 2000s, and Prn- isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn- isolates belong to MLVA-186, and 6 and 3 Prn- isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn- clinical strains (harboring prn1ΔSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn- isolates have a higher growth potential than the Prn+ back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn- strains have arisen and that Prn expression is not essential for fitness under these conditions. [ABSTRACT FROM AUTHOR]

Background: In the early stages of Pandemic (H1N1) 2009, border control measures were taken by quarantine stations to block the entry of infected individuals into Japan and community containment measures were implemented to prevent the spreading. The objectives of this study were to describe these measures and the characteristics of infected individuals, and to assess the measures' effectiveness. Methodology/Principal Findings: Border control and community containment measures implemented from April to June (Period I: April 28-May 21, Period II: May 22-June 18) 2009 were described. Number of individuals identified and disease characteristics were analyzed. For entry screening, a health declaration form and an infrared thermoscanner were used to detect symptomatic passengers. Passengers indicated for the rapid influenza test underwent the test followed by RT-PCR. Patients positive for H1N1 were isolated, and close contacts were quarantined. Entry cards were handed out to all asymptomatic passengers informing them about how to contact a health center in case they developed symptoms. Nine individuals were identified by entry screening and 1 during quarantine to have Pandemic (H1N1) 2009. Health monitoring by health centers was performed in period I for passengers arriving from affected countries and in period II for those who had come into contact with the individuals identified by entry screening. Health monitoring identified 3 infected individuals among 129,546 in Period I and 5 among 746 in Period II. Enhanced surveillance, which included mandatory reporting of details of the infected individuals, identified 812 individuals, 141 (18%) of whom had a history of international travel. Twenty-four of these 141 passengers picked up by enhanced surveillance had been developing symptoms on entry and were missed at screening. Conclusion/Significance: Symptomatic passengers were detected by the various entry screening measures put in place. Enhanced surveillance provided data for the improvement of public health measures in future pandemics. [ABSTRACT FROM AUTHOR]

Background: In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid. Methods/Results: To elucidate the existence and transmissibility of a2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009. Conclusions: These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-tohuman transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. [ABSTRACT FROM AUTHOR]

Anti-predator behaviors are essential to survival for most animals. The neural bases of such behaviors, however, remain largely unknown. Although honeybees commonly use their stingers to counterattack predators, the Japanese honeybee (Apis cerana japonica) uses a different strategy to fight against the giant hornet (Vespa mandarinia japonica). Instead of stinging the hornet, Japanese honeybees form a "hot defensive bee ball" by surrounding the hornet en masse, killing it with heat. The European honeybee (A. mellifera ligustica), on the other hand, does not exhibit this behavior, and their colonies are often destroyed by a hornet attack. In the present study, we attempted to analyze the neural basis of this behavior by mapping the active brain regions of Japanese honeybee workers during the formation of a hot defensive bee ball. First, we identified an A. cerana homolog (Acks = Apis cerana kakusei) of kakusei, an immediate early gene that we previously identified from A. mellifera, and showed that Acks has characteristics similar to kakusei and can be used to visualize active brain regions in A. cerana. Using Acks as a neural activity marker, we demonstrated that neural activity in the mushroom bodies, especially in Class II Kenyon cells, one subtype of mushroom body intrinsic neurons, and a restricted area between the dorsal lobes and the optic lobes was increased in the brains of Japanese honeybee workers involved in the formation of a hot defensive bee ball. In addition, workers exposed to 46°C heat also exhibited Acks expression patterns similar to those observed in the brains of workers involved in the formation of a hot defensive bee ball, suggesting that the neural activity observed in the brains of workers involved in the hot defensive bee ball mainly reflects thermal stimuli processing. [ABSTRACT FROM AUTHOR]

Commercial greenhouse growers in both Japan and China are increasingly using reared orange-tailed bumblebees known previously as Bombus hypocrita Pérez as pollinators. Phylogenetic analysis of the DNA (COI) barcodes with Bayesian methods shows that this "species" is a long-standing confusion of two cryptic species. We find that the orange-tailed bumblebees in North China are actually part of the widespread Russian (otherwise white-tailed) B. patagiatus Nylander (as B. patagiatus ganjsuensis Skorikov, n. comb.), whereas the orange-tailed bees in Japan are true B. hypocrita. This situation has been further complicated because two other cryptic species from North China that were previously confused with the Russian B. patagiatus are now recognised as separate: B. lantschouensis Vogt n. stat. and B. minshanensis Bischoff n. stat.. As demand for pollination services by greenhouse growers inevitably increases, these bees are more likely to be transported between countries. In order to conserve genetic resources of pollinator species for their option value for future food security, we advocate preventing trade and movement of B. patagiatus from China into Japan and of B. hypocrita from Japan into China. [ABSTRACT FROM AUTHOR]

During the last 90 years, the breeding of rice has delivered cultivars with improved agronomic and economic characteristics. Crossing of different lines and successive artificial selection of progeny based on their phenotypes have changed the chromosomal constitution of the ancestors of modern rice; however, the nature of these changes is unclear. The recent accumulation of data for genome-wide single-nucleotide polymorphisms (SNPs) in rice has allowed us to investigate the change in haplotype structure and composition. To assess the impact of these changes during modern breeding, we studied 177 Japanese rice accessions, which were categorized into three groups: landraces, improved cultivars developed from 1931 to 1974 (the early breeding phase), and improved cultivars developed from 1975 to 2005 (the late breeding phase). Phylogenetic tree and structure analysis indicated genetic differentiation between non-irrigated (upland) and irrigated (lowland) rice groups as well as genetic structuring within the irrigated rice group that corresponded to the existence of three subgroups. Pedigree analysis revealed that a limited number of landraces and cultivars was used for breeding at the beginning of the period of systematic breeding and that 11 landraces accounted for 70% of the ancestors of the modern improved cultivars. The values for linkage disequilibrium estimated from SNP alleles and the haplotype diversity determined from consecutive alleles in five-SNP windows indicated that haplotype blocks became less diverse over time as a result of the breeding process. A decrease in haplotype diversity, caused by a reduced number of polymorphisms in the haplotype blocks, was observed in several chromosomal regions. However, our results also indicate that new haplotype polymorphisms have been generated across the genome during the breeding process. These findings will facilitate our understanding of the association between particular haplotypes and desirable phenotypes in modern Japanese rice cultivars. [ABSTRACT FROM AUTHOR]