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To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association (P= 6.5 × 10−7) that was replicated in additional Japanese samples (P= 2.9 × 10−6. OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data (P= 5.0 × 10-15. Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples (P=0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution inPLA2G4Cthat encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.

Developing automated soybean seed counting tools will help automate yield prediction before harvesting and improving selection efficiency in breeding programs. An integrated approach for counting and localization is ideal for subsequent analysis. The traditional method of object counting is labor-intensive and error-prone and has low localization accuracy. To quantify soybean seed directly rather than sequentially, we propose a P2PNet-Soy method. Several strategies were considered to adjust the architecture and subsequent postprocessing to maximize model performance in seed counting and localization. First, unsupervised clustering was applied to merge closely located overcounts. Second, low-level features were included with high-level features to provide more information. Third, atrous convolution with different kernel sizes was applied to low- and high-level features to extract scale-invariant features to factor in soybean size variation. Fourth, channel and spatial attention effectively separated the foreground and background for easier soybean seed counting and localization. At last, the input image was added to these extracted features to improve model performance. Using 24 soybean accessions as experimental materials, we trained the model on field images of individual soybean plants obtained from one side and tested them on images obtained from the opposite side, with all the above strategies. The superiority of the proposed P2PNet-Soy in soybean seed counting and localization over the original P2PNet was confirmed by a reduction in the value of the mean absolute error, from 105.55 to 12.94. Furthermore, the trained model worked effectively on images obtained directly from the field without background interference.

Hashimoto’s encephalopathy with serum anti-NH2-terminal of α-enolase (NAE) antibodies occasionally displays clinical symptoms such as cerebellar ataxia and parkinsonism. We studied the frequency of anti-NAE antibodies in patients with Parkinson-plus syndrome. We examined the positive rates of anti-NAE antibodies in 47 patients with multiple system atrophy (MSA), 29 patients with Parkinson’s disease (PD), eight patients with corticobasal syndrome (CBS), and 18 patients with progressive supranuclear palsy (PSP) using conventional immunoblot analysis. Positive anti-NAE antibody rates of 31.9%, 10.3%, 50.0%, and 11.1% were reported in the MSA, PD, CBS, and PSP patients, respectively. The duration from onset to a wheelchair-bound state in seropositive MSA patients tended to be shorter than that in seronegative MSA patients. Anti-NAE antibodies are detected in some patients clinically diagnosed with MSA and CBS. Although its pathophysiological significance remains uncertain, serum anti-NAE antibodies might represent a prognostic marker in the clinical course of MSA.

Summary Background Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy. Methods We did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879. Findings Between Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI –2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [–1·6 to 3·6], –0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related. Interpretation A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy. Funding AbbVie Inc.

Cooked bean hardness is an important trait for the processing of soybean products such as nimame, natto, miso, and soy sauce. Previously, we showed that cooked bean hardness is primarily affected by the pectin methylesterase gene Glyma03g03360, and that calcium content has a secondary effect on this trait. To establish a simple and timely method for the evaluation of cooked bean hardness, primers of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) were designed to detect a single-nucleotide polymorphism of Glyma03g03360 and subsequently used to evaluate three soybean progeny lines. The determined genotypes were compared to those identified using the cleaved amplified polymorphic sequence (CAPS) method. Seven out of 284 lines presented different genotypes, which were determined using the two methods: A genotypes were incorrectly assigned as heterozygous by CAPS, suggesting that ARMS-PCR is more reliable. Glyma03g03360 genotypes could be used to evaluate cooked bean hardness, except for intermediate values. Cooked bean hardness within the same genotype groups was significantly correlated with calcium contents. These findings indicate that ARMS-PCR is useful for a marker-assisted selection of soybean with soft-cooked beans and that calcium content may be used for additional selection.

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters.Methods:18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke’s Cognitive Examination–Revised, and Frontal Assessment Battery, Unified Parkinson’s Disease Rating Scale Motor Score, and PSP Rating Scale.Results:18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP.Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.

Mirror writing (MW) is the production of individual letters, words, or word strings in the reverse direction. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and high MW rates have been reported in patients with PD. Thus, the present study sought to identify the factors that cause MW in patients with PD. We examined the frequency of MW in patients with PD and investigated the area of the brain where such frequency inversely correlates with reduced regional cerebral metabolic rates of glucose (rCMRglc). We also examined whether this area satisfied the motor and visual monitoring hypotheses of MW that have been presented in previous studies. Thirty-six subjects with idiopathic PD and 23 healthy controls were included in the study. We asked the participants to write down words, numerals, and sentences from left to right using their dominant and non-dominant hands. Patients with PD underwent an 18F-fluorodeoxyglucose positron emission tomography scan to measure the rCMRglc. Neither the patients with PD nor the healthy subjects exhibited MW in the use of the right hand. In the use of the left hand, MW occurred in 15 of the 36 patients with PD, but in none of the healthy controls. The right intraparietal sulcus was identified as the area where rCMRglc was inversely correlated with the number of left–right reversed characters. Previous functional imaging studies have suggested that the right superior parietal cortex and intraparietal sulcus play an important role in recognizing left–right reversed letters. Therefore, dysfunction in the intraparietal sulcus may hinder the recognition of left–right reversed characters, resulting in MW. Consequently, our findings in patients with PD are consistent with the visual-monitoring hypothesis of MW.

Background and purpose Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. Methods Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). Results The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. Conclusions Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Although an indeterminate growth habit is attractive to develop high-yield soybean varieties with higher number of pods (Glycine max (L). Merr.), lodging in indeterminate varieties remains a problem in Japan. As the semi-determinate varieties have shorter main stem length than the indeterminate varieties, this trait can be useful to improve varieties with high yield and low lodging risk. We introduced the genes Dt1 and Dt2, which regulate stem growth habit, into three determinate varieties by backcrossing and evaluated the resulting effects on yield and lodging tendency under four different growing environments. The yield and lodging degree of the semi-determinate and indeterminate lines were higher and more severe than those of the determinate lines. Despite the lower overall lodging score, the semi-determinate lines had marginally lower overall yield than that of the indeterminate lines. However, the effect of introduction of semi-determinate traits on yield and lodging degree was different in the three backgrounds, with the yield of semi-determinate lines being the highest and the difference in lodging degree between the semi-determinate and determinate lines being under 1.0 in one background. Therefore, semi-determinate growth habit has potential to develop high yielding varieties with low lodging risk.

Food contamination by cadmium (Cd) is a serious threat to human health. Thus, it is imperative to prevent Cd accumulation in staple crops like soybean. The development of low Cd accumulating cultivars is an effective solution. To this end, it is essential to identify the gene(s) controlling seed Cd accumulation. Although Glyma.09G055600 (GmHMA3) seems to be associated with Cd accumulation in soybean, it has not been established if it is responsible for seed Cd accumulation. In the present study, the effect of GmHMA3 on seed Cd accumulation in soybean was validated using three independent GmHMA3 mutants isolated from an ethyl methanesulfonate-induced soybean mutant library. Each of mutant had an amino acid substitution in GmHMA3 and segregating progenies were developed by crossing the original cultivar with each of the three mutants. The relationship between these three mutations and seed Cd accumulation was investigated. While two of them significantly increased seed Cd accumulation corresponding to previous reports of a natural missense mutation in GmHMA3, the other slightly decreased seed Cd accumulation. Overall, these results indicate that GmHMA3 is responsible for seed Cd accumulation in soybean.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a phenotypically and genetically heterogeneous group of neurological disorders that typically presents as early-onset lower limb dystonia with diurnal fluctuation, and exhibits a marked, persistent response to levodopa. Heterozygous loss-of-function mutations in the guanosine triphosphate cyclohydrolase 1 (GCH1) are the most common cause of DRD. In addition to the classic form of the disease, there have been a number of studies addressing atypical clinical features of GCH1 related DRD with variable age of onset. This report describes a 37-year-old Japanese male patient with a 10-year history of focal upper limb dystonia that initially emerged as task-specific, guitarist’s cramp. The dystonic symptoms responded very well to levodopa treatment, and genetic analysis identified a novel heterozygous mutation in the C-terminal catalytic domain of GCH1. Insufficient recognition of this treatable condition often leads to misdiagnosis, which causes delays in the patient receiving adequate dopamine replenishing therapy. A diagnostic trial with levodopa should be considered in all patients with relatively young-onset dystonia, whether they have classic features of DRD or not.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a phenotypically and genetically heterogeneous group of neurological disorders that typically presents as early-onset lower limb dystonia with diurnal fluctuation, and exhibits a marked, persistent response to levodopa. Heterozygous loss-of-function mutations in the guanosine triphosphate cyclohydrolase 1 (GCH1) are the most common cause of DRD. In addition to the classic form of the disease, there have been a number of studies addressing atypical clinical features of GCH1 related DRD with variable age of onset. This report describes a 37-year-old Japanese male patient with a 10-year history of focal upper limb dystonia that initially emerged as task-specific, guitarist’s cramp. The dystonic symptoms responded very well to levodopa treatment, and genetic analysis identified a novel heterozygous mutation in the C-terminal catalytic domain of GCH1. Insufficient recognition of this treatable condition often leads to misdiagnosis, which causes delays in the patient receiving adequate dopamine replenishing therapy. A diagnostic trial with levodopa should be considered in all patients with relatively young-onset dystonia, whether they have classic features of DRD or not.

Hashimoto's encephalopathy with serum anti-NHWe examined the positive rates of anti-NAE antibodies in 47 patients with multiple system atrophy (MSA), 29 patients with Parkinson's disease (PD), eight patients with corticobasal syndrome (CBS), and 18 patients with progressive supranuclear palsy (PSP) using conventional immunoblot analysis.Positive anti-NAE antibody rates of 31.9%, 10.3%, 50.0%, and 11.1% were reported in the MSA, PD, CBS, and PSP patients, respectively. The duration from onset to a wheelchair-bound state in seropositive MSA patients tended to be shorter than that in seronegative MSA patients.Anti-NAE antibodies are detected in some patients clinically diagnosed with MSA and CBS. Although its pathophysiological significance remains uncertain, serum anti-NAE antibodies might represent a prognostic marker in the clinical course of MSA.

Highlights • Pathological basis of primary progressive aphasia is heterogeneous. • Logopenic primary progressive aphasia can precede dementia with Lewy bodies (DLB). • Cholinesterase inhibitor can improve logopenic aphasia with DLB.

The timing of flower formation and length of the seed-filling period of indeterminate growth soybean varieties vary more than those of determinate varieties (Glycine max (L.) Merrill). These variations have been hypothesized to affect single seed weight and its uniformity which determine the processing quality of soybean used in foods. We derived near isogenic lines (NILs) with different growth characteristics from an indeterminate line (donor parent) and three determinate lines with heavy seeds (recurrent parents), and evaluated the effects of growth habit on seed weight and its uniformity. Each NIL population consisting of five indeterminate and five determinate BC4F4 lines tested at two locations in two different years with two replications. Split-plot analysis of variance, with main-plot and sub-plot being cross combination and growth habit, respectively, showed that indeterminate varieties had slightly heavier seeds than determinate varieties and that there was no significant difference in uniformity of single seed weights. The effects of growth habit on seed uniformity was related to genetic background, but differences between the two growth characteristics were less than the differences among genetic background. This indicates that indeterminate growth habit did not much influence seed weight or its uniformity.

Introduction Patients with HIV infection may have a higher prevalence of osteoporosis and osteopenia, as well as an increased risk of bone fracture compared with non-HIV-infected individuals. Antiretroviral therapy is thought to be one of factors associated to osteoporosis-related bone fractures. Objective The aim of this study was to assess the effects of long-term exposure to tenofovir disoproxil fumarate (TDF) on the cumulative risk of osteoporosis-related bone fractures in Japanese patients with HIV infection. Design This observational cohort study comprised a joint HIV-related drug survey of patients treated with TDF between April 2004 and March 2013. Methods Thirty-five healthcare facilities in Japan participated in the survey. The incidence of osteoporosis-related fractures was extracted from all adverse events (AEs) using standardized Medical Dictionary for Regulatory Activities queries, and used to calculate the fracture rate per 10,000 patient-years (PY). Kaplan–Meier analysis was used to estimate the cumulative probability of fracture during the study period. Results A total of 3251 patients who received TDF or TDF/emtricitabine between April 2004 and March 2013 were analyzed in this study; 93.5% of patients were male. The fracture rate was 13.5 per 10,000 PY in males and 42.2 per 10,000 PY in females. The mean age for male patients with osteoporosis-related fracture was 43.2 years, whereas it was 65.7 years in female patients. The cumulative probability of osteoporosis-related fracture increased after ≥ 5 years of TDF exposure. The rate of hip fracture (95% confidence interval) was 7.2 (3.1–14.2) per 10,000 PY. Conclusions Among HIV-infected patients in Japan, treatment with TDF for ≥ 5 years increases the risk of bone fractures in younger men, in addition to that seen in older post-menopausal women.

Mutations in DNAJC13 gene have been linked to familial form of Parkinson's disease (PD) with Lewy pathology. DNAJC13 is an endosome-related protein and believed to regulate endosomal membrane trafficking. However, the mechanistic link between DNAJC13 mutation and α-synuclein (αSYN) pathology toward neurodegeneration remains poorly understood. In this study, we showed that PD-linked N855S-mutant DNAJC13 caused αSYN accumulation in the endosomal compartment, presumably due to defective cargo trafficking from the early endosome to the late and/or recycling endosome. In vivo experiments using human αSYN transgenic flies showed that mutant DNAJC13 not only increased the amount of insoluble αSYN in fly head but also induced dopaminergic neurodegeneration, rough eye phenotype and age-dependent locomotor impairment. Together, these findings suggest that DNAJC13 mutation perturbs multi-directional endosomal trafficking, resulting in the aberrant endosomal retention of αSYN, which might predispose to the neurodegenerative process that leads to PD.

The timing of flower formation and length of the seed-filling period of indeterminate growth soybean varieties vary more than those of determinate varieties (Glycine max (L.) Merrill). These variations have been hypothesized to affect single seed weight and its uniformity which determine the processing quality of soybean used in foods. We derived near isogenic lines (NILs) with different growth characteristics from an indeterminate line (donor parent) and three determinate lines with heavy seeds (recurrent parents), and evaluated the effects of growth habit on seed weight and its uniformity. Each NIL population consisting of five indeterminate and five determinate BC4F4 lines tested at two locations in two different years with two replications. Split-plot analysis of variance, with main-plot and sub-plot being cross combination and growth habit, respectively, showed that indeterminate varieties had slightly heavier seeds than determinate varieties and that there was no significant difference in uniformity of single seed weights. The effects of growth habit on seed uniformity was related to genetic background, but differences between the two growth characteristics were less than the differences among genetic background. This indicates that indeterminate growth habit did not much influence seed weight or its uniformity.

Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with mitochondrial dysfunction being one of the causes. FSGS is known to be associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is a subclass of mitochondrial disease. However, it has rarely been reported in other mitochondrial disease subclasses. Here, we reported a 20-year-old man diagnosed with FSGS associated with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation. He presented with left ptosis, short stature, mild sensorineural deafness, and cardiac conduction block. A renal biopsy sample showed segmental sclerosis and adhesions between capillaries and Bowman’s capsule, indicating FSGS. Electron microscopy demonstrated abnormal aggregated mitochondria in podocytes, and the basement membrane and epithelial cells of Bowman’s capsule. Skeletal muscle biopsy also showed accumulation of abnormal mitochondria. mtDNA analysis identified heteroplasmic mtDNA 3243A>G mutation with no large-scale deletions. From these findings, we diagnosed the case as CPEO with multi-organ involvement including FSGS. Our report demonstrates that CPEO, as well as MELAS, can be associated with FSGS. Because mitochondrial disease presents with a variety of clinical symptoms, atypical cases with non-classical manifestations are observed. Thus, mitochondrial disease should be considered as an underlying cause of FSGS with systemic manifestations even with atypical phenotypes.

The neuropathological hallmarks of Parkinson's disease (PD) include the appearance of α-synuclein (α-SYN)-positive Lewy bodies (LBs) and the loss of catecholaminergic neurons. Thus, a potential mechanism promoting the uptake of extracellular α-SYN may exist in susceptible neurons. Of the various differentially expressed proteins, we are interested in flotillin (FLOT)-1 because this protein is highly expressed in the brainstem catecholaminergic neurons and is strikingly up-regulated in PD brains. In this study, we found that extracellular monomeric and fibrillar α-SYN can potentiate FLOT1-dopamine transporter (DAT) binding and pre-endocytic clustering of DAT on the cell surface, thereby facilitating DAT endocytosis and down-regulating its transporter activity. Moreover, we demonstrated that α-SYN itself exploited the DAT endocytic process to enter dopaminergic neuron-like cells, and both FLOT1 and DAT were found to be the components of LBs. Altogether, these findings revealed a novel role of extracellular α-SYN on cellular trafficking of DAT and may provide a rationale for the cell type-specific, functional, and pathologic alterations in PD.-Kobayashi, J., Hasegawa, T., Sugeno, N., Yoshida, S., Akiyama, T., Fujimori, K., Hatakeyama, H., Miki, Y., Tomiyama, A., Kawata, Y., Fukuda, M., Kawahata, I., Yamakuni, T., Ezura, M., Kikuchi, A., Baba, T., Takeda, A., Kanzaki, M., Wakabayashi, K., Okano, H., Aoki, M. Extracellular α-synuclein enters dopaminergic cells by modulating flotillin-1-assisted dopamine transporter endocytosis.

High-density integration technologies with copper (Cu) through-silicon via (TSV) have emerged as viable alternatives for achieving the requisite integration densities for the portable electronics and micro-electro-mechanical systems (MEMSs) package. However, significant thermo-mechanical stresses can be introduced in integrated structures during the manufacturing process due to mismatches of thermal expansion and the mechanical properties between Cu and silicon (Si). The high-density integration demands an interconnection material with a strong mechanical strength and small thermal expansion mismatch. In this study, a novel electroplating method is developed for the synthesis of a graphene-copper (G-Cu) composite with electrochemically exfoliated graphenes. The fabrication and evaluation of the G-Cu composite microstructures, including the microcantilevers and micromirrors supported by the composite, are reported. We evaluated not only the micromechanical properties of the G-Cu composite based on in-situ mechanical resonant frequency measurements using a laser Doppler vibrometer but also the coefficients of thermal expansion (CTE) of the composite based on curvature radius measurements at a temperature range of 20–200 °C. The Young’s modulus and shear modulus of the composite are approximately 123 and 51 GPa, which are 1.25 times greater and 1.22 times greater, respectively, than those of pure Cu due to the reinforcement of graphene. The G-Cu composite exhibits a 23% lower CTE than Cu without sacrificing electrical conductivity. These results show that the mechanically strengthened G-Cu composite with reduced thermal expansion is an ideal and reliable interconnection material instead of Cu for complex integration structures., Circuits: Copper-graphene interconnects A graphene-copper composite exhibits a coefficient of thermal expansion closer to silicon, as compared to pure copper, suggesting its use for interconnects on circuit boards. Copper is widely used for interconnects in silicon-based electronics due to its high electrical conductivity. However, mismatch in thermal expansion coefficient between copper and silicon generates large internal stresses, potentially causing failure in the long-term. Now, a team led by Takahito Ono from Tohoku University reinforce copper with graphene flakes via an electroplating fabrication approach, achieving higher stiffness and a coefficient of thermal expansion 23% lower than pure copper. These results suggest that this material might enable high-density circuits that can resist internal stresses as a result of thermal expansion.

Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein.

Three versatile QTL for soybean downy mildew resistance in Japan were detected using five RIL populations and confirmed using recombinant fixed pairs or a backcrossed line. Downy mildew reduces soybean seed quality and size. It is a problem in Japan, where 90% of soybean grown is used as food. In the USA, 33 downy mildew races have been reported, but race differentiation in Japan is unclear. To identify quantitative trait loci (QTL) for downy mildew resistance effective in the Kanto and Tohoku regions, we performed QTL analysis using five populations of recombinant inbred lines (RILs) originated from ‘Natto-shoryu’ × ‘Tachinagaha’ (NT), ‘Natto-shoryu’ × ‘Suzumaru’, ‘Satonohohoemi’ × ‘Fukuibuki’ (SF), ‘Kinusayaka’ × ‘COL/Akita/2009/TARC/1,’ and ‘YR-82’ × ‘Harosoy’ over a 4-year period (2014–2017). We evaluated spontaneously developed symptoms of the RILs and applied 112–233 polymorphic markers to each population. Out of 31 QTL detected, we found five on chromosome 3 in three populations and another five on chromosome 7 in three populations. Other QTL were detected in one population, nine of them in different years. In the NT population, two QTL were detected in a 3.0-Mb region on chromosome 7 and in an 8.1-Mb region on chromosome 18 by evaluating nine recombinant fixed pairs in both Kanto and Tohoku regions. In the SF population, a QTL on chromosome 8 was detected in both regions. This QTL was introduced into the ‘Satonohohoemi’ background by backcrossing, and its effect was confirmed in both regions. In summary, two QTL on chromosomes 7 and 18 from the NT population and one QTL on chromosome 8 from the SF population were confirmed to be effective in both Tohoku and Kanto regions.

International audience; Objective : Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series.Methods : We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants.Results : In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3).Interpretation : The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

The present study was conducted to evaluate the benefits of indeterminate growth habit in breeding to improve yield potential of Japanese soybean varieties, which exclusively have determinate growth habit. Two populations of recombinant inbred lines (RILs) derived from crosses between determinate Japanese cultivars and indeterminate US cultivars were grown in Akita and Kyoto, and seed weight per plant (SW) and its components were compared between indeterminate and determinate RILs. The difference of SW between the two growth habits in RILs varied depending on maturation time. The SW of early indeterminate lines was significantly higher than that of early determinate ones in Akita, but not in Kyoto. Among yield components, the number of seeds per pod was constantly larger in indeterminate lines than that in determinate ones irrespective of maturation time. The number of seeds per plant and the number of pods per plant of the indeterminate lines were greater than those of the determinate lines in early maturation in Akita. These results suggest that the indeterminate growth habit is an advantageous characteristic in breeding for high yield of early maturing soybean varieties in the Tohoku region.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself. Therefore, there is an urgent need for disease modification in terms of the delay or prevention of neurodegeneration. Recent advances in genetic and biochemical studies have provided unifying conceptual frameworks of the pathogenesis of PD. Particularly, membrane trafficking has aroused special attention as an initiator or enhancer of the neurodegenerative process that leads to PD. Defects in the cellular trafficking pathway result in synaptic dysfunction and the accumulation of misfolded α-synuclein. Likewise, changes in intracellular sorting and degradation profoundly influence the cellular trafficking of misfolded proteins, thereby facilitating the cell-to-cell spreading of hazardous α-synuclein species in a prion-like manner. Here, we will review our current knowledge of the functional roles of membrane trafficking in PD and will discuss how this cellular process could induce or facilitate the functional and pathological alterations in this disease.

We detected a QTL for single seed weight in soybean that was stable across multiple environments and genetic backgrounds with the use of two recombinant inbred line populations. Single seed weight (SSW) in soybean is a key determinant of both seed yield and the quality of soy food products, and it exhibits wide variation. SSW is under genetic control, but the molecular mechanisms of such control remain unclear. We have now investigated quantitative trait loci (QTLs) for SSW in soybean and have identified such a QTL that is stable across multiple environments and genetic backgrounds. Two populations of 225 and 250 recombinant inbred lines were developed from crosses between Japanese and US cultivars of soybean that differ in SSW by a factor of ~2, and these populations were grown in at least three different environments. A whole-genome panel comprising 304 simple sequence repeat (SSR) loci was applied to mapping in each population. We identified 15 significant QTLs for SSW dispersed among 11 chromosomes in the two populations. One QTL located between Sat_284 and Sat_292 on chromosome 17 was detected (3.6

Freezing of gait (FOG) is one of the factors that reduce the quality of life in patients with Parkinson's disease (PD). Imagining bicycling before gait start provided improvement in FOG in 2 PD patients. Imagining and mimicking bicycling after the initiation of gait allowed the rhythmic gait to continue without interruption. We suggest that imagining and mimicking bicycling, which are nonexternal cues, could serve as a helpful therapeutic approach for the intractable freezing and interruption of gait of PD patients.

Demyelinating polyneuropathy associated with amyotrophic lateral sclerosis (ALS) is quite rare. We herein present the case of a woman patient with a 12-year history of chronic inflammatory demyelinating polyneuropathy (CIDP)-like polyneuropathy who later developed bulbar palsy and respiratory failure. The autopsy findings revealed neuronal loss in the anterior horn and primary motor cortex with degeneration of the corticospinal tracts. Diffuse phosphorylated TAR DNA-binding protein of 43 kDa inclusions were observed in the anterior horn and cerebral cortices, including the temporal lobe. The final diagnosis was ALS with CIDP-like polyneuropathy. Compared with other reports of ALS with CIDP-like polyneuropathy, the present patient was younger and followed a relatively long clinical course, with no upper motor neuron signs.

Dementia is one of the most debilitating symptoms of Parkinson's disease (PD), but the development of dementia is still difficult to predict at early stages of the disease. We recently found that hyposmia, one of the most typical non-motor features of PD, was a predictive feature of Parkinson's disease with dementia (PDD). In that work, multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in scores on the odor stick identification test for Japanese (OSIT-J). We also found an association between severe hyposmia and a specific pattern of cerebral metabolic decline, which was identical to findings observed in PDD. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and atrophy of focal brain structures, including the amygdala and other limbic structures. Our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of PDD. We have now started a randomized, double-blind study using donepezil for the PD group with severe hyposmia. We hope that this clinical trial will allow us to establish a therapeutic intervention that can improve the prognosis of advanced PD.

Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disease involving parkinsonism, ataxia, and autonomic failure, in any combination. The unifying histopathological hallmark of MSA is the appearance of α-synuclein (αSYN)-positive, triangular-shaped glial cytoplasmic inclusion (GCI) in affected brain regions including striatonigral and/or olivopontocerebellar systems. It is known that GCI follows the regions showing neuronal loss and gliosis, and the incidence of GCI is well correlated with disease severity and duration, suggesting that the oligodendroglial αSYN pathology in MSA would be a prerequisite for the disease rather than a consequence of glio-neuronal degeneration. The mechanisms underlying the neuronal cell loss followed by oligodendroglial degeneration in MSA still remain elusive; however, recent observations from cultured cells, animal models, neuropathological and genetic studies have highlighted the several etiopathological factors including mitochondrial dysfunction, oxidative stress, aberrant misfolded protein processing and neuroinflammation. In the present review, we summarize a general overview of potential pathogenic processes and discuss the topics for debate especially focusing on the mechanisms by which αSYN accumulation in oligodendrocytes can secondarily lead to neuronal cell death.

Seed saponin composition of 3025 wild soybean (Glycine soja Sieb. and Zucc.) accessions collected from nine regions of Korea was analysed by thin-layer chromatography to determine its polymorphic variation and geographical distribution and find mutants in saponin components. The saponin composition of seed hypocotyls was primarily divided into seven phenotypes, designated as Aa, Ab, AaBc, AbBc, Aa+α, AaBc+α and AbBc+α. The predominant phenotypes were AaBc (55%), Aa (33%), AaBc+α (7.5%) and Aa+α (3.3%). The frequencies of Ab, AbBc and AbBc+α were very low (0.3-0.5%). Codominant alleles Sg-1a and Sg-1b and dominant allele Sg-4 occupied 98.6, 1.1 and 63.3%, respectively. Alleles Sg-3 and Sg-5 were found to be dominant in all the analysed accessions except the mutants. Three accessions were discovered as mutants via LC-PDA/MS/MS. The accession CWS0115 did not produce saponin Aa and Ax, CWS2133 did not produce saponin Aa and Ab and CWS5095 did not produce any group A saponins. These newly determined mutants might be utilized in producing a new soybean variety with good taste as well as in biosynthetic studies.

Objective:To determine whether 18F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS).Methods:We evaluated the in vitro binding of 3H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, 18F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD).Results:3H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher 18F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher 18F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism.Conclusions:18F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. 18F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.

We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.

Endosomal sorting required for transport (ESCRT) complexes orchestrate endo-lysosomal sorting of ubiquitinated proteins, multivesicular body formation and autophagic degradation. Defects in the ESCRT pathway have been implicated in many neurodegenerative diseases, but the underlying molecular mechanisms that link them to neurodegeneration remain unknown. In this study, we showed that forebrain-specific ablation of ESCRT-0/Hrs induced marked hippocampal neuronal cell loss accompanied by the accumulation of ubiquitinated proteins, including α-synuclein, TDP-43 and huntingtin as well as the autophagic substrate SQSTM1/p62. Consistent with this, silencing of Hrs in cultured cells not only led to α-synuclein and TDP-43 accumulation in addition to impaired autophagic flux but also suppressed cell viability through the induction of ER stress followed by the activation of JNK and RIPK1, a key regulator of necroptosis. Moreover, necrostatin-1, a specific inhibitor of RIPK1 and pan-caspase inhibitors partially reduced the neurotoxicity in the Hrs-silenced cells. Altogether, these findings suggest that the disruption of ESCRT-0/Hrs in the nervous system compromises autophagic/lysosomal degradation of neurodegenerative disease-related proteins, which thereby triggers ER stress-mediated apoptotic and necroptotic cell death.

Objective To investigate the cortical metabolic alterations that precedes longitudinal cognitive decline in Parkinson's disease (PD). Methods We analyzed the data of 46 PD patients who did not have dementia at baseline and completed 3-year follow-up. Based on the results of general cognitive, memory and visuospatial tests, patients were classified into cognitively normal PD (PD-CogNL), PD with mild cognitive impairment (PD-MCI), and PD dementia (PDD). The regional cerebral glucose metabolism at rest was measured using 18F-fluorodeoxyglucose positron emission tomography. Voxel-wise effect size analyses were performed to delineate abnormal metabolic patterns associated with changes in cognitive status in PD. Results At baseline, 29 patients had PD-CogNL, and 17 patients had PD-MCI. At follow-up, 28 patients had PD-CogNL, 12 patients had PD-MCI, and 6 patients developed PDD. Seventeen of 29 PD-CogNL patients remained to be PD-CogNL, and 9 PD-CogNL patients converted to PD-MCI. Eleven PD-MCI patients reverted to normal cognition during follow-up. 3 PD-CogNL and 3 PD-MCI patients developed PDD. Cognitively stable PD-CogNL group had frontal predominant hypometabolism. PDD converters showed parieto-occipital hypometabolism at baseline regardless of whether a patient's initial cognitive status is PD-CogNL or PD-MCI. Conclusions Parieto-occipital hypometabolism is a good predictor of early dementia conversion in PD.

Saponins are sterols or triterpene glycosides that are widely distributed in plants. The biosynthesis of soybean saponins is thought to involve many kinds of glycosyltransferases, which is reflected in their structural diversity. Here, we performed linkage analyses of the Sg-3 and Sg-4 loci, which may control the sugar chain composition at the C-3 sugar moieties of the soybean saponin aglycones soyasapogenols A and B. The Sg-3 locus, which controls the production of group A saponin Af, was mapped to chromosome (Chr-) 10. The Sg-4 locus, which controls the production of DDMP saponin βa, was mapped to Chr-1. To elucidate the preference of sugar chain formation at the C-3 and C-22 positions, we analyzed the F(2) population derived from a cross between a mutant variety, Kinusayaka (sg-1(0)), for the sugar chain structure at C-22 position, and Mikuriya-ao (sg-3), with respect to the segregation of the composition of the group A saponins, and found that the formation of these sugar chains was independently regulated. Furthermore, a novel saponin, predicted to be A0-γg, 3-O-[β-d-galactopyranosyl (1→2)-β-d-glucuronopyranosyl]-22-O-α-l-arabinopyranosyl-soyasapogenol A, appeared in the hypocotyl of F(2) individuals with genotype sg-1(0)/sg-1(0)sg-3/sg-3.

The peanut stunt virus (PSV) causes yield losses in soybean and reduced seed quality due to seed mottling. The objectives of this study were to determine the phenotypic reactions of soybean germplasms to inoculation with two PSV isolates (PSV-K, PSV-T), the inheritance of PSV resistance in soybean cultivars, and the locus of the PSV resistance gene. We investigated the PSV resistance of 132 soybean cultivars to both PSV isolates; of these, 73 cultivars exhibited resistance to both PSV isolates. Three resistant cultivars (Harosoy, Tsurunotamago 1 and Hyuga) were crossed with the susceptible cultivar Enrei. The crosses were evaluated in the F(1), F(2) and F(2:3) generations for their reactions to inoculation with the two PSV isolates. In an allelism test, we crossed Harosoy and Tsurunotamago 1 with the resistant cultivar Hyuga. The results revealed that PSV resistance in these cultivars is controlled by a single dominant gene at the same locus. We have proposed Rpsv1, as the name of the resistance gene in Hyuga. We also constructed a linkage map using recombinant inbred lines between Hyuga × Enrei using 176 SSR markers. We mapped Rpsv1 near the Satt435 locus on soybean chromosome 7.

Dementia is one of the most debilitating symptoms of Parkinson's disease. A recent longitudinal study suggests that up to 80% of patients with Parkinson's disease will eventually develop dementia. Despite its clinical importance, the development of dementia is still difficult to predict at early stages. We previously identified olfactory dysfunction as one of the most important indicators of cortical hypometabolism in Parkinson's disease. In this study, we investigated the possible associations between olfactory dysfunction and the risk of developing dementia within a 3-year observation period. Forty-four patients with Parkinson's disease without dementia underwent the odour stick identification test for Japanese, memory and visuoperceptual assessments, (18)F-fluorodeoxyglucose positron emission tomography scans and magnetic resonance imaging scans at baseline and 3 years later. A subgroup of patients with Parkinson's disease who exhibited severe hyposmia at baseline showed more pronounced cognitive decline at the follow-up survey. By the end of the study, 10 of 44 patients with Parkinson's disease had developed dementia, all of whom had severe hyposmia at baseline. The multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in the score of odour stick identification test for Japanese. We also found an association between severe hyposmia and a characteristic distribution of cerebral metabolic decline, which was identical to that of dementia associated with Parkinson's disease. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and the atrophy of focal brain structures, including the amygdala and other limbic structures. Together, our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of Parkinson's disease dementia.

Hyposmia is one of the cardinal early symptoms of Parkinson disease (PD). Accumulating clinical and pathological evidence suggests that dysfunction of the olfactory-related cortices may be responsible for the impaired olfactory processing observed in PD; however, there are no clear data showing a direct association between altered brain metabolism and hyposmia in PD. In this study, we evaluated brain glucose metabolism and smell-identification ability in 69 Japanese patients with nondemented PD. Olfactory function was assessed using the Odor Stick Identification Test for Japanese. The regional cerebral metabolic rate of glucose consumption at rest was measured using (18)F-fluorodeoxyglucose positron emission tomography and was analyzed using SPM-based group comparisons and the brain-behavior partial least-squares method. We found that olfactory dysfunction was closely related to cognitive dysfunction, including memory impairment. Moreover, brain-behavior partial least-squares analysis revealed that odor-identification performance was closely associated with broad cortical dysfunction, including dysfunction of the piriform cortex and amygdala. Our results suggest that the cognitive deficit in olfactory perception is an important aspect of hyposmia in PD and that this deficit is caused by altered brain metabolism in the amygdala and piriform cortex.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder presenting variable combinations of parkinsonism, cerebellar ataxia, corticospinal and autonomic dysfunction. Alpha-synuclein (α-SYN)-immunopositive glial cytoplasmic inclusions (GCIs) represent the neuropathological hallmark of MSA, and tubulin polymerization promoting protein (TPPP)/p25 in oligodendroglia has been known as a potent stimulator of α-SYN aggregation. To gain insight into the molecular pathomechanisms of GCI formation and subsequent oligodendroglial degeneration, we ectopically expressed α-SYN and TPPP in HEK293T and oligodendroglial KG1C cell lines. Here we showed that TPPP specifically accelerated α-SYN oligomer formation and co-immunoprecipitation analysis revealed the specific interaction of TPPP and α-SYN. Moreover, phosphorylation of α-SYN at Ser-129 facilitated the TPPP-mediated α-SYN oligomerization. TPPP facilitated α-SYN-positive cytoplasmic perinuclear inclusions mimicking GCI in both cell lines; however, apoptotic cell death was only observed in KG1C cells. This apoptotic cell death was partly rescued by sirtuin 2 (SIRT2) inhibition. Together, our results provide further insight into the molecular pathogenesis of MSA and potential therapeutic approaches.

The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.

Saponins are a diverse group of secondary metabolites widely distributed in plants. Some saponins in soybean seeds have medicinal properties, but the terminal acetylated sugar at the C-22 position of group A saponins in seed hypocotyls causes a bitter and astringent taste. We used cultivated and wild soybean accessions classified into four different group A saponin phenotypes, including non-acetylated A0-αg and deacetyl-Af, as parents to obtain four F2 populations and a population of recombinant inbred lines to test their genetic relationship. The gene controlling the phenotype of the group A saponins in each line was mapped near the simple sequence repeat marker Satt336 on soybean chromosome 7 (linkage group M). An allelism test of the A0-αg and deacetyl-Af variants revealed no segregation of Aa and Ab phenotypes in the progeny, although the genes controlling the two phenotypes have been assigned to two different loci, Sg-1 and Sg-2. These results suggest that the four group A saponin phenotypes are controlled by multiple alleles at the single locus Sg-1.

Background and Objective:Calcium channel antagonists (calcium channel blockers [CCBs]) are often used in the treatment of patients with hypertension to achieve strict blood pressure (BP) targets. In the present study, we compared the antihypertensive effects (determined by home BP [HBP] measurements) and the effects on renal function of benidipine (hydrochloride) and amlodipine (mesylate), a commonly used CCB. Methods:Changes in HBP and urinary albumin excretion (UAE) were investigated in 47 benidipine and 37 amlodipine recipients with essential hypertension and albuminuria between January 2007 and December 2007. Results:Both benidipine and amlodipine significantly reduced morning and evening HBP over a 12-month period. Both medications also significantly reduced UAE compared with pretreatment values; however, the reduction in UAE observed in the benidipine group occurred independent of the drug’s antihypertensive effects, whereas a positive correlation was shown between the reduction in morning systolic BP and UAE in the amlodipine group. Conclusion:These results demonstrate that benidipine favourably affects renal function in patients with essential hypertension compared with amlodipine, suggesting that the clinical benefits of benidipine as an antihypertensive drug include a renoprotective effect.