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TUBB4A gene variants cause dystonia type 4 and hypomyelination with atrophy of the basal ganglia and cerebellum. We report the case of a child with delayed motor development, intellectual disability, and dystonia. Magnetic resonance imaging revealed hypomyelination and progressive cerebellar atrophy without atrophy of the basal ganglia. Whole-exome sequencing revealed a de novo heterozygous variant, c.1088T > C, p.(Met363Thr), in TUBB4A. The present case further supports the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants., (© 2022. The Author(s).)

The southern root-knot nematode (SRKN; Meloidogyne incognita ) is a typical parasitic nematode that affects sweetpotato [ Ipomoea batatas (L.) Lam.], causing a significant decrease in crop yield and commercial value. In Japan, the SRKN is classified into 10 races: SP1-SP5, SP6-1, SP6-2, and SP7-SP9, with the dominant race differing according to the cultivation area. Soil insecticides have previously been used to reduce the soil density of SRKNs; however, this practice is both costly and labor intensive. Therefore, the development of SRKN-resistant sweetpotato lines and cultivars is necessary. However, due to the complexity of polyploid inheritance and the highly heterogeneous genomic composition of sweetpotato, genetic information and research for this species are significantly lacking compared to those for other major diploid crop species. In this study, we utilized the recently developed genome-wide association approach, which uses multiple-dose markers to assess autopolyploid species. We performed an association analysis to investigate resistance toward SRKN-SP2, which is the major race in areas with high sweetpotato production in Japan. The segregation ratio of resistant and susceptible lines in the F 1 mapping population derived from the resistant "J-Red" and susceptible "Choshu" cultivars was fitted to 1: 3, suggesting that resistance to SP2 may be regulated by two loci present in the simplex. By aligning the double digest restriction-site associated DNA sequencing reads to the published Ipomoea trifida reference sequence, 46,982 single nucleotide polymorphisms (SNPs) were identified (sequencing depth > 200). The association study yielded its highest peak on chromosome 7 (Chr07) and second highest peak on chromosome 3 (Chr03), presenting as a single-dose in both loci. Selective DNA markers were developed to screen for resistant plants using the SNPs identified on Chr03 and Chr07. Our results showed that SRKN-SP2-resistant plants were selected with a probability of approximately 70% when combining the two selective DNA markers. This study serves as a model for the identification of genomic regions that control agricultural traits and the elucidation of their effects, and is expected to greatly advance marker-assisted breeding and association studies in polyploid crop species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Obata, Tabuchi, Kurihara, Yamamoto, Shirasawa and Monden.)

Background: Infants with trisomy 13 have a very high mortality rate. However, aggressive interventions for their complications, can improve their prognosis and may, thereby, increase the number of long-term survivors with trisomy 13. To date, there is no study on the psychomotor developmental progress of patients with trisomy 13. We conducted this survey to clarify the prognostic factors, living circumstances, and developmental status of infants the trisomy 13., Methods: Patients with trisomy 13 who were admitted to the Department of Pediatrics, Jichi Medical University Hospital were enrolled. Their clinical data were investigated retrospectively using clinical records., Results: Nine patients with trisomy 13 were enrolled and divided into the early death (died at <1 year) and long-term survival (survived for >1 year) groups. All the early death group patients had severe congenital heart disease. Heart failure at under 1 year of age was associated with early death. All the long-term survival group patients underwent operations (e.g. tracheostomy or gastrostomy) and all used home nursing and/or a social care service. Three patients used home mechanical ventilation. None of the patients was able to stand alone or speak intelligible words. Two patients without severe brain anomalies were able to roll over, sit up, and smile by 3 years of age., Conclusions: Long-term survivors with trisomy 13 require extensive nursing and medical care. It is important to provide medical and welfare services to reduce the burden on families. In patients without severe brain anomalies, psychomotor development may be expected. However, no clear developmental prognostic factors were found., (© 2022 Japan Pediatric Society.)

The ability to understand the way other people see the world differs from one's own viewpoint is referred to as ''visual perspective-taking'' (VPT). Previous studies have demonstrated the behavioral performance in level 2 VPT (VPT2), the ability to understand that two different observers can have unique visual experiences of the same scene or object depending on the observers' physical location, changes during childhood. However, the developmental aspects underlying the neural mechanisms of VPT2 remains unknown. We measured the hemodynamic responses to a VPT2 task using functional near-infrared spectroscopy, with mental rotation (MR) as a control task in 7- to 11-year-old and 11- to 16-year-old groups. In the VPT2 task, participants were required to mentally compute the perspective of a toy on the turntable from that of a doll placed in a different location from the observer. For the MR task, participants reported their perspectives after the toy was rotated. We found significantly higher oxy-hemoglobin changes during the VPT2 task than the MR task in the 7- to 11-year-old group but not in the 11- to 16-year-old group, in the right middle and superior temporal, angular gyrus and frontal regions. These findings highlight the important role of the right temporoparietal region in processing perspective, up to 11 years., (© 2022 Wiley Periodicals LLC.)

Background: The Eyberg Child Behavior Inventory (ECBI) is one of the standardized parent rating scales used to identify disruptive behavior problems in children in Western countries. This study aimed to determine norms for the Japanese version of the ECBI, including clinical cutoff scores among the general population in Japan., Methods: This study established norms for the Japanese version of the ECBI using a sample of 1,992 parents of children aged 2-7, living in Japan. The research evaluates the validity and the reliability of the ECBI scores for the Intensity Scale and the Problem Scale. After validation, a clinical cutoff value of the ECBI scores was calculated, setting the cutoff to above the +1 standard deviation (SD) level based on the population distribution., Results: The means of the Intensity and Problem Scale scores were 100.07 and 6.57, respectively. Cronbach's α for both the Intensity and the Problem scores was 0.91. At this point, we propose cutoff scores of 125 for the Intensity Scale and 14 for the Problem Scale., Conclusions: Our results suggest that the Japanese version of the ECBI is highly reliable and may be useful as a tool for assessing behavior problems in children., (© 2021 Japan Pediatric Society.)

Difficulties with visual perspective-taking among individuals with autism spectrum disorders remain poorly understood. Many studies have presumed that first-person visual input can be mentally transformed to a third-person perspective during visual perspective-taking tasks; however, existing research has not fully revealed the computational strategy used by those with autism spectrum disorders for taking another person's perspective. In this study, we designed a novel approach to test a strategy using the opposite-directional effect among children with autism spectrum disorders. This effect refers to how a third-person perspective as a visual input alters a cognitive process. We directly manipulated participants' visual perspective by placing a camera at different positions; participants could watch themselves from a third-person perspective during a reaching task with no endpoint feedback. During a baseline task, endpoint bias (with endpoint feedback but no visual transformation) did not differ significantly between groups. However, the endpoint was affected by extrinsic coordinate information in the control group relative to the autism spectrum disorders group when the visual perspective was transformed. These results indicate an increased reliance on proprioception during the reaching task with perspective manipulation in the autism spectrum disorders group., (© 2021. The Author(s).)

Because weevils are the most damaging pests of sweetpotato, the development of cultivars resistant to weevil species is considered the most important aspect in sweetpotato breeding. However, the genes and the underlying molecular mechanisms related to weevil resistance are yet to be elucidated. In this study, we performed an RNA sequencing-based transcriptome analysis using the resistant Kyushu No. 166 (K166) and susceptible Tamayutaka cultivars. The weevil resistance test showed a significant difference between the two cultivars at 30 days after the inoculation, specifically in the weevil growth stage and the suppressed weevil pupation that was only observed in K166. Differential expression and gene ontology analyses revealed that the genes upregulated after inoculation in K166 were related to phosphorylation, metabolic, and cellular processes. Because the weevil resistance was considered to be related to the suppression of larval pupation, we investigated the juvenile hormone (JH)-related genes involved in the inhibition of insect metamorphosis. We found that the expression of some terpenoid-related genes, which are classified as plant-derived JHs, was significantly increased in K166. This is the first study involving a comprehensive gene expression analysis that provides new insights about the genes and mechanisms associated with weevil resistance in sweetpotato.

Objective: In the current study, we explored the neural substrate for acute effects of guanfacine extended release (GXR) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD), using functional near-infrared spectroscopy (fNIRS). Methods: Following a GXR washout period, 12 AD HD children (6-10 years old) performed a go/no-go task before and 3 h after GXR or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design study. In the primary analysis, fNIRS was used to monitor the right prefrontal cortical hemodynamics of the participants, where our former studies showed consistent dysfunction and osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine hydrochloride (ATX) elicited recovery. We examined the inter-medication contrast, comparing the effect of GXR against the placebo. In the exploratory analysis, we explored neural responses in regions other than the right prefrontal cortex (PFC). Results: In the primary analysis, we observed no significant main effects or interactions of medication type and age in month (two-way mixed ANCOVA, Fs < 0.20, all ps > .05). However, in the post-hoc analysis, we observed significant change in the oxy-Hb signal in the right angular gyrus (AG) for inter-medication (one sample t -test, p < 0.05, uncorrected, Cohen's d = 0.71). Conclusions: These results are different from the neuropharmacological effects of OROS-MPH and ATX, which, in an upregulated manner, reduced right PFC function in ADHD children during inhibitory tasks. This analysis, while limited by its secondary nature, suggested that the improved cognitive performance was associated with activation in the right AG, which might serve as a biological marker to monitor the effect of GXR in the ADHD children., Competing Interests: This study was funded by Shionogi & Co., Ltd. and Takeda Pharmaceutical Company Limited. The funders were involved in the design of the study and reviewed the manuscript for publication but had no role in conducting the study: collection, management, and analysis. YM reported receiving lecture fees from Nobelpharma Co., Ltd., Eli Lilly Japan K.K., Shionogi & Co., Ltd., and Takeda Pharmaceutical Company Limited. TY reported receiving a research grant from Eisai Co., Ltd. And lecture fees from Novartis Pharma K.K. ID reported receiving a research grant from Saizeriya Co., Ltd., Nichirei Corporation, Kasugai Seika Co., Ltd., and Shiseido Company. Limited. AM was a full-time employee of Hitachi, Ltd. and holds stock in Hitachi, Ltd. and Company. SS is a full-time employee of Hitachi, Ltd. YM, ID, SS, and AM have a licensed patent (WO2017142732, WO2016189955, and US 10,835,169 B2) outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MY declared a past co-authorship with the authors TI, TT, TY, ID, and YM to the handling Editor., (Copyright © 2021 Ikeda, Inoue, Tanaka, Hashimoto, Sutoko, Tokuda, Kyutoku, Maki, Yamagata, Dan and Monden.)

Background: High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10-24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds., Methods: This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration., Results: A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01)., Conclusion: The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed)., Trial Registration: University Hospital Medical Information Network ( UMIN000014665 ). Registered 27 July 2014 - Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000017058.

Intravenous corticosteroids have been regarded as the first-line therapy of anti-myelin-oligodendrocyte glycoprotein antibody (MOG-Ab)-positive acute disseminated encephalomyelitis (ADEM). While steroids are the first-choice therapy, MOG-Ab-positive ADEM has a high relapse rate. In some cases, MOG-Ab-positive ADEM relapses even in a low-MOG-Abs state. There is no evidence-based rule supporting steroid tapering. We herein report a case of MOG-Ab-positive ADEM in which recurrence was preventing by tapering steroids under MOG-Ab seronegativity confirmation. In some cases, the MOG-Ab titer may be an important index for tapering steroids to prevent relapse., Competing Interests: Declaration of Competing Interest There is no conflict of interest for this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the commonly used techniques for drug delivery is to temporarily increase the permeability of tissue barriers. Acoustic energies such as ultrasound and shock waves are known to modulate tissue permeability. Recently, it was found that shock waves modulate the blood-brain barrier in the rat brain without injection of contrast agents such as microbubbles. This finding implies that modulation of other tissue barriers by shock wave exposure without contrast agents may be possible. To examine whether the modulation is also possible with other tissue barriers, we here investigated whether shock waves would modulate an in vitro tissue barrier model consisting of epithelial cells cultured on culture inserts. The permeability of the epithelium sheets evaluated by trans-epithelial electrical resistance (TEER) was increased following shock waves at a peak pressure of 11 MPa. The increased permeability recovered within 2 h. This enhancement was realized with one-shot low-energy shock waves having an acoustic energy of 0.013 mJ/mm 2 . Monitoring the peak pressures in every exposure revealed that the minimum peak pressure required for the enhancement is 2.9 MPa. These results indicate that shock wave exposure has the potential to temporarily increase the permeability of epithelium barriers to enhance drug delivery without contrast agents. Graphical abstract Enhancements of epithelial barrier permeability were evaluated by trans-epithelial electrical resistance (TEER) before and after shock wave exposures.

Autism spectrum disorders (ASD) are associated with face perception atypicalities, and atypical experience with faces has been proposed as an underlying explanation. Studying the own-race advantage (ORA) for face recognition can reveal the effect of experience on face perception in ASD, although the small number of studies in the area present mixed findings. This study probed the ORA in ASD by comparing two cultural groups simultaneously for the first time. Children with ASD in the UK (N = 16) and Japan (N = 26) were compared with age- and ability-matched typically developing (TD) children in the UK (N = 16) and Japan (N = 26). Participants completed a two-alternative forced-choice task, whereby they had to recognize a just seen face from a foil which was manipulated in one of four ways (IC: identity change; EE: easy eyes; HE: hard eyes; HM: hard mouth). Face stimuli were Asian and Caucasian, and thus the same stimuli were own and other race depending on the cultural group. The ASD groups in the UK and Japan did not show impaired face recognition abilities, or impairments with recognizing faces depending on manipulations to the eye region, and importantly they showed an ORA. There was considerable heterogeneity in the presence of the ORA in ASD and TD and also across cultures. Children in Japan had higher accuracy than children in the UK, and TD children in Japan did not show an ORA. This cross-cultural study challenges the view that atypical experiences with faces lead to a reduced/absent ORA in ASD., (© 2020 John Wiley & Sons Ltd.)

Next-generation sequencing (NGS)-based genotyping methods can generate numerous genetic markers in a single experiment and have contributed to plant genetic mapping. However, for high precision genetic analysis, the complicated genetic segregation mode in polyploid organisms requires high-coverage NGS data and elaborate analytical algorithms. In the present study, we propose a simple strategy for the genetic mapping of polyploids using low-coverage NGS data. The validity of the strategy was investigated using simulated data. Previous studies indicated that accurate allele dosage estimation from low-coverage NGS data (read depth < 40) is difficult. Therefore, we used allele dosage probabilities calculated from read counts in association analyses to detect loci associated with phenotypic variations. The allele dosage probabilities showed significant detection power, although higher allele dosage estimation accuracy resulted in higher detection power. On the contrary, differences in the segregation patterns between the marker and causal genes resulted in a drastic decrease in detection power even if the marker and casual genes were in complete linkage and the allele dosage estimation was accurate. These results indicated that the use of a larger number of markers is advantageous, even if the accuracy of allele dosage estimation is low. Finally, we applied the strategy for the genetic mapping of autohexaploid sweet potato ( Ipomoea batatas ) populations to detect loci associated with agronomic traits. Our strategy could constitute a cost-effective approach for preliminary experiments done performed to large-scale studies., (Copyright © 2020 Yamamoto et al.)

Silica cell walls of diatoms have attracted attention as a source of nanostructured functional materials and have immense potential for a variety of applications. Previous studies of silica cell wall formation have identified numerous involved proteins, but most of these proteins are species-specific and are not conserved among diatoms. However, because the basic process of diatom cell wall formation is common to all diatom species, ubiquitous proteins and molecules will reveal the mechanisms of cell wall formation. In this study, we assembled de novo transcriptomes of three diatom species, Nitzschia palea, Achnanthes kuwaitensis, and Pseudoleyanella lunata, and compared protein-coding genes of five genome-sequenced diatom species. These analyses revealed a number of diatom-specific genes that encode putative endoplasmic reticulum-targeting proteins. Significant numbers of these proteins showed homology to silicanin-1, which is a conserved diatom protein that reportedly contributes to cell wall formation. These proteins also included a previously unrecognized SET domain protein methyltransferase family that may regulate functions of cell wall formation-related proteins and long-chain polyamines. Proteomic analysis of cell wall-associated proteins in N. palea identified a protein that is also encoded by one of the diatom-specific genes. Expression analysis showed that candidate genes were upregulated in response to silicon, suggesting that these genes play roles in silica cell wall formation. These candidate genes can facilitate further investigations of silica cell wall formation in diatoms.

While sweetpotato ( Ipomoea batatas L.) improvement has generally been done by field-based selection, molecular genetic studies on traits of interest, i.e., molecular markers are needed for enhancing the breeding program of this world's 7 th most important crop, as such markers facilitate marker-assisted selection. Here, we performed a combined approach of QTLs analyses and GWAS of storage root β-carotene content (BC), dry-matter (DM) and starch content (SC) using the genetic linkage maps constructed with 5,952 and 5,640 SNPs obtained from F 1 progenies between cultivars 'J-Red' and 'Choshu'. BC was negatively correlated with DM (r = -0.45) and SC (r = -0.51), while DM was positively correlated with SC (r = 0.94). In both parental maps, a total of five, two and five QTL regions on linkage groups 7 and 8 were associated with BC, DM and SC, respectively. In GWAS of BC, one strong signal ( P = 1.04 × 10 -9 ) was observed on linkage group 8, which co-located with one of the above QTL regions. The SNPs markers found here, particularly for β-carotene, would be useful base resources for future marker-assisted selection program with this trait., (Copyright © 2020 by JAPANESE SOCIETY OF BREEDING.)

In this study, DNA markers were developed for discrimination of strawberry ( Fragaria × ananassa L.) cultivars based on retrotransposon insertion polymorphisms. We performed a comprehensive genomic search to identify retrotransposon insertion sites and subsequently selected one retrotransposon family, designated CL3, which provided reliable discrimination among strawberry cultivars. Through analyses of 75 strawberry cultivars, we developed eight cultivar-specific markers based on CL3 retrotransposon insertion sites. Used in combination with 10 additional polymorphic markers, we differentiated 35 strawberry cultivars commonly cultivated in Japan. In addition, we demonstrated that the retrotransposon-based markers were effective for PCR detection of DNA extracted from processed food materials, whereas a SSR marker was ineffective. These results indicated that the retrotransposon-based markers are useful for cultivar discrimination for processed food products, such as jams, in which DNA may be fragmented or degraded., (Copyright © 2020 by JAPANESE SOCIETY OF BREEDING.)

Significance: It has been reported that children with attention-deficit hyperactivity disorder (ADHD) have impairment in the recognition of angry but not of happy facial expressions, and they show atypical cortical activation patterns in response to facial expressions. However, little is known about neural mechanisms underlying the impaired recognition of facial expressions in school-aged children with ADHD and the effects of acute medication on their processing of facial expressions. Aim: We aimed to investigate the possibility that acute administration of methylphenidate (MPH) affects processing of facial expressions in ADHD children. Approach: We measured the hemodynamic changes in the bilateral temporo-occipital areas of ADHD children observing the happy and angry facial expressions before and 1.5 h after MPH or placebo administration in a randomized, double-blind, placebo-controlled, crossover design study. Results: We found that, regardless of medication, happy expressions induced increased oxyhemoglobin (oxy-Hb) responses in the right inferior occipital region but not in the superior temporal region. For angry expressions, oxy-Hb responses increased after MPH administration, but not after placebo administration, in the left inferior occipital area, whereas there was no significant activation before MPH administration. Conclusions: Our results suggest that (1) ADHD children consistently recruit the right inferior occipital regions to process happy expressions and (2) MPH administration to ADHD children enhances cortical activation in the left inferior occipital regions when they process angry expressions., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Background: The pathogenesis of acute encephalopathy (AE) remains unclear, and a biomarker has not been identified., Methods: Levels of 49 cytokines and chemokines, including osteopontin (OPN), were measured in serum and cerebrospinal fluid (CSF) of children with AE (n = 17) or febrile convulsion (FC; n = 8; control group). The AE group included acute necrotizing encephalopathy (n = 1), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 3), clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS; n = 4), and unclassified acute encephalopathy (UCAE; n = 9) that does not meet the criteria of syndrome classification. Five individuals with AE had neurological sequelae or death (poor prognosis), whereas 12 were alive without neurological sequelae (good prognosis)., Results: The CSF:serum ratios of OPN, CC chemokine ligand (CCL)4, and interleukin (IL)-10 were significantly higher in AE than in FC. The CSF levels of macrophage inhibitory factor (MIF) and leukemia inhibitory factor (LIF) were significantly higher in the poor-prognosis group than in the good-prognosis group. The CSF:serum ratios of OPN were significantly higher in AESD and in MERS than in FC. The CSF:serum ratios of MIF and OPN were higher in MERS than in UCAE or FC., Conclusion: Our results suggest that microglia-related cytokines and chemokines such as OPN, MIF, and LIF could be novel biomarkers of AE, in addition to the previously reported IL-10 and CCL4, and that MIF and LIF may be markers of poor prognosis., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Connectivity between brain regions has been redefined beyond a stationary state. Even when a person is in a resting state, brain connectivity dynamically shifts. However, shifted brain connectivity under externally evoked stimulus is still little understood. The current study, therefore, focuses on task-based dynamic functional-connectivity (FC) analysis of brain signals measured by functional near-infrared spectroscopy (fNIRS). We hypothesize that a stimulus may influence not only brain connectivity but also the occurrence probabilities of task-related and task-irrelevant connectivity states. fNIRS measurement (of the prefrontal-to-inferior parietal lobes) was conducted on 21 typically developing (TD) and 21 age-matched attention-deficit/hyperactivity disorder (ADHD) children performing an inhibitory control task, namely, the Go/No-Go (GNG) task. It has been reported that ADHD children lack inhibitory control; differences between TD and ADHD children in terms of task-based dynamic FC were also evaluated. Four connectivity states were found to occur during the temporal task course. Two dominant connectivity states (states 1 and 2) are characterized by strong connectivities within the frontoparietal network (occurrence probabilities of 40%-56% and 26%-29%), and presumptively interpreted as task-related states. A connectivity state (state 3) shows strong connectivities in the bilateral medial frontal-to-parietal cortices (occurrence probability of 7-15%). The strong connectivities were found at the overlapped regions related the default mode network (DMN). Another connectivity state (state 4) visualizes strong connectivities in all measured regions (occurrence probability of 10%-16%). A global effect coming from cerebral vascular may highly influence this connectivity state. During the GNG stimulus interval, the ADHD children tended to show decreased occurrence probability of the dominant connectivity state and increased occurrence probability of other connectivity states (states 3 and 4). Bringing a new perspective to explain neuropathophysiology, these findings suggest atypical dynamic network recruitment to accommodate task demands in ADHD children., (Copyright © 2020 Sutoko, Monden, Tokuda, Ikeda, Nagashima, Funane, Atsumori, Kiguchi, Maki, Yamagata and Dan.)

Key Message: We apply the GWAS to sweet potato genome, and identified the SNPs associated with yield and weevil resistance. The sweet potato (Ipomoea batatas (L.) Lam) is a highly heterozygous, outcrossing, polyploid species, which presents challenges for genetic analysis. Therefore, we considered that genome-wide association studies (GWAS) may be applied to the study of the sweet potato genome. The yield of two sweet potato varieties [Purple Sweet Lord (PSL) and 90IDN-47] was assessed at two locations (Kumamoto and Okinawa prefectures) in Japan in 2013 and the yield scores were used for GWAS. The results showed that there were several single nucleotide polymorphisms (SNP) above the significance thresholds in PSL; two peaks were detected in Kumamoto and Okinawa on the Ib03-3 and Ib01-4 linkage groups of PSL, respectively. As for 90IDN-47, one relatively high peak was detected in Kumamoto on the Ib13-8 linkage group. Interestingly, although high peaks above significance thresholds were detected in Kumamoto and Okinawa in PSL, the peaks were located in different linkage groups. This result suggests that the genetic regions controlling yield may change in response to environmental conditions. Additionally, we investigated the degree of weevil damage to the plants, which is the greatest problem in sweet potato cultivation in Okinawa. In this experiment, no SNPs were identified above the significance thresholds. However, one relatively high peak was found in the 90IDN-47 genotype, which showed resistance to weevils. On the other hand, one relatively high peak was also detected in the PSL genotype, which showed susceptibility to weevils. These results suggest that two regions could affect weevil resistance and may contain the gene(s) controlling weevil resistance.

The southern root-knot nematode, Meloidogyne incognita, is a pest that decreases yield and the quality of sweetpotato [Ipomoea batatas (L.) Lam.]. There is a demand to produce resistant cultivars and develop DNA markers to select this trait. However, sweetpotato is hexaploid, highly heterozygous, and has an enormous genome (∼3 Gb), which makes genetic linkage analysis difficult. In this study, a high-density linkage map was constructed based on retrotransposon insertion polymorphism, simple sequence repeat, and single nucleotide polymorphism markers. The markers were developed using F1 progeny between J-Red, which exhibits resistance to multiple races of M. incognita, and Choshu, which is susceptible to multiple races of such pest. Quantitative trait locus (QTL) analysis and a genome-wide association study detected highly effective QTLs for resistance against three races, namely, SP1, SP4, and SP6-1, in the Ib01-6 J-Red linkage group. A polymerase chain reaction marker that can identify genotypes based on single nucleotide polymorphisms located in this QTL region can discriminate resistance from susceptibility in the F1 progeny at a rate of 70%. Thus, this marker could be helpful in selecting sweetpotato cultivars that are resistant to multiple races of M. incognita., (© The Author(s) 2019. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Connectivity impairment has frequently been associated with the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Although the connectivity of the resting state has mainly been studied, we expect the transition between baseline and task may also be impaired in ADHD children. Twenty-three typically developing (i.e., control) and 36 disordered (ADHD and autism-comorbid ADHD) children were subjected to connectivity analysis. Specifically, they performed an attention task, visual oddball, while their brains were measured by functional near-infrared spectroscopy. The results of the measurements revealed three key findings. First, the control group maintained attentive connectivity, even in the baseline interval. Meanwhile, the disordered group showed enhanced bilateral intra- and interhemispheric connectivities while performing the task. However, right intrahemispheric connectivity was found to be weaker than those for the control group. Second, connectivity and activation characteristics might not be positively correlated with each other. In our previous results, disordered children lacked activation in the right middle frontal gyrus. However, within region connectivity of the right middle frontal gyrus was relatively strong in the baseline interval and significantly increased in the task interval. Third, the connectivity-based biomarker performed better than the activation-based biomarker in terms of screening. Activation and connectivity features were independently optimized and cross validated to obtain the best performing threshold-based classifier. The effectiveness of connectivity features, which brought significantly higher training accuracy than the optimum activation features, was confirmed (88% versus 76%). The optimum screening features were characterized by two trends: (1) strong connectivities of right frontal, left frontal, and left parietal lobes and (2) weak connectivities of left frontal, left parietal, and right parietal lobes in the control group. We conclude that the attentive task-based connectivity effectively shows the difference between control and disordered children and may represent pathological characteristics to be feasibly implemented as a supporting tool for clinical screening., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Attention deficit/hyperactivity disorder (ADHD) has been frequently reported as co-occurring with autism spectrum disorder (ASD). However, ASD-comorbid ADHD is difficult to diagnose since clinically significant symptoms are similar in both disorders. Therefore, we propose a classification method of differentially recognizing the ASD-comorbid condition in ADHD children. The classification method was investigated based on functional brain imaging measured by near-infrared spectroscopy (NIRS) during a go/no-go task. Optimization and cross-validation of the classification method was carried out in medicated-naïve and methylphenidate (MPH) administered ADHD and ASD-comorbid ADHD children (randomized, double-blind, placebo-controlled, and crossover design) to select robust parameters and cut-off thresholds. The parameters could be defined as either single or averaged multi-channel task-evoked activations under an administration condition (i.e., pre-medication, post-MPH, and post-placebo). The ADHD children were distinguished by significantly high MPH-evoked activation in the right hemisphere near the midline vertex. The ASD-comorbid ADHD children tended to have low activation responses in all regions. High specificity (86 ± 4.1%; mean ± SD), sensitivity (93 ± 7.3%), and accuracy (82 ± 1.6%) were obtained using the activation of oxygenated-hemoglobin concentration change in right middle frontal, angular, and precentral gyri under MPH medication. Therefore, the significantly differing MPH-evoked responses are potentially effective features and as supporting differential diagnostic tools.

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of trans-Golgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria.

[This corrects the article DOI: 10.1117/1.NPh.5.4.045001.].

Functional near-infrared spectroscopy (fNIRS) signals are prone to problems caused by motion artifacts and physiological noises. These noises unfortunately reduce the fNIRS sensitivity in detecting the evoked brain activation while increasing the risk of statistical error. In fNIRS measurements, the repetitive resting-stimulus cycle (so-called block-design analysis) is commonly adapted to increase the sample number. However, these blocks are often affected by noises. Therefore, we developed an adaptive algorithm to identify, reject, and select the noise-free and/or least noisy blocks in accordance with the preset acceptance rate. The main features of this algorithm are personalized evaluation for individual data and controlled rejection to maintain the sample number. Three typical noise criteria (sudden amplitude change, shifted baseline, and minimum intertrial correlation) were adopted. Depending on the quality of the dataset used, the algorithm may require some or all noise criteria with distinct parameters. Aiming for real applications in a pediatric study, we applied this algorithm to fNIRS datasets obtained from attention deficit/hyperactivity disorder (ADHD) children as had been studied previously. These datasets were divided for training and validation purposes. A validation process was done to examine the feasibility of the algorithm regardless of the types of datasets, including those obtained under sample population (ADHD or typical developing children), intervention (nonmedication and drug/placebo administration), and measurement (task paradigm) conditions. The algorithm was optimized so as to enhance reproducibility of previous inferences. The optimum algorithm design involved all criteria ordered sequentially (0.047 mM mm of amplitude change, 0.029    mM    mm / s of baseline slope, and 0.6 × interquartile range of outlier threshold for each criterion, respectively) and presented complete reproducibility in both training and validation datasets. Compared to the visual-based rejection as done in the previous studies, the algorithm achieved 71.8% rejection accuracy. This suggests that the algorithm has robustness and potential to substitute for visual artifact-detection.

Background: The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known., Patient: We are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti-myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by recurrent ON. She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment with AZA when CD19 cells reappeared 6 months after the first rituximab infusion. However, she has not relapsed since her CD19 count was reduced and kept low with rituximab infusion., Conclusions: It is conceivable that anti-MOG antibodies are involved in the pathology of "ADEM followed by recurrent ON," and that the early introduction of rituximab, which is involved in the suppression of antibody production and has effects on CD20 T lymphocytes, may be a feasible treatment for ON. Due to the small number of patients, additional reports on prospectively followed patients are needed., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Alexander disease (AxD) is a progressive neurodegenerative disease caused by a mutation in the glial fibrillary acid protein (GFAP) gene. A 4-year-old boy presented several times with hemiclonic seizures with eye deviation for a few minutes at 28 days after birth. Electroencephalogram showed independent sharp waves in the right and left temporal area. Magnetic resonance imaging showed high intensity T1-weighted images in the white matter of the frontal lobe and basal ganglia. He showed no head control at 4 years of age, and his weight gain was insufficient. He did not show macrocephaly. At 4 years of age, he died of bacterial pneumonia and septic shock. He was diagnosed with AxD, and direct sequencing revealed a de novo known mutation, c. 239 T > C, p.(F80S), in GFAP. Hela and U2-OS cells transfected with GFAP cDNA with c. 239 T > C showed dot-like cytoplasmic aggregation, similar to R239C, a common mutation found in severe infantile AxD. Aggregation in the cytoplasm caused by a GFAP mutation is a hallmark of AxD. Although there is only one previous report of a patient with an F80S mutation, our data support that F80S can cause the severe, infantile form of AxD., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is characterized by impairment in social communication and the presence of restricted and repetitive behaviors and interests. Executive function impairment is reportedly partially responsible for these symptoms. Executive function includes planning, flexibility, and inhibitory control. Although planning and flexibility in ASD have been consistently reported as atypical, the atypicality of inhibitory control remains controversial. As most previous studies have used nonsocial stimuli to investigate inhibitory control in ASD, the effects of socially relevant information on the inhibitory control system in individuals with ASD remain unclear. Therefore, we developed a go/no-go task with gaze stimuli and measured hemodynamic responses in the right prefrontal cortex (PFC), involved in inhibitory processing in both typically developing (TD) children and children with ASD, using functional near-infrared spectroscopy. Direct gaze induced commission errors to similar extents in both groups. Contrary to the behavioral responses, neural activation in the right PFC was modulated by gaze direction only in the TD group. These findings suggest that the gaze-processing mechanisms in the prefrontal region may be affected by atypical gaze processing in other brain regions during an inhibitory control task with socially relevant information in ASD.

Leigh syndrome, which is a common phenotype of pediatric mitochondrial disease, is a progressive neurodegenerative disease. The typical neuroimaging findings of Leigh syndrome include bilateral symmetric lesions in the basal ganglia and/or the brainstem. However, there are a few reports on spinal cord involvement in patients with Leigh syndrome. In the present case, magnetic resonance imaging (MRI) obtained during infancy revealed symmetric lesions in the substantia nigra of a patient with Leigh syndrome with an NDUFA1 mutation; lesions of the bilateral putamen and brainstem were subsequently observed. Additionally, our patient presented large and extended spinal cord lesions. Therefore, this case is suggesting that we should consider the occurrence of spinal cord lesions as an atypical finding in Leigh syndrome., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Chlorophyll is an essential molecule for acquiring light energy during photosynthesis. Mutations that result in chlorophyll retention during leaf senescence are called 'stay-green' mutants. One of the several types of stay-green mutants, Type E, accumulates high levels of chlorophyll in the pre-senescent leaves, resulting in delayed yellowing. We isolated delayed yellowing1-1 (dye1-1), a rice mutant whose yellowing is delayed in the field. dye1-1 accumulated more chlorophyll than the wild-type in the pre-senescent and senescent leaves, but did not retain leaf functionality in the 'senescent green leaves', suggesting that dye1-1 is a Type E stay-green mutant. Positional cloning revealed that DYE1 encodes Lhca4, a subunit of the light-harvesting complex I (LHCI). In dye1-1, amino acid substitution occurs at the location of a highly conserved amino acid residue involved in pigment binding; indeed, a severely impaired structure of the PSI-LHCI super-complex in dye1-1 was observed in a blue native PAGE analysis. Nevertheless, the biomass and carbon assimilation rate of dye1-1 were comparable to those in the wild-type. Interestingly, Lhcb1, a trimeric LHCII protein, was highly accumulated in dye1-1, in the chlorophyll-protein complexes. The high accumulation of LHCII in the LHCI mutant dye1 suggests a novel functional interaction between LHCI and LHCII.

Background: In recent years, a resurgence in the number of infants with vitamin D deficiency has been noted. In addition to seasonal differences in exposure to ultraviolet (UV) rays, regional differences in dietary habits and lifestyles may affect susceptibility to vitamin D deficiency. No studies have been conducted, however, on infants in multiple regions of Japan to determine the extent of differences in vitamin D status., Methods: 25-Hydroxyvitamin D (25OHD) was measured on radioimmunoassay in 126 infants aged 2-4 years, who participated in the Pilot Study of the Japan Environment and Children's Study (JECS) by the Ministry of Environment of Japan. A multiple regression model with 25OHD level as the outcome variable, and season and region as explanatory variables, was generated., Results: Both region and season during which infants participated in this study significantly affected 25OHD level (P = 0.0087 and <0.0001, respectively; Wald test). Reflecting decreased exposure to UV rays, infants who were examined in winter had lower 25OHD than those examined in summer. Infants from both Fukuoka Prefecture (33°N) and Kumamoto Prefecture (32°N), however, had lower 25OHD than those from Tochigi Prefecture (36°N), contrary to expectations given the extent of UV exposure., Conclusions: Regional differences in daily habits and/or environmental factors affect 25OHD level in Japanese infants. The JECS is expected to identify those factors to provide guidance on preventing infantile vitamin D deficiency., (© 2017 Japan Pediatric Society.)

Although previous studies have revealed the role of oxytocin (OT) in parental behavior, the role of OT has not been investigated through the direct assessment of prefrontal brain activation during parenting. By using functional near-infrared spectroscopy, we aimed to show the relationship between parental [maternal ( N  = 15) and paternal ( N  = 21)] OT levels and the activation of the prefrontal cortex (PFC), while holding their infants after separation. Baseline OT levels were measured in the subjects' saliva samples before the experiment. Prefrontal brain activation was assessed in participants sitting alone on a chair (i.e., separation from their infant for 120 s) and during the target period (i.e., holding their infant for 45 s), which was done in triplicate. The oxygen hemoglobin (oxy-Hb) dissociation curve significantly increased in 9 out of 22 channels on the PFC when maternal and paternal samples were combined. However, only the fathers showed a correlation between salivary OT and oxy-Hb signal. Furthermore, while holding their infants, high-OT fathers showed left hemispheric dominance compared to low-OT fathers, while high-OT mothers showed right hemispheric dominance compared to low-OT mothers. This study showed that fathers with high-OT levels showed neural activation with left hemispheric dominance, while holding their infants, suggesting that increase of OT level might activate paternal PFC related to parenting behavior, although the same is not true for mothers.

Introduction: Relationships between adipokines, adiposity and severity of acute viral bronchiolitis in infancy have not been elucidated., Materials and Methods: We investigated the relationships between three serum adipokines (leptin, adiponectin and TNF-α), physique index (Kaup index) and clinical severity in 13 bronchiolitis infants. Seven healthy infants were enrolled as the control group. We used Modified Pulmonary Index Score (MPIS) to evaluate bronchiolitis severity., Results: No significant differences in adipokine levels were found between groups. In bronchiolitis infants, Kaup index negatively correlated with MPIS (r = -0.614, p = 0.03). A positive correlation was observed between the serum leptin/adiponectin ratio and MPIS (r = 0.618, p = 0.03), although correlations were not observed between respective serum adipokines levels and MPIS. Serum leptin and adiponectin had significantly negative correlations with age (r = 0.815, p = 0.001 and r = 0.566, p = 0.04, respectively), but not Kaup index., Conclusion: The severity of viral bronchiolitis in infancy may be related to the adipokine profile, but not adiposity.

We report the case of a 19-year-old female patient who had progressive chorea associated with a GNAO1 mutation. Chorea was refractory to multiple anticonvulsants, and the patient suffered from tiapride-induced neuroleptic malignant syndrome. After identification of a GNAO1 missense mutation at the age of 18years, topiramate treatment was initiated and the frequency of chorea decreased dramatically. The efficacy of topiramate may have been related to the inhibitory modulation of voltage-activated Ca 2+ channels. Given the side effects and complications associated with neuroleptics and deep brain stimulation, respectively, topiramate is recommended for the first-line management of severe chorea associated with a GNAO1 mutation., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Sweetpotato is one of the most important food crop species in the world, with more than 104,000,000 tons produced each year, and the breeding of superior cultivars with agronomically important traits, such as improved disease resistance, yield, and nutrient richness, is necessary, especially in developing countries. However, as a result of the crop's complex genomic architecture, which results from its hexaploidy (2n = 6× = 90), high heterozygosity, huge genome, and outcrossing nature, the analysis of genetic linkage in sweetpotato has been challenging. In addition, the lack of whole genome sequences or gene annotations for cultivated hexaploids has interrupted the validation of mapped QTL regions and gene cloning. In spite of these technical difficulties, linkage map construction and QTL mapping analysis have been reported. This review summarizes the results of these linkage analyses, which used SSR, AFLP, and retrotransposon-based molecular markers, and describes future directions for the genetic analysis and marker-assisted breeding of this important but genetically complex crop species.

We are reporting on a case of pediatric anti-NMDAR encephalitis with autonomic instability. The patient showed little response to first-line treatment of steroid and IVIG. We initiated plasma exchange, also a first-line treatment. This worsened his autonomic instability, resulting in hypotensive shock. He responded well to rituximab and cyclophosphamide, second-line therapies. Anti-NMDAR encephalitis is often accompanied by autonomic instability. Our and other reported cases, raise the question of plasma exchange as a first-line therapy for pediatric NMDAR encephalitis, which is frequently accompanied by autonomic instability. Plasma exchange should be performed cautiously in such patients., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objectives: Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells., Study Design: Animal experiment using eight beagles (including three controls)., Methods: A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed., Results: A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site., Conclusion: The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

Purpose: To investigate the current status of fungal keratitis in Japan., Methods: The patients with fungal keratitis were examined at 27 facilities in Japan from November 1st 2011 to October 31st 2013, concerning isolates, patient background, clinical findings, treatment and prognosis., Results: Out of 139 cases, 133 were diagnosed as fungal keratitis, of which fungi were isolated from 72 samples of 71 cases (yeast-like fungi 32 strains and filamentous fungi 40 strains). The corrected visual acuity at the first visit of 88 cases (66.2%) was less than 20/200 and 42 cases (31.6%) were involved with deep stromal lesions, indicating high proportion of severe cases in this study. Three months later, 56 cases (42.1%) were still under treatment, and corrected visual acuity of 57 cases (42.9%) was less than 20/200. In cases with yeast-like fungi, there were significantly more cases with past history of corneal diseases, ocular surgery including keratoplasty, and eye drops' use such as steroids than those with filamentous fungi. On the other hand, there were significantly more cases of filamentous fungi, with trauma on the onset and with intervention of previously attending doctors than those with yeast-like fungi. Logistic regression analyses revealed that contact lens wearing was a significant factor of good prognosis, and yeast-like fungi as one of poor outcome compared with no fungal isolation., Conclusion: Although the choice of antifungal drugs has been increasing, fungal keratitis is still severe, refractory and vision-threatening disease.

Purpose: To investigate the causative fungi of fungal keratitis in Japan and their drug susceptibility., Methods: Identification and antifungal susceptibility test for 8 drugs (micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, miconazole and pimaricin) were performed using isolated fungi from patients with fungal keratitis treated at 27 facilities in Japan between November 1, 2011 and October 31, 2013., Results: Fungal strains were detected in 72 (50.7%) out of 142 samples. The major isolates were Fusarium spp. (18), Candida parapsilosis (12), C. albicans (11) and Alternaria spp. (6), in all, fungi of 31 species were identified by gene analysis. In the yeast-like fungi, susceptibility rates were evident for more than 80% in voriconazole, pimaricin, flucytosine, micafungin, amphotericin B and fluconazole. In filamentous fungi, the susceptibility rate was less than 50% except for PMR (90%). Fusarium spp., which were susceptible to amphotericin B and pimaricin, showed lower susceptibility rates compared with other genera., Conclusions: Although various genera and species of fungi cause fungal keratitis, the obtained drug susceptibility data in this study demonstrates the different susceptibility patterns among the major isolates (Fusarium spp., C. parapsilosis, C. albicans and other groups). This is important evidence useful for fungal keratitis treatment.

De novo GNAO1 variants have been found in four patients including three patients with Ohtahara syndrome and one patient with childhood epilepsy. In addition, two patients showed involuntary movements, suggesting that GNAO1 variants can cause various neurological phenotypes. Here we report an additional four patients with de novo missense GNAO1 variants, one of which was identical to that of the previously reported. All the three novel variants were predicted to impair Gαo function by structural evaluation. Two patients showed early-onset epileptic encephalopathy, presenting with migrating or multifocal partial seizures in their clinical course, but the remaining two patients showed no or a few seizures. All the four patients showed severe intellectual disability, motor developmental delay, and involuntary movements. Progressive cerebral atrophy and thin corpus callosum were common features in brain images. Our study demonstrated that GNAO1 variants can cause involuntary movements and severe developmental delay with/without seizures, including various types of early-onset epileptic encephalopathy.

While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD), an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS), which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs) and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level.

Sweetpotato (Ipomoea batatas L.) is an outcrossing hexaploid species with a large number of chromosomes (2n = 6x = 90). Although sweetpotato is one of the world's most important crops, genetic analysis of the species has been hindered by its genetic complexity combined with the lack of a whole genome sequence. In the present study, we constructed a genetic linkage map based on retrotransposon insertion polymorphisms using a mapping population derived from a cross between 'Purple Sweet Lord' (PSL) and '90IDN-47' cultivars. High-throughput sequencing and subsequent data analyses identified many Rtsp-1 retrotransposon insertion sites, and their allele dosages (simplex, duplex, triplex, or double-simplex) were determined based on segregation ratios in the mapping population. Using a pseudo-testcross strategy, 43 and 47 linkage groups were generated for PSL and 90IDN-47, respectively. Interestingly, most of these insertions (~90%) were present in a simplex manner, indicating their utility for linkage map construction in polyploid species. Additionally, our approach led to savings of time and labor for genotyping. Although the number of markers herein was insufficient for map-based cloning, our trial analysis exhibited the utility of retrotransposon-based markers for linkage map construction in sweetpotato.

In many crop species, DNA fingerprinting is required for the precise identification of cultivars to protect the rights of breeders. Many families of retrotransposons have multiple copies throughout the eukaryotic genome and their integrated copies are inherited genetically. Thus, their insertion polymorphisms among cultivars are useful for DNA fingerprinting. In this study, we conducted a DNA fingerprinting based on the insertion polymorphisms of active retrotransposon families (Rtsp-1 and LIb) in sweet potato. Using 38 cultivars, we identified 2,024 insertion sites in the two families with an Illumina MiSeq sequencing platform. Of these insertion sites, 91.4% appeared to be polymorphic among the cultivars and 376 cultivar-specific insertion sites were identified, which were converted directly into cultivar-specific sequence-characterized amplified region (SCAR) markers. A phylogenetic tree was constructed using these insertion sites, which corresponded well with known pedigree information, thereby indicating their suitability for genetic diversity studies. Thus, the genome-wide comparative analysis of active retrotransposon insertion sites using the bench-top MiSeq sequencing platform is highly effective for DNA fingerprinting without any requirement for whole genome sequence information. This approach may facilitate the development of practical polymerase chain reaction-based cultivar diagnostic system and could also be applied to the determination of genetic relationships., (© The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

The current study aimed to explore the neural substrate for atomoxetine effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 15 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after atomoxetine or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Fifteen age-, gender-, and intelligence quotient-matched normal controls without atomoxetine administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices. The right prefrontal and parietal activation was normalized after atomoxetine administration in ADHD children. This was in contrast to our previous study using a similar protocol showing methylphenidate-induced normalization of only the right prefrontal function. fNIRS allows the detection of differential neuropharmacological profiles of both substances in the attentional network: the neuropharmacological effects of atomoxetine to upregulate the noradrenergic system reflected in the right prefrontal and inferior parietal activations and those of methylphenidate to upregulate the dopamine system reflected in the prefrontal cortex activation.

In many crops species, the development of a rapid and precise cultivar discrimination system has been required for plant breeding and patent protection of plant cultivars and agricultural products. Here, we successfully evaluated strawberry cultivars via a novel method, namely, the single tag hybridization (STH) chromatographic printed array strip (PAS) using the PCR products of eight genomic regions. In a previous study, we showed that genotyping of eight genomic regions derived from FaRE1 retrotransposon insertion site enabled to discriminate 32 strawberry cultivars precisely, however, this method required agarose/acrylamide gel electrophoresis, thus has the difficulty for practical application. In contrast, novel DNA detection method in this study has some great advantages over standard DNA detection methods, including agarose/acrylamide gel electrophoresis, because it produces signals for DNA detection with dramatically higher sensitivity in a shorter time without any preparation or staining of a gel. Moreover, this method enables the visualization of multiplex signals simultaneously in a single reaction using several independent amplification products. We expect that this novel method will become a rapid and convenient cultivar screening assay for practical purposes, and will be widely applied to various situations, including laboratory research, and on-site inspection of plant cultivars and agricultural products., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.