Pyramiding of multiple strong-culm genes originating from indica and tropical japonica to the temperate japonica rice.

Severe lodging has recurrently occurred at strong typhoon's hitting in recent climate change. The identification of quantitative trait loci and their responsible genes associated with a strong culm and their pyramiding are important for developing high-yielding varieties with a superior lodging resistance. To evaluate the effects of four strong-culm genes on lodging resistance, the temperate japonica near isogenic line (NIL) with the introgressed SCM1 or SCM2 locus of the indica variety, Habataki and the other NIL with the introgeressed SCM3 or SCM4 locus of the tropical japonica variety, Chugoku 117 were developed. Then, we developed the pyramiding lines with double,triple and quadruple combinations derived from step-by-step crosses among NIL-SCM1-NIL-SCM4. Quadruple pyramiding line (NIL-SCM1 + 2 + 3 + 4) showed the largest culm diameter and the highest culm strength among the combinations and increased spikelet number due to the pleiotropic effects of these genes. Pyramiding of strong culm genes resulted in much increased culm thickness, culm strength and spikelet number due to their additive effect. SCM1 mainly contributed to enhance their pyramiding effect. These results in this study suggest the importance of identifying the combinations of superior alleles of strong culm genes among natural variation and pyramiding these genes for improving high-yielding varieties with a superior lodging resistance.

Element Mapping in Single-Atom-Width Platinum-Iridium Wires.

Single-atom-width wires (SAWWs) of platinum-iridium (PtIr) alloy were produced by mechanical breaking inside a transmission electron microscope. The formation dynamics, the atomic configuration, and the conductance were observed in situ. From the observed lattice images of the SAWWs and image simulation, the structure models, i.e., the configurations of atom position and element allocation, were constructed. Using the experiment-based structural models, the first-principle calculation of the conductance was performed. The atomic configuration and element allocation of the observed SAWWs were identified via the combination of the lattice imaging and calculation. The conductance of PtIr SAWWs changed in complexity for different element allocation in addition to the wire length and the configuration of the constituent atoms, which was difficult to presage from the conductance features of pure metal SAWWs. The present study revealed that the conductance of alloy SAWWs can be controlled by element allocation.

Amyloid beta25-35 impairs docosahexaenoic acid efflux by down-regulating fatty acid transport protein 1 (FATP1/SLC27A1) protein expression in human brain capillary endothelial cells.

Decreased levels of docosahexaenoic acid (DHA), an endogenous neuroprotective compound, in the brain are associated with the development of Alzheimer's disease (AD). We previously showed that DHA is a substrate of fatty acid transport protein 1 (FATP1/SLC27A1), and FATP1 is localized at the abluminal membrane of brain capillary endothelial cells. We hypothesized that amyloid ß (Aß) decreases FATP1-mediated cellular efflux (i.e. supply to the brain) of DHA at the blood-brain barrier (BBB). Here, we tested this hypothesis using a human cerebral microvascular endothelial cell line, human cerebral microvessel endothelial cells (hCMEC/D3), as a BBB model. The efflux of DHA-d5 by hCMEC/D3 cells increased time-dependently up to 3 min. Knock-down of FATP1 with specific siRNA indicated that FATP1-mediated efflux accounts for 47.0% of this DHA-d5 efflux. In hCMEC/D3 cells treated with Aß25-35 (10 µM/24 h), which we employed as an in vitro model of the BBB in AD, FATP1 protein expression in the plasma membrane was decreased by 96.0%, which was greater than the decrease in the whole-cell lysate, and the DHA-d5 efflux was decreased by 68.3%. Of this 68.3% decrease, 45.1% (47.0 × 0.96) is accounted for by the decrease in FATP1-mediated efflux and the remaining 23.2% is presumably mediated by other mechanism(s). Thus, we have established for the first time that FATP1 is a major contributor to DHA efflux from human brain capillary endothelial cells, and its efflux activity at the abluminal membrane of the cells is blocked by Aß. This may explain the decreased DHA level in the brain of AD patients. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.

We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324.

WIPPER: an accurate and efficient field phenotyping platform for large-scale applications.

More accurate, rapid, and easy phenotyping tools are required to match the recent advances in high-throughput genotyping for accelerating breeding and genetic analysis. The conventional data recording in field notebooks and then inputting data to computers for further analysis is inefficient, time-consuming, laborious, and prone to human error. Here, we report WIPPER (for Wireless Plant Phenotyper), a new phenotyping platform that combines field phenotyping and data recording with the aid of Bluetooth communication, thus saving time and labor not only for field data recoding but also for inputting data to computers. Additionally, it eliminates the risk of human error associated with phenotyping and inputting data. We applied WIPPER to 100 individuals of a rice recombinant inbred line (RIL) for measuring leaf width and relative chlorophyll content (SPAD value), and were able to record an accurate data in a significantly reduced time compared with the conventional method of data collection. We are currently using WIPPER for routine management of rice germplasm including recording and documenting information on phenotypic data, seeds, and DNA for their accelerated utilization in crop breeding.

Isolation of a novel lodging resistance QTL gene involved in strigolactone signaling and its pyramiding with a QTL gene involved in another mechanism.

Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait locus (QTL), STRONG CULM3 (SCM3), the causal gene of which is identical to rice TEOSINTE BRANCHED1 (OsTB1), a gene previously reported to positively control strigolactone (SL) signaling. A near-isogenic line (NIL) carrying SCM3 showed enhanced culm strength and increased spikelet number despite the expected decrease in tiller number, indicating that SL also has a positive role in enhancing culm strength and spikelet number. We produced a pyramiding line carrying SCM3 and SCM2, another QTL encoding APO1 involved in panicle development. The NIL-SCM2+SCM3 showed a much stronger culm than NIL-SCM2 and NIL-SCM3 and an increased spikelet number caused by the additive effect of these QTLs. We discuss the importance of utilizing suitable alleles of these STRONG CULM QTLs without inducing detrimental traits for breeding.

Isolation of a novel lodging resistance QTL gene involved in strigolactone signaling and its pyramiding with a QTL gene involved in another mechanism.

Lodging has been a major roadblock to attaining increased crop productivity. In an attempt to understand the mechanism for culm strength in rice, we isolated an effective quantitative trait loci (QTL), STRONG CULM3 (SCM3), the causal gene of which is identical to rice TEOSINTE BRANCHED1 (OsTB1), a gene previously reported to positively control strigolactone (SL) signaling. A near-isogenic line (NIL) carrying SCM3 showed enhanced culm strength and increased spikelet number despite the expected decrease in tiller number, indicating that SL also has a positive role in enhancing culm strength and spikelet number. We produced a pyramiding line carrying SCM3 and SCM2, another QTL encoding APO1 involved in panicle development. The NIL-SCM2+SCM3 showed a much stronger culm than NIL-SCM2 and NIL-SCM3 and an increased spikelet number caused by the additive effect of these QTLs. We discuss the importance of utilizing suitable alleles of these STRONG CULM QTLs without inducing detrimental traits for breeding.

Differentiation between amnestic-mild cognitive impairment and early-stage Alzheimer's disease using the Frontal Assessment Battery test.

BACKGROUND: Previous research has described the executive dysfunction that occurs in patients with amnestic-mild cognitive impairments (A-MCI) and early-stage Alzheimer's disease (EAD), which are comparatively similar stages of dementia. The aim of the present cross-sectional study is to evaluate executive dysfunction using the Frontal Assessment Battery (FAB) screening test in two groups and to investigate the interaction with other cognitive impairments. METHODS: Among 170 consecutive patients with Alzheimer's disease or A-MCI, we recruited 48 subjects who were under 75 years of age and had been diagnosed as having either A-MCI or EAD. We then compared the total and the subtest scores of the mini-mental state examination (MMSE) and the FAB between the two groups. Moreover, we investigated the statistical interactive associations of the FAB subtest scores with the influential MMSE subtest scores or the diagnosis (A-MCI or EAD). RESULTS: No significant differences in the age, sex ratio, duration of illness, and education years were observed between the two groups. However, significant differences in the FAB total and subtest scores (conflicting instructions and go/no-go) were found between the two groups. Furthermore, significant differences in the MMSE total and subtest scores (orientation, memory delayed recall, and attention and calculation) were also noted between the two groups. In a generalized linear model analysis, only two FAB subtest scores (conflicting instructions and go/no-go) were significantly influenced by the diagnosis (A-MCI or EAD) in a manner that was independent of the interaction with the orientation or memory delayed recall. CONCLUSION: The present findings suggest that the FAB total score and subtest scores reflecting interference performances (conflicting instructions and go/no-go) significantly declined in patients with EAD, independent of the disorientation and memory disorder. Such characteristics of neuropsychological screening test scores may be useful to clinicians for differentiating EAD and A-MCI at bedside.

Association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease.

BACKGROUND: To address the functional roles of genetic polymorphisms of brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross-sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non-memory cognitive impairment. METHODS: One hundred and sixty-nine outpatients with AD or amnestic mild cognitive impairment (A-MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G (n = 45), G/A (n = 104), and A/A (n = 20); and (ii) C270T: C/C (n = 160), C/T (n = 9), and T/T (n = 0). Then, age, sex ratio, duration of illness (months), education years, Mini-Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. RESULTS: Significant differences were found in the total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave-AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). CONCLUSION: Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non-memory cognitive impairment in Japanese patients with AD.

Association between executive dysfunction and hippocampal volume in Alzheimer's disease.

BACKGROUND: Some previous research has hypothesized that executive dysfunction in patients with early Alzheimer's disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function. METHODS: From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimer's disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group. RESULTS: The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05). CONCLUSION: These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

New approach for rice improvement using a pleiotropic QTL gene for lodging resistance and yield.

The use of fertilizer results in tall rice plants that are susceptible to lodging and results in reduced plant yields. In this study, using chromosome segment substitution lines, we identified an effective quantitative trait loci (QTL) for culm strength, which was designated STRONG CULM2 (SCM2). Positional cloning of the gene revealed that SCM2 was identical to ABERRANT PANICLE ORGANIZATION1 (APO1), a gene previously reported to control panicle structure. A near-isogenic line carrying SCM2 showed enhanced culm strength and increased spikelet number because of the pleiotropic effects of the gene. Although SCM2 is a gain-of-function mutant of APO1, it does not have the negative effects reported for APO1 overexpression mutants, such as decreased panicle number and abnormal spikelet morphology. The identification of lodging-resistance genes by QTL analysis combined with positional cloning is a useful approach for improving lodging resistance and overall productivity in rice.

Relationship of frontal lobe dysfunction and aberrant motor behaviors in patients with Alzheimer's disease.

BACKGROUND: In order to address the neuropsychological pathogenesis of aberrant motor behaviors in Alzheimer's disease (AD), we used a cross-sectional study design to investigate the association between frontal lobe function, including executive function, and activity disturbances (wandering, purposeless activities and inappropriate activities). METHODS: Among 75 consecutive outpatients with AD, 50 subjects with a Clinical Dementia Rating (CDR) score of 1 or 2 were selected and divided into two groups based on data obtained from interviews with their caregivers: an aberrant motor behaviors (AMB) group (n = 22), and a non-aberrant motor behaviors (NAMB) group (n = 28). Aberrant motor behavior was defined according to whether the "activity disturbance" score (ranging from 0 to 9) of the Behavioral Pathology in Alzheimer Disease (Behave-AD) scale was 0 or >or=1. The total and subtest scores of the Frontal Assessment Battery (FAB) were then compared between the two groups. RESULTS: Significant differences were found between the FAB total (P < 0.05) and the subtest scores (lexical fluency, conflicting instructions; P < 0.05) in the two groups. The FAB score was significantly associated with the activity disturbance score (r = -0.49; P<0.001). A stepwise multiple regression analysis showed that only the FAB score significantly influenced the activity disturbance score (P < 0.001). CONCLUSIONS: This finding suggested that in addition to episodic memory disturbance, frontal lobe dysfunctions might lead patients with AD to develop aberrant motor behavior.

The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson's disease.

Visual hallucinations (VHs) are common psychiatric symptoms in patients with long-standing Parkinson's disease (PD). Treatment with neuroleptics or withdrawal of anti-PD drugs may improve VHs but will worsen motor dysfunctions. The authors report on 3 patients with long-standing PD who were treated with the cholinesterase inhibitor donepezil for the treatment of VHs. Each received a daily dose of 5 mg of donepezil, after reducing or discontinuing anti-PD medications had failed to relieve the VHs. In 2 patients (patient 1, 2), donepezil decreased VHs without worsening motor dysfunctions. In addition, the cognitive status of patient 2 improved. In patient 3, donepezil also resolved VHs, but delusions developed during treatment. After discontinuing donepezil, delusions disappeared and VHs reappeared. Donepezil may ameliorate visual hallucinations in PD patients, but controlled, double-blind trials are necessary to further clarify the effect of this drug on VHs in PD.

[Case of prolonged recovery from serotonin syndrome caused by paroxetine].

We report a case of serotonin syndrome in a patient being treated with paroxetine for depression. Despite prompt discontinuation of medication, his serotonin syndrome continued for 10 days before full consciousness was restored. The patient was a 48-year-old male with chief complaints of hypobulia and suicidal thoughts. He consulted as a psychiatric outpatient, and oral paroxetine 20 mg/day, etizolam 1.0 mg/day, and brotizolam 0.25 mg/day were immediately started. Upsurge of feeling and disinhibition state were noted the following day, then on treatment day 6 his condition deteriorated to substupor state and he was admitted for further treatment. On admission, change of mental condition (consciousness disturbance), perspiration, hyperreflexia, myoclonus and tremor were seen, and serotonin syndrome caused by paroxetine was suspected. Paroxetine was thus discontinued, and under intravenous drip his condition gradually improved. However, it was not until the 10th hospital day that he became fully alert. In examinations, no infectious, metabolic or organic diseases were detected. The patient's condition often improves with in 24 hours of discontinuation of the causative medication in serotonin syndrome. Symptoms continued for 10 days in this patient, however, perhaps because paroxetine was administered for 6 days before discontinuation. In addition, interaction with other medications may have occurred. Therefore, when serotonin syndrome is suspected, prompt discontinuation of the suspected causative medication, followed by close monitoring of the pharmacokinetics is warranted.