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In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (−8.33% [interquartile range: −43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (−‍1.50 [−9.25, 0.00], P = 0.015) and median percent change (−13.33% [−50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

•The effect of ambient pressure on the temperature characteristics of LNH3spray was investigated.•As the ambient air pressure increases, the equilibrium temperatures of the droplet and vapor phases increase.•At moderately high pressures, accounting for flash evaporation in addition to equilibrium evaporation is essential.•LNH3spray flames can be stabilized using preheated swirling airflow.•NO and unburnt NH3in LNH3spray flames also show a trade-off relationship.

There is compelling evidence that glial-immune interactions contribute to the progression of neurodegenerative diseases. The adaptive immune response has been implicated in disease processes of amyotrophic lateral sclerosis (ALS), but it remains unknown if innate immune signaling also contributes to ALS progression. Here we report that deficiency of the innate immune adaptor TIR domain-containing adaptor inducing interferon-β (TRIF), which is essential for certain Toll-like receptor (TLR) signaling cascades, significantly shortens survival time and accelerates disease progression of ALS mice. While myeloid differentiation factor 88 (MyD88) is also a crucial adaptor for most TLR signaling pathways, MyD88 deficiency had only a marginal impact on disease course. Moreover, TRIF deficiency reduced the number of natural killer (NK), NK-T-lymphocytes, and CD8-T cells infiltrating into the spinal cord of ALS mice, but experimental modulation of these populations did not substantially influence survival time. Instead, we found that aberrantly activated astrocytes expressing Mac2, p62, and apoptotic markers were accumulated in the lesions of TRIF-deficient ALS mice, and that the number of aberrantly activated astrocytes was negatively correlated with survival time. These findings suggest that TRIF pathway plays an important role in protecting a microenvironment surrounding motor neurons by eliminating aberrantly activated astrocytes.

Supplemental Digital Content is available in the text.Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which motor neurons selectively degenerate. Superoxide dismutase 1 (SOD1) was found to be a causative gene of familial ALS, and mutant SOD1transgenic mice recapitulated ALS phenotypes. Analysis of these mice showed accumulation of misfolded SOD1 protein in motor neurons. Misfolded SOD1 accumulation was found in spinal motor neurons of both familial ALS patients with the SOD1mutation and sporadic ALS patients. However, it is unclear what condition causes wild-type SOD1 misfolding in patients without the SOD1mutation. Here, we generated induced pluripotent stem cells from mutant SOD1transgenic mice, wild-type SOD1transgenic mice, and control mice, and differentiated them into spinal motor neurons to analyze misfolded SOD1 accumulation. We found that misfolded SOD1 protein was accumulated in spinal motor neurons of both mutant and wild-type SOD1transgenic mice as detected by a specific antibody against the misfolded conformation of SOD1. These results suggest that an increased expression level of wild-type SOD1may accelerate the ALS pathology and that our in vitromodel would be a useful tool for misfolded SOD1 research.

Axonal Charcot–Marie–Tooth disease (CMT) is most frequently caused by mutations in the MFN2gene (CMT2A) that can lead to various clinical phenotypes. The age at disease onset varies, but most cases occur before adolescence. We report two Japanese sisters who presented with middle-age-onset peripheral neuropathy with distinct clinical features. In the affected sisters, a homozygous missense mutation, c.1894C>T, p.R632W, corresponding to the transmembrane domain of MFN2was identified; this mutation was heterozygous in another non-affected sibling, demonstrating co-segregation of the genotype and phenotype. The patients developed adult-onset slowly progressive muscle weakness that was predominant in the calf muscles and sensory disturbance. Magnetic resonance imaging revealed diffuse atrophy of the spinal cord, especially in the thoracic segment, and mild atrophy of the parietal lobe and the cerebellum in both patients. Electron microscopy of the sural nerve revealed clusters of round and swollen mitochondria. This is the first case report of adult-onset CMT2A with an autosomal-recessive inheritance pattern. The phenotype caused by the MFN2mutation in these cases is very mild, considering that the mutation causes middle-aged-onset Charcot–Marie–Tooth even in the homozygous state. The mechanism of MFN2mutation-induced toxicity is an interesting theme that awaits further investigations.

Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.3 (AARS2_v001):c.1145C>A and NM_020745.3 (AARS2_v001):c.2255+1G>A was identified. Neither of the mutations has been previously reported, and this is the first report of alanyl-transfer RNA synthetase 2 mutation in Asia. We anticipate that further studies of the molecular basis of leukodystrophy will provide insight into its pathogenesis and hopefully lead to sophisticated diagnostic and treatment strategies.

The immunostimulation effects of yellowtail heart extracts were examined. Screening various parts of the yellowtail viscera, we found that extracts from the yellowtail heart enhanced IgM production by human hybridoma HB4C5 cells. Yellowtail heart extracts heated at 121 °C for 20 min and dialyzed showed the highest IgM production-stimulating activity toward HB4C5 cells. Also, immunoglobulin production by mouse spleen lymphocytes was stimulated by yellowtail heart extracts in vitro, and lymphocytes derived from mice administered the extract for 20 d were activated in vivo. Yellowtail heart extracts were partially purified by anion-exchange chromatography, and fractions containing a 33 kDa-protein exhibited immunostimulating activity. LC-MS/MS analysis revealed that the 33 kDa-protein was most similar to tropomyosin-4 from various fishes. Purified tropomyosin from porcine muscle enhanced IgM production by HB4C5 cells. This means that tropomyosin-4 is one of the immunostimulating substances in the yellowtail heart.

Negative bias on transfer gate in 4-transistor CMOS imager pixel is an efficient way to reduce dark current generated at the Si-SiO2 interface. But further lowering of negative bias increases dark current noise. In this paper, detailed cause analysis of dark current noise generated when negative bias is applied and the key technology to reduce the dark current noise are shown. The dark output level of hot pixel follows a Trap-Assisted-Tunneling (TAT) dark current electric field dependency. Device simulation shows that the generation of high electric field is attributed to the large voltage difference between the high concentration hole accumulation layer under negatively biased transfer gate and n- layer of FD edge along transfer gate. The reduction of dark current in FD is experimentally observed when the n- dopnat concentration at FD edge is decreased and when a gate insulator thickness is increased. The results show that the mechanism of the dark current increase is Gate-Induced-Leak (GIL) TAT generated by high electric field at the edge of a FD along negatively biased transfer gate. The reduction of the maximum electric filed at the FD edge by reducing FD dopant concentration is one of the key to suppress the GIL - TAT dark current.

A 60-year-old man presented with muscle stiffness. He had tended to fall since childhood. His parents were first cousins, and his relatives had no symptoms. Examination showed myotonia in ocular, hand, and limb muscles, followed by improvement with repeated activity (warm-up phenomenon; Video 1). Cold exposure did not aggravate myotonia. His lower legs showed muscle hypertrophy. Genetic tests showed a homozygous p.M560T mutation in the CLCN1gene, which encodes skeletal muscle chloride channel 1, consistent with autosomal recessive myotonia congenita (Becker disease).1Although treatment with mexiletine or phenytoin did not improve his symptoms, carbamazepine (350 mg/d) did, especially the walking disturbance (Video 2). Although the warm-up phenomenon is sometimes also observed in sodium channel myotonia,2it is characteristic of myotonia congenita and an important clue for the diagnosis.

Increased blood-DNA breakage was observed in diseased pearl oysters. They showed significant formation of 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), whereas the oysters that had a low mortality rate from the disease had high activity of superoxide dismutase (SOD) and low amounts of 8-OHdG and MDA. These results suggest that radical damage had occurred only in the diseased pearl oysters with the cytolysis of their haemocytes, which was related to the mass mortality of the Japanese pearl oysters.

•1st study of LNH3 spray combustion at actual micro gas turbine operating conditions.•Novel combustors with and without wall cooling were developed and tested.•Higher combustor inlet temperature & CH4 fuel content reduced emissions, even NOx.•Low combustor heat loss improved flame stability, reduced NOx, N2O and NH3 emissions.•More homogenous droplets distribution required to improve pure LNH3 spray combustion.

The pathomechanisms and treatment strategy for rare presentations of reversible cerebral vasoconstriction syndrome (RCVS) with anti-phospholipid syndrome (APS) remain to be determined. We report a 67-year-old woman with APS who presented with ischemic stroke due to RCVS. She was treated with low-dose cilostazol and lomerizine hydrochloride, which resulted in functional improvement and recovery of vasoconstriction within 12 weeks. Her plasma endothelin-1 level was decreased after relief of vasoconstriction, compared with the pre-treatment condition. Increased plasma endothelin-1 may be related to the underlying pathomechanism of RCVS with APS, against which cilostazol and lomerizine hydrochloride could be effective.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant white matter disease that causes adult-onset cognitive impairment. The clinical manifestations are a variable combination of personality and behavioral changes, cognitive decline, parkinsonism, spasticity, and epilepsy. In 2012, mutations in the gene encoding colony stimulating factor 1 receptor (CSF1R) were identified as the cause of HDLS. As the numbers of reported mutations are limited, the understanding of whole pathogenesis needs accumulation of disease-causing mutations with detailed clinical descriptions. We describe a Japanese family with autosomal dominant adult-onset cognitive impairment and characteristic white matter lesions. Genetic testing revealed a novel p.A792D mutation in the tyrosine kinase domain of CSF1Rin two affected family members. The symptom profile of the present cases mostly matched the previously reported cases, with the notable exceptions of late-onset and long disease duration.

Abstract: Uniparental inheritance of the chloroplast genome has been observed in a wide variety of green plants. In Chlamydomonas this phenomenon, which can be selectively inhibited by UV irradiation of mt + gametes, has been shown cytologically to be due to the preferential degradation of mt −-derived chloroplast nucleoids in young zygotes. The zygote-specific pair of zys1 genes, zys1A and zys1B, is expressed earliest among five genes isolated from a “10-min” zygote library. We report here that the ZYS1 protein, which is encoded by the invertedly duplicated zys1 gene, accumulates in zygotes and is localized in nuclei. In addition, when mt + gametes (but not mt − gametes) are UV-irradiated before mating, only very limited accumulation of ZYS1 protein can be detected in the resulting zygotes.

Our previous data showed that F344/DuCrj and LEW/Crj rat strains bearing the type a catalase-1 locus (CS1^a) are sensitive to the promoting activity of sodium L-ascorbate (Na-AsA) in 2-stage urinary bladder carcinogenesis, whereas ODS/Shi and WS/Shi rat strains bearing the type b catalase-1 locus (CS1^b) are resistant. In present study, we investigated the susceptibility of F344/Shi rats also bearing the CS1 to the Na-AsA-promoting effects on bladder tumor development. Male rats, 6 weeks old, were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks, then fed either basal diet supplemented with 5% Na-AsA or no chemicals for 32 weeks. The rats given BBN alone had a few small carcinomas in the urinary bladder. In contrast, animals administered BBN-Na-AsA had many large carcinomas. Administration of Na-AsA was associated with significant elevation of urinary pH and L-ascorbic acid. The results indicate that F344/Shi rats are sensitive to the promoting effects of Na-AsA on 2-stage urinary bladder carcinogenesis, and thus that the CS1 locus may not influence susceptibility to promotion. Teratogenesis Carcinog. Mutagen. 18:27–33, 1998. © 1998 Wiley-Liss, Inc.

Rat strain differences in sensitivity to the promoting effect of sodium L‐ascorbate (SA) on the development of urinary bladder tumors were investigated. In experiment 1, WS/Shi (WS), ODS/Shi‐od/od (ODS), and LEW/Crj (LEW) rats were initiated with 0.05%N‐butyl‐N‐(4‐hydroxybutyl)‐nitrosamine (BBN) in their drinking water and subsequently given basal Oriental MF diet (M) with or without a 5% SA supplement. In LEW rats the SA treatment increased the induction of neoplastic lesions in the urinary bladder, whereas WS and ODS animals proved unresponsive to its promoting effects. In experiment 2, WS and F344 rats were maintained on two kinds of commercial basal diets, M and CLEA CA‐1 (C), during administration of SA, since dietary factors can influence promoting effects. Feeding M during the promotion period in F344 rats yielded significantly more neoplastic lesions than feeding C, but in WS rats no such dietary influence was apparent. In experiment 3, strain differences in biosynthesis of α‐2u‐globulin (α2u‐g) were assessed because both α2u‐g in the urine and administration of sodium salts of organic acids such as SA have been reported to be involved in tumor promotion. Immunohistochemical analysis of renal tubules and Western blotting analysis of urine revealed the presence of α2u‐g in all three strains examined. These data suggest that differences in susceptibility to promotion are due to genetic factors rather than dietary factors and the ability to synthesize . α2u‐g.

In order to establish a basis for transformation technology in the petroleum plant Euphorbia tirucalli, the callus of the plant was infected with Agrobacterium, washed with distilled water, sterilized with distilled water containing 100 mg/l of carbenicillin, selected on solidified B5 medium containing 13 mg/l of G418 and 100 mg/l of carbenicillin, and then on solidified B5 medium containing 25 mg/l of G418 and 100 mg/l of carbenicillin for the transgenic calli, and then the callus lines were subcultured successively on solidified B5 medium containing 50 mg/l of G418. We performed PCR analysis of sterilized G418-resistant callus line DNA and concluded that the gene introduced was integrated into the callus genome.

To reduce the number of crystal defects in a p+Si diffusion layer by a low-thermal-budget annealing process, we have examined crystal recovery in the amorphous layer formed by the cryogenic implantation of germanium and boron combined with sub-melt laser spike annealing (LSA). The cryogenic implantation at [?]150 degC is very effective in suppressing vacancy clustering, which is advantageous for rapid crystal recovery during annealing. The crystallinity after LSA is shown to be very high and comparable to that after rapid thermal annealing (RTA) owing to the cryogenic implantation, although LSA is a low-thermal-budget annealing process that can suppress boron diffusion effectively. It is also shown that in the p+Si diffusion layer, there is high contact resistance due to the incomplete formation of a metal silicide contact, which originates from insufficient outdiffusion of surface contaminants such as fluorine. To widely utilize the marked reduction in the number of crystal defects, sufficient removal of surface contaminants will be required in the low-thermal-budget process.

The complete life cycle of a pennellid copepod Peniculus minuticaudaeShiino, 1956 is proposed based on the discovery of all post-embryonic stages together with the post-metamorphic adult females infecting the fins of threadsail filefish Stephanolepis cirrhifer(Monacanthidae) cultured in a fish farm at Ehime Prefecture, Japan. The hatching stage was the infective copepodid. The life cycle of P. minuticaudaeconsists of six stages separated by moults: the copepodid, four chalimi and adult. In this study, the adult males were observed frequently in precopulatory amplexus with various stages of females however, copulation occurs only between adults. Fertilized pre-metamorphic adult females carrying spermatophores may detach from the host and settle again before undergoing massive differential growth into the post-metamorphic adult female. Comparison of the life cycle of P. minuticaudaehas been made with three known pennellids: Lernaeocera branchialis(Linnaeus, 1767), Cardiodectes medusaeus(Wilson, 1908) and Lernaeenicus sprattae(Sowerby, 1806). Among the compared species, P. minuticaudaeis the first ectoparasitic pennellid to be discovered to complete its life cycle on a single host without any change in infection site preferences between infective copepodid and fertilized pre-metamorphic female.

It is shown that a low-sheet-resistance p-type diffusion layer with a small diffusion depth can be fabricated efficiently by cryogenic boron and germanium implantation combined with low-temperature (400 degC) microwave annealing. Compared with the conventional annealing at 1000 degC, a much smaller diffusion depth is obtained at the same sheet resistance. The low sheet resistance at 400 degC is due to microwave absorption in the surface amorphous layer, which is formed by cryogenic germanium implantation. However, the pn junction leakage was worse than that in conventional annealing, because crystal defects remain near the amorphous/crystal interface after microwave annealing. It is found that the pn junction leakage is improved greatly by cryogenic germanium implantation. These results show that a suitable combination of cryogenic implantation and microwave annealing is very promising for p-type diffusion layer technology.

The transcriptional activity of morphologically intact proplastid-nuclei (synonymous with proplastid-nucleoids) isolated from cultured tobacco cells (line BY-2) was examined by an assay of transcription in vitro and Southern hybridization. The isolated proplastid-nuclei incorporated about 7 pmol of UTP into RNA per microgram of DNA during a 60-min incubation. This incorporation of UTP was identified as synthesis of RNA that was dependent on DNA-dependent RNA polymerase. Heparin, a potent inhibitor of initiation of transcription, had no inhibitory effect, suggesting that the transcriptional activity in the isolated proplastid-nuclei is primarily due to chain elongation of nascent transcripts. The compactly organized, chromatin-like structure of the proplastid-nuclei was maintained during the assay of transcription in vitro under suitable conditions. Southern hybridization studies revealed that the pattern of transcripts generated in vitro by the isolated proplastid-nuclei were similar to that of transcripts produced in a lysed proplastid system and that of RNA accumulated in the living cells. Therefore, the system for the assay of transcription in vitro using isolated proplastid-nuclei seems to provide a suitable method for analyzing the relationship between the transcriptional regulation of plastid genes and the structural changes in plastid-nuclei.

The 5′-upstream region (2.4 kb) of the gene for phytochrome I from Pisum sativum (phyl) was fused to the uidA gene from Escherichia coli that encodes β-glucuronidase (GUS). The resulting PHY-GUS fusion was introduced into Petunia hybrida and was used as a reporter of the expression of the phyI gene which was recognized by GUS activity. The PHY-GUS fusion was expressed at a relatively high level when transgenic plants were grown in the dark, while leaves and stems of light-grown plants showed background activity. Flowers of light-grown plants were shown to have significant levels of GUS activity but roots did not have such activity. When light-grown transgenic plants were transferred to the dark, they expressed the activity at levels that corresponded to those of dark-grown plants. Light treatment prior to growth in darkness revealed red/far-red reversibility of recovery of the activity. Thus, the 2.4-kb fragment from the 5′ region of the phyI gene carries the information necessary for the light-repressible autoregulation.