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To report on the effects of a smartphone application, among the medical staff and medical students, for learning English as a foreign language. We conducted an exploratory quasi-experimental study among eight medical staff and 10 medical students in Japan. The participants used an application called ABC Talking (created by ABC Talking Laboratories Inc, currently unavailable due to application renewal), loaded onto their smartphones, to talk with native English speakers from overseas. The participants used the application for five minutes twice a day over five consecutive days as per their convenience. The study collected quantitative and qualitative data using assessments on the participants' listening and speaking skills and questionnaire. The assessment scores of the first five sessions were compared to those of the last five. Average self-assessment scores and teacher assessment scores were compared using a -test. A paired -test was performed on quantitative data of the questionnaire, and content analysis was performed on qualitative data. More than 80% of the calls were made from home and 70% occurred between 9PM and 1AM. The participants' self-assessment scores on their listening and speaking skills increased significantly from the first five sessions to the last five sessions (14.8-26.1%). However, there was no significant change in the assessments by the teachers (-4.5-2.1%). The self-assessment scores of those with low English proficiency were lower than the teachers' assessment scores. Improvement of communicative self-confidence and communicative competence, two factors that affect willingness to communicate, were seen from the questionnaire. Using smartphone applications allows on-demand English training, which may be especially useful to medical staff and students who have unpredictable work schedules. Teachers should be aware that learners tend to assess themselves lower than their actual ability so that they can give appropriate feedback to the learners.

Suspense and surprise, as common and crucial elements of interest realised in literary fiction, are analysed closely in a sample of short stories, so as to develop a detailed explanation of how these forms of interest are created in literary texts, and to propose models for them. Creating suspense involves more conditions, necessary and optional, and more complication than surprise: the several optional conditions mainly serve to intensify the feeling of suspense the reader experiences. Surprise requires two necessary and sufficient conditions, with only a couple of optional conditions to maintain or ensure coherence in the text. The differences are considered attributable to a more fundamental difference between suspense and surprise as emotions. Suspense can be regarded as a progressive emotion, whereas surprise is a perfective emotion. As such, suspense as an interest is considered as a process-oriented interest, while surprise is an effect-oriented one. Suspense is mostly experienced while reading and has the reader involved with the story. Surprise drives the reader to reassess the story in the new light it throws on events and to look for some further message; this is often a main aim of the literary fiction which ends in surprise.

Abstract RationaleThe effects of hypnotics on automobile driving have been attracting increasing attention. However, few driving simulators (DSs) have been confirmed to have acceptable reliability and validity for assessing the next-day residual effects of zopiclone as a positive control on driving performance.ObjectiveTo investigate whether a new DS could permit detection of the next-day residual effects of zopiclone on driving performance.MethodsIn this double-blind, randomized, placebo-controlled crossover trial, 28 healthy males received zopiclone 7.5 mg at bedtime on days 1 and 8 and placebo on the other days over a period of 16 days. The participants took part in three driving tasks—road-tracking, car-following, and harsh-braking—using a DS on days 2 and 9 at 9-h post-dosing. Scores on the Karolinska Sleepiness Scale and Profile of Mood States-Second Edition were then assessed, as was the serum concentration of zopiclone.ResultsThe estimated differences in the standard deviation of lateral position (cm) in the road-tracking task between the zopiclone and placebo groups on days 2 and 9 were 3.75 cm (90% confidence interval (CI): 1.71–5.79) and 4.07 cm (90% CI: 2.02–6.11), respectively. The estimated differences in the distance coefficient of variation in the car-following task and in the brake reaction time in the harsh-braking task between the zopiclone and placebo groups on day 2 were 4.31 (90% CI: 1.94–6.69) and 24.6 ms (90% CI: 12.7–36.4), respectively.ConclusionsThe DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance.

Pyruvate transporter is BASS2 Many of the plastid-localized metabolic pathways of plants, including the C 4 photosynthetic pathway that operates in many crop plants, depend critically on the import of pyruvate. The pyruvate transporter has proved elusive, but has now been identified as the bile acid:sodium symporter family protein 2 (BASS2). The BASS2 protein is found in the chloroplast envelope membrane, and is highly abundant in C 4 plants. Orthologues of BASS2 are present in all the genomes of land plants characterized so far, thus indicating the widespread importance of sodium-coupled pyruvate import in plastids. Pyruvate serves as a metabolic precursor for many plastid-localized biosynthetic pathways, such as those for fatty acids 1 , terpenoids 2 and branched-chain amino acids 3 . In spite of the importance of pyruvate uptake into plastids (organelles within cells of plants and algae), the molecular mechanisms of this uptake have not yet been explored. This is mainly because pyruvate is a relatively small compound that is able to passively permeate lipid bilayers 4 , which precludes accurate measurement of pyruvate transport activity in reconstituted liposomes. Using differential transcriptome analyses of C 3 and C 4 plants of the genera Flaveria and Cleome , here we have identified a novel gene that is abundant in C 4 species, named BASS2 ( BILE ACID:SODIUM SYMPORTER FAMILY PROTEIN 2 ). The BASS2 protein is localized at the chloroplast envelope membrane, and is highly abundant in C 4 plants that have the sodium-dependent pyruvate transporter. Recombinant BASS2 shows sodium-dependent pyruvate uptake activity. Sodium influx is balanced by a sodium:proton antiporter (NHD1), which was mimicked in recombinant Escherichia coli cells expressing both BASS2 and NHD1. Arabidopsis thaliana bass2 mutants lack pyruvate uptake into chloroplasts, which affects plastid-localized isopentenyl diphosphate synthesis, as evidenced by increased sensitivity of such mutants to mevastatin, an inhibitor of cytosolic isopentenyl diphosphate biosynthesis. We thus provide molecular evidence for a sodium-coupled metabolite transporter in plastid envelopes. Orthologues of BASS2 can be detected in all the genomes of land plants that have been characterized so far, thus indicating the widespread importance of sodium-coupled pyruvate import into plastids.

This case–control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical ( · OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O 2 ·− ) and alkoxyl radical (RO · ) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of · OH, O 2 ·− , and RO · scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM ( des ktop-equipped SPIM for c leared specimens), a low-cost ($20,000–50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced ( https://github.com/dbsb-juntendo/descSPIM ), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies. Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

Purpose To analyze the initiation of compaction in human embryos in vitro by using time-lapse cinematography (TLC), with the goal of determining the precise timing of compaction and clarifying the morphological changes underlying the compaction process. Methods One hundred and fifteen embryos donated by couples with no further need for embryo-transfer were used in this study. Donated embryos were thawed and processed, and then their morphological behavior during the initiation of compaction was dynamically observed via time-lapse cinematography (TLC) for 5 days. Results Although the initiation of compaction occurred throughout the period from the 4-cell to 16-cell stage, 99 (86.1 %) embryos initiated compaction at the 8-cell stage or later, with initiation at the 8-cell stage being most frequent (22.6 %). Of these 99 embryos, 49.5 % developed into good-quality blastocysts. In contrast, of the 16 (13.9 %) embryos that initiated compaction prior to the 8-cell stage, only 18.8 % developed into good-quality blastocysts. Embryos that initiated compaction before the 8-cell stage showed significantly higher numbers of multinucleated blastomeres, due to asynchronism in nuclear division at the third mitotic division resulting from cytokinetic failure. Conclusions The initiation of compaction primarily occurs at the third mitotic division or later in human embryos. Embryos that initiate compaction before the 8-cell stage are usually associated with aberrant embryonic development (i.e., cytokinetic failure accompanied by karyokinesis).

Purpose Normally fertilized zygotes generally show two pronuclei (2PN) and the extrusion of the second polar body. Conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI) often result in abnormal monopronuclear (1PN), tripronuclear (3PN), or other polypronuclear zygotes. In this study, we performed combined analyses of the methylation status of pronuclei (PN) and the number of centrosomes, to reveal the abnormal fertilization status in human zygotes. Method We used differences in DNA methylation status (5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)) to discriminate between male and female PN in human zygotes. These results were also used to analyze the centrosome number to indicate how many sperm entered into the oocyte. Result Immunofluorescent analysis shows that all of the normal 2PN zygotes had one 5mC/5hmC double-positive PN and one 5mC-positive PN, whereas a parthenogenetically activated oocyte had only 5mC staining of the PN. All of the zygotes derived from ICSI (1PN, 3PN) had two centrosomes as did all of the 2PN zygotes derived from c-IVF. Of the 1PN zygotes derived from c-IVF, more than 50 % had staining for both 5mC and 5hmC in a single PN, and one or two centrosomes, indicating fertilization by a single sperm. Meanwhile, most of 3PN zygotes derived from c-IVF had a 5mC-positive PN and two 5mC/5hmC double-positive PNs, and had four or five centrosomes, suggesting polyspermy. Conclusions We have established a reliable method to identify the PN origin based on the epigenetic status of the genome and have complemented these results by counting the centrosomes of zygotes.

Background The decline in glomerular filtration rate is an unfortunate consequence of chronic kidney disease (CKD). People diagnosed with CKD are limited to managing the illness with a combination of lifestyle changes and pharmaceutical agents that target the renin–angiotensin–aldosterone system pathway. Researchers are investigating the potential of herbal agents, such as Astragali Radix, as treatment options in CKD. However, few studies have investigated this compound, and even fewer have examined the oral administration of the compound concerning its significance in bioavailability, as well as realistic compliance of daily medicinal use among potential users. We investigated the clinical effects of the oral administration of Astragali Radix as a renoprotective medicinal agent. Methods A total of 16 participants with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 (CKD stage 3b) were included in the study. Approximately 10 g per day of Astragali Radix was mixed with 200 mL of water and infused by heating until the volume was reduced to 100 mL, which was set as the daily dose. All patients continued to take the Western pharmacological agents after initiating adjunctive treatment with Astragali Radix. The Benjamini–Hochberg (false discovery rate (FDR) correction) method and paired t -test were used to compare each participant’s baseline eGFR with their follow-up eGFR at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 years after adjunctive treatment with oral Astragali Radix extract. Results After starting Astragali Radix treatment, the mean eGFR of the subjects significantly increased from 34.3 ± 5.3 to 45.5 ± 10.7 mL/min/1.73 m 2 at 1 year (15 cases); 46.2 ± 10.5 mL/min/1.73 m 2 at 2 years (14 cases); 45.0 ± 10.0 mL/min/1.73 m 2 at 3 years (13 cases); and 42.2 ± 8.5 mL/min/1.73 m 2 at 5 years (11 cases). Only one case showed increased urine protein levels during the 5-year study period, while urine protein levels of other individuals did not increase. The major side effects of taking Astragali Radix were skin rash and an urticaria-like allergic reaction, which was observed in three excluded participants in the initial period. Conclusions These results suggest that Astragali Radix can preserve and potentially improve long-term eGFR in patients with CKD stage G3b or G4. Astragali Radix may be an option for treating CKD mainly caused by diabetes or hypertension.

Background Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin. Results We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandible (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyzed the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1 , an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs. Conclusions Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.