Adopting Moodle:Case Studies in the Diffusion of Innovation

This joint research paper among five part-time English teachers at Maebashi Kyoai Gakuen University, hereafter called Kyoai University, represents a focused practical application of Action Research based on CALL (Computer Assisted Language Learning) in the classroom and syllabus. This research builds upon the history and development of CALL at the University, including previous research based on student perceptions of CALL (Deadman, 2014) and teacher’s perceptions and evaluations of multimedia technologies (Mason, 2014). The paper details and investigates how CALL is adopted amongst the teachers in this study, through the existent software Moodle (Modular Object-Oriented Dynamic Learning Environment). Two of the members of this group have used Moodle, whereas the three other part-time teachers have had limited exposure and experience using it. The aim of this research group is to peer-teach each other in a community of practice, in order that our own technology skills increase, ultimately transferring this to better learning experiences for the students. The paper will use teachers experience, observations and planning to detail the purposefulness of technology in the curriculum; the teacher’s own perceptions of the technology; the subsequent selection, planning and design of appropriate class-specific Moodle applications; and each teacher’s initial evaluations of Moodle as they begin to construct their own Moodle accounts for various classes.　A general　e-mail was sent to all Japanese part-time teachers who would be interested in jointly partaking in a research paper, based on the above considerations. As such, the members of this research paper are equal in membership and responsibility for the research, as per the ethical considerations of practitioner research (Hammersley, M., Gomm, R., and Woods, P., 2003)

Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA) alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Huntington’s disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general

Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data

SummaryCellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data

Genome-Edited Triple-Recessive Mutation AltersSeed Dormancy in Wheat

1Common wheat has three sets of sub-genomes, making mutations difficult to observe, especially for traits controlled by recessive genes. Here, we produced hexaploid wheat lines with loss of function of homeoalleles of Qsd1, which controls seed dormancy in barley, by Agrobacterium-mediated CRISPR/Cas9. Of the eight transformed wheat events produced, three independent events carrying multiple mutations in wheat Qsd1 homeoalleles were obtained. Notably, one line had mutations in every homeoallele. We crossed this plant with wild-type cultivar Fielder to generate a transgene-free triple-recessive mutant, as revealed by Mendelian segregation. The mutant showed a significantly longer seed dormancy period than wild-type, which may result in reduced pre-harvest sprouting of grains on spikes. PCR, southern blotting, and whole-genome shotgun sequencing revealed that this segregant lacked transgenes in its genomic sequence. This technique serves as a model for trait improvement in wheat, particularly for genetically recessive traits, based on locus information from diploid barley

Metastatic skull tumors: MRI features and a new conventional classification

Skull metastases are malignant bone tumors which are increasing in incidence. The objectives of this study were to characterize the MR imaging features, locations, and extent of metastatic skull tumors to determine the frequency of the symptomatic disease, and to assess patient outcomes. Between September 2002 and March 2008, 175 patients undergoing routine head MR imaging were found to have metastatic skull tumors. Contrast-enhanced study with fat suppression was used in some cases when required. Classification of metastases was simplified to three yes/no questions: first, with regard to location (either in the calvarium or in the cranial base); second, with regard to distribution within the plane of the cranial bone (either “circumscribed” meaning clearly demarcated and confined to one bone, or “diffuse” and likely to spread across a suture to another bone); and third, with regard to invasion (“intraosseous” in cranial bones only, or “invasive” spreading from the skull, either out into the scalp or inward to the dura and perhaps further in). Primary sites were breast cancer (55%), lung cancer (14%), prostate cancer (6%), malignant lymphoma (5%), and others (20%). The mean time from primary diagnosis to skull metastasis diagnosis was 71 months for cases of breast cancer, 26 months for prostate cancer, 9 months for lung cancer, and 4 months for malignant lymphoma. Calvarial circumscribed intraosseous metastases were found most frequently (27%). The patients were mainly asymptomatic. However, some patients suffered from local pain or cranial nerve palsies that harmed their quality of life. Treatment, mainly for symptomatic cases, was by local or whole-skull irradiation. Metastatic skull tumors are not rare, and most are calvarial circumscribed intraosseous tumors. MR images contribute to understanding their type, location, and multiplicity, and their relationship to the brain, cranial nerves, and dural sinuses. Radiation therapy improved the QOL of patients with neurological symptoms

Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

Background: Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results: To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions: Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.ArticleBMC GENOMICS. 14:248 (2013)journal articl

Separated Transcriptomes of Male Gametophyte and Tapetum in Rice: Validity of a Laser Microdissection (LM) Microarray

In flowering plants, the male gametophyte, the pollen, develops in the anther. Complex patterns of gene expression in both the gametophytic and sporophytic tissues of the anther regulate this process. The gene expression profiles of the microspore/pollen and the sporophytic tapetum are of particular interest. In this study, a microarray technique combined with laser microdissection (44K LM-microarray) was developed and used to characterize separately the transcriptomes of the microspore/pollen and tapetum in rice. Expression profiles of 11 known tapetum specific-genes were consistent with previous reports. Based on their spatial and temporal expression patterns, 140 genes which had been previously defined as anther specific were further classified as male gametophyte specific (71 genes, 51%), tapetum-specific (seven genes, 5%) or expressed in both male gametophyte and tapetum (62 genes, 44%). These results indicate that the 44K LM-microarray is a reliable tool to analyze the gene expression profiles of two important cell types in the anther, the microspore/pollen and tapetum

正常眼圧緑内障患者の眼圧日内変動と血圧との関係

正常眼圧緑内障の危険因子として唯一エビデンスが確立されているのは眼圧だけであり,その眼圧の高い値と大きな変動幅が疾患の進行に関与すると言われている.今回筆者らは血圧が正常眼圧緑内障進行の危険因子となりうるか否を検討した.対象は未治療の正常眼圧緑内障患者81例とし各患者の最高眼圧を示す時間帯および,眼圧変動幅を決定した.血圧の検討は収縮期140mmHgあるいは拡張期90mmHg以上を示す患者を高血圧群,収縮期血圧100mmHg以下を示す患者を低血圧群,それ以外の患者を正常血圧群と定義し各群における最高眼圧を示す時間帯,眼圧変動幅を比較した.全81例における平均日内変動幅は4.9mmHgであった.眼圧日内変動測定の結果眼圧が21mmHg以上で開放隅角緑内障と診断名が変更された症例は10例(12%)であった.最高眼圧を示す時間帯では午前型が35例(43.2%),午後型が16例(19.8%),夜型が5例(6.2%),深夜早朝型が21例(25.9%)であった.一方,日内変動幅が3mmHg未満で平坦型と分類されたのは4例(5%)であった.患者血圧群別の分類と眼圧変動幅は低血圧群15例で6.3mmHgと,正常血圧群10例の4.6mmHg,高血圧群56例の4.4mmHgと比較して有意に大きな変動幅を示した.(p<0.05).以上の結果から外来時眼圧が正常眼圧でも,再検で開放隅角緑内障と診断される症例があること,そして低血圧の症例では眼圧変動幅が大きい高いため低血圧が正常眼圧緑内障進行の一つの危険因子になりうると考えられた.Normal tension glaucoma is seen in many cases of glaucoma in Japan. Although this type of glaucoma may cause blindness, the mechanism leading to vision loss has yet to be explained. This disease has no effective treatment or prevention. No evidence exists for other risk factors except for intraocular pressure (IOP). Higher IOP and larger variability of IOP are known to be involved in progression. This study investigated whether blood pressure might be a risk factor for progression of normal tension glaucoma. The subjects were 81 patients with untreated normal tension glaucoma, and diurnal variation of intraocular pressure (IOP) and blood pressure were monitored. As for IOP, the period of time to reach the peak and diurnal variation of IOP were identified. The patients were classified by blood pressure: hypertension group (systolic ≧ 140 mmHg or diastolic ≧ 90 mmHg), hypotension group (systolic ≦ 100 mmHg) and normotension group (not applicable for the above two groups), and the time of the day when peak IOP was reached and diurnal variation of IOP were compared among the three groups. The mean diurnal variation of IOP in the 81 patients was 4.9 mmHg. Ten patients (12%) were diagnosed with open-angle glaucoma, not normal tension glaucoma, because they had IOP of ≧ 21 mmHg. Of 51 patients with a peak IOP in the daytime, 35 patients (43.2%) were morning type (9am - 12noon) and 16 patients (19.8%) were afternoon type (3pm - 6pm). Twenty-six patients had their peak at night: 5 patients (6.2%) were night type (9pm - Oam) and 21 patients (25.9%) were after-midnight to early morning type (3am - 6am) . The remaining 4 patients (5%) were regarded as flat type since their diurnal variations were 3 mmHg or lower. Comparing mean diurnal variations among the three blood pres-sure groups, the hypotension group (6.3 mmHg; n=15) was significantly larger than the normotension group (4.6 mmHg; n=10) and the hypertension group (4.4 mmHg; n=56) (p < 0.05). In conclusion, these results suggest that some patients may be found to have open-angle glaucoma in re-examination even if their IOPs in an outpatient clinic are normal, and that hypotension is potentially a risk factor for progression of normal tension glaucoma because many patients with hypotension show large diurnal variations