Proof validation and modification by example generation: A classroom-based intervention in secondary school geometry

ArticleProceedings of the 13th International Congress on Mathematical Education (ICME-13). Hamburg, Germany, 2016-7-24/31, ICME. (2016)journal articl

DFL2, a New Member of the Arabidopsis GH3 Gene Family, is Involved in Red Light-Specific Hypocotyl Elongation

A new GH3-related gene, designated DFL2, causes a short hypocotyl phenotype when overexpressed under red and blue light and a long hypocotyl when antisensed under red light conditions. Higher expression of this gene was observed in continuous white, blue and far-red light but the expression level was low in red light and darkness. DFL2 gene expression was induced transiently with red light pulse treatment. DFL2 transgenic plants exhibited a normal root phenotype including primary root elongation and lateral root formation, although primary root elongation was inhibited in antisense transgenic plants only under red light. The adult phenotypes of sense and antisense transgenic plants were not different from that of wild type. DFL2 promoter activity was observed in the hypocotyl. Our results suggest that DFL2 is located downstream of red light signal transduction and determines the degree of hypocotyl elongation.publishersversionPeer reviewe

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

Purpose: To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods: This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results: The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P＜0.001), neutrophils and MMP-9 (P＜0.001), macrophages and KL-6 (P＜0.01), total cell count and IL-8 (P＜0.05), neutrophils and IL-8 (P＜0.05), and macrophages and MMP-9 (P＜0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P＜0.005) and neutrophils (P＜0.005) in sputum. Conclusion: These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan

Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials

Hypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET®2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph®) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP

Roles of 5-HT1A receptor in the expression of AMPA receptor and BDNF in developing mouse cortical neurons

The possible interactions between serotonergic and glutamatergic systems during neural development and under the pathogenesis of depression remain unclear. We now investigated roles of 5-HT1A receptor in the mRNA expression of AMPA receptor subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18 were cultured for 3 days or 14 days and then treated with 5-HT1A receptor agonist (8-OH-DPAT) for 3 h or 24 h. In neurons cultured for 3 days, 8-OH-DPAT treatment for both 3 h and 24 h increased the mRNA levels of BDNF and GluR1, but not GluR2. In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA levels. Next, we examined in vivo roles of 5-HT1A receptor by administration of 8-OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH-DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no effects on the mRNA expression of GluR1 and GluR2. Taken together, the present study suggests that 5-HT1A receptor activation modulates mRNA expression of AMPA receptor subunit and BDNF in cortical neurons, and the effects are different between in vitro and in vivo

Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609

Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5′AMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKα and CaMKKβ) with a similar potency (Ki = 0.35 μM for CaMKKα, and Ki = 0.2 μM for CaMKKβ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of ∼0.3 μM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases

A mid term comparison of open wedge high tibial osteotomy vs unicompartmental knee arthroplasty for medial compartment osteoarthritis of the knee

<p>Abstract</p> <p>Background</p> <p>The choice of surgical treatments for unicompartmental osteoarthritis (OA) of the knee is still somewhat controversial. Midterm results from cases treated using unicompartmental knee arthroplasty (UKA) or open wedge high tibial osteotomy (OWHTO) were evaluated retrospectively.</p> <p>Methods</p> <p>Twenty-seven knees of 24 patients with varus deformities underwent OWHTO and 30 knees of 18 patients underwent UKA surgeries for the treatment of medial compartmental osteoarthritis (OA). The KSS score, FTA, range of motion and complications were evaluated before and after surgery.</p> <p>Results</p> <p>The preoperative mean KSS scores were 49 points in the OWHTO group and 62 in the UKA group which improved postoperatively to 89 (excellent; 19 knees, good; 8 knees), and 88 (excellent; 25, good; 4, fair; 1), respectively. There was no significant difference between the OWHTO and UKA scores. Seventeen patients in the OWHTO group could sit comfortably in the formal Japanese style after surgery. The preoperative mean FTA values for the OWHTO and UKA groups were 182 degrees and 184, and at follow-up measured 169 and 170, respectively. In the UKA group, the femoral component and the polyethylene insertion in one patient was exchanged at 5 years post-surgery and revision TKAs were performed in 2 cases. In the OWHTO group, one tibial plateau fracture and one subcutaneous tissue infection were noted.</p> <p>Conclusions</p> <p>Treatment options should be carefully considered for each OA patient in accordance with their activity levels, grade of advanced OA, age, and range of motion of the knee. OWHTO shows an improved indication for active patients with a good range of motion of the knee.</p