キョウイン ヨウセイ ニオケル ズガ コウサク リッタイ ヒョウゲン ノ カダイ ケンキュウ : ネンド ゾウケイ ノ ジュギョウ ジッセン ナイヨウ オ チュウシン ニ

In the New Guidelines for teaching arts and crafts in elementary schools, "What will become possible?" is an assessment criterion with the aim of developing students\u27 abilities in relation to the three common pillars of each subject. Students who aspire to be arts and crafts teachers must have a certain level of practical skills to expand the lesson. Hence, we examined whether the process of competence development for student modeling is appropriate in arts and crafts, which the author is responsible for. To improve proficiency in production techniques, we found that it was effective to add the purpose of creation to the creative approach envisioned from the materials

Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells

Cancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan-HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)-amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2-amplified gastric cancer cells. Two afatinib-resistant gastric cancer cell lines were established from 2 HER2-amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87-derived resistant cells, whereas it was upregulated in SNU216-derived resistant cells. In the N87-derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216-derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2-driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance

Diseño de sistema de alcantarillado sanitario y ampliación del sistema de agua potable del Barrio Villa Vallarta en la Ciudad de Managua

El presente estudio monográfico denominado "DISEÑO DEL SISTEMA DE ALCANTARILLADO SANITARIO Y AMPLIACIÓN DEL SISTEMA DE AGUA POTABLE EN EL BARRIO VILLA VALLARTA'', tiene como propósito mejorar las condiciones higiénico-sanitarias de la población, djsminuir el índice de mortalidad infantil y promover cambios de comportamientos en los miembros de las familias beneficiadas, para que mejoren su nivel de vida. EI Barrio Villa Vallarta se encuentra ubicado en la parie Nor-Este de la ciudad de Managua, localizándose en la zona alta del Acueducto de Managua; específicamente está ubicado en el Distrito No. Vl de la municipalidad de Managua. Se caracteriza por ser una zona de alta densidad debido que en dicho Barrio se encuentran construcciones sencillas y lotes con dimensiones y áreas homogéneas, de aproximadamente | 05 m2. Esta conformado por 393 viviendas,13 manzanas, 9 calles y 3 avenidas, alcanzando un área total de aproximadamente 67, 327.81 m2, incluyendo calles, avenidas y un área comunal de 1,575.45 m2 La calles miden aproximadamente 750.45 m2 Para formular el estudio monográfico, primeramente se realizó un diagnóstico situacional a través de ntrevistas y encuesta dirigidas. a funcionarios, líderes comunales y familias del Barrio. Posteriormente se efectuará el estudio topográfico y el estudio de suelo para conocer las características del terreno y la clasificación o tipo de suelo que predomina en el Barrio. Además se realizó la valoración del Sistema de Alcantarillado Sanitario y Sistema de Agua Potable existente

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations

チイキ ノ トクセイ オ イカシタ チュウガッコウ ビジュツカ ノ キョウイク ナイヨウ : ビジュツ キョウイク ノ ラーニング リソース トシテノ トクシマ ブンカザイ タンキュウ

In Japan\u27s education that has a centralized character, how to reflect the environment surrounding schools into the educational contents is one of the important themes. Regarding the contents of art subject, it is often taken up as masterpieces of Western art and Japanese national treasures in the domain of appreciation. As the subject of learning, Masterpieces of Western art and the national treasure of Japan occupy the center position. Although we have no objection of learning on such learning subjects to guarantee the quality of education, we will emphasize the value of cultural properties more familiar to our students on this paper. Because we recognize that Japanese education is at a turning point shifting to so−called "active learning" inducing learners\u27 subjective studies. Based on these recognitions, we\u27ll examine the reason why learning about the familiar cultural properties promoting the subjective learning. In order to avoid showing only abstract debate and to suggest proposal for teaching materialization, Tokushima cultural heritage will be taken up as learning resources and we\u27ll discuss the methods and procedures how to incorporate them into the content of art classes in junior high school

ARTADE2DB: Improved Statistical Inferences for Arabidopsis Gene Functions and Structure Predictions by Dynamic Structure-Based Dynamic Expression (DSDE) Analyses

Recent advances in technologies for observing high-resolution genomic activities, such as whole-genome tiling arrays and high-throughput sequencers, provide detailed information for understanding genome functions. However, the functions of 50% of known Arabidopsis thaliana genes remain unknown or are annotated only on the basis of static analyses such as protein motifs or similarities. In this paper, we describe dynamic structure-based dynamic expression (DSDE) analysis, which sequentially predicts both structural and functional features of transcripts. We show that DSDE analysis inferred gene functions 12% more precisely than static structure-based dynamic expression (SSDE) analysis or conventional co-expression analysis based on previously determined gene structures of A. thaliana. This result suggests that more precise structural information than the fixed conventional annotated structures is crucial for co-expression analysis in systems biology of transcriptional regulation and dynamics. Our DSDE method, ARabidopsis Tiling-Array-based Detection of Exons version 2 and over-representation analysis (ARTADE2-ORA), precisely predicts each gene structure by combining two statistical analyses: a probe-wise co-expression analysis of multiple transcriptome measurements and a Markov model analysis of genome sequences. ARTADE2-ORA successfully identified the true functions of about 90% of functionally annotated genes, inferred the functions of 98% of functionally unknown genes and predicted 1,489 new gene structures and functions. We developed a database ARTADE2DB that integrates not only the information predicted by ARTADE2-ORA but also annotations and other functional information, such as phenotypes and literature citations, and is expected to contribute to the study of the functional genomics of A. thaliana. URL: http://artade.org

ズガ コウサクカ カラ ビジュツカ ソシテ ビジュツ エ ソノ ヒロガリ ト ツナガリ ノ ケントウ : キョウカショ デ オシエラレテイル コト オシエラレテイナイ コト オシエルベキ コト

Courses of Study clearly define what to teach in Course of Arts and Crafts, and the manual of Courses of Study concretely explained that in detail. In Course of Arts and Crafts, Teacher proposes activities as "subject matter" which includes contents of instruction. Textbook can be thought of as collection of subject matters. Course of Arts and Crafts is connected to Course of Arts in junior high school in many contents, and the next stage is Arts in culture. In this paper, we will investigate today’s contents of subject matter in Course of Arts and Crafts from the view point of Arts as culture. This investigation explains what is not treated in current Course of Arts and Crafts and what to be treated as Course of Arts and Crafts in future

Interaction between NANOS2 and the CCR4-NOT Deadenylation Complex Is Essential for Male Germ Cell Development in Mouse

Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs) of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10) fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s) that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection