Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure

AbstractK103N mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confers high-level resistance against non-nucleoside RT inhibitors (NNRTIs) and it easily occurs partly because it arises by a single nucleotide substitution from wild-type K103. There are polymorphisms at codon 103 of HIV-1 RT. We found K103R polymorphic mutation in 3.3% of treatment-naive HIV-1-infected patients. R103N does not seem to occur as easily as K103N because R103N requires two nucleotide substitutions. To induce NNRTI resistance-associated mutations, HIV-1K103R was propagated in the presence of increasing concentrations of efavirez (EFV) or nevirapine (NVP). V179D emerged in all three EFV cultures and in two of four NVP cultures. R103G emerged by a single nucleotide substitution in one of three EFV cultures. R103N did not emerge in any of 7 NNRTI cultures. Analysis of recombinant HIV-1s showed that HIV-1K103R/V179D was significantly resistant and HIV-1K103G was moderately resistant against EFV and NVP

Influencia de la entonación española en la percepción del acento por parte de estudiantes japoneses

Japanese learners of Spanish sometimes fail to perceive the stresses when listening to Spanish utterances. Results of a perceptual experiment with 270 stimuli and 94 informants (43 Spanish and 51 Japanese) reveal that, while Spanish speakers perceive the stresses with great certainty in all the studied contexts, Japanese speakers tend to fail to do so when the word is pronounced with rising intonation. The cause of this is the difference in phonetic realizations of Spanish stresses and those of Japanese accents. Japanese learners should be taught that the Spanish stressed syllables are not always pronounced with a high pitch.Los estudiantes japoneses de español no siempre son capaces de percibir los acentos al escuchar enunciados en dicho idioma. Los resultados de un experimento de percepción con 270 estímulos y 94 sujetos (43 españoles y 51 japoneses) revelan que, mientras los hablantes nativos de español pueden hacerlo con mucha certeza en todas las situaciones estudiadas, los hablantes de japonés tienden a no poder hacerlo cuando la palabra es pronunciada con una entonación ascendente. Esto se debe a la diferencia entre las realizaciones fonéticas de los acentos españoles y las de los acentos japoneses. Se debería instruir a los estudiantes japoneses que las sílabas acentuadas del español no siempre se pronuncian con un tono alto

大学生のメンタルヘルス教育－メンタルヘルスに関する意識調査より－ : 研究調査報告

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新入生におけるGHQの基礎資料 : 研究調査報告

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Mineral trioxide aggregate induces osteoblastogenesis via Atf6

AbstractMineral trioxide aggregate (MTA) has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III) and matrix metalloproteinases (MMP-9 and MMP-13), suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin) but not Bmp2 (bone morphogenetic protein-2) mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER) stress response transcription factor) mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6) markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection