Pragmatic Awareness of Japanese EFL Learners in Relation to Individual Differences: A Cluster Analytic Approach

This study investigated the relationships between pragmatic awareness and learner types drawn from pro les of learners’ motivation and pro ciency, thus providing insight into the interplay of learner factors in contrast to previous studies describing the relationships between single variables. In addition to a modi ed replication of Bardovi-Harlig and Dörnyei’s (1998) study in the Japanese EFL context, this study incorporated measures of motivation based on Self-Determination Theory and learners’ pro ciency. Cluster analysis sorted 69 Japanese EFL learners into three distinct subgroups based on their con guration of motivation and pro ciency; in particular, they differed on their levels of intrinsic motivation and pro ciency. Their pragmatic awareness was later compared by use of one-way ANOVA. The results illustrated that two groups with more self-determined motivation showed sharper perception of pragmatic inappropriateness than the group with lower intrinsic motivation, even though its pro ciency was higher. Based on the “noticing hypothesis” (Schmidt, 1995), we propose that intrinsically motivated learners are likely to process L2 pragmatic input at the level of ‘understanding,’ whereas those with lower motivational pro les only ‘notice the form’ but do not process it at the ‘understanding’ level. Proficiency is not in itself a suffcient condition for enabling ‘understanding.

The First Interferometric Measurements of NH2D/NH3 Ratio in Hot Corinos

The chemical evolution of nitrogen during star and planet formation is still not fully understood. Ammonia (NH3) is a key specie in the understanding of the molecular evolution in star-forming clouds and nitrogen isotope fractionation. In this paper, we present high-spatial-resolution observations of multiple emission lines of NH3 toward the protobinary system NGC1333 IRAS4A with the Karl G. Jansky Very Large Array. We spatially resolved the binary (hereafter, 4A1 and 4A2) and detected compact emission of NH3 transitions with high excitation energies (≳100 K) from the vicinity of the protostars, indicating the NH3 ice has sublimated at the inner hot region. The NH3 column density is estimated to be ∼1017-1018 cm−2. We also detected two NH2D transitions, allowing us to constrain the deuterium fractionation of ammonia. The NH2D/NH3 ratios are as high as ∼0.3-1 in both 4A1 and 4A2. From comparisons with the astrochemical models in the literature, the high NH2D/NH3 ratios suggest that the formation of NH3 ices mainly started in the prestellar phase after the formation of bulk water ice finished, and that the primary nitrogen reservoir in the star-forming cloud could be atomic nitrogen (or N atoms) rather than nitrogen-bearing species such as N2 and NH3. The implications on the physical properties of IRAS4A’s cores are discussed as well

The First Interferometric Measurements of NH₂D/NH₃ Ratio in Hot Corinos

The chemical evolution of nitrogen during star and planet formation is still not fully understood. Ammonia (NH_{3}) is a key specie in the understanding of the molecular evolution in star-forming clouds and nitrogen isotope fractionation. In this paper, we present high-spatial-resolution observations of multiple emission lines of NH_{3} toward the protobinary system NGC1333 IRAS4A with the Karl G. Jansky Very Large Array. We spatially resolved the binary (hereafter, 4A1 and 4A2) and detected compact emission of NH3 transitions with high excitation energies (≳100 K) from the vicinity of the protostars, indicating the NH_{3} ice has sublimated at the inner hot region. The NH3 column density is estimated to be ∼10^{17}–10^{18} cm^{−2}. We also detected two NH_{2}D transitions, allowing us to constrain the deuterium fractionation of ammonia. The NH_{2}D/NH_{3} ratios are as high as ∼0.3–1 in both 4A1 and 4A2. From comparisons with the astrochemical models in the literature, the high NH_{2}D/NH_{3} ratios suggest that the formation of NH3 ices mainly started in the prestellar phase after the formation of bulk water ice finished, and that the primary nitrogen reservoir in the star-forming cloud could be atomic nitrogen (or N atoms) rather than nitrogen-bearing species such as N_{2} and NH_{3}. The implications on the physical properties of IRAS4A's cores are discussed as well

Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model

ヒトiPS細胞分化モデルを用いた膵内胚葉分化におけるHHEXの役割の解明. 京都大学プレスリリース. 2023-06-09.Identification of HHEX as a crucial factor in pancreatic endoderm differentiation using a human iPS cell differentiation model. 京都大学プレスリリース. 2023-06-15.For pluripotent stem cell (PSC)-based regenerative therapy against diabetes, the differentiation efficiency to pancreatic lineage cells needs to be improved based on the mechanistic understanding of pancreatic differentiation. Here, we aimed to elucidate the molecular mechanisms underlying pancreatic endoderm differentiation by searching for factors that regulate a crucial pancreatic endoderm marker gene, NKX6.1. Unbiasedly screening an siRNA knockdown library, we identified a candidate transcription factor, HHEX. HHEX knockdown suppressed the expression of another pancreatic endoderm marker gene, PTF1A, as well as NKX6.1, independently of PDX1, a known regulator of NKX6.1 expression. In contrast, the overexpression of HHEX upregulated the expressions of NKX6.1 and PTF1A. RNA-seq analysis showed decreased expressions of several genes related to pancreatic development, such as NKX6.1, PTF1A, ONECUT1 and ONECUT3, in HHEX knockdown pancreatic endoderm. These results suggest that HHEX plays a key role in pancreatic endoderm differentiation

Antitumor Effects of a Sirtuin Inhibitor, Tenovin-6, against Gastric Cancer Cells via Death Receptor 5 Up-Regulation

Up-regulated sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53). Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5). In the KatoIII cell line (TP53-null), DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors

Physcomitrella patens Has Kinase-LRR R Gene Homologs and Interacting Proteins

Peer reviewe

Augmented antitumor activity of 5‐fluorouracil by double knockdown of MDM4 and MDM2 in colon and gastric cancer cells

Inactivation of the TP53 tumor suppressor gene is essential during cancer development and progression. Mutations of TP53 are often missense and occur in various human cancers. In some fraction of wild‐type (wt) TP53 tumors, p53 is inactivated by upregulated murine double minute homolog 2 (MDM2) and MDM4. We previously reported that simultaneous knockdown of MDM4 and MDM2 using synthetic DNA‐modified siRNAs revived p53 activity and synergistically inhibited in vitro cell growth in cancer cells with wt TP53 and high MDM4 expression (wtTP53/highMDM4). In the present study, MDM4/MDM2 double knockdown with the siRNAs enhanced 5‐fluorouracil (5‐FU)‐induced p53 activation, arrested the cell cycle at G1 phase, and potentiated the antitumor effect of 5‐FU in wtTP53/highMDM4 human colon (HCT116 and LoVo) and gastric (SNU‐1 and NUGC‐4) cancer cells. Exposure to 5‐FU alone induced MDM2 as well as p21 and PUMA by p53 activation. As p53‐MDM2 forms a negative feedback loop, enhancement of the antitumor effect of 5‐FU by MDM4/MDM2 double knockdown could be attributed to blocking of the feedback mechanism in addition to direct suppression of these p53 antagonists. Intratumor injection of the MDM4/MDM2 siRNAs suppressed in vivo tumor growth and boosted the antitumor effect of 5‐FU in an athymic mouse xenograft model using HCT116 cells. These results suggest that a combination of MDM4/MDM2 knockdown and conventional cytotoxic drugs could be a promising treatment strategy for wtTP53/highMDM4 gastrointestinal cancers

抗体クラススィッチ過程の活性化自由エネルギー

Membrane-bound form IgM (IgM_m) and total IgM (IgM_t) transcriptions were measured by real time PCR method in the thymus and the spleen of BALB/c male mice and the change of logIgMmagMt ratios with age were detected. Kinetics was applied and both the rate constant k_1, corresponding to the process in which IgM_mtranscribing cells differentiate into ones transcribing secretory type IgM and k_2, corresponding to the process in which those into cells transcribing other class Ig, were determined. ΔG_1^* and ΔG_2^*, free energy of activation corresponding to k_1 and k_2 process in each, were calculated from k_1 and k_2 by application of theory of absolute reaction rate. ΔG_1^* and ΔG_2^* were 110 to 120 kJ/mol both in the thymus and in the spleen. By considering the phenomenal differences in k_1 and k_2 processes, the difference of ΔG_2^* and ΔG_1^* might be able to regard as the free energy of immunoglobulin class switch process ΔG_c^* . The values of ΔG_c^* were small unexpectedly, 2. 9 kJ/mol in the thymus and 5. 7 kJ/mol in the spleen