‘Aboutness’ Relation in Japanese Topicalization: An Analysis of the NP1 wa NP2 da Construction

This study investigates the comprehension of a Japanese topicalized construction with the structure NP1 wa (topic) NP2 da (copula) by native speakers of Japanese. The meaning of this kind of sentence can be extremely ambiguous when NP1 and NP2 do not refer to an identical referent. However, it is usually not considered ambiguous when used in a particular context since the context indicates how it is meant to be understood. This study examines the uses of this construction in experimentally controlled contexts. The results indicate the significant effects of the syntactic or semantic relation with the particular verb in the context and the NP2 or information about a particular place presented by a locative frame. These results facilitate a new understanding of the ‘aboutness’ relation, which is established through the process of interpreting an NP1 wa NP2 da sentence in the context

Understanding and Interpreting Japanese NP1 WA NP2 DA Sentences: Mechanism and Contextual Factors

This dissertation investigates the contextual factors that affect the understanding and interpretation of one Japanese topicalized construction, NP1 wa NP2 da sentences, by native speakers of Japanese. The construction allows two possibilities in the relation between the NP1 and the NP2. When the two NPs are not syntactically connected (Type I), the sentence is generally vague, and a particular context is required to specify the meaning. When they are syntactically connected (Type II), they can refer to a semantically identical referent, and the sentence is naturally interpreted as an identity sentence. The aim of the study is to examine how context determines the meaning of Type I and Type II NP1 wa NP2 da sentences. These sentences were examined in a set of controlled experimental contexts by two kinds of test: Understandability and Interpretation. Results showed that readers generally tried to connect the NP 1 wa NP2 da sentences to the context syntactically, semantically, or pragmatically when the sentences were presented in a context. Specifically, a syntactic and semantic relation with a particular verb in the preceding context sentence and the NP2 or information about a particular place presented by a locative frame enhanced the comprehension of Type I NP1 wa NP2 da sentences. When these contextual factors were presented consistently and appropriately, Type II NP1 wa NP2 da sentences could be interpreted as non-identity sentences. When such context was not available, the interpretations tended to depend on the sentence-internal conceptual connection between the NP1 and the NP2 in both types of NP1 wa NP2 da sentences. These results suggest the reader\u27s use of their linguistic and pragmatic knowledge differs according to the context and sentence type. The results also reveal a new understanding of the \u27aboutness\u27 relation, a notion that accounts for the non-syntactic connections between the topic and the predicate. Specifically, in the process of understanding NP1 wa NP2 da sentences, establishing an \u27aboutness\u27 relation refers to the process of finding an appropriate predicate in the context to create a proposition to connect the predicate (NP2) to the topic NP (NP1)

Inhibition and Adjective Learning in Bilingual and Monolingual Children

The ability to control attention – by inhibiting pre-potent, yet no longer relevant information – is an essential skill in all of human learning, and increasing evidence suggests that this ability is enhanced in language learning environments in which the learner is managing and using more than one language. One question waiting to be addressed is whether such efficient attentional control plays a role in word learning. That is, children who must manage two languages also must manage to learn two languages and the advantages of more efficient attentional control may benefit aspects of language learning within each language. This study compared bilingual and monolingual children’s performances in an artificial word-learning task and in a non-linguistic task that measures attention control. Three-year-old monolingual and bilingual children with similar vocabulary development participated in these tasks. The results replicate earlier work showing advanced attentional control among bilingual children and suggest that this better attentional control may also benefit better performance in novel adjective learning. The findings provide the first direct evidence of a relation between performances in an artificial word-learning task and in an attentional control task. We discuss this finding with respect to the general relevance of attentional control for lexical learning in all children and with respect to current views of bilingual children’s word learning

Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

転写因子HAND1とHAND2の発現パターンと役割の解明 --ヒトiPS細胞から増殖能の高い心筋細胞を回収する--. 京都大学プレスリリース. 2021-07-27.Three genes determine heart cell growth. 京都大学プレスリリース. 2021-07-27.Hand1 and Hand2 are transcriptional factors, and knockout mice of these genes show left and right ventricular hypoplasia, respectively. However, their function and expression in human cardiogenesis are not well studied. To delineate their expressions and assess their functions in human cardiomyocytes (CMs) in vitro, we established two triple-reporter human induced pluripotent stem cell lines that express HAND1[mCherry], HAND2[EGFP] and either MYH6-driven iRFP670 or tagBFP constitutively and investigated their expression dynamics during cardiac differentiation. On day 5 of the differentiation, HAND1 expression marked cardiac progenitor cells. We profiled the CM subpopulations on day 20 with RNA sequencing and found that mCherry+ CMs showed higher proliferative ability than mCherry− CMs and identified a gene network of LEF1, HAND1, and HAND2 to regulate proliferation in CMs. Finally, we identified CD105 as a surface marker of highly proliferative CMs

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet

Background Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Methods Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. Results After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. Conclusions Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression

Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification

<p>Abstract</p> <p>Background</p> <p>Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9.</p> <p>Results</p> <p>CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain <it>in vivo </it>and <it>in vitro</it>. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating <it>Cyclin D1 </it>expression and cell cycle progression of chondrocytes.</p> <p>Conclusion</p> <p>These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.</p

CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells

CDH18は胎児期の心外膜細胞の指標であり胎児心外膜から平滑筋細胞の分化を制御している. 京都大学プレスリリース. 2022-02-09.Using stem cells to regenerate the heart. 京都大学プレスリリース. 2022-02-09.The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) via epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a biomarker defining lineage specification in human active epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results highlight the importance of tracing CDH18 expression in hiPSC-derived epicardial cells, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells