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While understanding and expressing causal relations are universal aspects of human cognition, language users may differ in their capacity to perceive, interpret, and express events. One source of variation in descriptions of caused motion events is agentivity, which refers to the attribution of a result to the agent's action. Depending on the perspective taken, the same event may be described with agentive or non-agentive interpretations. Does language play a role in how people construe and express caused motion events? The present study investigated the use of agentive vs. non-agentive language by speakers of different languages (i.e., monolingual speakers of English and Korean, and Korean learners of English). All three groups described prototypical causal events similarly, using agentive language (active transitive sentences). However, when it came to non-prototypical causal events (where the agent was not shown in the scene), they diverged in their choice of language: English speakers favored agentive language (passive transitive sentences), whereas Korean speakers preferred non-agentive language (intransitive sentences). Korean learners of English patterned with Korean speakers, demonstrating L1 influence on their use of English. These findings highlight the effects of language on motion event construal.

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To develop an efficient vector for mitochondria-targeted drug delivery, we synthesized triphenylphosphonium (TPP)-modified glycol chitosan polymeric microspheres that had a unique chemical structure with both lipophilic phenyl groups and cationic phosphonium. Notably, TPP can easily pass through the phospholipid bilayer of mitochondria, thereby resulting in specific accumulation of a combined drug molecule in the mitochondria due to the membrane potential between TPP and its membrane. Therefore, TPP has been widely used as a mitochondria-targeting moiety. Triphenylphosphonium-glycol chitosan derivatives (GC-TPP and GME-TPP) with two different degrees of substitution (11% and 36%) were prepared by amidation and Michael addition. The chemical structures of GC-TPP and GME-TPP were characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectroscopy, and their sizes were measured via field emission scanning electron microscopy and dynamic light scattering. Cellular uptake through flow cytometric analysis and confocal microscopy confirmed that both GC-TPP and GME-TPP were well introduced into cells, targeting the mitochondria. In addition, cytotoxicity testing of the most common cell lines, such as HEK293, HeLa, NIH3T3, and HepG2, indicated the absence of polymer toxicity. To evaluate the carrier effectiveness of TPP for drug delivery, doxorubicin (Dox) was used as an anticancer drug. Confocal microscopy images showed that Dox-loaded GME-TPP accumulated inside cells more than Dox-loaded GC-TPP. The anticancer effects of Dox were also determined by MTT assay, apoptosis/necrosis assay, and three-dimensional spheroids. In summary, the results indicate that GC-TPP and GME-TPP microspheres possess great potential as effective drug delivery carriers.

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BACKGROUND: Borderline personality disorder (BPD) show different course and treatment compared to major depressive disorder (MDD). Early life stress may increase BPD onset; however, resilience may play a protective role against the development of psychopathology. The goal of this study was to compare the early life stress, resilience, and the clinical characteristics of emotional dysregulation in patients with MDD with and without comorbid BPD. METHODS: Thirty patients with both BPD and MDD, 25 patients with MDD alone, and 25 age- and sex- matched healthy controls, participated in this study. Analysis of variance was used to compare the early life stress, resilience, and emotional dysregulation among groups. Also, multivariate logistic regression models were used to identify the relationship of the early life stress and resilience domains with BPD comorbidity within MDD patients. RESULTS: The domains of emotional abuse and self-regulation ability were significantly associated with BPD comorbidity and BPD severity. In emotional dysregulation, difficulty scores of impulsivity, coping strategies, and emotion clarity domains were significantly increased in patients with both BPD and MDD compared to patients with MDD alone. LIMITATIONS: The relatively small sample size may contribute to reduce statistical power of investigation. CONCLUSIONS: Emotional abuse experiences in early life, and deficits in self-regulation, are significantly associated with comorbid BPD in patients with MDD. A comprehensive evaluation including early life stress, resilience and emotion regulation ability may help to identify comorbid BPD in patients with MDD and develop treatment strategies.

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A glycol chitosan-based polymer that spontaneously assembles with plasmid DNA into nanorods was evaluated as a non-viral vector for gene delivery. Glycol chitosan-methyl acrylate-polyethylenimine (GMP) was synthesized by grafting polyethylenimine onto glycol chitosan via amidation after Michael addition using methyl acrylate. Gel retardation and PicoGreen assay experiments showed complete complex formation with plasmid DNA. GMP/pDNA complexes were characterized using biophysical techniques and were found to be positively charged rod-shape structures with widths in the nanometer scale and lengths in the micrometer scale. Transfection efficiency and cytotoxicity of GMP polymer was evaluated in human epithelial ovary carcinoma (HeLa) cells, human embryonic kidney 293 (HEK293) cells, and human hepatocellular liver carcinoma (HepG2) cells, in comparison to high molecular weight polyethylenimine, a commonly used transfection reagent. Intracellular polymer uptake was compared and confirmed by confocal microscopy. The results demonstrate that GMP, a hybrid polymer of glycol chitosan grafted with branched polyethylenimine, may serve as a promising vehicle for efficient gene delivery.

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Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR), consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.

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